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From neuroimaging to patients' bench: what we have learnt from trigemino-autonomic pain syndromes.
Trigeminal autonomic cephalalgias (TACs) are primary headaches including cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). A number of neuroimaging studies have been conducted in last decade showing involvement of brain areas included in the pain matrix. Apart from pain matrix involvement, other neuroimaging findings data deserve special attention. The hypothalamic activation reported in the course of TAC attacks coupled with the efficacy of hypothalamic neurostimulation to treat drug-resistant TAC forms clearly indicate the posterior hypothalamus as a crucial area in TAC pathophysiology. In animal models this brain area has been shown to modulate craniofacial pain; moreover, hypothalamic activation occurs in other pain conditions, suggesting that posterior hypothalamus has a more complex role in TAC pathophysiology rather than simply being considered as a trigger. In contrast, hypothalamic activation may serve as a crucial area in terminating rather than triggering attacks. It also could lead to a central condition facilitating initiation of TAC attacks.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effects of cytokines on nitric oxide pathways in human vasculature.
Proinflammatory cytokines exert a number of important effects on vascular reactivity. At one end of the spectrum, certain cytokines may induce vascular paresis leading to profound vasodilatation and hyporesponsiveness to constrictor stimuli. This may be relevant to the pathogenesis of septic shock and other types of inflammatory vasodilatation. At the other end of the spectrum, inflammatory cytokines can impair endothelium-dependent dilatation and the endothelium may lose its ability to respond to circulating hormones or autacoids. This effect may case a predisposition to vessel spasm, thrombosis or atherogenesis. Studies in human vessels suggest that interleukin-1 is particularly important as a mediator of inflammatory dilatation; the underlying mechanisms include induction of the inducible isoform of nitric oxide synthase in vascular smooth muscle, or over-production of nitric oxide from the endothelial isoform of nitric oxide synthase. Induction of the enzyme GTP cyclohydrolase 1 and consequent production of tetrahydrobiopterin contributes to the increase in the activity of endothelial nitric oxide synthase. In contrast, tumour necrosis factor-alpha considerably impairs endothelium-dependent relaxation. The mechanisms of these effects are not yet fully understood, but tumour necrosis factor can induce endothelial dysfunction in human endothelial cells in culture, and human blood vessels in vitro and in vivo. The implications of these observations for cardiovascular disease are discussed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Evaluation of laparoscopic-assisted ovariohysterectomy for treatment of canine pyometra.
To describe a technique for treating pyometra in dogs using a 3-portal laparoscopic-assisted ovariohysterectomy (LAOVH) and evaluate outcome. Retrospective case series. Dogs (n = 12). Dogs with open or closed-cervix pyometra with moderately sized (1-4 cm) uterine horn diameters based on preoperative ultrasonography and no evidence of perforation were included in the study. A 3-portal technique for LAOVH was used. A wound retraction device was inserted into the caudal portal after enlargement of the incision to 3-4 cm to simplify removal of the uterus with minimal tension. Twelve dogs (median weight, 23.3 kg; range, 2.1-46.0 kg) met the inclusion criteria. Median uterine diameter was 3.0 cm (range, 1.2-4.0 cm). Median surgical time for LAOVH was 107 minutes (range, 82-120 minutes). Complications included mild hemorrhage from the uterine vessels in 1 dog during uterine removal through the wound retraction device and intra-abdominal uterine rupture in 1 dog which necessitated conversion to an open approach. All dogs recovered from surgery and were discharged. LAOVH can be used for treatment of select cases of canine pyometra. Careful case selection is mandatory to improve success and minimize conversion to an open approach. Gentle handling of the reproductive organs is imperative to avoid iatrogenic uterine rupture.
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{
"pile_set_name": "PubMed Abstracts"
}
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The time and history-dependent viscoelastic properties of the canine medical collateral ligament.
The viscoelastic properties of the canine medial collateral ligament (MCL) were investigated. Stress-strain relationships at different strain rates, long-term stress relaxation and cyclic stress-strain curves of the MCL were obtained experimentally using a bone-MCL-bone preparation. The experimental data were used in conjunction with the quasi-linear viscoelastic theory as proposed by Fung [15] to characterize the reduced relaxation function, G(t) and elastic response sigma e (epsilon) of this tissue. It was found that the quasi-linear viscoelastic theory can adequately describe the time and history-dependent rheological properties of the canine medial collateral ligament.
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{
"pile_set_name": "PubMed Abstracts"
}
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Measurement methods of drug consumption as a secondary judgment criterion for clinical trials in chronic rheumatic diseases.
Drug consumption is sometimes used as a secondary judgment criterion for clinical trials. Many measurement methods are available to quantify drug consumption. Several methods were applied in a rheumatic disease trial involving 121 patients with chronic low back pain who lived around Saint-Nectaire, France, and who participated in the trial from April to November 1993 to determine an easily used and practical measurement method to detect a significant drug consumption change over time. Analgesic and nonsteroidal antiinflammatory drugs (NSAIDs) were classified according to the anatomical therapeutic chemical classification. Consumption was quantified on a weekly basis in number of tablets (method 1), unit of defined daily dose (method 2), milligrams of active principle (method 3), and NSAID equivalence score (method 4). These methods were applied in a randomized clinical trial of spa therapy on sufferers of chronic low back pain. An analysis of variance with repeated measures showed a significant difference in drug consumption between treatment and control groups detected by all methods, except for the NSAID consumption measured with method 3. The comparison of each method by the relative efficiency index indicated that method 1 had a greater sensitivity for detecting changes of drug consumption. Tablet count appears to be a more sensitive and more practical method for detecting a drug consumption change in clinical trials.
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{
"pile_set_name": "PubMed Abstracts"
}
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Virus-like peptide vaccines against Abeta N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant.
Immunotherapy against the Abeta peptide is increasingly viewed as an effective means of preventing and even decreasing Abeta deposition in transgenic mouse models and human cases of Alzheimer's disease. A prior active immunization trial was halted due to adverse events which occurred subsequent to a change in the adjuvant used in the vaccine preparation. Although widely used in experimental studies, adjuvants available for use in vaccines intended for humans are limited. We compared two vaccine preparations in which an immunogenic bacteriophage was conjugated with either an N-terminal (Abeta1-9) or C-terminal (Abeta28-40) peptide sequence from the Abeta molecule. We found that both produced significant antibody titers without use of additional adjuvants. Surprisingly, the response to the N terminal sequence was comprised largely of a stable IgM response, while the C-terminal vaccine produced an IgG response with minimal IgM reactivity. Both of these immunogens reduced Abeta levels when tissues were examined 8 months after the first inoculation. These data demonstrate that (a) C-terminal specific vaccines can effectively lower Abeta and (b) IgM antibodies against Abeta may be capable of lowering Abeta, possibly through action in the brain rather than the periphery.
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{
"pile_set_name": "PubMed Abstracts"
}
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MicroRNAs as regulators and effectors of hematopoietic transcription factors.
Hematopoiesis is a highly-regulated development process orchestrated by lineage-specific transcription factors that direct the generation of all mature blood cells types, including red blood cells, megakaryocytes, granulocytes, monocytes, and lymphocytes. Under homeostatic conditions, the hematopoietic system of the typical adult generates over 1011 blood cells daily throughout life. In addition, hematopoiesis must be responsive to acute challenges due to blood loss or infection. MicroRNAs (miRs) cooperate with transcription factors to regulate all aspects of hematopoiesis, including stem cell maintenance, lineage selection, cell expansion, and terminal differentiation. Distinct miR expression patterns are associated with specific hematopoietic lineages and stages of differentiation and functional analyses have elucidated essential roles for miRs in regulating cell transitions, lineage selection, maturation, and function. MiRs function as downstream effectors of hematopoietic transcription factors and as upstream regulators to control transcription factor levels. Multiple miRs have been shown to play essential roles. Regulatory networks comprised of differentially expressed lineage-specific miRs and hematopoietic transcription factors are involved in controlling the quiescence and self-renewal of hematopoietic stem cells as well as proliferation and differentiation of lineage-specific progenitor cells during erythropoiesis, myelopoiesis, and lymphopoiesis. This review focuses on hematopoietic miRs that function as upstream regulators of central hematopoietic transcription factors required for normal hematopoiesis. This article is categorized under: RNA in Disease and Development > RNA in Development Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
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{
"pile_set_name": "PubMed Abstracts"
}
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Optical liquid ring resonator sensor.
We demonstrate a robust and highly responsive optical microsensor, which probes the refractive index of liquids flowing along a ~ 100 mum radius channel formed in a polymer matrix. Sensing is based on measurement of the transmission spectrum of the whispering gallery modes, which are excited across the liquid channel by an optical microfiber imbedded into the polymer. The achieved sensitivity is 800 nm/RIU. Potentially, it is straightforward to assemble the sensing elements of this type into a lab-on-the-chip imbedded in a solidified optical material.
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{
"pile_set_name": "PubMed Abstracts"
}
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Morphological study of vascular dissemination in a metastatic hepatocellular carcinoma model in the monkey.
In this report we describe a metastatic monkey hepatocellular carcinoma (HCC) model in which intravascular metastatic development is clearly evident. The tumor-bearing livers contained intravenous tumor thrombi at different stages of progression within the small branches of the portal vein. These ranged from mural tumor thrombi lined with CD31-positive endothelial cells to tumor thrombi that had completely occluded the vascular lumen. Intravenous tumor expansion was frequently accompanied by the appearance of CD31-positive microvessels within the tumor thrombi and fibrous perivascular thickening, giving rise to isolated tumor nodules within the portal areas. Intravascular expansion of disseminating HCC was also evident within small branches of the pulmonary arteries in the lungs. These findings indicate that metastases of HCC can become established while still at an intravascular stage, suggesting that the direct interaction between tumor cells and parenchymal cells predicted from experimental rodent metastasis models is not a prerequisite for the metastatic development of these tumors.
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{
"pile_set_name": "PubMed Abstracts"
}
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Ca2+-movements in muscle modulated by the state of K+-channels in the sarcoplasmic reticulum membranes.
1. A procedure has been developed to load Ca2+ reversibly by the sarcoplasmic reticulum (SR) of mechanically skinned muscle fibres from the toad Bufo marinus under controlled conditions and was employed to investigate the effects of conditions known to reduce the K+ conductance located in the SR-membrane during Ca2+-loading on the amount of Ca2+ releasable by caffeine. 2. The amount of releasable Ca2+ was markedly increased compared to controls when 4-aminopyridine (4AP) (6 microM to 2 mM), tetraethylammonium (TEA), decamethonium (0.5 mM) or procaine (1 mM) were present in the Ca2+-loading solutions. All these substances are known to act as SR-K+-channel blockers. 3. The increased amount of releasable Ca2+ in the presence of the K+-channel blocker 4AP was observed both at low (0.3 mM) and at higher (1 mM) Mg2+ concentrations and was not affected by verapamil (20 microM), a known Ca2+-channel blocker of the sarcolemma nor by the Na+-K+ pump inhibitor, ouabain (1 mM). 4. In the presence of 0.1-5 microM ruthenium red, a known inhibitor of Ca2+ induced Ca2+ release from the SR, the amount of releasable Ca2+ was greatly increased by up to 300%. Addition of between 50 microM and 1.6 mM 4AP to ruthenium red Ca2+ loading solution modified differently the amount of releasable Ca2+, suggesting that the mechanism of action of 4AP is different from that of ruthenium red. 5. When all K+ ions in the loading solution were replaced by the less permeant Na+ ions the amount of releasable Ca2+ ions was also increased. 6. These results indicate that the amount of releasable Ca2+ from the SR is consistently modified under conditions aimed at interfering with the state of SR-K+-channels, suggesting that SR-K+-channels may play an important physiological role in the modulation of excitation-contraction coupling. One possible mechanism involving SR-K+-channels which could explain our results is discussed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sleep architecture in adolescents hospitalized during a suicidal crisis.
Rates of suicide attempts in Canadian youths are concerning. Adolescence is a sensitive period for the emergence of both sleep and mood problems, two major risk factors for suicidality. This naturalistic study aimed to define the sleep profile of adolescents under the combined influence of suicidality, depression and pharmacotherapy during hospitalization for a suicidal crisis. Seventeen suicidal adolescents (15.0 + 1.2years, 82% females) with major depression were recruited from a Canadian pedopsychiatric inpatient unit. Seventeen non-depressed adolescents were retrospectively collated from another database (15.0 + 1.1years, 83% females). None of the participants had a history of sleep disorders or significant medical conditions. Compared to controls, suicidal adolescents had a longer sleep onset latency (Z = -4.5, p < 0.001), longer REM latency (Z = -3.2, p = 0.001), higher percentage of NREM1 sleep t(33) = -2.6, p = 0.020), and higher REM density (Z = -2.8, p = 0.004) than controls. Higher REM density correlated with higher CDI-II scores (r = 0.55, p = 0.27) A significant interaction indicated that the two groups had similar NREM3 percentages in the first two-thirds of the night, but that the suicidal group had significantly lower NREM3 percentage than the controls in the last third of the night (F(2,66) = 3.4, p = 0.041). Significant sleep abnormalities were observed during hospitalization for a suicidal crisis in a sample of depressed and mostly medicated adolescents. This included sleep initiation and REM sleep latency abnormalities, shallower sleep and high REM density. Future studies should decipher the relative effects of depression, suicidality and medication on sleep. These findings stress the need to address sleep disturbances in the management of suicidality in adolescents.
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{
"pile_set_name": "PubMed Abstracts"
}
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Vav-dependent and vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulus.
We show in this study that B cell activation following high avidity ligation of IgM or coligation of membrane Ig with CD19 elicits similar levels of Ca(2+) flux using different mechanisms. Each form of activation requires the function of Vav and PI3K. However, Vav regulates Ca(2+) flux independently of PI3K following anti-IgM cross-linking. By contrast, Vav function is essential for PI3K activation following membrane Ig (mIg)/CD19 coligation. Inhibition of PI3K revealed anti-IgM-stimulated Ca(2+) flux has a PI3K-independent component, while Ca(2+) flux following mIg/CD19 coligation is totally PI3K dependent. The p85alpha and p110delta subunits of PI3K both participate in anti-IgM and mIg/CD19 coligation-induced Ca(2+) flux, although the defects are not as severe as observed after pharmacological inhibition. This may reflect the recruitment of additional PI3K subunits, as we found that p110alpha becomes associated with CD19 upon B cell activation. These data show that the nature of the Ag encountered by B cells determines the contribution of Vav proteins to PI3K activation. Our results indicate that the strong signals delivered by multivalent cross-linking agents activate B cells in a qualitatively different manner from those triggered by coreceptor recruitment.
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{
"pile_set_name": "PubMed Abstracts"
}
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Vertebral osteomyelitis and epidural abscesses caused by Prevotella oralis: a case report.
An interesting case of pyogenic vertebral osteomyelitis with multiple epidural abscesses caused by non-pigmented Prevotella oralis is reported. The patient was a 68-year-old female who presented to the emergency room (ER) with severe pain and tenderness in her lower back with fever. She had recently undergone esophagogastroduodensoscopy (EGD) for complaints of esophageal reflux, which showed submucosal cyst in the esophagus. Magnetic resonance imaging (MRI) of the thoracic spine revealed multiple spinal epidural abscesses with signal enhancement at the level of T6 and T7, suggestive of vertebral osteomyelitis. Two blood cultures drawn one hour apart grew Prevotella oralis. The body fluid aspirated from the abscesses was also positive for the anaerobic commensal P. oralis. Necrosis associated with the submucosal cyst was implicated as the cause of sepsis and osteomyelitis due to this organism.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Expression and clinical significance of bone morphogenetic protein 6 in human breast cancer].
To investigate the expression pattern and clinical significance of bone morphogenetic protein 6 (BMP6) in breast tissues. The tumor and adjacent noncancerous tissues were harvested from 36 cases of breast cancer, the expression level of BMP6 mRNA of each sample was measured by quantitative RT-PCR. Immunohistochemistry study was used to examine BMP6 protein expression in 80 cases of breast cancer, then the relationship between the expression of BMP6 and relevant clinical and pathological parameters was analyzed. BMP6 mRNA expression in breast cancer was significantly reduced when compared with normal breast tissues (P< 0.01), BMP6 mRNA level in estrogen receptor-positive (ER) breast cancer was distinctly higher than that in ER breast cancer. The expression of BMP6 mRNA was correlated to tumor grade (P < 0.01). The expression level of BMP6 protein in breast cancer was associated to ER and PR status, histological grade and Ki-67 status (P < 0.05), but not correlated to age, tumor size, human epidermal factor receptor 2 (Her2) status and molecular subtypes of breast cancer (P > 0.05). The ectopic expression of BMP6 may play an important role in the development and progression of breast cancer.
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{
"pile_set_name": "PubMed Abstracts"
}
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The spectroscopy of very cold gases.
The technique of supersonic free jet spectroscopy can be used to study the structure and dynamics of molecules which have been cooled to far below their boiling points but which remain in the gas phase. Cooling of the internal degress of freedom, the molecular rotations and vibrations, produces a highly resolved and greatly simplified molecular spectrum. The principles of the technique are discussed and its utility is demonstrated by two examples. the spectroscopy of porphyrins in the gas phase and the photochemistry of van der Waals molecules.
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{
"pile_set_name": "PubMed Abstracts"
}
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Intimal hyperplasia enhances myosin phosphorylation in rabbit carotid artery.
We examined physiological events in the hyperplastic artery, using a method based on the mechanical responsiveness and myosin light-chain phosphorylation in response to various stimulants. Six weeks after endothelial denudation by ballooning of the right carotid artery, strips of this artery with moderate intimal hyperplasia (intimal area was 30-50% of medial area in 20 of 28 rabbits) were used for experiments. Strips from the left carotid served as the normal control. When the hyperplastic artery was stimulated with 30 microM PGF2 alpha, the maximal tension (232.4 +/- 49.1 mg/mg dry wt, mean +/- SD) was significantly higher (P < 0.05) than that of the control (129.5 +/- 16.4 mg/mg). The maximal extent of myosin light-chain monophosphorylation (45.4 +/- 8.9%) and diphosphorylation (10.9 +/- 5.2%) in the hyperplastic artery was significantly higher (P < 0.05) than that in the control artery (33.0 +/- 4.8 and 4.0 +/- 4.8%, respectively). The monophosphorylation of the myosin light chain in the hyperplastic artery was sustained for up to 20 min, while that in the control artery decreased to the basal level within 20 min. Similar observations were obtained by stimulation with 60 mM K+ or 30 microM norepinephrine. Dose-response curves of the development of tension in the hyperplastic artery to various agonists (K+, PGF2 alpha, norepinephrine) shifted upward the curves for the control artery. These results suggest that qualitative changes in the characteristics of smooth muscle cells may occur in the intimal hyperplastic portion, including a hyperreactive contraction associated with enhanced and sustained phosphorylation of the myosin light chain.
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{
"pile_set_name": "PubMed Abstracts"
}
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Suppressive Effects of Eviprostat, a Phytotherapeutic Agent, on Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated with Brachytherapy.
Eviprostat is an anti-oxidant, anti-inflammatory phytotherapeutic agent that is commonly used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia in Japan and Germany. Prostate cancer patients treated with brachytherapy generally have complaints of LUTS for several months postoperatively. We investigated the protective effects of Eviprostat against the development of LUTS in 37 patients, who had received (125) I prostate brachytherapy as monotherapy. These patients were divided into two groups, an Eviprostat-treated group (n = 18) and an untreated control (n = 19), whose background had no significant difference. The group treated with Eviprostat was prophylactically medicated from 3 weeks preoperatively until 3 months postoperatively. Symptom scores and quality of life for urination were evaluated according to the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) on preoperative day 1, and postoperative months 1, 3 and 6. Both the scores of IPSS and the levels of quality of life in EPIC were significantly worse at 1 month postoperatively compared to the pretreatment baseline, and thereafter progressively improved in both groups. Eviprostat-treated patients showed significantly better recovery compared to Eviprostat-untreated control at 6 months postoperatively, with respect to urinary summary score, urinary function and urinary irritation/obstruction subscales in EPIC. Moreover, the feeling of incomplete emptying in IPSS and the urinary irritation/obstruction subscale in EPIC were significantly improved at 3 months postoperatively compared to the peak impairment at 1 month in the Eviprostat-treated group. It is possible that Eviprostat has the potential to ameliorate postoperative LUTS caused by brachytherapy.
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{
"pile_set_name": "PubMed Abstracts"
}
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Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract.
Cardiac neural crest ablation results in primary myocardial dysfunction and failure of the secondary heart field to add the definitive myocardium to the cardiac outflow tract. The current study was undertaken to understand the changes in myocardial characteristics in the heart tube, including volume, proliferation, and cell size when the myocardium from the secondary heart field fails to be added to the primary heart tube. We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions. Proliferation measured by 5-bromo-2'-deoxyuridine incorporation was elevated at only one stage during looping, cell death was normal and myocardial cell size was increased. Taken together, these results indicate that there are fewer myocytes in the heart. By incubation day 8 when the heart would have normally completed septation, the anterior (ventral) wall of the right ventricle and right ventricular outflow tract was significantly thinner in the neural crest-ablated embryos than normal, but the thickness of the compact myocardium was normal in all other regions of the heart. The decreased volume and number of myocardial cells in the heart tube after neural crest ablation most likely reflects the amount of myocardium added by the secondary heart field.
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{
"pile_set_name": "PubMed Abstracts"
}
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Comparing wound closure using tissue glue versus subcuticular suture for pediatric surgical incisions: a prospective, randomised trial.
Tissue adhesives have gained favour for quicker and painless closure of lacerations. To compare the tissue adhesive 2-octylcyanoacrylate with our current standard subcuticular suture for closure of surgical incisions in children, looking at outcome measures of time efficiency, cosmesis, and wound complications, a prospective, randomised, controlled trial was conducted at our institution's ambulatory surgery centre. All healthy patients undergoing unilateral or bilateral herniotomies were recruited prospectively with informed consent and randomly allocated to suture or glue. The exclusion criteria were neonates or children with allergy to tissue glue. Time of wound closure was measured from the subcutaneous layer to application of the dressing. An independent, blinded observer assessed cosmesis at 2 to 3 weeks using a validated wound scale ranging from worst (0) to best (6). Parent satisfaction with wound appearance was recorded on a 100-mm visual analogue scale (VAS). A total of 59 patients were recruited into the study with 26 in the glue group and 33 in the suture group. There was no difference in mean time of closure (glue 181 +/- 62 s vs suture 161 +/- 45 s, P = 0.18). Two patients in each group had a suboptimal Hollander wound score of 5 (7.7% glue, 6.1% suture). There was also no difference in parent satisfaction (VAS: glue 78 +/- 19 mm vs suture 81 +/- 15 mm, P = 0.68). No patient reported any rash, wound infection, or dehiscence. Tissue glue is easy to use with no complications and has equivalent cosmetic results, but is not faster than a subcuticular suture.
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{
"pile_set_name": "PubMed Abstracts"
}
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Laboratory Evaluation of Peripheral Neuropathy.
Peripheral neuropathy is a common neurological disorder, with high prevalence especially in the aged population. The general evaluative approach is to first identify the type of peripheral neuropathy prior to investigating for a possible underlying etiology, which is an increasingly important endeavor, as many causes of peripheral neuropathy are now recognized as treatable. To this end, laboratory testing plays an important adjunctive role to a detailed history and examination. This review will discuss possible diagnostic laboratory testing pathways for different types of peripheral neuropathy, with the goal of minimizing costs and false-positive results while maximizing the likelihood of identifying a potentially reversible etiology.
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{
"pile_set_name": "PubMed Abstracts"
}
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[The diagnosis of poisonings by toxic fungi].
Investigations carried out by the author resulted in elaboration of a probability differential diagnostic algorithm of intoxications with poisonous fungi based on a mathematical evaluation of the informative value of clinico-laboratory signs of intoxication. This method made it possible within a short time to determine the group of poisonous fungi that caused intoxication and to real differential diagnosis and institute timely adequate treatment.
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{
"pile_set_name": "PubMed Abstracts"
}
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Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell.
This study was undertaken to determine whether simultaneous administration of both alcohol and nicotine systemically would result in an additive dopamine release in the nucleus accumbens (NACC). Moreover, to also investigate whether nicotinic receptors may be mediating these effects of alcohol and nicotine, the effects of mecamylamine, a nicotinic receptor antagonist was also evaluated. Microdialysis was applied to measure the dopamine overflow in the shell region of NACC. All drugs were administered intraperitoneally. The doses of alcohol ranged from 0.5-2.0 g/kg, and nicotine and mecamylamine 0.25-1.0 mg/kg. An additive effect of combined alcohol and nicotine on dopamine release was obtained. This effect of alcohol and nicotine was dose-dependently blocked by mecamylamine pre-treatment. These findings further support the hypothesis that an additive effect of alcohol and nicotine on the mesolimbic 'reward pathway' may contribute to the high incidence of smoking in alcoholics. Furthermore, nicotinic antagonists can block such effects of combined alcohol and nicotine.
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{
"pile_set_name": "PubMed Abstracts"
}
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Founder effect in spinal and bulbar muscular atrophy (SBMA).
We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium. There was no allelic association between the (CAG)n and (GGC)n microsatellites among control subjects as well as SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.
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{
"pile_set_name": "PubMed Abstracts"
}
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Opportunistic infections.
When confronted with infections in an immunosuppressed immune-incompetent patient, it is important to have a pathophysiologic approach. A knowledge of the types and sources of microorganisms likely to be associated with breakdown of various types of host defenses is essential in the care of such patients. Newer pathogens are continuously being described and an awareness of underlying mechanisms is the keystone of early diagnosis and modern management.
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{
"pile_set_name": "PubMed Abstracts"
}
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Diet and obstructive lung diseases.
The results presented in this review suggest that the impact of nutrition on obstructive lung disease is most evident for antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to the lung, antioxidants could modulate the development of chronic lung diseases and lung function decrement. Antioxidant vitamins could also play an important role in gene-environment interactions in complex lung diseases such as childhood asthma. Data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements; however, relevant data are still sparse. Although epidemiologic data suggest that consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation, there are no clear data on which nutrients might be most relevant. While some studies evaluate daily intake of vitamin C, other studies use fruit consumption as a surrogate for antioxidant intake. Given the dietary intercorrelations among antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as well as other micronutrients, it may be difficult to isolate a specific effect. Some population subgroups with higher levels of oxidative stress, such as cigarette smokers, may be more likely to benefit from dietary supplementation, since some studies have suggested that antioxidant intake may have a greater impact in this group. Studies of lung function decrement and COPD in adults suggest that daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178 mg/day) was approximately three times the Recommended Dietary Allowance. Although the amplitude of the effect was modest, if these effects accumulate over 20-30 years, they could have a meaningful impact on the rate at which pulmonary function declines, particularly in symptomatic subjects (85). Longitudinal data support the hypothesis that fresh fruit consumption has a beneficial impact on the lung (95). Among children, consumption of fresh fruit, particularly fruit high in vitamin C, has been related to a lower prevalence of asthma symptoms and higher lung function (64). This effect was observed event at low levels of fruit consumption (one or two servings per week vs. less than one serving per week), which suggests that a small increase in dietary intake could have a beneficial effect. Consumption of fish has also been related to lower airway hyperreactivity among children (75) and higher lung function in adults (100); however, longitudinal data do not provide evidence that increased omega-3 fatty acid intake protects against lung disease (101). Experimental studies of persons with asthma suggest that magnesium infusion may have a place in the acute treatment of asthma, but it does not seem to have long-term benefits. The studies of sodium, selenium, and fish oils do not show convincing evidence of clinical benefits. Studies of vitamin C supplementation suggest a short-term protective effect on airway responsiveness and pulmonary function. It remains to be proven whether consistent use of vitamin C would have a protective effect on the evolution of chronic asthma. Results from supplementation studies conducted among subjects exposed to high levels of oxidants (57-60) suggest that daily intake of antioxidant vitamins exceeding the Recommended Dietary Allowance may have a beneficial effect on lung airways and that intake higher than the Recommended Dietary Allowance should be recommended for populations chronically exposed to photooxidant air pollutants (such as ozone), cigarette smoking, or vigorous exercise. It is difficult to determine the amounts of antioxidant vitamins that people should consume. In particular, although vitamin C was shown to have maximum bioavailability when given in a single dose of 200 mg (102), experiments on which this finding was based were conducted under normal conditions. Guidelines from the US National Cancer Institute (103) recommend consumption of five servings of fruit and vegetables daily, corresponding to a vitamin C intake exceeding 200 mg. Dietary surveys carried out in the US population indicate that less than 12 percent of US children and adults meet this recommended level of intake (104). Diet appears to be an important cofactor in the development of obstructive lung disease, although data are still sparse. There is a need for further research in experimental and epidemiologic settings to better understand the physiologic effects of antioxidant vitamins, omega-3 fatty acids, and other nutrients on lung tissues. The impact of diet on the incidence and evolution of asthma and COPD should be investigated using a cohort design that accounts for known risk factors. This will allow researchers to evaluate the exposure-disease relation over an adequate time frame and obtain insight into the causality of the relation. Some of these studies should enroll infants and young children to determine the impact of early diet on respiratory health. Research should also focus on the equally challenging policy issues--namely, finding effective methods of convincing people to increase their daily consumption of fresh fruits and vegetables, to stop smoking cigarettes, and to minimize their environmental and occupational exposure to pollutants and other agents that cause respiratory disease.
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{
"pile_set_name": "PubMed Abstracts"
}
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Nanometre resolution using high-resolution scanning electron microscopy corroborated by atomic force microscopy.
The resolving power of high-resolution scanning electron microscopy was judged using topographical height data from atomic force microscopy in order to assess the technique as a tool for understanding nanoporous crystal growth.
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{
"pile_set_name": "PubMed Abstracts"
}
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A clinical study of quazepam in hospitalized patients with insomnia.
The efficacy of quazepam (Sch-16134) 15 mg capsules as a hypnotic has been compared with that of placebo in a 9-day study, using a parallel-group design. The physician's global evaluation numerically favoured quazepam 63% (nineteen of thirty) over placebo 50% (fifteen of thirty). Furthermore, it demonstrated greater improvement in Hypnotic Activity Index and Sleep Quality Index from baseline scores, and caused no adverse reactions.
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{
"pile_set_name": "PubMed Abstracts"
}
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Lignin-Enzyme Interactions in the Hydrolysis of Lignocellulosic Biomass.
Lignin is central to overcoming recalcitrance in the enzyme hydrolysis of lignocellulose. While the term implies a physical barrier in the cell wall structure, there are also important biochemical components that direct interactions between lignin and the hydrolytic enzymes that attack cellulose in plant cell walls. Progress toward a deeper understanding of the lignin synthesis pathway - and the consistency between a range of observations over the past 40 years in the very extensive literature on cellulose hydrolysis - is resulting in advances in reducing a major impediment to cellulose conversion: the cost of enzymes. This review addresses lignin and its role in the hydrolysis of hardwood and other lignocellulosic residues.
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{
"pile_set_name": "PubMed Abstracts"
}
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Economic evaluation of the routine childhood immunization program in the United States, 2009.
To evaluate the economic impact of the 2009 routine US childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate, hepatitis A, and rotavirus vaccines; influenza vaccine was not included. Decision analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported during 2005 to 2009. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and work time lost. All costs were inflated to 2009 dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2009 US birth cohort of 4,261,494 infants over their lifetime was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine childhood immunization were calculated. Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent ∼42,000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1. From both direct cost and societal perspectives, vaccinating children as recommended with these vaccines results in substantial cost savings.
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{
"pile_set_name": "PubMed Abstracts"
}
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Red palm oil as a source of vitamin A for mothers and children: impact of a pilot project in Burkina Faso.
To demonstrate the effectiveness of the commercial introduction of red palm oil (RPO) as a source of vitamin A (VA) for mothers and children in a non-consuming area, as a dietary diversification strategy. A pre-post intervention design (no control area) was used to assess changes in VA intake and status over a 24-month pilot project. The pilot project involved RPO promotion in 10 villages and an urban area in east-central Burkina Faso, targeting approximately 10 000 women and children aged <5 years. A random sample of 210 mother-child (12-36-months-old) pairs was selected in seven out of the 11 pilot sites for the evaluation. After 24 months, RPO was reportedly consumed by nearly 45% of mothers and children in the previous week. VA intake increased from 235+/-23 microg retinol activity equivalents (RAE) to 655+/-144 microg RAE in mothers (41 to 120% of safe intake level), and from 164+/-14 microg RAE to 514+/-77 microg RAE in children (36 to 97%). Rates of serum retinol <0.70 micromol l(-1) decreased from 61.8+/-8.0% to 28.2+/-11.0% in mothers, and from 84.5+/-6.4% to 66.9+/-11.2% in children. Those with a lower initial concentration of serum retinol showed a higher serum retinol response adjusted for VA intake. Commercial distribution of RPO was effective in reducing VA deficiency in the pilot sites. While it is promising as part of a national strategy, additional public health and food-based measures are needed to control VA malnutrition, which remained high in the RPO project area.
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{
"pile_set_name": "PubMed Abstracts"
}
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Promoting participation in physical activity using framed messages: an application of prospect theory.
Messages designed to motivate participation in physical activity usually emphasize the benefits of physical activity (gain-framed) as well as the costs of inactivity (loss-framed). The framing implications of prospect theory suggest that the effectiveness of these messages could be enhanced by providing gain-framed information only. We compared the effectiveness of gain-, loss-, and mixed-framed messages for promoting moderate to vigorous physical activity. Randomized trial. Sedentary, healthy callers to the US National Cancer Institute's Cancer Information Service (N=322) received gain-, loss-, or mixed-framed messages on three occasions (baseline, Week 1, and Week 5). Social cognitive variables and self-reported physical activity were assessed at baseline, Week 2, and Week 9. Separate regression analyses were conducted to examine message effects at each assessment point. At Week 2, gain- and mixed-framed messages resulted in stronger intentions and greater self-efficacy than loss-framed messages. At Week 9, gain-framed messages resulted in greater physical activity participation than loss- or mixed-framed messages. Social cognitive variables at Week 2 did not mediate the Week 9 framing effects on physical activity participation. Using gain-framed messages exclusively may be a means of increasing the efficacy of physical activity materials.
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{
"pile_set_name": "PubMed Abstracts"
}
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Exercise adherence and intervention effects of two school-based resistance training programs for adolescents.
The aim of this study was to evaluate the efficacy and feasibility of two school-based RT programs to improve muscular fitness and body composition in adolescents. The study was conducted in Australia from July 2008 to June 2009. Participants [n=108, mean age (SD)=15.0 (0.7) years] were randomized to free weights (n=37) or elastic tubing (n=41) RT groups and a control group was recruited (n=30). Participants in the RT groups completed 2 sets of 10-12 repetitions on 10 exercises for 8 weeks. Waist circumference, body composition (bioelectrical impedance analysis) and muscular strength (bench press and leg press) were assessed at baseline and posttest. Boys (p<0.001) and girls (p<0.01) in both RT groups improved their body composition over the study period. Boys in both RT groups significantly improved both upper and lower body strength and their improvements were significantly greater than changes observed in the control group. Girls in the free weights groups achieved larger improvements in lower body strength compared to the control group (p<0.05). Free weights and elastic tubing RT are feasible and effective strategies for improving aspects of health-related fitness in adolescents.
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{
"pile_set_name": "PubMed Abstracts"
}
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Ovulating induction methods in rabbit does: the pituitary and ovarian responses.
The aim of this study was to compare the pituitary and ovarian responses in rabbit does subjected to different methods of ovulation induction. Forty-eight receptive females were randomly distributed into six groups (N = 8) and were inseminated with standard glass catheters. Buserelin intramuscular (BM) does were inseminated using a pool of fresh heterospermic semen and an intramuscular injection of 1 μg of buserelin acetate to induce ovulation. Buserelin intravaginal (BV) does were inseminated in a similar way, but ovulation was induced with the GnRH analogue (10 μg of buserelin acetate) combined with 0.5 mL of semen extender. The raw semen (R) and saline groups (S) were inseminated with undiluted semen or saline, respectively, without any inducer of ovulation. Another group (A) received lumbar anaesthesia (1.5 mL of 2% lidocaine), and only the empty catheter was introduced into the vagina. The AR does were treated the same way as group A but were inseminated with raw semen instead of an empty catheter. Blood samples were collected to determine the LH concentrations before and after AI (30, 60, 90, and 120 minutes). Ovulation, pregnancy, and conception rates were determined after euthanasia on day 14 post AI. Ovulating does had higher mean LH concentrations than nonovulating does (197.9 vs. 45.9 ng/mL; P < 0.05). The ovulation rates of buserelin intramuscular and intravaginal does were 100%, and the pregnancy rates were 87.5% and 100%, respectively. Rabbit does in groups A and AR did not ovulate and had similar mean plasma LH concentrations after 60 minutes compared with the S group (49.4 and 49.2 ng/mL vs. 41.6 ng/mL, respectively), which reached ovulation and pregnancy rates of 37.5%. Does inseminated only with raw semen had an ovulation rate of 75% and a pregnancy rate of 62.5%; they also demonstrated higher plasma LH concentrations than does of the S, A, and AR groups. In conclusion, ovulation in rabbit does can be induced by exogenous GnRH administration (im and intravaginal). The high plasma LH concentration and ovulation rate in the R group with respect to the S and A groups could weakly indicate the presence of some molecules in the seminal plasma that could act on or be absorbed by vaginal mucosa. Sensory stimulation and "seminal factors" probably exert a synergy on the ovulation response as demonstrated by the comparison of LH release and the ovulation response in the R, S, RA, and A groups.
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{
"pile_set_name": "PubMed Abstracts"
}
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Intracranial portion of the trochlear nerve and dorsal oblique muscle composition in dog: a structural and ultrastructural study.
In the present investigation the right intracranial portion of the trochlear nerves and dorsal oblique muscle of the right ocular globe were removed from six adult dogs and analyzed by light and electron microscopy. Unmyelinated fibers were observed in the analyzed nerves. The number, diameter, area, and density of myelinated fibers were determined, as were corresponding axon area and diameter and myelin sheath thickness. Frequency histograms of myelin sheath thickness and fiber size show a bimodal distribution with a similar proportion of large and small fibers. Muscle samples were taken from the central portion of the muscle belly, subsequently frozen, cut, and stained with m-ATPase at pH 4.6. Fibers were classified as Type 1 or Type 2 according to their reaction to the m-ATPase and detailed morphologic and morphometric studies were made. The muscles showed two clearly distinct layers, a central layer and a peripheral layer, chiefly composed of Type 2 fibers. The fibers in the central layer were larger in size than those in the peripheral layer.
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{
"pile_set_name": "PubMed Abstracts"
}
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The frontal assessment battery (FAB) reveals neurocognitive dysfunction in substance-dependent individuals in distinct executive domains: Abstract reasoning, motor programming, and cognitive flexibility.
Substance-dependence is highly associated with executive cognitive function (ECF) impairments. However, considering that it is difficult to assess ECF clinically, the aim of the present study was to examine the feasibility of a brief neuropsychological tool (the Frontal Assessment Battery - FAB) to detect specific ECF impairments in a sample of substance-dependent individuals (SDI). Sixty-two subjects participated in this study. Thirty DSM-IV-diagnosed SDI, after 2weeks of abstinence, and 32 healthy individuals (control group) were evaluated with FAB and other ECF-related tasks: digits forward (DF), digits backward (DB), Stroop Color Word Test (SCWT), and Wisconsin Card Sorting Test (WCST). SDI did not differ from the control group on sociodemographic variables or IQ. However, SDI performed below the controls in DF, DB, and FAB. The SDI were cognitively impaired in 3 of the 6 cognitive domains assessed by the FAB: abstract reasoning, motor programming, and cognitive flexibility. The FAB correlated with DF, SCWT, and WCST. In addition, some neuropsychological measures were correlated with the amount of alcohol, cannabis, and cocaine use. In conclusion, SDI performed more poorly than the comparison group on the FAB and the FAB's results were associated with other ECF-related tasks. The results suggested a negative impact of alcohol, cannabis, and cocaine use on the ECF. The FAB may be useful in assisting professionals as an instrument to screen for ECF-related deficits in SDI.
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{
"pile_set_name": "PubMed Abstracts"
}
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Prediction models for early risk detection of cardiovascular event.
Cardiovascular disease (CVD) is the major cause of death globally. More people die of CVDs each year than from any other disease. Over 80% of CVD deaths occur in low and middle income countries and occur almost equally in male and female. In this paper, different computational models based on Bayesian Networks, Multilayer Perceptron,Radial Basis Function and Logistic Regression methods are presented to predict early risk detection of the cardiovascular event. A total of 929 (626 male and 303 female) heart attack data are used to construct the models.The models are tested using combined as well as separate male and female data. Among the models used, it is found that the Multilayer Perceptron model yields the best accuracy result.
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{
"pile_set_name": "PubMed Abstracts"
}
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Limited sampling strategy for mycophenolic acid in Japanese heart transplant recipients: comparison of cyclosporin and tacrolimus treatment.
The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC(0-12 h)) was evaluated. The MPA AUC(0-12 h) h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 mug . h/ml and from 39.19 to 93.18 mug . h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC(0-12 h) based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC(0-12 h) in the CsA group was a 3-time-point model that included C(0 h), C(1 h) and C(2 h) (r(2), 0.96; mean prediction error, 0.15+/-7.85%); a 2-time-point model that included C(0 h), and C(2 h) (r(2), 0.94; mean prediction error, 0.495+/-10.35%) was also reliable. In the FK group, a 3-time-point model that included C(1 h), C(2 h) and C(4h) (r(2), 0.73; mean prediction error, 2.73+/-17.09%) was the best model for predicting the full MPA AUC(0-12 h), but it was not reliable in clinical practice. A 3-(C(0 h), C(1 h) and C(2 h)) and a 2-time-point model (C(0 h) and C(2 h)) are useful for predicting the full MPA AUC(0-12 h) in Japanese heart transplant recipients treated with CsA but not with FK.
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{
"pile_set_name": "PubMed Abstracts"
}
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Analysis of the drop-out rate in patients receiving mepolizumab for severe asthma in real life.
Mepolizumab (anti IL-5, monoclonal antibody) is commercially available in Italy since more than one year for the treatment of severe hypereosinophilic asthma. Its efficacy and safety were evaluated in several regulatory trials. The characteristics of this drug in real life began to be assessed only recently. We describe herein the drop-out rate observed with mepolizumab in real life, because this datum can indirectly reflect the safety and tolerability aspects. The demographic and clinical data of patients receiving mepolizumab for severe asthma were collected, and the number and reasons for discontinuation of the treatment were analyzed. The database involves 143 patients (67 male, age range 19-80 year) who received at least one dose of mepolizumab. The observed discontinuation rate was 6/143 (4.2%). Five out of 6 discontinuations were due to lack of response, and one was an adverse event (urticaria) probably related to the treatment. There was no clinical difference between the drop-out group and the patients still ongoing. As compared to the clinical trials published the discontinuation rate was lower in our population, especially for adverse events (7% vs 23.7%). Thus, the tolerability of mepolizumab, as derived from discontinuations, seems to be better in real-life than in clinical trials.
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{
"pile_set_name": "PubMed Abstracts"
}
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Comment on "Plasma fireball: A unique tool to fabricate patterned nanodots" [Rev. Sci. Instrum. 88, 063507 (2017)].
The article of Chauhan et al. ["Plasma fireball: A unique tool to fabricate patterned nanodots," Rev. Sci. Instrum. 88(6), 063507 (2017)] describes the very interesting idea of utilising the plasma phenomenon of fireballs for the creation of patterned nanodots on a GaSb substrate. For this purpose, the authors obtained a large plasma fireball in a magnetised background plasma and used it to accelerate ions in the sheath, which surrounds such a fireball. Chauhan et al. were able to demonstrate the production of large ion fluxes that can be extracted from the fireball and that the properties of these fluxes define the geometric structure of the nanodots on the substrate surface. Hence, the nanodot pattern can be easily controlled by the discharge parameters of the plasma fireball. This is clearly a novel method of fireball-induced surface modification. However, plasma fireballs themselves have been known for about hundred years, although as a very particular plasma phenomenon. Therefore, this letter aims at providing some additional background information and references on this topic for the interested reader.
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{
"pile_set_name": "PubMed Abstracts"
}
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Copeptin decrease from admission to discharge has favorable prognostic value for 90-day events in patients admitted with dyspnea.
With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.
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{
"pile_set_name": "PubMed Abstracts"
}
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Cultural traits and immigration: hostility and suicidality in Chinese Canadian students.
Suicidality has been related to inwardly directed aggression. We compared convenience samples of 89 Canadian students of Chinese origin (CC) and 81 Canadian students from other backgrounds on measures of suicidality, hostility and aggression. The Chinese Canadian group reported higher levels of suicidality and hostility than the group of other Canadians. However, aggressive behaviors directed toward self or others were less frequent among Chinese Canadians. No differences were found between men and women. The results are interpreted by invoking the influence of Chinese culture on emotional restraint, particularly as regards aggressiveness.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Kinsbourne syndrome: review of our cases].
The childhood opsoclonus-myoclonus or Kinsbourne syndrome, is a uncommon process, of acute or subacute beginning, which affects infant and children. It's course is characterized by opsoclonus, polimyoclonias and cerebellar ataxia. The disease is frequently associated to neuroblastoma (46%). We present a retrospective study on 9 patients, emphasizing the clinical presentation and the evolution aspects. We found changes in the EEG in three cases. Most surprising is the scarce incidence of neuroblastoma, which has been found only in a one out of nine patients. We found three cases with relapse during the treatment or on withdrawal and one of them relapsed twice again. The evolution has been variable, since 5/9 patient have presented some type of mild or moderate neuro-psychological sequelae. Out of three patient with relapses, two presented permanent neurological sequelae. A patient which suffered three relapses, is also the one which presents more serious sequelae.
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{
"pile_set_name": "PubMed Abstracts"
}
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BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma.
Melanoma is the most lethal form of skin cancer, and the incidence and mortality rates are rapidly rising. Epidemiologically, high numbers of nevi (moles) are associated with higher risk of melanoma . The majority of melanomas exhibit activating mutations in the serine/threonine kinase BRAF . BRAF mutations may be critical for the initiation of melanoma ; however, the direct role of BRAF in nevi and melanoma has not been tested in an animal model. To directly test the role of activated BRAF in nevus and melanoma development, we have generated transgenic zebrafish expressing the most common BRAF mutant form (V600E) under the control of the melanocyte mitfa promoter. Expression of mutant, but not wild-type, BRAF led to dramatic patches of ectopic melanocytes, which we have termed fish (f)-nevi. Remarkably, in p53-deficient fish, activated BRAF induced formation of melanocyte lesions that rapidly developed into invasive melanomas, which resembled human melanomas and could be serially transplanted. These data provide direct evidence that BRAF activation is sufficient for f-nevus formation, that BRAF activation is among the primary events in melanoma development, and that the p53 and BRAF pathways interact genetically to produce melanoma.
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{
"pile_set_name": "PubMed Abstracts"
}
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The influence of relativistic energy losses on bandgap determination using valence EELS.
Since monochromated transmission electron microscopes have become available, the determination of bandgaps and optical properties using electron energy loss spectrometry (EELS) has again attracted interest. The underlying idea is very simple: below the bandgap energy no transitions can contribute to the valence EELS signal. However, the bandgap cannot be directly read out from the recorded data. Therefore the optical properties cannot be determined correctly from the low loss using the Kramers-Kronig relations. We will discuss under which conditions relativistic effects may be suppressed. It is demonstrated that scanning TEM (STEM) geometry is not applicable for most bandgap measurements.
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{
"pile_set_name": "PubMed Abstracts"
}
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Inpatient intervention slashes risk of re-hospitalization in CHF patients.
Many patients don't understand critical self-care tasks such as how to follow an appropriate diet, resulting in unnecessary complications and costly hospitalizations. However, a new study shows that a straightforward approach to educating patients hospitalized with CHF can dramatically slash the chances of re-hospitalization--and the approach may produce similar benefits in outpatients as well.
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{
"pile_set_name": "PubMed Abstracts"
}
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High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer.
To evaluate the effect of high-dose chemotherapy in the treatment of metastatic breast cancer, we performed a phase II trial of a single treatment with high-dose cyclophosphamide (5,625 mg/m2), cisplatin (165 mg/m2), and carmustine (600 mg/m2), or melphalan (40 mg/m2) and bone marrow support as the initial chemotherapy for metastatic breast cancer. Twenty-two premenopausal patients with estrogen receptor negative, measurable metastatic disease were treated. Twelve of 22 patients (54%) obtained a complete response at a median 18 days. The overall response rate is 73% (complete and partial response). Median duration of response in the patients achieving complete response was 9.0 months with a median duration of survival for complete responders that is currently undefined. Relapse occurred predominantly at sites of pretreatment bulk disease or within areas of previous radiation therapy. Toxicity was frequent and five patients died of therapy-related complications. The results indicate that a single treatment with intensive combination alkylating agents with bone marrow support can produce more rapid and frequent complete responses than conventional chemotherapy when used as initial chemotherapy for metastatic breast cancer, although median disease-free and overall survival is not improved. Three patients (14%) remain in unmaintained remission beyond 16 months.
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{
"pile_set_name": "PubMed Abstracts"
}
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Epidemic diphtheria in the 1990s: Azerbaijan.
The diphtheria epidemic in the former Soviet Union reached Azerbaijan in 1991, when 66 cases of diphtheria were reported, a number that compared with 4 cases in 1990. From 1990-1996, 2182 cases of diphtheria and 286 diphtheria fatalities (case fatality rate: 13.1%) were reported in Azerbaijan, primarily among persons 5-39 years of age. Almost 45% of cases and 61% of deaths occurred among children 5-14 years of age. The high burden of severe disease among children and young adults suggested a different pattern of preexisting immunity against diphtheria in the Azerbaijani population than was observed in the concurrent diphtheria epidemic in Russia. Because resources were limited in Azerbaijan, mass immunization of the population was carried out in stages, focusing initially on school-aged children. Mass immunization campaigns targeting children were moderately successful in stabilizing the epidemic; mass immunization campaigns targeting both adults and children were eventually needed to fully stop the epidemic.
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{
"pile_set_name": "PubMed Abstracts"
}
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A primer on critical care pharmacy services.
The intensive care unit (ICU) continues to be a major focus of decentralized pharmacy activities in health systems that care for critically ill patients. This is not surprising, given the need for rapid decision-making involving unstable patients, the large number of powerful medications typically used per patient, the high cost of many drugs used in the ICU and, most importantly, the evidence demonstrating the benefits of having a pharmacist as part of an interdisciplinary team. The purpose of this paper is to highlight important issues to consider when introducing or developing critical care pharmacy services beginning with the establishment of basic services and continuing through practitioner development, guideline/protocol development and implementation, patient safety, residency training, and research.
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{
"pile_set_name": "PubMed Abstracts"
}
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Glucocorticoids interact with the basolateral amygdala beta-adrenoceptor--cAMP/cAMP/PKA system in influencing memory consolidation.
Infusion of a beta-adrenoceptor antagonist into the basolateral nucleus of the amygdala (BLA) blocks memory enhancement induced by systemic or intra-BLA administration of a glucocorticoid receptor (GR) agonist. As there is evidence that glucocorticoids interact with the noradrenergic signalling pathway in activating adenosine 3prime prime or minute,5prime prime or minute-cyclic monophosphate (cAMP), the present experiments examined whether glucocorticoids influence the beta-adrenoceptor--cAMP system in the BLA in modulating memory consolidation. Male, Sprague--Dawley rats received bilateral infusions of atenolol (a beta-adrenoceptor antagonist), prazosin (an alpha1-adrenoceptor antagonist) or Rp-cAMPS (a protein kinase A inhibitor) into the BLA 10 min before inhibitory avoidance training and immediate post-training intra-BLA infusions of the GR agonist, RU 28362. Atenolol and Rp-cAMPS, but not prazosin, blocked 48-h retention enhancement induced by RU 28362. A second series of experiments investigated whether a GR antagonist alters the effect of noradrenergic activation in the BLA on memory consolidation. Bilateral intra-BLA infusions of the GR antagonist, RU 38486, administered 10 min before inhibitory avoidance training completely blocked retention enhancement induced by alpha1-adrenoceptor activation and attenuated the dose--response effects of post-training intra-BLA infusions of clenbuterol (a beta-adrenoceptor agonist). However, the GR antagonist did not alter retention enhancement induced by post-training intra-BLA infusions of 8-Br-cAMP (a synthetic cAMP analogue). These findings suggest that glucocorticoids influence the efficacy of noradrenergic stimulation in the BLA on memory consolidation via an interaction with the beta-adrenoceptor--cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site.
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{
"pile_set_name": "PubMed Abstracts"
}
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The physical interactions between p37env-mos and tubulin structures.
The c-mos protein has been reported to be complexed with tubulin and to co-localize with microtubules in unfertilized Xenopus eggs as well as in NIH3T3 cells transformed by the Xenopus c-mos gene. We performed experiments to determine whether the viral mos protein, p37v-mos, also associates with tubulin. Both mouse c-mos and v-mos proteins synthesized in vitro co-polymerized with tubulin. Upon incubation at 37 degrees C, essentially all of the mos protein (both viral and cellular) co-polymerized with tubulin, while more than 50% of the tubulin remained in the depolymerized state. The mos-tubulin interaction was specific, as indicated by the insolubility of the v-mos protein following a second cycle of temperature-dependent depolymerization/polymerization. Beta-tubulin was shown to co-precipitate with p37v-mos and to be phosphorylated by the mos kinase in vitro. Although both v-mos and c-mos proteins co-polymerize with tubulin, p37v-mos behaved differently from p39c-mos on gel filtration columns under conditions that favor disassembly of microtubules. Like Xenopus c-mos, the bulk of the mouse c-mos protein synthesized in vitro appeared in structures that fractionate at about 500 kDa. In contrast to c-mos, the majority of the v-mos protein, either isolated from stably transformed NIH3T3 cells or synthesized in vitro, eluted in the 100 kDa fraction, co-fractionating with tubulin dimers. Therefore, the v-mos protein appears to have a higher affinity for unpolymerized tubulin than c-mos, under conditions that favor disassembly of microtubules.
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{
"pile_set_name": "PubMed Abstracts"
}
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Evaluation of minimally invasive therapies and rationale for a prospective randomized trial to evaluate selective intra-arterial lysis for clinically complete central retinal artery occlusion.
To determine the effect of commonly used minimally invasive treatments for clinically complete nonarteritic central retinal artery occlusion (CRAO) and design a prospective randomized trial to evaluate selective intra-arterial lysis for this condition. In this retrospective noncomparative case series, all medical records of patients with a diagnosis of CRAO treated at the Department of Ophthalmology, Ludwig-Maximilians-Universität, Munich, Germany, from 1994 through 1999 were reviewed for treatments administered and course of visual acuity. Best-corrected visual acuity (BCVA) at initial and last visit. We identified 102 patient medical records; 71 were suitable for further analysis. Forty-four (62%) of the 71 patients included were treated with oral acetylsalicylate; 44 (62%), with oral acetazolamide; 32 (45%), with ocular massage; 22 (31%), with isovolemic hemodilution; 19 (27%), with oral pentoxifylline; 8 (11%), with topical beta-blocker; 6 (8%), with paracentesis of the anterior chamber; 4 (6%), with subcutaneous heparin. A mean +/- SD number of treatments of 2.5 +/- 1.4 was administered per patient, and BCVA increased by a mean +/- SD number of Snellen lines of 0.7 +/- 2.8. The BCVA in 11 patients (15%) increased by 3 or more lines. Multivariate stepwise regression did not reveal any single or combination treatment as a significant factor for improvement in BCVA. Patient age and duration of visual impairment before initial examination were not significant predictors of final BCVA. Commonly used minimally invasive treatments of CRAO do not improve the natural course of the disease. A prospective trial by the European Assessment Group for Lysis in the Eye is under way to evaluate selective intra-arterial lysis, and in this trial some of these minimally invasive treatments are used in the control group.
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{
"pile_set_name": "PubMed Abstracts"
}
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The long-term course after treatment of acute anterior cruciate ligament ruptures. A 9 to 16 year followup.
Acute total ACL (N = 60) and concomitant medial collateral ligament (N = 46) ruptures were repaired in 60 patients (mean age, 28 years) without augmentation. Menisci were removed in 23 knees. Fifty-three (88%) of the patients were reexamined 9 to 16 years later with special emphasis on manual and instrumented stability testing (Stryker, Genucom), knee function score (Lysholm), and activity level (Tegner). Standing roentgenograms (30 degrees of knee flexion) were taken in 69% of the patients. At followup, an ACL reconstruction had been performed in seven patients (12%) due to symptomatic instability. Sixty-four percent of the knees had a positive Lachman sign and 40% a positive pivot shift. Sagittal laxity difference was +3 mm or more in 57%. Knee function score was a mean of 86 +/- 12 points. The mean activity level had changed from recreational team sports (Level 7) to recreational individual sports (Level 5). Only patients with good knee stability were able to perform demanding sports and could continue at their desired activity level. Osteoarthritis of slight to moderate degree (Fairbank I/II) was found in 58% of the patients younger than 35 years of age at the time of trauma and in 87% of the older patients. Knees with intact menisci had less osteoarthritis than knees with removed menisci (P less than 0.05).
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{
"pile_set_name": "PubMed Abstracts"
}
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[LongoVital in the prevention of recurrent aphthous stomatitis. 1].
LongoVital (LV) (DK. reg. no. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. The present study was undertaken to investigate prevention of recurrent aphthous ulceration (RAU) during daily intake of LV for six months as compared with placebo in a double-blind, randomised clinical, cross-over 1-year study. The population comprised 29 otherwise healthy minor RAU patients (18F, 11M) mean age 36 (18-67), with an estimated average number of recurrences the previous year of 12.8 (3-30). The number of recurrences was significantly reduced on treatment with LV during the latter four of the six months (p less than 0.01) where 31% were totally free of recurrences. Subjective all-over evaluation of treatment period was significantly in favour of LV. LV induced no adverse reactions and is the first harmless systemic treatment which has proved better than placebo in the prevention of RAU.
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{
"pile_set_name": "PubMed Abstracts"
}
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Venous thrombosis: who should be screened for thrombophilia in 2014?
Venous thromboembolism (VTE) is a chronic disease. Recurrence can be prevented by anticoagulants, albeit at the cost of bleeding. Assessing the risk of recurrence is important to balance the risks and benefits of anticoagulation. Numerous laboratory risk factors of VTE have been identified, which has lead to a practice called laboratory thrombophilia screening--a procedure in which patients with a prior VTE are systematically offered laboratory testing with the purpose of identifying the risk factors. The knowledge of these factors should improve counseling patients regarding their duration of anticoagulation. However, this approach has failed. For some factors including coagulation inhibitors and phospholipid antibodies, the evidence that they increase the recurrence risk is weak. The extent to which other defects (factor V Leiden, prothrombin mutation) increase the recurrence risk is irrelevant. Patients can have multiple risk factors, and it is unknown to what extent their interactions increase the recurrence risk. Some assay systems have technical limitations, which restrict their general applicability. Meaningful studies comparing treatment strategies regarding the recurrence risk in VTE patients with a distinct laboratory abnormality are lacking. Routine testing for heritable defects can cause unnecessary concerns and uncertainty both in patients and relatives, and might also lead to overtreatment. The absence of a laboratory abnormality does not necessarily mean that the recurrence risk is low. A negative result could thus potentially result in a false sense of safety for patients and physicians, and consequently in undertreatment. In summary, routine laboratory thrombophilia screening is no longer warranted.
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{
"pile_set_name": "PubMed Abstracts"
}
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Use of CFU-GM assay for prediction of human maximum tolerated dose of a new antitumoral drug: Yondelis (ET-743).
Acute cytotoxic exposure causes decreases in bone marrow progenitors that precedes the neutrophil nadir. Experiments in animal models reveal a relationship between the reduction in granulocyte-macrophage progenitors (CFU-GM) and the decrease in absolute neutrophil count [Toxicol. Pathol. 21 (1993) 241]. Recently, the prevalidation of a model for predicting acute neutropenia by the CFU-GM assay has been reported [Toxicol. In Vitro 15 (2001) 729]. The model was based on prediction of human MTD by adjusting the animal-derived MTD for the differential sensitivity between CFU-GM from animal species and humans. In this study, this model has been applied on a new antitumoral drug, Yondelis (Ecteinascidin; ET-743). Preclinical studies showed that hematotoxicity was the main side effect in mice, being the MTD of 600 microg/m2 [Drugs Future 21 (1996) 1155]. The sensitivity of myeloid progenitors was higher in mice than in humans, with IC90 values of 0.69+/-0.22 nM and 1.31+/-0.21 nM for murine and human CFU-GMs respectively. This study predicts a human MTD of 1145 microg/m2. The reported human MTD of ET-743 given as a 24-h continuous infusion every 3 weeks is 1800 microg/m2 [J. Clin. Oncol. 19 (2001) 1256]. Since our predicted MTD is within fourfold of the actual MTD (the interspecies variation in tolerated dose due to differences in clearance rates, metabolism pathways and infusion rate) the result confirms the profit of the prediction model.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Clinical study on intact gamma-globulin (SM-4300) in surgical severe bacterial infections].
Intact gamma-globulin (SM-4300) was studied for its clinical efficacy in 13 of 23 cases of surgical severe bacterial infections. The drug was administered intravenously either 2.5 g/day for 3 days or 5 g for a day and the results were as follows. Clinical effects of SM-4300 in 13 cases of surgical severe bacterial infections were excellent in 1 case, good in 3, fair in 3 and poor in 6. SM-4300 was effective in all of 5 cases of intraperitoneal abscess. The elevation of serum IgG was observed after the administration of SM-4300 in all cases tested. As to complement, the slight elevation of serum CH50 was observed in the half of cases documented. Clinical side effects were not confirmed in any case. These results suggest that intact gamma-globulin (SM-4300) was effective in combination with antibiotics.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Practical importance of the exact diagnosis of fetal arrhythmias].
Ultrasound M-mode examinations were performed at 78 pregnant women in the second half of pregnancy during 1 year period, because of fetal dysrhythmia. Distribution of the diagnoses of the fetuses: near 40% sinus rhythm, 5.13% organic heart diseases, 48.72% supraventricular arrhythmia, 5.13% atrioventricular block, 1.28% ventricular extrasystole. In 11.54% of the cases intrauterine treatment was necessary (supraventricular tachycardia) for prevention the congestive heart failure. The transplacental treatments were as follows: in 3 cases digitalis, in 3 cases digitalis + verapamil, in 3 cases digitalis + amiodaron. In two cases (refractory to the mentioned treatments) direct intrafunicular, intravascular digitalis + amiodaron treatment was reasonable. Being the correct diagnosis of dysrhythmias possible only with ultrasound M-mode examination, all of the recognised cases have to be sent to adequate ward, where a suitable equipment is available.
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{
"pile_set_name": "PubMed Abstracts"
}
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Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats.
We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sadness, socialisation and shifted perceptions: school pupils' stories of a pre-nursing scholarship.
Providing opportunities for aspirant nurses to obtain pre-nursing experience features prominently in the UK Government's response to The Francis Inquiry. Evidence from the USA suggests that pre-nursing experiences, such as summer camps, have the potential to contribute to effective nurse recruitment, selection and retention strategies. However, few similar pre-nursing experiences exist in the UK, and none have been evaluated. This paper reports the experiences of participation in a pilot pre-nursing scholarship among secondary school pupils in Scotland. To explore pupils' experiences of a pre-nursing scholarship to inform future design and delivery of similar programmes in the UK and internationally. Qualitative focus group study. Two university campuses in Scotland. Twenty-two secondary school students (all female, aged 15-18 years). Two focus groups were facilitated through the use of 'anecdote circles' to elicit pupils' stories of their scholarship experience. Anecdote circles allowed each pupil to share their story in turn and then collectively assemble, figuratively and physically through interlocking written cards, shared stories of the scholarship. Discussions were audio recorded and transcribed verbatim. Data were analysed thematically. Three stories emerged: 1) sadness; 2) socialisation; and, 3) shifted perceptions. Sad stories were transformative affirming the pupils' desire to become a nurse. Stories of socialisation revealed how demonstrating practical skills affirmed the pupils' ability and suitability to nurse. Perceptions of the life and work of a (student) nurse, their future career, and the lives of older adults, shifted through the scholarship, especially during practice learning experience. Storytelling revealed how a pre-nursing scholarship helped secondary school pupils to decide whether to pursue a nursing career by providing an opportunity to explore their ability, suitability and desire for nursing. The practice learning experience emerged as an important element of this decision-making process and should be integrated into similar pre-nursing experiences.
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{
"pile_set_name": "PubMed Abstracts"
}
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The role of magnetic stimulation in the diagnosis of multiple sclerosis.
Magnetic stimulation was used to measure motor conduction time (MCT) between head and neck, and head and lumbar region, as well as amplitude of the motor evoked potential (MEP) in normal subjects and patients with multiple sclerosis (MS). Patients with definite MS had significantly longer MCTs and smaller amplitude MEPs than normal subjects when recording from arm and leg muscles. In a comparison with visual evoked potential (VEP) recordings, head to neck MCTs were abnormal less often than VEPs, and VEPs detected more silent lesions. Recording from leg as well as arm muscles significantly increased the yield of abnormal MCT measurements. The detection of silent lesions in the patients with definite MS was improved, but there was no improvement in the non-definite cases. Amplitude measurements provided very little extra diagnostic information over MCT measurements alone and did not improve the detection of silent lesions. Interside MCT differences yielded extra abnormalities when recording from the arms but not the legs. Interside MCT abnormalities increased the detection of silent lesions in both the definite and non-definite categories. It was concluded that the majority of useful diagnostic information in patients with MS should be obtainable from bilateral MCT (head to neck) measurements, together with estimation of interside MCT differences. However, VEP recording is a better diagnostic test for MS than MEP recording as more silent lesions are detected. This may be because MCT abnormalities tend to reflect the degree of pyramidal disability.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sample preparation and biostatistics for integrated genomics approaches.
Genomics is based on the ability to determine the transcriptome, proteome, and metabolome of a cell. These technologies only have added value when they are integrated and based on robust and reproducible workflows. This chapter describes the experimental design, sampling, sample pretreatment, data evaluation, integration, and interpretation. The actual generation of the data is not covered in this chapter since it is highly depended on available equipment and infrastructure. The enormous amount of data generated by these technologies are integrated and interpreted inorder to generate leads for strain and process improvement. Biostatistics are becoming very important for the whole work flow therefore, some general recommendations how to set up experimental design and how to use biostatistics in enhancing the quality of the data and the selection of biological relevant leads for strain engineering and target identification are described.
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{
"pile_set_name": "PubMed Abstracts"
}
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Surgical outcomes of a civil war in a neighbouring country.
The civil war in Syria began on 15 March 2011, and many of the injured were treated in the neighbouring country of Turkey. This study reports the surgical outcomes of this war, in a tertiary centre in Turkey. 159 patients with civilian war injuries in Syria who were admitted to the General Surgery Department in the Research and Training Hospital of the Medical School of Mustafa Kemal University, Hatay, Turkey, between 2011 and 2012 were analysed regarding the age, sex, injury type, history of previous surgery for the injury, types of abdominal injuries (solid or luminal organ), the status of isolated abdominal injuries or multiple injuries, mortality, length of hospital stay and injury severity scoring. The median age of the patients was 30.05 (18-66 years) years. Most of the injuries were gunshot wounds (99 of 116 patients, 85.3%). Primary and previously operated patients were transferred to our clinic in a median time of 6.28±4.44 h and 58.11±44.08 h, respectively. Most of the patients had intestinal injuries; although a limited number of patients with colorectal injuries were treated with primary repair, stoma was the major surgical option due to the gross peritoneal contamination secondary to prolonged transport time. Two women and 21 men died. The major cause of death was multiorgan failure secondary to sepsis (18 patients). In the case of civil war in the bordering countries, it is recommended that precautions are taken, such as transformation of nearby civilian hospitals into military ones and employment of experienced trauma surgeons in these hospitals to provide effective medical care. Damage control procedures can avoid fatalities especially before the lethal triad of physiological demise occurs. Rapid transport of the wounded to the nearest medical centre is the key point in countries neighbouring a civil war.
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{
"pile_set_name": "PubMed Abstracts"
}
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Establishment of a biorepository for migraine research: the experience of Interinstitutional Multidisciplinary BioBank (BioBIM).
The development of Biobanks and recent advances in molecular biology have enhanced the possibility to accelerate translational research studies. The Interinstitutional Multidisciplinary BioBank (BioBIM) is organized in a large healthy donors collection and pathology-based biobanks with the aim to provide a service for development of interdisciplinary studies. A new pathology-based biobank has been organized to specifically collect biospecimen from patients affected by migraine, with the final goal to centralize data, collect blood, plasma, serum, DNA and RNA of patients with this disease. The BioBIM is fully equipped for the automation of sampling/processing, storage and tracking of biospecimens. Standard Operating Procedures have been developed for processing and storage phases as well as archive of clinical data. The availability of biospecimens and clinical data will constitute a resource for various research projects.
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{
"pile_set_name": "PubMed Abstracts"
}
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Severe aseptic leucoencephalopathy as immune reconstitution inflammatory syndrome in Caucasian and African patients.
Immune reconstitution inflammatory syndrome (IRIS) after HAART may become manifest in form of aseptic severe leucoencephalopathy. All HIV-1-positive patients in this case series had widespread laboratory tests and follow-up MRI in order to investigate the course and the underlying pathophysiology of IRIS-associated leucoencephalopathy. All patients were treated with corticosteroids, in spite of additional immunosuppression. Three patients were successfully treated with corticosteroids and survived up to now, one died. A neuropathological examination was performed showing massive aseptic intraparenchymal and perivascular invasion of cytotoxic CD8 cells. It is assumed that IRIS-associated leucoencephalopathy is based on other preconditions in Africans and Caucasians.
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{
"pile_set_name": "PubMed Abstracts"
}
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N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence.
Myristoylation by the myristoyl-CoA:protein N-myristoyltransferase (NMT) is an important lipid anchor modification of eukaryotic and viral proteins. Automated prediction of N-terminal N-myristoylation from the substrate protein sequence alone is necessary for large-scale sequence annotation projects but it requires a low rate of false positive hits in addition to a sufficient sensitivity. Our previous analysis of substrate protein sequence variability, NMT sequences and 3D structures has revealed motif properties in addition to the known PROSITE motif that are utilized in a new predictor described here. The composite prediction function (with separate ad hoc parameterization (a) for queries from non-fungal eukaryotes and their viruses and (b) for sequences from fungal species) consists of terms evaluating amino acid type preferences at sequences positions close to the N terminus as well as terms penalizing deviations from the physical property pattern of amino acid side-chains encoded in multi-residue correlation within the motif sequence. The algorithm has been validated with a self-consistency and two jack-knife tests for the learning set as well as with kinetic data for model substrates. The sensitivity in recognizing documented NMT substrates is above 95 % for both taxon-specific versions. The corresponding rate of false positive prediction (for sequences with an N-terminal glycine residue) is close to 0.5 %; thus, the technique is applicable for large-scale automated sequence database annotation. The predictor is available as public WWW-server with the URL http://mendel.imp.univie.ac.at/myristate/. Additionally, we propose a version of the predictor that identifies a number of proteolytic protein processing sites at internal glycine residues and that evaluates possible N-terminal myristoylation of the protein fragments.A scan of public protein databases revealed new potential NMT targets for which the myristoyl modification may be of critical importance for biological function. Among others, the list includes kinases, phosphatases, proteasomal regulatory subunit 4, kinase interacting proteins KIP1/KIP2, protozoan flagellar proteins, homologues of mitochondrial translocase TOM40, of the neuronal calcium sensor NCS-1 and of the cytochrome c-type heme lyase CCHL. Analyses of complete eukaryote genomes indicate that about 0.5 % of all encoded proteins are apparent NMT substrates except for a higher fraction in Arabidopsis thaliana ( approximately 0.8 %).
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{
"pile_set_name": "PubMed Abstracts"
}
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Treatment of hyponatremia: a quantitative analysis.
The bulk of clinical and experimental evidence seems to support the view that a catastrophic outcome can accompany rapid correction of chronic hyponatremia. However, the dilemma that faces the clinicians is controlling the rate at which the serum sodium concentration is increased during the treatment of hyponatremia. We present a case of severe hyponatremia and hypokalemia to illustrate, in a quantitative fashion, that the increase in serum sodium concentration will be determined not only by the tonicity of infused fluids, but also, and to a major degree, by the rate of excretion of free water by the kidney. A rapid increase in serum sodium concentration would occur if antidiuretic hormone (ADH) release is inhibited and water diuresis ensues. We suggest that the administration of potassium chloride (orally or via a central line) would have been the appropriate therapy for this patient.
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{
"pile_set_name": "PubMed Abstracts"
}
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Developing fluorogenic RNA-cleaving DNAzymes for biosensing applications.
Deoxyribozymes (or DNAzymes) are single-stranded DNA molecules that have the ability to catalyze a chemical reaction. Currently, DNAzymes have to be isolated from random-sequence DNA libraries by a process known as in vitro selection (IVS) because no naturally occurring DNAzyme has been discovered. Several IVS studies have led to the isolation of many RNA-cleaving DNAzymes (RNase DNAzymes), which catalyze the transesterification of a phosphodiester linkage in an RNA substrate, resulting in its cleavage. An RNase DNAzyme and its substrate can be modified with a pair of donor and acceptor fluorophores (or a fluorophore and quencher pair) to create a fluorescence-signaling system (a signaling DNAzyme) where the RNA-cleaving activity of the DNAzyme is reported through the generation of a fluorescent signal. A signaling DNAzyme can be further coupled with an aptamer (a target-binding nucleic acid sequence) to generate a fluorogenic aptazyme in which the aptamer-target interaction confers an allosteric control of the coupled RNA-cleaving and fluorescence-signaling activity of the DNAzyme. Fluorogenic aptazymes can be exploited as valuable molecular tools for biosensing applications. In this chapter, we provide both a detailed description of methods for isolation of signaling DNAzymes by IVS and general approaches for rational engineering of fluorogenic aptazymes for target detection.
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{
"pile_set_name": "PubMed Abstracts"
}
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Fluoropolymer surface coatings to control droplets in microfluidic devices.
We have demonstrated the application of low surface energy fluoropolymer coatings onto poly(dimethylsiloxane) (PDMS) microfluidic devices for droplet formation and extraction-induced merger of droplets. Initiated chemical vapor deposition (iCVD) was used to pattern fluoropolymer coatings within microchannels based on geometrical constraints. In a two-phase flow system, the range of accessible flow rates for droplet formation was greatly enhanced in the coated devices. The ability to controllably apply the coating only at the inlet facilitated a method for merging droplets. An organic spacer droplet was extracted from between a pair of aqueous droplets. The size of the organic droplet and the flow rate controlled the time to merge the aqueous droplets; the process of merging was independent of the droplet sizes. Extraction-induced droplet merging is a robust method for manipulating droplets that could be applied in translating multi-step reactions to microfluidic platforms.
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{
"pile_set_name": "PubMed Abstracts"
}
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Analysis of dopamine D4 receptor gene polymorphism using microchip electrophoresis.
A microfabricated electrophoresis device was used for rapid polymerase chain reaction product analysis in genotyping the dopamine D4 receptor gene (DRD4) 48 base pairs repeat polymorphism. An allelic ladder, prepared from homozygous individuals, was used as internal standard during the microchip electrophoresis based analysis. Comparison of this novel separation method with the conventional slab gel and previously reported ultra-thin-layer techniques confirmed the reliability of this new method. Genotyping of 332 healthy Hungarian individuals gave the following allele frequencies: two-repeat: 0.089; three-repeat: 0.026; four-repeat: 0.674; five-repeat: 0.011; six-repeat: 0.002; seven-repeat: 0.189; eight-repeat: 0.011. The genotype frequencies obtained showed no deviation from the Hardy-Weinberg equilibrium (p>0.903), further underlying the reliability of this new genotyping technique.
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{
"pile_set_name": "PubMed Abstracts"
}
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Are pancreatoenteric anastomoses improved by duct-to-mucosa sutures?
The patency of anastomoses joining the pancreas to either a Roux-Y loop of jejunum or the stomach was evaluated in 26 dogs. At a preliminary operation, the head and uncinate process of the pancreas were resected while carefully preserving the duodenal blood supply. The remaining body and tail of the pancreas were totally obstructed. After obstruction for a mean of 22 (range: 6 to 42) days, one of three anastomoses was performed: (1) inversion pancreatogastrostomy with two layers of sutures; (2) a similar inversion pancreatojejunostomy to the side of a Roux-Y jejunal loop; or (3) pancreatojejunostomy in which the major duct was joined to the jejunal mucosa with interrupted sutures. Six animals were kept for controls. Anastomotic patency was assessed after 8 to 12 weeks by pancreatography, with minimal pressures to achieve anastomotic flow recorded. Weight trends were consistent with anastomotic status. The eight dogs with duct-to-mucosa sutures clearly achieved superior anastomotic patency.
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{
"pile_set_name": "PubMed Abstracts"
}
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Viridans streptococcal shock in bone marrow transplantation patients.
We have recognized a rapidly progressive, often fatal shock syndrome associated with viridans streptococcal sepsis following bone marrow transplantation (BMT). Of 832 patients receiving a marrow transplant at the University of Minnesota between 1976 and 1988, including 123 with viridans streptococcal bacteremia, 10 patients (8%) developed clinical shock within an average of 2 days (range 0-4 days) of their first positive blood culture. Viridans streptococcal shock occurred in patients early in the transplantation course, between 1 and 28 (median 6) days following BMT when all 10 patients were neutropenic. Six of the 10 patients died as a consequence of their shock or from subsequent complications. The most frequent (6 of 10 patients) viridans streptococcal species isolated in the shock patients was Streptococcus mitis. Of multiple factors analyzed for increased risk of developing viridans streptococcal shock, only younger patient age was significantly associated with the development of shock. Although 58% of BMT recipients with viridans streptococcal bacteremia were younger than 15 years, all 10 patients comprising the shock population were < 15 years of age (P < 0.02). We speculate that certain streptococcal strains may trigger fulminant shock in the immunocompromised BMT patient.
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{
"pile_set_name": "PubMed Abstracts"
}
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Esthesioneuroblastoma: ultrastructural, immunohistological and biochemical investigation of one case.
A case of esthesioneuroblastoma, the pathological diagnosis of which almost always causes great difficulties, was investigated ultrastructurally, biochemically, and immunohistologically, using antibodies against the five known types of intermediate filaments [keratin, vimentin, desmin, glial fibrillary acidic protein (GFAP) and neurofilaments]. The tumour cells did not react with antibodies against any of the five intermediate filament proteins. Ultrastructural investigations showed dense cored secretory granules in the cytoplasm and cell processes. Thus, immunohistology offers by "exclusion" a differential diagnosis to avoid often misdiagnosed tumours (undifferentiated carcinomas, embryonal rhabdomyosarcomas, and malignant lymphomas), since carcinomas react with antikeratin, embryonal rhabdomyosarcomas with antibodies to desmin and malignant lymphomas show immunofluorescence with antibodies to vimentin. The biological behaviour (age distribution, tendency to metastasize), the normal values of biochemical parameters, homovanillic acid and vanilmandelic acid (HVA, VMA), and the absence of neurofilaments distinguish this type of tumour from the peripheral sympathetic neuroblastoma.
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{
"pile_set_name": "PubMed Abstracts"
}
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A double-blind, placebo-controlled trial of tiagabine given three-times daily as add-on therapy for refractory partial seizures. Northern European Tiagabine Study Group.
In a multicentre, double-blind, parallel-group, placebo-controlled trial, a three-times daily regimen of tiagabine was evaluated as add-on therapy in 154 adult patients with refractory partial seizures. A total of 77 patients were randomised to treatment in each arm. Tiagabine HCl was titrated from an initial dose of 12-30 mg/day over 4 weeks. During the 12-week fixed-dose period, there was a significant reduction in the median 4-weekly seizure rate for all partial seizures and simple partial seizures (P < 0.05 in each case). Furthermore, the proportion of patients with a reduction of 50% or more in all partial seizures was higher in the tiagabine group than in the placebo group (14 versus 6%), though the difference did not achieve statistical significance. The difference with respect to simple partial seizures was significant (21 versus 6%, P < 0.01). The percentage of patients achieving an increase of at least 50% in the proportion of days free of all partial seizures was significantly greater in the tiagabine group compared to placebo (14 versus 4%, P<0.01). Tiagabine did not appear to influence the plasma concentrations of other concomitant antiepileptic drugs and was generally well tolerated, with most drug-related adverse events being mild or moderate in severity. The most common adverse events were dizziness, asthenia, headache and somnolence. Adverse event incidence was similar between tiagabine and placebo groups, except for dizziness which was more common with tiagabine (29 versus 10%, P < 0.01). Tiagabine had no significant effects on laboratory tests or vital signs. The present study shows that tiagabine, at a dose of 10 mg administered three-times daily, which is at the lower end of the usual recommended dose range (30-50 mg/day, tiagabine base), is generally well tolerated and demonstrates efficacy for the treatment of refractory partial seizures.
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{
"pile_set_name": "PubMed Abstracts"
}
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Investigating the Effect of Social Robot Embodiment.
The experiment described in this paper is an early assessment to identify if the embodiment of a verbal and visual user interaction system in a robot is more effective in people with dementia than when using the same system in a simple laptop. This study provides input for the robot's design.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Blackfan-Diamond disease with ambiguous genitalia].
The Authors describe a case of Blackfan-Diamond anemia with ambiguous genitalia and other minor anomalies. They point out the elements of differential diagnosis with other precocious erythroblastopenic conditions and suppose a recessive inheritance of the disease because of family consanguinity in two generations.
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{
"pile_set_name": "PubMed Abstracts"
}
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Selection and Validation of Reference Genes for RT-PCR Expression Analysis of Candidate Genes Involved in Morphine-Induced Conditioned Place Preference Mice.
The expression of reference genes should be constitutively stable under the experimental conditions, so determining stable reference genes is critical for obtaining reliable results in gene expression studies. Morphine addiction persistently influences neurotransmitters and signal transduction systems, which may negatively alter behavioral responses at the cellular levels and interfere the expression of reference genes. In order to research morphine dependence, animal models are commonly used in physiology, pathology, and therapeutics field since human trials have many limitations. Therefore, it is necessary to select stable reference genes in standardized animal model. The objective of this study is to find out a set of optimal reference genes to standardize the gene expression of morphine-induced conditioned place preference (CPP) mice. During the process, eight reference genes were chosen. Then, the stability of their expression in two different brain tissues (Caudate Putamen and Hippocampus) was tested in two developmental stages (puberty and adult) under two treatments (physiological saline as control and morphine). Based on two algorithm-based methods (geNorm and NormFinder), which can rank and assess the stability of expression of eight reference genes, thereby quantifying the transcriptional levels of these genes by high sensitive, specific, and accurate real-time quantitative reverse transcription PCR (RT-qPCR) assays.
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{
"pile_set_name": "PubMed Abstracts"
}
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Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching?
The Eurotransplant Senior Program (ESP) neglects HLA matching for elderly (≥65 years) kidney transplant recipients (KTR). Few data regarding the influence of DR matching on clinical and immunologic outcome in elderly KTR exist. This retrospective long-term observational study included 244 elderly out of n = 972 adult KTR between 2004 and 2014. Data analysis included patient and graft survival, biopsy-proven rejections [T-cell-mediated rejections (TCMR) and antibody-mediated rejections] and development of de novo donor-specific HLA antibodies (DSA). Outcome data were assessed over a maximum period of 10 years. Due to the nature of the ESP, elderly KTR showed significantly more HLA mismatches, shorter time on dialysis and shorter cold ischaemia time. Elderly KTR had significantly worse graft and patient survival, and after 7 years, the rate of de novo DSA (33 versus 25%, P = 0.034) and TCMR (39 versus 27%, P < 0.001) was significantly higher compared with younger KTR. Multivariate analysis identified donor age, delayed graft function and HLA-DR mismatches as independent risk factors for TCMR. Within the group of elderly KTR, HLA-DR mismatches were associated with a significantly higher incidence of TCMR and development of de novo DSA. Occurrence of TCMR and de novo DSA in elderly KTR resulted in significantly worse graft survival. In elderly KTR, HLA-DR mismatches are independent risk factors for TCMR and the development of all classes of de novo DSA, both of which significantly impair graft survival. Introduction of HLA-DR matching in elderly KTR might significantly improve immunologic and overall outcome.
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{
"pile_set_name": "PubMed Abstracts"
}
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Care of nursing home residents by advanced practice nurses. A review of the literature.
The complexity of care in nursing homes has steadily increased during the past several years. Many nursing homes now provide care for both short-stay and long-stay patients who range in age from young to very old. At the same time, there has been a shortage of primary care physicians to provide care while nursing homes have been under intense scrutiny and pressure to improve the quality of care provided. Advanced practice nurses (APNs) are increasingly evident members of the nursing home workforce, providing both primary care to individual residents in collaboration with physicians and consultative services to nursing homes. This article reviews the research that documents the relationship between APNs and improved quality of care and begins a discussion of what constitutes APN best practices in the nursing home setting.
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{
"pile_set_name": "PubMed Abstracts"
}
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Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia.
The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan® procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.
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{
"pile_set_name": "PubMed Abstracts"
}
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Sexual assault in the lives of urban sex workers: a descriptive and comparative analysis.
This exploratory study contributes to the sparse literature on sexually assaulted sex workers. We examined 462 sexual assault cases seen at an emergency department-based sexual assault service and reported to the police between 1993 and 1997. More than one fifth of victims were sex workers. We compared them to other victims on victim characteristics, assault characteristics, and medical-legal findings. Relative to other victims, sex workers were younger, had lower incomes, and were more likely to be heroin and/or cocaine users. They suffered a greater number of injuries and forensic samples collected from their bodies were more likely to test positive for sperm and/or semen. These victims were also less likely to have been using alcohol and/or marijuana prior to the assault and to be emotionally expressed during the medical- legal examination. The substantial proportion of sex workers in the study population suggests that attention to their particular needs should be an important part of hospital-based sexual assault services. Clinical implications and directions for future research are discussed.
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{
"pile_set_name": "PubMed Abstracts"
}
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Rapid analytical methods for on-site triage for traumatic brain injury.
Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.
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{
"pile_set_name": "PubMed Abstracts"
}
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Hearing where we're coming from--ethically and professionally.
Anthropologists concerned about the discipline's ability to cope ethically and ethnographically with a globalized world should not dismiss too hastily the methodology--and the ethics built into it--that anthropology developed over the last century. This methodology of making "displacing" translations, based on ethnographic experience and a politics of translation, can still provide a workable ethics and a viable labor of ethnography even in the world at present.
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{
"pile_set_name": "PubMed Abstracts"
}
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Estimation of the tissue composition of the tumour mass in neuroblastoma using segmented CT images.
Neuroblastoma is the most common extra-cranial, solid, malignant tumour in children. Advances in radiology have made possible the detection and staging of the disease. Nevertheless, there is no method available at present that can go beyond detection and qualitative analysis, towards quantitative assessment of the tissue composition of the primary tumour mass in neuroblastoma. Such quantitative analysis could provide important information and serve as a decision-support tool to the radiologist and the oncologist, result in better treatment and follow-up and even lead to the avoidance of delayed surgery. The problem investigated was the improvement of the analysis of the primary tumour mass, in patients with neuroblastoma, using X-ray computed tomography (CT) images. A methodology was proposed for the estimation of the tissue content of the mass: it comprised a Gaussian mixture model for estimation, from segmented CT images, of the tissue composition of the primary tumour. To demonstrate the potential of the method, the results are presented of its application to ten CT examinations of four patients. The method provides quantitative information, and it was observed that the tumour in one of the patients reduced from 523 cm3 to 81 cm3 in volume, with an increase in calcification from about 20% to about 88% of the tumour volume, in response to chemotherapy over a period of five months. Results indicate that the proposed technique may be of considerable value in assessing the response to therapy of patients with neuroblastoma.
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{
"pile_set_name": "PubMed Abstracts"
}
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Unique chromosome rearrangements in karyotypes of yellow-necked mice (Apodemus flavicollis) from various populations.
Cytogenetic monitoring of yellow-necked mouse populations in various parts of the species range revealed deviations from the standard chromosome set in two individuals (Female from the Bryanskaya region and Male from the Samarskaya region). In both of them the wholly acrocentric chromosome set was supplemented by a large unpaired submetacentric chromosome. The C-banding showed no structural homology between these newly formed chromosomes. Obviously, they had been produced by different mechanisms, which may include amplification of paracentromeric heterochromatin in a large chromosome (Female) and classical Robertsonian fusion of two acrocentrics (Male). The low frequency and nonhomologous state of these rearrangements suggest their mutational origin.
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{
"pile_set_name": "PubMed Abstracts"
}
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Implement balanced scorecard to translate strategic plan into actionable objectives.
Faced with challenges ranging from declining reimbursement to staff shortages, health care organizations--integrated delivery systems, physician group practices, disease management providers, and others--increasingly are turning to general business models to map out step-by-step action plans for performance measurement and process improvement. Creating a "balanced scorecard" is an obvious starting point for assessing and improving clinical and financial performance.
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{
"pile_set_name": "PubMed Abstracts"
}
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Solubilisation and characterisation of a putative quisqualate-type glutamate receptor from chick brain.
The brains of 1-day-old chicks were shown to be a rich source of binding sites with the pharmacological characteristics expected of a quisqualate-type glutamate receptor. alpha-[3H]Amino-3-hydroxy-5-methylisoxazolepropionate ([3H]AMPA) bound with KD and Bmax values, measured at 0 degree C in the presence of the chaotrope potassium thiocyanate, of 55 nM and 2.6 pmol/mg protein. The regional localisations of [3H]AMPA and [3H]kainate binding sites were manifestly different. The membrane-bound [3H]AMPA binding sites were efficiently solubilised by N-octyl-beta-D-glucopyranoside (1%) in the presence of 0.2 M thiocyanate. In the detergent extract the affinity was 69 nM and there was an apparent increase in the number of sites (Bmax, 4.6 pmol/mg protein). The rank order of potency for competitive ligands in displacing [3H]AMPA binding was quisqualate approximately AMPA greater than 6-cyano-7-nitroquinoxaline-2,3-dione greater than L-glutamate greater than kainate and was identical for the membrane-bound and solubilised sites. Dissociation was biphasic with rate constants of 0.117 min-1 and 0.015 min-1. The association rate constants for [3H]AMPA at the solubilised sites were 1.45 x 10(6) M-1 min-1 and 6.55 x 10(6) M-1 min-1. The kinetically derived KD values were 80.7 nM and 2.3 nM. The detection of higher affinity binding sites by kinetic analysis but not by equilibrium binding may be explained by the greater sensitivity of dissociation data to small populations of high-affinity sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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{
"pile_set_name": "PubMed Abstracts"
}
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High doses of L-carnitine in acute myocardial infarction: metabolic and antiarrhythmic effects.
Fatty acids accumulate in the muscle cells in some carnitine deficiency syndromes due to a variety of genetic defects in intermediary metabolism. L-Carnitine administration may relieve this excess by transporting acyl compounds out of the cell as acylcarnitine. Similar fatty acid accumulation occurs during myocardial ischaemia because of the decreased rate of beta-oxidation, and this has been put forward as a cause of ventricular arrhythmias. This study was carried out to investigate whether administration of high doses of i.v. L-carnitine in patients with acute myocardial infarction could increase urinary excretion of acylcarnitine and reduce early ventricular arrhythmias. Fifty-six patients suffering from acute myocardial infarction, admitted to the Coronary Unit between 3 and 12 h after the onset of symptoms, were included in the study. The design of the study was double blind, parallel and placebo controlled. Allocation of treatment to patients was done randomly after stratification (time from onset of pain and site of infarction). The first group (28 patients) received intravenous L-carnitine at a dose of 100 mg kg-1 b.w. every 12 h for 36 h while the second group (28 patients) received placebo intravenously. Immediately before starting treatment two blood samples were taken (at 5-min intervals) and a further 16 samples were taken at regular intervals over the following 48 h. Patients' urine was collected over the same period of time. Concentrations of free carnitine, short chain acylcarnitine esters and long chain acylcarnitine esters in serum and urine were measured.(ABSTRACT TRUNCATED AT 250 WORDS)
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{
"pile_set_name": "PubMed Abstracts"
}
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Correlation among crystal shape, absolute configuration, and circular dichroism spectrum of enantiomorphs of Tris[2-(((2-phenylimidazol-4-yl)methylidene)amino)ethyl]-aminemetal(II) nitrate-methanol (1/1).
A series of metal(II) complexes of a tripod-type ligand with the chemical formulas [M(H(3)L)](NO(3))(2).MeOH (M = Mn (1), Fe (2), Co (3), Ni (4), Zn (6)) and [Cu(H(3)L)](NO(3))(2).CH(3)CN.H(2)O (5) were synthesized and characterized (H(3)L = tris[2-(((2-phenylimidazol-4-yl)methylidene)amino)ethyl]amine). The crystal structures were determined, in which those of 1-4 and 6 are isomorphous and conglomerates, because they crystallize into the acentric space group P2(1)2(1)2(1). Each metal(II) ion of 1-4 and 6 assumes an octahedral coordination environment with the N(6) donor atoms of the tripod ligand and becomes either a C (clockwise) or an A (anticlockwise) enantiomorph because of the screw arrangement of the tripod-type ligand around the metal(II) ion. The crystals were divided into two groups, where their crystal shapes are mirror images and their CD spectra show enantiomeric patterns. The circular dichroism (CD) spectrum of the crystal used for the X-ray analysis was measured. The absolute configuration of the enantiomorph of the crystal used for the X-ray analysis was determined by the Flack parameter. The correlation among the crystal shape, the absolute configuration, and the CD spectral pattern was thus confirmed for 1-4 and 6. On the other hand, 5 assumes a square pyramidal coordination geometry with the N(5) donor atoms, and hence, there are no optical isomers.
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{
"pile_set_name": "PubMed Abstracts"
}
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[Malfunction of a mitral bioprosthesis, hemolysis and acute renal insufficiency].
Intravascular hemolysis is a rare complication following valvular replacement, particularly with bioprostheses. It is generally secondary to prosthetic malfunction and is the cause of anemia. We report a rare case of acute renal insufficiency and severe hemolysis caused by malfunction of a bioprosthesis in the mitral position.
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{
"pile_set_name": "PubMed Abstracts"
}
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Non-Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency that Developed into Symptomatic Severe Hyponatremia.
A 78-year-old woman diagnosed with non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency had been under glucocorticoid replacement therapy since the age of 17 years. After several weeks of suffering from gastroenteritis with vomiting, she presented with disturbance of consciousness, hypotension, dehydration, and severe hyponatremia (108 mEq/L) and a markedly increased serum vasopressin concentration (45.5 pg/mL). She regained consciousness after correcting her body-fluid balance with hypertonic saline and intravenous hydrocortisone sodium therapy. Her hyponatremia was likely caused by extra-renal sodium loss and impaired water excretion induced by an increase of serum vasopressin due to volume depletion and glucocorticoid deficiency.
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{
"pile_set_name": "PubMed Abstracts"
}
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Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer.
To better direct targeted therapies to the patients with tumors that express the target, there is an urgent need for blood-based assays that provide expression information on a consistent basis in real time with minimal patient discomfort. We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer. Blood was collected from 63 patients with metastatic prostate cancer. CTCs were isolated by the Cell Search system, which uses antibodies to epithelial cell adhesion marker and immunomagnetic capture. CTCs were defined as nucleated cells positive for cytokeratins and negative for CD45. Captured cells were analyzed by immunofluorescence, Papanicolau staining, and fluorescence in situ hybridization. Most patients (65%) had 5 or more CTCs per 7.5 mL blood sample. Cell counts were consistent between laboratories (c = 0.99) and did not change significantly over 72 or 96 h of storage before processing (c = 0.99). Their identity as prostate cancer cells was confirmed by conventional cytologic analysis. Molecular profiling, including analysis of epidermal growth factor receptor (EGFR) expression, chromosome ploidy, and androgen receptor (AR) gene amplification, was possible for all prostate cancer patients with >or=5 CTCs. The analysis of cancer-related alterations at the DNA and protein level from CTCs is feasible in a hospital-based clinical laboratory. The alterations observed in EGFR and AR suggest that the methodology may have a role in clinical decision making.
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{
"pile_set_name": "PubMed Abstracts"
}
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MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction.
MAP kinase kinase (MAPKK) was purified 30,000-fold to homogeneity from extracts of rabbit skeletal muscle and shown to be a monomeric protein of apparent molecular mass 44 kDa. MAPKK activated the 42 kDa isoform of MAP kinase by phosphorylation of Thr-183 and Tyr-185, and phosphorylated itself slowly on tyrosine, threonine and serine residues, establishing that it is a 'dual specificity' protein kinase. Peptide sequences from MAPKK were homologous to other protein serine/threonine kinases, especially to the subfamily that includes yeast protein kinases that lie upstream of yeast MAP kinase homologues in the pheromone-dependent mating pathways.
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{
"pile_set_name": "PubMed Abstracts"
}
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Detection of decrements and increments in sinusoids at high overall levels.
Thresholds for the detection of decrements in level of sinusoidal signals were measured as a function of duration (2, 4, 6, 10, and 14 ms), level (70, 80, and 90 dB SPL) and frequency (250, 500, 1000, 2000, and 4000 Hz). Seven normally hearing listeners were tested at each frequency (with different subjects for each frequency). Thresholds for detecting a 10-ms increment in level were also measured. The sinusoids were presented in a background noise low-pass filtered at 5 kHz, which was intended to mask spectral splatter associated with the decrement or increment. Performance improved with increasing frequency for all decrement and increment durations. Performance also tended to improve with increasing level at 2000 and 4000 Hz. The results were analyzed using a four-stage model consisting of an auditory filter centered on the signal frequency, a compressive nonlinearity, a sliding temporal integrator and a decision mechanism. The analysis indicated that the improved performance with increasing frequency and increasing level could be attributed partly to off-frequency listening; for the two highest center frequencies, subjects probably made use of the output of an auditory filter centered above the signal frequency, where changes in excitation level associated with an increment or decrement were magnified. The measurements at 4000 Hz were repeated using a broadband background noise (15-kHz bandwidth), which would prevent the use of information from auditory filters centered far above the signal frequency. Performance was poorer than when low-pass noise was used, but still improved somewhat with increasing level. The slight improvement in performance with increasing level can be accounted for by a reduced compressive linearity at high levels. A good fit to the data could be obtained by assuming that the equivalent rectangular duration (ERD) of the temporal integrator was invariant with level, but that the compressive nonlinearity varied with level in a similar way to basilar-membrane input-output functions. The nonlinearity appears to be somewhat less compressive at 250 Hz than at higher center frequencies. The ERD is about 7 ms regardless of center frequency.
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{
"pile_set_name": "PubMed Abstracts"
}
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Automatic stratification of prostate tumour aggressiveness using multiparametric MRI: a horizontal comparison of texture features.
Background: Previous studies have identified apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can stratify prostate cancer into high- and low-grade disease (HG and LG, respectively). In this study, we consider the improvement of incorporating texture features (TFs) from T2-weighted (T2w) multiparametric magnetic resonance imaging (mpMRI) relative to mpMRI alone to predict HG and LG disease. Material and methods: In vivo mpMRI was acquired from 30 patients prior to radical prostatectomy. Sequences included T2w imaging, DWI and dynamic contrast enhanced (DCE) MRI. In vivo mpMRI data were co-registered with 'ground truth' histology. Tumours were delineated on the histology with Gleason scores (GSs) and classed as HG if GS ≥ 4 + 3, or LG if GS ≤ 3 + 4. Texture features based on three statistical families, namely the grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRLM) and the grey-level size zone matrix (GLSZM), were computed from T2w images. Logistic regression models were trained using different feature subsets to classify each lesion as either HG or LG. To avoid overfitting, fivefold cross validation was applied on feature selection, model training and performance evaluation. Performance of all models generated was evaluated using the area under the curve (AUC) method. Results: Consistent with previous studies, ADC was found to discriminate between HG and LG with an AUC of 0.76. Of the three statistical TF families, GLCM (plus select mpMRI features including ADC) scored the highest AUC (0.84) with GLRLM plus mpMRI similarly performing well (AUC = 0.82). When all TFs were considered in combination, an AUC of 0.91 (95% confidence interval 0.87-0.95) was achieved. Conclusions: Incorporating T2w TFs significantly improved model performance for classifying prostate tumour aggressiveness. This result, however, requires further validation in a larger patient cohort.
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{
"pile_set_name": "PubMed Abstracts"
}
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Abnormal bone mineral accrual in adolescent girls with anorexia nervosa.
Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean +/- SEM, 15.4 +/- 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); P = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 +/- 0.001 g/cm(2).month vs. 0.000 +/- 0.001 g/cm(2).month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 micro g/liter.month, vs. control, -1.1 +/- 0.4 micro g/liter.month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter.month, vs. control, -1.5 +/- 0.4 U/liter.month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol creatinine (cr).month, vs. control, -0.4 +/- 0.1 nmol/mmol cr.month; P = 0.005], and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN.
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{
"pile_set_name": "PubMed Abstracts"
}
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Clinical predictors of acute respiratory acidosis during exacerbation of asthma and chronic obstructive pulmonary disease.
Mechanical ventilation (MV) during exacerbation of asthma or chronic obstructive pulmonary disease (COPD) is unequivocally needed when apnoea, cardiorespiratory arrest, coma, hypoxia or treatment failure is present. The need is less clear when the patient can respond, has intact airway reflexes and spontaneous respiration. In this situation, acidosis is an important factor in the decision to institute MV. This study aimed to provide a clinical means of identifying patients with acute respiratory acidosis (ARA) in a setting where blood gas analysis is unavailable. We undertook a prospective, observational study of consecutive patients who presented to two emergency departments with severe and life-threatening exacerbation of asthma or COPD. Each underwent clinical assessment, treatment and blood gas analysis. The outcome measure was ARA or mixed ARA and metabolic acidosis. A total of 127 episodes in patients aged 15-90 years (65.3% males and 34.7% females) were included in the study. Of these, 62.2% had asthma and 37.8% had COPD; 71.7% had life-threatening and 28.3% had severe attacks. Overall, the adjusted odds ratio (and 95% confidence intervals) for predictors of ARA were 7.09 (1.79-28.06) for drowsiness, 4.11 (1.31-12.88) for flushing, 3.34 (1.01-11.02) for having COPD and 2.86 (1.01-8.07) for intercostal retractions. In conclusion, with drowsiness, the likelihood of ARA is about seven times higher. The presence of flushing, COPD and intercostal retractions also increase the risk of ARA.
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{
"pile_set_name": "PubMed Abstracts"
}
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Washout of 133-xenon as an objective assessment of paranasal sinus ventilation in endoscopic sinus surgery.
Endoscopic sinus surgery (ESS) is today a common method for the treatment of chronic rhinosinusitis. Assessment of the results has been based mainly upon subjective evaluation, and only a few reports present objective measurements. In the present study, the 133-xenon washout technique was used for preoperative and postoperative evaluation of paranasal sinus ventilation in 12 patients selected for ESS. The postoperative half-times (T1/2) of 133-xenon washout were lower in the sinuses with abnormal preoperative half-times (T1/2), especially in the maxillary sinuses, where the postoperative T1/2 was 44 (22 to 150) minutes (median and quartiles, Q1-Q3) as compared with a preoperative T1/2 of 202 (94 to 278) minutes. The postoperative evaluation included a questionnaire and a follow-up visit with endoscopy and measurements of nasal nitric oxide. The results showed that patients who declared a marked reduction in symptoms exhibited significantly improved sinus ventilation. However, no direct correlation was found between improvement in ventilation and symptom improvement. Nine of the 12 patients showed improvement on endoscopy, and these patients also exhibited improved sinus ventilation. The postoperative nasal nitric oxide levels were within the normal range in 11 of the 12 patients; the other patient showed pathological T1/2 values for all paranasal sinuses. The 133-xenon washout technique is thus a method that can be used for objective evaluation of the ventilation of the paranasal sinuses before and after ESS procedures. However, the technique cannot be used to evaluate sinuses with totally obstructed ostia or postoperative sinuses with very wide neoostia, as rapid washout may lead to no activity remaining at the time of measurement.
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{
"pile_set_name": "PubMed Abstracts"
}
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Clinical characteristics and treatment responses in new-onset epilepsy in the elderly.
Epidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. We searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. We identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. The most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.
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{
"pile_set_name": "PubMed Abstracts"
}
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Drug dosing during continuous arteriovenous hemofiltration.
An overview of continuous arteriovenous hemofiltration (CAVH), which is an alternative to hemodialysis and peritoneal dialysis in the management of acute renal failure, is provided, and literature concerning drug clearance via hemofiltration is reviewed. CAVH is a slow, continuous process that removes, by convective mass transport, non-protein-bound solutes smaller than 10,000 daltons from blood diverted through an extracorporeal filter. The system provides a creatinine clearance of approximately 10 mL/min. The sieving coefficient of a particular compound reflects its ability to permeate the filter membrane and is primarily influenced by protein binding. Clearance of a compound depends on its sieving coefficient and the ultrafiltration rate. Methods for estimating drug clearance, the amount of drug removed per time interval, and appropriate drug dosages are discussed. Many drugs commonly used in an intensive-care setting, including aminoglycosides, cephalosporins, acyclovir, vancomycin, phenobarbital, ranitidine, and theophylline, can be expected to have a limited but clinically important clearance during CAVH. CAVH substantially enhances the current treatment of acute renal failure; although limited data for specific drugs are available in the literature, drug dosages may be adjusted based on the methods outlined in this review.
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{
"pile_set_name": "PubMed Abstracts"
}
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Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy.
Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In addition, conditional analyses revealed a further four secondary signals at three known cytokine loci. Integration, through the use of Bayesian colocalization analysis, of publicly available GWAS summary statistics with the cytokine network associations revealed shared causal variants between the eight cytokine loci and other traits; in particular, cytokine network variants at the ABO, SERPINE2, and ZFPM2 loci showed pleiotropic effects on the production of immune-related proteins, on metabolic traits such as lipoprotein and lipid levels, on blood-cell-related traits such as platelet count, and on disease traits such as coronary artery disease and type 2 diabetes.
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{
"pile_set_name": "PubMed Abstracts"
}
|
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