title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Carbamazepine and diclofenac: removal in wastewater treatment plants and occurrence in water bodies. | In the aquatic environment, pharmaceuticals have been widely found. Among them, carbamazepine and diclofenac were detected at the highest frequency. To evaluate the worldwide environmental impacts of both drugs, their global consumption volumes are estimated, based on the dose per capita. The metabolites of these pharmaceuticals are also of environmental concerns, especially trans-10,11-dihydro-10,11- dihydroxycarbamazepine (CBZ-diol) which probably has a similar concentration in water bodies to that of its parent drug. The removal efficiencies and mechanisms of both drugs in the wastewater treatment plants (WWTPs) are discussed with the actual state of knowledge. The occurrences of both drugs are examined in various water bodies including WWTP effluents, surface waters, groundwater and drinking water. Their chemical, physical and pharmacological properties are also addressed in context, which can largely influence their environmental behaviors. The ecotoxicological studies of both drugs imply that they do not easily cause acute toxic effects at their environmental concentrations. However their chronic effects need cautious attention. | 18,793,791 |
Right atrium contractility and right ventricular diastolic function assessed by pulsed tissue Doppler imaging can predict brain natriuretic peptide in adults with acquired pulmonary hypertension. | We evaluated right atrial (RA) contractility and right ventricular (RV) diastolic function in adult patients with acquired chronic pulmonary hypertension (PH) by pulsed Tissue Doppler Imaging (TDI) and assessed their relationship with serum brain natriuretic peptide (BNP). Systolic myocardial wave (Sa), early diastolic myocardial wave (Ea), and late diastolic myocardial wave (Aa) at the tricuspid annulus were recorded in 77 consecutive patients with acquired PH. Early (E) RV inflow waves were recorded from 4-chamber views. RV Aa was regarded as the parameter of RA contractility and RV E/Ea was taken as the parameter of RV diastolic function using TDI. All subjects had elevated BNP (mean 188.9 +/- 244.0 pg/dl) and pulmonary arterial systolic pressure (PASP) estimated at 62.9 +/- 26.7 mm Hg. BNP levels were positively correlated with RV E/Ea, Aa and PASP (r = 0.47, p < 0.0001 and r = 0.35, p < 0.01, respectively) but negatively with Aa (r = -0.29, p < 0.05). Next, all predictor variables were used in a multiple regression model with serum BNP values as dependent variables, refined to include 3 predictors: RV E/Ea, Aa, and PASP, which were all found to influence serum BNP values (p < 0.0001) by the formula Y = 34.1X1**-19.11X2**+2.95X3* (**p < 0.001, *p < 0.01) where Y = BNP, X1 = E/Ea of RV, X2 = Aa, and X3 = PASP (standard regression coefficients were 0.37, -0.34 and 0.34, respectively). Serum BNP correlates with RA contractility and RV diastolic dysfunction by RV TDI in adults with acquired PH. Increased BNP may be related to decreased RA systolic function and RV diastolic function in these patients. | 18,793,807 |
Insulin-like growth factor binding protein-1 is a long-term predictor of heart failure in survivors of a first acute myocardial infarction and population controls. | Only a few studies have investigated the prospective relationship between insulin-like growth factor binding protein-1 (IGFBP-1) and cardiovascular events and the results are conflicting. In this prospective cohort study, we followed both cases, i.e. survivors of a first acute myocardial infarction (AMI) and their age, sex and hospital catchment area matched controls of a large population-based case-control study for 8 years for total and cardiac mortality, AMI, stroke and hospitalization for heart failure (HF). Levels of IGFBP-1 were measured three months after AMI in a stable metabolic phase in 853 patients. For 1106 control subjects, the time of measurement was as close as possible to that of 'his/her' case. Established cardiovascular risk and prognostic factors were also determined. Higher IGFBP-1 values predicted hospitalization for HF during follow-up both in the patient and the control cohort. Control subjects with higher IGFBP-1 values had elevated mortality when compared to those with the lowest quartile. The associations between IGFBP-1 and other outcomes investigated in this study, i.e. mortality among patients, AMI or stroke among patients and controls were weak and statistically not significant. Levels of IGFBP-1 consistently predicted HF both among survivors of a first AMI and their matched controls. Our results suggest that IGFBP-1 levels might also predict mortality in a population free of previous AMI. | 18,793,810 |
Bilateral adrenal hyperplasia complicated with severe ischemic stroke in a young patient. | A young patient suffered from acute right hemiparesis, facial weakness and Broca's aphasia with multiple brain lesions due to severe hypertension. His evaluation for secondary causes of hypertension revealed hyperaldosteronism due to bilateral adrenal hyperplasia. Treatment is based primarily on spironolactone and ACE inhibitors. Two years later he was in an outstanding clinical condition with few remained neurological symptoms and his blood pressure well controlled. | 18,793,812 |
Impact of gender in primary prevention of coronary heart disease with statin therapy: a meta-analysis. | Evidence of lipid-lowering from clinical trials that included women is adequate to support their use in secondary prevention in women with known coronary disease. However the role of statin therapy in primary prevention is still controversial, in particular for female gender. The aim of our study is to perform a meta-analysis comparing by gender the cardiovascular outcomes related to statin therapy in primary prevention. We performed a meta-analysis including 8 randomized controlled trials (19,052 and 30,194 men, mean follow-up 3.9 years) that assessed the cardiovascular outcomes related to statin therapy, including studies that provided sex-specific results. MEDLINE and the Cochrane Database, were searched for articles published in English and other languages up to March 2008. Statins do not appear to have a beneficial effect on total mortality for both men and women in primary prevention over the 2.8- to 5.3 year study period (men: 95% Confidence Interval (CI) 0.83-1.04; comparison p = 0.22; women: 0.96; CI 0.81-1.13; p = 0.61). Statin therapy reduced the risk of coronary heart disease (CHD) events in men (0.59; CI 0.48-0.74; p = 0.0001), however in women this risk reduction was weakly significant (0.89 CI 0.79-1.00; p = 0.05) and disappeared when in sensitivity analysis, trials not entirely of primary prevention were excluded (HPS, PROSPER) (0.95 CI 0.78-1.16; comparison p = 0.562). Our study showed that statin therapy reduced the risk of CHD events in men without prior cardiovascular disease, but not in women. Statins did not reduce the risk of total mortality both in men and women. | 18,793,814 |
Effect of capric, lauric and alpha-linolenic acids on the division time distributions of single cells of Staphylococcus aureus. | The effect of non-inhibitory concentrations of capric, lauric and alpha-linolenic acids (C10:0, C12:0 and C18:3 respectively) on the division time distribution of single cells of Staphylococcus aureus was evaluated at pH 7 and pH 5. The effect of the initial cell concentration on the lag time of growing cell populations was also assessed. The statistical properties of the division times (defined as the time interval from birth to next binary fission for a single cell) were studied using the method of Elfwing et al. [Elfwing, A., Le Marc, Y., Baranyi, J., Ballagi, A., 2004. Observing the growth and division of large number of individual bacteria using image analysis. Applied and Environmental Microbiology 70, 675-678]. The division times were significantly longer in the presence of free fatty acids than in the control. Shorter division intervals were detected at pH 7 than at pH 5 in the control experiment and in the presence of C10:0. However, both C12:0 and C18:3 slowed down the growth, regardless of the pH. The observed division time distributions were used to simulate growth curves from different inoculum sizes using the stochastic birth process described by Pin and Baranyi [Pin, C., Baranyi, J., 2006. Kinetics of single cells: observation and modelling of a stochastic process. Applied and Environmental Microbiology 72, 2163-2169]. The output of the simulation results were compared with observed data. The lag times fitted to simulated growth curves were in good agreement with those fitted to growth curves measured by plate counts. The averaged out effect of the population masked the effect of the free fatty acids and pH on the division times of single cells. | 18,793,815 |
Cutaneous manifestations of human toxocariasis. | Human toxocariasis is a parasitic disease characterized by the presence of larvae of the genus Toxocara in human tissues. T canis and T cati, the adult roundworms of which are found in dog and cat intestines, respectively, are the most common causative agents of the disease. Toxocaral larvae usually cause two severe syndromes: visceral larva migrans and ocular larva migrans, depending on the location of the larvae. Two other syndromes, covert toxocariasis and common toxocariasis, which are less typical and not as severe, have also been described. During the last two decades, cutaneous manifestations such as chronic urticaria, chronic pruritus, and miscellaneous eczema, in patients with Toxocara antibodies, have been studied by different authors. In some cases, these cutaneous manifestations are the only signs indicating the presence of the disease, and they are cured after antihelmintic treatment when there is good patient compliance. In this review, we focus on these particular skin manifestations regarding their clinical description, diagnosis, and treatment. | 18,793,816 |
Investigation of the accumulation of aromatic compounds during biogas production from kitchen waste. | This paper presents laboratory scale studies on the anaerobic degradation of kitchen waste, with a high protein and fat content, using a quasi-continuous co-digestion process. The increased accumulation of non-degraded intermediates as an indication of process imbalances was examined in experiments where the substrate load was gradually increased. In addition to the critical rise of known toxic metabolites like ammonia, hydrogen sulphide or volatile fatty acids, aromatic acids accumulated with increasing substrate loading. These metabolites could be identified as intermediates from the anaerobe degradation of the aromatic amino acids phenylalanine, tyrosine and tryptophan. In most experiments the important finding was the early detection of aromatics, especially phenylacetic acid, even before the monitoring of volatile fatty acid concentrations gave an indication of a process imbalance. This demonstrates the potential use aromatic acids as indicators for an upcoming process failure. | 18,793,837 |
The effect of disk rotational speed on oxygen transfer in rotating biological contactors. | Lab-scale experiments using a synthetic wastewater were carried out to assess the influence of disk rotational speed on oxygen transfer rate in a RBC unit in the presence of biomass. The overall oxygen transfer coefficient (K(L)a) was computed. Five different disk rotational speeds were tested, in the typical RBC operating range (3-10 RPM). The soluble organic substrate was monitored through TOC analysis. Influent hydraulic organic loadings were in the range of 5.4-35.2 g TOC/m(2)d. The set of kinetic coefficients calculated fitting the experimental data by the selected model resulted in good agreement with the value reported in literature. A correlation for K(L)a as a function of disk rotational speed and disk diameter was obtained. Accordingly, a new expression of the enhancement factor of oxygen transfer was found, and compared to literature data. | 18,793,838 |
Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam. | The effects of nefopam and ketamine on pain control and rehabilitation after total knee replacement were compared in a prospective, double blinded study. Seventy-five patients were randomly assigned to receive a 0.2mg kg(-1) bolus of nefopam or ketamine, followed by a 120microg kg(-1) h(-1) continuous infusion until the end of surgery, and 60microg kg(-1) h(-1) until the second postoperative day, or an equal volume of saline considered as placebo. Pain scores measured on a visual analog scale at rest and on mobilization, and patient-controlled intravenous morphine consumption, were assessed during 48h. We measured the maximal knee flexion on the third postoperative day, and the delay to obtain a 90 degrees flexion. Ketamine and nefopam reduced morphine consumption (p<0.0001). Pain scores, were lower at rest and on mobilization in the ketamine group compared to the two other groups at all times of measurement. Pain score were lower in patients receiving nefopam compared to placebo, on arrival in the recovery room and at 2h. Ketamine improved knee flexion on post operative day 3 (59 degrees [33-63] vs. 50 degrees [47-55] and 50 degrees [44-55] in ketamine, placebo and nefopam groups, respectively, p<0.0002) and decreased the delay to flex the knee at 90 degrees (9.1+/-4.2 vs. 12.3+/-4.0 days, in ketamine and placebo groups, respectively, p=0.01). Ketamine produces opioid-sparing, decreases pain intensity, and improves mobilization after total knee replacement. Nefopam achieves less significant results in that circumstances. | 18,793,861 |
Is 'ideal' sitting posture real? Measurement of spinal curves in four sitting postures. | There is a lack of quantitative evidence for spinal postures that are advocated as 'ideal' in clinical ergonomics for sitting. This study quantified surface spinal curves and examined whether subjects could imitate clinically 'ideal' directions of spinal curve at thoraco-lumbar and lumbar regions: (i) flat - at both regions (ii) long lordosis - lordotic at both regions (iii) short lordosis - thoracic kyphosis and lumbar lordosis. Ten healthy male subjects had 3-D motion sensors adhered to the skin so that sagittal spinal curves were represented by angles at thoracic (lines between T1-T5 and T5-T10), thoraco-lumbar (T5-T10 and T10-L3) and lumbar regions (T10-L3 and L3-S2). Subjects attempted to imitate pictures of spinal curves for the flat, long lordosis, short lordosis and a slumped posture, and were then given feedback/manual facilitation to achieve the postures. Repeated measures analysis of variance was used to compare spinal angles between posture and facilitation conditions. Results show that although subjects imitated postures with the same curve direction at thoraco-lumbar and lumbar regions (slumped, flat or long lordosis), they required feedback/manual facilitation to differentiate the regional curves for the short lordosis posture. Further study is needed to determine whether the clinically proposed 'ideal' postures provide clinical advantages. | 18,793,867 |
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target. | Tuberculosis (TB) is still a major public health problem, compounded by the human immunodeficiency virus (HIV)-TB co-infection and recent emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR)-TB. Novel anti-TB drugs are urgently required. In this context, the 2C-methyl-d-erythritol 4-phosphate (MEP) pathway of Mycobacterium tuberculosis has drawn attention; it is one of several pathways vital for M. tuberculosis viability and the human host lacks homologous enzymes. Thus, the MEP pathway promises bacterium-specific drug targets and the potential for identification of lead compounds unencumbered by target-based toxicity. Indeed, fosmidomycin is now known to inhibit the second step in the MEP pathway. This review describes the cardinal features of the main enzymes of the MEP pathway in M. tuberculosis and how these can be manipulated in high throughput screening campaigns in the search for new anti-infectives against TB. | 18,793,870 |
Overcoming pubic arch interference with free-hand needle placement in men undergoing prostate brachytherapy. | The present study evaluates the postimplant dosimetry when free-hand needles were placed to overcome interference from the pubic arch. A review of all patients who underwent prostate brachytherapy at our institution from 2001 to 2006 was performed. Postimplant dosimetry in men requiring free-hand needle placement was compared with postimplant dosimetry in men not requiring free-hand needle placement. Of the 145 patients who underwent prostate brachytherapy, 8 patients required free-hand needle placement. The mean prostate volume in the free-hand needle cohort was 46.0cc with a mean of 3.4 free-hand needles placed. In the 137 patients not requiring free-hand needle placement, the mean volume was 39.7cc. The mean D(90), V(100), V(150), and rectal V(100) for the free-hand cohort was 129.5%, 96.3%, 81.6%, and 1.45cc, respectively. The mean D(90), V(100), V(150), and rectal V(100) in men not requiring free-hand needle placement was 126.8%, 97.1%, 78.7%, and 1.03cc, respectively. The present study finds that adequate postimplant dosimetry can be obtained if free-hand needles are required due to pubic arch interference. | 18,793,877 |
Prion disease: the implications for dentistry. | The aim of this article was to provide the dental community with a brief overview of the characteristics, risk of transmission, and the infection-control implications of prions in dentistry. MEDLINE, EMBASE, CINAHL, The Cochrane Library, and relevant databases were searched, and a targeted internet search was conducted up to July 2007. Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases that are rapidly progressive and always fatal, with no approved cure, and their definite diagnosis can only be obtained at post mortem autopsy. The causative agent, prion protein, resists conventional sterilization methods especially when infected tissue becomes dried onto glass or metal surfaces. To date, there are no reported definite or suspected cases of disease transmission arising from dental procedures, and there seems to be no correlation between dental treatment and TSEs. Because there is a theoretical but real risk of transmission of prion disease from dental instruments (although it is extremely low, especially in North America), as a general rule, appropriate family and medical history (including the risk for prion diseases) should be obtained from all patients, before all dental procedures. TSE research regarding diagnosis, transmission, treatment, and inactivation of prions and other transmissible amyloidoses are ongoing, and, thus, dental professionals should maintain optimal and up-to-date standards of knowledge, infection control, and decontamination. | 18,793,912 |
Confocal laser scanning microscopy is appropriate to detect viability of Enterococcus faecalis in infected dentin. | The purpose of this study was to explore the potential of confocal laser scanning microscopy (CLSM) for in situ identification of live and dead Enterococcus faecalis in infected dentin. Eight cylindrical dentin specimens were infected with Enterococcus faecalis in BHI for 21 days. After the experimental period, the specimens were stained with fluorescein diacetate (FDA) and propidium iodide (PI) or acridine orange (0.01%) and analyzed by CLSM. Two noninfected dentin specimens were used as negative controls. CLSM analysis shows that the discrimination between viable (green) and dead (red) bacteria in infected dentinal tubules could be observed after staining with FDA/PI. Acridine orange was able to show metabolic activity of the E. faecalis cells inside the dentinal tubules showed by its red fluorescence. The viability of bacteria in infected dentin can be determined in situ by CLSM. FDA/PI and acridine orange are useful for this technique. | 18,793,919 |
Comparison of effects of ProTaper, HeroShaper, and Gates Glidden Burs on cervical dentin thickness and root canal volume by using multislice computed tomography. | The purpose of this study was to compare the effects of 3 different instruments used to prepare curved root canals on the remaining cervical dentin thickness and total amount of dentin removed from root canals during instrumentation by using multislice computed tomography. Mesiobuccal canals of 45 mandibular first molars with curvature between 30-40 degrees were divided into 3 equal groups: ProTaper, Hero Shaper, and Gates Glidden Bur with Flex-R hand file. Cervical dentin thickness and canal volume were measured before and after instrumentation by using multislice computed tomography and image analysis software. The results indicated that ProTaper removed significantly less cervical dentin from distal wall of the root (dangerous zone) than HeroShaper and Gates Glidden Bur (P < .05). The total dentin removed during canal instrumentation was significantly more with ProTaper system (P < .05). | 18,793,924 |
A scanning electron microscopic evaluation of the effectiveness of the F-file versus ultrasonic activation of a K-file to remove smear layer. | The objective of this study was to compare the effectiveness of F-files and ultrasonics to remove the smear layer from instrumented root canals when irrigated with sodium hypochlorite and EDTA. Sixty healthy human premolar teeth were instrumented with ProTaper file series to F3, and the canals were enlarged with Profiles 35/.06, 40/.06, and 45/.06. The canals were then instrumented with either the F-file or an ultrasonically activated #20 K-file with or without EDTA. The removal of smear layer was visualized using blind scanning electron microscopic micrographs. There appeared to be little difference between the F-file and the ultrasonically activated #20 K-file in removal of the smear layer with or without EDTA. The effect of ultrasonic activation appeared to be self-limiting with high-volume flushes of irrigant. It appears the F-file was not any more beneficial in removing smear layer. Conversely, smear layer removal appears to be mostly influenced by the introduction of an EDTA rinse. | 18,793,930 |
Therapeutic interventions for vitiligo. | Current treatments for vitiligo, a common pigmentary disorder affecting around 1% of the world's population, are largely unsatisfactory. We sought to report a Cochrane review of all interventions for the treatment of vitiligo. We systematically searched a range of databases for randomized controlled trials. At least two reviewers independently assessed study eligibility, methodological quality, and extracted data. Nineteen trials were included. We found moderate evidence of the benefit of topical steroids. Our search uncovered limited to moderate evidence for various types and regimens of phototherapy (ultraviolet [UV] A and UVB) used alone or in combination with oral and topical treatments. Topical khellin combined with UVA should be questioned in view of the lack of available evidence of benefit. There is limited evidence of the benefit of topical tacrolimus and topical calcipotriol used in conjunction with UV light, and for oral ginkgo biloba, and thin split-thickness grafts. Studies generally were poorly designed and reported. Variations in study design and different outcome measures limit the evidence for the different therapeutic options. The best evidence from individual trials showed short-term benefit from topical steroids and various forms of UV light with topical preparations. Long-term follow-up and patient-centered outcomes should be incorporated in study design and psychologic interventions need more attention. | 18,793,940 |
Targeting pro-apoptotic trail receptors sensitizes HeLa cervical cancer cells to irradiation-induced apoptosis. | To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. Recombinant human TRAIL (rhTRAIL) and the agonistic antibodies against DR4 and DR5 were added to irradiated HeLa cells. The effect was evaluated with apoptosis and cytotoxicity assays and at the protein level. Membrane receptor expression was measured with flow cytometry. Small-interfering RNA against p53, DR4, and DR5 was used to investigate their function on the combined effect. rhTRAIL and the agonistic DR4 and DR5 antibodies strongly enhanced 10-Gy-induced apoptosis. This extra effect was 22%, 23%, and 29% for rhTRAIL, DR4, and DR5, respectively. Irradiation increased p53 expression and increased the membrane expression of DR5 and DR4. p53 suppression, as well as small-interfering RNA against DR5, resulted in a significant downregulation of DR5 membrane expression but did not affect apoptosis induced by irradiation and rhTRAIL. After small-interfering RNA against DR4, rhTRAIL-induced apoptosis and the additive effect of irradiation on rhTRAIL-induced apoptosis were abrogated, implicating an important role for DR4 in apoptosis induced through irradiation in combination with rhTRAIL. Irradiation-induced apoptosis is strongly enhanced by targeting the pro-apoptotic TRAIL receptors DR4 or DR5. Irradiation results in a p53-dependent increase in DR5 membrane expression. The sensitizing effect of rhTRAIL on irradiation in the HeLa cell line is, however especially mediated through the DR4 receptor. | 18,793,956 |
RLIP76 in defense of radiation poisoning. | To determine the role of RLIP76 in providing protection from radiation and chemotherapy. In the present report, we used RLIP76 to refer to both the mouse (Ralbp1) and the human (RLIP76) 76-kDa splice variant proteins (RLIP76) for convenience and to avoid confusion. In other reports, Ralbp1 refers to the mouse enzyme (encoded by the Ralbp1 gene), which is structurally and functionally homologous to RLIP76, the human protein encoded by the human RALBP1 gene. Median lethal dose studies were performed in RLIP76(-/-) and RLIP76(+/+) C57B mice after treatment with a single dose of RLIP76 liposomes 14 h after whole body radiation. The radiosensitivity of the cultured mouse embryonic fibroblasts and the effects of buthionine sulfoximine (BSO), amifostine, c-jun N-terminal kinase (JNK), protein kinase B (Akt), and MAPK/ERK kinase (MEK) were determined by colony-forming assays. Glutathione-linked enzyme activities were measured by spectrophotometric assays, glutathione by dithiobis-2-nitrobenzoic acid (DTNB), lipid hydroperoxides by iodometric titration, and aldehydes and metabolites by thiobarbitauric acid reactive substances and liquid chromatography-mass spectrometry (LCMS). RLIP76(-/-) mice were significantly more sensitive to radiation than were the wild-type, and RLIP76 liposomes prolonged survival in a dose-dependent manner in both genotypes. The levels of 4-hydroxynonenal and glutathione-conjugate of 4-hydroxynonenal were significantly increased in RLIP76(-/-) tissues compared with RLIP76(+/+). RLIP76(-/-) mouse embryonic fibroblasts were markedly more radiosensitive than RLIP76(+/+) mouse embryonic fibroblasts, despite increased glutathione levels in the former. RLIP76 augmentation had a remarkably greater protective effect compared with amifostine. The magnitude of effects of RLIP76 loss on radiation sensitivity was greater than those caused by perturbations of JNK, MEK, or Akt, and the effects of RLIP76 loss could not be completely compensated for by modulating the levels of these signaling proteins. The results of our study have shown that RLIP76 plays a central role in radiation resistance. | 18,793,957 |
Alpha-1-antitrypsin deficiency panniculitis. | Alpha-1-antitrypsin deficiency is a congenital error of metabolism linked to pulmonary (emphysema) and liver (cirrhosis) disease. Since 1972, panniculitis has been associated with this deficiency, initially related to Weber-Christian syndrome and finally as a differentiated entity. Clinical manifestations typically consist of wide nodular lesions on the trunk and proximal extremities that evolve to ulceration and drainage. Histopathologically it presents as a mixed septal-lobular panniculitis pattern with some typical findings referred. Differential diagnosis from other types of panniculitis and neutrophilic dermatosis must be established. Different treatments, including tetracyclines, dapsone, and alpha-1-antitrypsin repositioning, have shown variable efficacy in controlling this disease. | 18,793,976 |
Sclerosing panniculitis. | Sclerosing panniculitis is a chronic panniculitis characterized by skin induration and hyperpigmentation of one or both legs that often occurs in patients who have venous insufficiency. The indurated plaques are often painful and the legs frequently have a characteristic "inverted wine bottle" appearance. Histopathology is characterized by mostly lobular panniculitis with necrosis of fat and without vasculitis, and in fully developed lesions by septal sclerosis and membranocystic changes. Treatment of sclerosing panniculitis includes compression therapy with graded stockings and anabolic steroids. | 18,793,983 |
Factitial panniculitis. | Factitial panniculitides are subcutaneous tissue injuries produced by external agents or actions. In most cases, factitial panniculitis is caused by self-injection of different substances. Factitial panniculitis can also appear as an iatrogenic consequence of injections of drugs or immunization agents. The clinical features of factitial panniculitis are quite variable, depending on the inciting agent. The histopathology of factitial panniculitis usually shows a pattern of an acute lobular panniculitis associated with fat necrosis and an abundant inflammatory infiltrate predominantly composed of neutrophils. | 18,793,986 |
Urodynamic evaluation of the bladder and pelvic floor. | Pelvic floor disorders including lower urinary tract dysfunction are common, and may be evaluated by urodynamic tests, such as cystometry, uroflowmetry, pressure flow studies, electromyography, and video-urodynamics. These urodynamic tests provide objective information regarding the normal and abnormal function of the urinary tract and pelvic floor, and provide a better understanding of the pathophysiologic processes that cause lower urinary tract symptoms. This article describes typical urodynamic studies and their roles in the evaluation of common pelvic floor disorders, including stress urinary incontinence, overactive bladder, and pelvic organ prolapse. | 18,793,995 |
Hemorrhoids and fissure in ano. | Hemorrhoids and anal fissures are common benign anorectal conditions that form a significant part of a colorectal surgeon's workload. This review summarizes and evaluates the current techniques available in their management. | 18,794,000 |
Economic antecedents of prone infant sleep placement among black mothers. | Black infants die from sudden infant death syndrome at twice the incidence observed among non-Hispanic white infants. Explanations for this disparity include a two-fold greater prevalence of prone (i.e., stomach) infant sleep placement among black caregivers. I test the hypothesis that the contraction of state economies may contribute to this disparity by increasing the risk of prone infant sleep placement among black mothers. I retrieved data from the Bureau of Labor Statistics employment series and 33,518 black mothers in 26 states participating in the 1996-2002 Pregnancy Risk Assessment Monitoring System. I use weighted multivariable analyses to control for individual characteristics and state and time trends. Black mothers exhibit an elevated risk of reporting prone placement one month following statewide declines in employment (adjusted odds ratio for a one percent decline = 1.11, 95% CI 1.01 to 1.22). This risk remains elevated after control for individual variables. In contrast, I find no association between the economy and prone placement among white mothers. Statewide economic decline may reduce adherence to the recommended non-prone infant sleep position among black, but not white, mothers. Additional research among black caregivers should determine which mechanisms connect economic downturns to prone infant sleep placement. | 18,794,008 |
Nitric oxide and cardiovascular and renal effects. | Nitric oxide (NO) has multiple protective effects for regulating the cardiovascular and renal systems. The major functions include endothelium-dependent relaxation, anti-inflammatory effects, as well as antihypertrophic and antithrombotic activities. Many of the activities mediated by NO are systematically antagonized by angiotensin-II (Ang II), a vasconstrictor peptide. Studies described in the review below have demonstrated that the balance between NO and Ang II activities rather than the absolute concentration of each molecule determines their effects on the physiology and pathophysiology of the cardiovascular and renal systems. NO donors have been used for years as therapeutic agents for a range of cardiovascular conditions including angina, myocardial infarction and for the reduction of arterial stiffness. An understanding of the mechanisms underlying the effects of these medications will enable the development of novel therapies to balance the effects of NO in the cardiovascular system. | 18,794,014 |
Adolescent pregnancy in a Greek public hospital during a six-year period (2000-2005)--a retrospective study. | Adolescent pregnancy constitutes a multidimensional social problem in modern Greece. The purpose of this study was to investigate the trends of teenage childbearing and to determine the relationship between the incidence of teenage pregnancy and immigrant status of the mother. This is a retrospective correlational study. The birth registry of the hospital was examined for a 6-year period, from January 2000 to December 2005. Information about the age and nationality of the mothers was collected. The hospital under investigation is Tzaneio Hospital, a public general hospital that provides health services to the residents of Piraeus, a large municipality next to Athens. During the study period 4628 women gave birth at Tzaneio Hospital, among which 349 (7.54%) were under the age of 19. The study hypothesis, that adolescent childbearing prevails among immigrant population, was confirmed (P < 0.01). Teenage pregnancy rate remains high among some subsamples of the population, such as immigrants. The Greek government, health professionals, and sexuality educators should all work together in order to confront this problem. | 18,794,021 |
Hormonal contraception and blood lead levels in inner-city adolescent girls. | Physiological states of estrogen deficiency can lead to bone demineralization. Lead is stored in bone and may be released into blood during demineralization. The contraceptive injection depomedroxyprogesterone acetate (DMPA) is associated with estrogen deficiency and bone demineralization and, we hypothesized, may be associated with toxic blood lead levels in adolescents at high risk for lead exposure. We sought to compare blood lead levels in inner-city adolescent girls using DMPA with levels in those using oral contraceptive pills (OCP) and those taking no hormones and to examine the influence of lead exposure and reproductive history on blood lead levels in the total sample. Cross-sectional survey of a clinical convenience sample. Inner-city adolescent clinic in an academic medical center. 174 females aged 13-21 years; 86% minority ethnicity. None. Measurement of blood lead levels and an 82-item questionnaire examining lead exposure and reproductive history. 28 subjects were using DMPA, 25 used OCPs, and 121 used no hormones. Mean blood lead level in the total sample of 174 was 1.6 mug/dL, SD = 1.1. Many subjects had environmental risk factors for lead exposure and 15% reported one or more past pregnancies. Mean blood lead levels for subjects with the various environmental and reproductive risk factors ranged from 1.2 microg/dL to 2.0 microg/dL and were not different from levels for subjects without such risk factors. Mean blood lead levels for subjects in the 3 hormonal groups were significantly different (2.1 vs. 1.2 vs.1.5 microg/dL in DMPA, OCP, and no hormone groups respectively, P = 0.007). We dichotomized the blood lead levels into "High" > or =4 microg/dL, or "Low" <4 microg/dL. We found that a significantly higher proportion of girls using DMPA (4/28) than those not using any hormone (2/121) had "High" levels (P = 0.012). Despite reported high-risk exposure to lead and the possibility of long-term accumulation of lead in bone, we did not find elevated blood levels in our sample. However, DMPA-treated girls were significantly more likely to have higher mean blood lead levels than OCP users and non-hormone users. In addition, DMPA users were more likely to have blood lead levels more than two standard deviations above the mean for the sample as a whole than untreated girls. Further studies are needed to examine low-level lead poisoning in adolescents and the consequences of contraceptive choices on bone health. | 18,794,022 |
Use/misuse of over-the-counter medications and associated adverse drug events among HIV-infected patients. | Self-medication practices and polypharmacy are common among human immunodeficiency virus (HIV)-infected patients. Inappropriate use of over-the-counter (OTC) medications potentiates the risk for drug misuse and adverse drug events (ADEs). To investigate use and misuse of OTC medications in HIV-infected patients and determine related ADEs. A nonexperimental cross-sectional field study design was used. Study subjects were HIV-infected patients from a local HIV clinic in Houston, TX. Information on subject demographics, OTC medication use, and ADEs experienced were obtained using combined self-administered questionnaire and personal interview techniques. Misuse was divided into 3 categories: strength/frequency misuse, length misuse, and condition misuse. Data were analyzed using descriptive and Chi-square analyses. A total of 215 completed surveys were obtained, with a net response rate of 63.6%. The mean (+/-SD) age of the respondents was 45 (+/-8.32) years and 69% were males. Analgesics/antipyretics (64.2%) were the most commonly used OTC medications of which nonsteroidal agents accounted for the greatest proportion (38.4%). Of the respondents, 80 (37.2%) misused OTC medications. The highest incidence occurred in length misuse (46.3%), followed by strength/frequency misuse (45.6%), and condition misuse (8.1%). Categories of misuse overlapped in 30 cases (20.1%). Thirty-six (16.7%) participants experienced at least one or more ADEs related to OTC medication use/misuse. Occurrence of ADEs was significantly higher in patients who misused OTC medications compared with those who did not (P < .05). Analgesics/antipyretics were the most commonly used OTC medications by HIV-infected patients. The incidence of misuse and ADEs associated with OTC medications were documented with the sample. Keeping in mind the limitations of study design, our findings suggest that misuse of OTC medications in HIV-infected patients may increase the incidence of ADEs experienced. | 18,794,039 |
The Translational Research Working Group developmental pathway for image-based assessment modalities. | The Image-based assessment modality (IM) pathway refers to one of six Translational Research Working Group (TRWG) pathways that, together, describe the core domains of early translational cancer research. This pathway focuses on approaches that are based on the interaction of energy and living organisms to analyze tissue noninvasively so as to reveal properties relevant to the detection, diagnosis, or prognosis of cancer and precancer; or the response of the cancer to therapy. Examples include, but are not limited to, magnetic resonance imaging and positron emission tomography, as well as contemporary contrast agents designed to probe specific molecular constituents of tumors. The IM pathway is presented as a general outline of the steps required for the effective development, optimization, testing, and validation of image-based modalities. The distinctive features of the IM pathway and issues encountered that represent obstacles to effective and efficient progress through the pathway are discussed. The IM pathway also forms a framework to identify opportunities to address current barriers and is expected to adapt and evolve as the field advances. | 18,794,075 |
Translational Research Working Group developmental pathway for immune response modifiers. | The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of the investment of National Cancer Institute in translational research and envision its future. The Translational Research Working Group conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of immune response modifiers such as vaccines and cytokines. A hallmark of the Immune Response Modifier Developmental Pathway is the coordinated development of multiple components. The Immune Response Modifier Pathway was conceived not as a comprehensive description of the corresponding real-world processes but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper discusses key challenges associated with the immune response modifier agent development process in light of the pathway. | 18,794,077 |
The Translational Research Working Group developmental pathway for lifestyle alterations. | The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of National Cancer Institute's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of lifestyle alterations, which can, variously, be recommended to prevent cancer, modify a patient's adherence and response to cancer treatment, ameliorate side effects of cancer treatments, or improve prognosis and quality of life in cancer patients and survivors. The lifestyle alteration pathway was conceived not as a comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate lifestyle alteration through the translational process up to the point where it could be handed off for definitive testing, when appropriate. This article discusses key issues associated with the development of lifestyle alterations in light of the pathway. | 18,794,079 |
Control of cell growth and survival by enzymes of the fatty acid synthesis pathway in HCT-116 colon cancer cells. | For many tumor cells, de novo lipogenesis is a requirement for growth and survival. A considerable body of work suggests that inhibition of this pathway may be a powerful approach to antineoplastic therapy. It has recently been shown that inhibition of various steps in the lipogenic pathway individually can induce apoptosis or loss of viability in tumor cells. However, it is not clear whether quantitative differences exist in the ability of lipogenic enzymes to control tumor cell survival. We present a systematic approach that allows for a direct comparison of the control of lipogenic pathway enzymes over tumor cell growth and apoptosis using different cancer cells. RNA interference-mediated, graded down-regulation of fatty acid synthase (FAS) pathway enzymes was employed in combination with measurements of lipogenesis, apoptosis, and cell growth. In applying RNA interference titrations to two lipogenic enzymes, acetyl-CoA carboxylase 1 (ACC1) and FAS, we show that ACC1 and FAS both significantly control cell growth and apoptosis in HCT-116 cells. These results also extend to PC-3 and A2780 cancer cells. Control of tumor cell survival by different steps in de novo lipogenesis can be quantified. Because ACC1 and FAS both significantly control tumor cell growth and apoptosis, we propose that pharmacologic inhibitors of either enzyme might be useful agents in targeting cancer cells that critically rely on fatty acid synthesis. The experimental approach described here may be extended to other targets or disease-relevant pathways to identify steps suitable for therapeutic intervention. | 18,794,082 |
Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods. | Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated. | 18,794,089 |
Prognostic impact of bim, puma, and noxa expression in human colon carcinomas. | Proapoptotic BH3-only proteins (Bim, Bad, Bid, Puma, and Noxa) initiate apoptosis by binding to regulatory sites on antiapoptotic Bcl-2 proteins, directly neutralizing their cytoprotective function. Expression of these proteins in colon cancer patients may account for differences in recurrence and survival rates. Archival tumor-node-metastasis stage II and III primary colon carcinomas from patients treated in 5-fluorouracil-based adjuvant therapy trials were studied. Immunohistochemical analysis of Bim, Puma, and Noxa proteins was done using tissue microarrays (n = 431). Immunoscores were determined and correlated with clinicopathologic variables and disease-free survival (DFS) and overall survival (OS) rates. Elevated expression of proapoptotic Bim (hazard ratio, 0.65; 95% confidence interval, 0.44-0.97; P = 0.033) and Puma (hazard ratio, 0.59; 95% confidence interval, 0.37-0.93; P = 0.022), but not Noxa, proteins in the tumor cytoplasm was significantly associated with more favorable OS in a univariate analysis, and elevated Bim expression was also associated with better DFS (P = 0.023). Patient age, tumor stage, and histologic grade were also prognostic. Multivariate Cox analysis showed that Bim (DFS, P = 0.030; OS, P = 0.045) and Puma (OS, P = 0.037) expression were independent predictors of OS after adjustment for histologic grade, tumor stage, age, and treatment. Furthermore, the combined variable of Bim and Puma was highly discriminant for both DFS (P = 0.0034) and OS (P = 0.0011). The proapoptotic BH3-only proteins Bim and Puma can provide prognostic information for stage II and III colon cancer patients receiving 5-fluorouracil-based adjuvant chemotherapy. Furthermore, our results support BH3-only proteins as molecular targets of novel anticancer drugs. | 18,794,091 |
WNT5A expression increases during melanoma progression and correlates with outcome. | Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16(ink4a) was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression (P = 0.013), whereas there was diminishing p16(ink4a) expression (P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis (P = 0.001 and 0.003, respectively). Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome. | 18,794,093 |
Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer. | To identify biomarkers and gene expression profile signatures to distinguish patients with partial response (PR) from those with stable disease (SD) and progressive disease (PD). Twenty patients with inflammatory breast cancer and one patient with locally advanced breast cancer received one cycle of bevacizumab followed by six cycles of bevacizumab plus docetaxel-doxorubicin before surgery. Baseline angiogenic/tumor markers were examined by immunohistochemistry and gene expression profiles were measured by Agilent Whole Human Genome arrays. All were assessed for clinical response. Fourteen patients (67%, 95% confidence interval, 43-85.4%) had PR, five had SD, and two had PD. Expression of CD31 and platelet-derived growth factor receptor-beta (PDGFR-beta) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; P = 0.0004; PDGFR-beta median, 5.9 versus 0.6; P = 0.01). Tumor VEGF-A showed a trend towards association with response (2.65 versus 0.25; P = 0.04). pVEGFR2(Y996), pVEGFR2(Y951), MVD, Ki67, apoptosis, grade, ER, HER-2/neu, and p53 were not associated with response. Twenty-six of 1,339 Gene Ontology (GO) classes at the gene transcriptional level were differentially expressed between patients with PR and SD/PD (P < 0.005). Representative significant GO classes include spindle (11 genes; P = 0.001), vascular endothelial growth factor receptor activity including PDGFR-beta (5 genes; P = 0.002), and cell motility including CD31 (80 genes; P = 0.005). Baseline CD31, PDGFR-beta, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy. | 18,794,102 |
Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation. | Somatic mutations of the adenomatous polyposis coli (APC) gene are initiating events in the majority of sporadic colon cancers. A common characteristic of such tumors is reduction in the number of goblet cells that produce the mucin MUC2, the principal component of intestinal mucus. Consistent with these observations, we showed that Muc2 deficiency results in the spontaneous development of tumors along the entire gastrointestinal tract, independently of deregulated Wnt signaling. To dissect the complex interaction between Muc2 and Apc in intestinal tumorigenesis and to elucidate the mechanisms of tumor formation in Muc2(-/-) mice, we crossed the Muc2(-/-) mouse with two mouse models, Apc(1638N/+) and Apc(Min/+), each of which carries an inactivated Apc allele. The introduction of mutant Muc2 into Apc(1638N/+) and Apc(Min/+) mice greatly increased transformation induced by the Apc mutation and significantly shifted tumor development toward the colon as a function of Muc2 gene dosage. Furthermore, we showed that in compound double mutant mice, deregulation of Wnt signaling was the dominant mechanism of tumor formation. The increased tumor burden in the distal colon of Muc2/Apc double mutant mice was similar to the phenotype observed in Apc(Min/+) mice that are challenged to mount an inflammatory response, and consistent with this, gene expression profiles of epithelial cells from flat mucosa of Muc2-deficient mice suggested that Muc2 deficiency was associated with low levels of subclinical chronic inflammation. We hypothesize that Muc2(-/-) tumors develop through an inflammation-related pathway that is distinct from and can complement mechanisms of tumorigenesis in Apc(+/-) mice. | 18,794,118 |
CYR61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma. | Radiotherapy is widely used to treat human cancer. Patients locally recurring after radiotherapy, however, have increased risk of metastatic progression and poor prognosis. The clinical management of postradiation recurrences remains an unresolved issue. Tumors growing in preirradiated tissues have an increased fraction of hypoxic cells and are more metastatic, a condition known as tumor bed effect. The transcription factor hypoxia inducible factor (HIF)-1 promotes invasion and metastasis of hypoxic tumors, but its role in the tumor bed effect has not been reported. Here, we show that tumor cells derived from SCCVII and HCT116 tumors growing in a preirradiated bed, or selected in vitro through repeated cycles of severe hypoxia, retain invasive and metastatic capacities when returned to normoxia. HIF activity, although facilitating metastatic spreading of tumors growing in a preirradiated bed, is not essential. Through gene expression profiling and gain- and loss-of-function experiments, we identified the matricellular protein CYR61 and alphaVbeta5 integrin as proteins cooperating to mediate these effects. The anti-alphaV integrin monoclonal antibody 17E6 and the small molecular alphaVbeta3/alphaVbeta5 integrin inhibitor EMD121974 suppressed invasion and metastasis induced by CYR61 and attenuated metastasis of tumors growing within a preirradiated field. These results represent a conceptual advance to the understanding of the tumor bed effect and identify CYR61 and alphaVbeta5 integrin as proteins that cooperate to mediate metastasis. They also identify alphaV integrin inhibition as a potential therapeutic approach for preventing metastasis in patients at risk for postradiation recurrences. | 18,794,119 |
Systemic targeting of CpG-ODN to the tumor microenvironment with anti-neu-CpG hybrid molecule and T regulatory cell depletion induces memory responses in BALB-neuT tolerant mice. | We have shown that neu transgenic mice are immunotolerant and that immunizations with dendritic cells (DC) pulsed with neu-derived antigens were not able to control tumor growth in these animals. We tested whether, by modulating the tumor microenvironment with Toll-like receptor ligands, it could be possible to induce the activation of antitumor responses in neu mice. Our results indicate that only intratumoral (i.t.) injections of CpG-ODN induce an antitumor response in neu mice. To target the CpG-ODN to the tumor site anywhere within the body, we chemically conjugated an anti-Her-2/neu monoclonal antibody (mAb) with CpG-ODN. The anti-neu-CpG hybrid molecule retained its ability to bind to Her-2/neu(+) tumors, activate DCs, and induce antitumor responses. Our results indicated that injections of anti-neu-CpG induced the rejection of primary tumors in 100% of BALB/c mice and only in approximately 30% of BALB-neuT mice. After challenging the BALB/c and BALB-neuT mice, we observed that BALB/c mice developed a protective memory response; in contrast, BALB-neuT mice succumbed to the challenge. After injections of anti-neu-CpG, T regulatory cells (T-reg) were drastically reduced at the tumor site, but a large number were still present in the lymphoid organs. When BALB-neuT mice were treated with anti-neu-CpG plus anti-GITR mAb, but not with anti-CD25 mAb, 100% of the BALB-neuT mice rejected the primary tumor and developed a protective memory response indicating the critical role of T-regs in regulating the repertoire against self antigens. Taken together, these results indicate that CpG-ODN-targeted therapy and depletion of T-regs optimally activate a primary response and generate a protective memory response against self-tumor antigens. | 18,794,141 |
Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation. | Cyclin-dependent kinase (cdk)-3, a member of the cdk family of kinases, plays a critical role in cell cycle regulation and is involved in G(0)-G(1) and G(1)-S cell cycle transitions. However, the role of cdk3 in cell proliferation, as well as cell transformation, is not yet clearly understood. Here, we report that the protein expression level of cdk3 is higher in human cancer cell lines and human glioblastoma tissue compared with normal brain tissue. Furthermore, we found that cdk3 phosphorylates activating transcription factor 1 (ATF1) at serine 63 and enhances the transactivation and transcriptional activities of ATF1. Results also indicated that siRNA directed against cdk3 (si-cdk3) suppresses ATF1 activity, resulting in inhibition of proliferation and growth of human glioblastoma T98G cells in soft agar. Importantly, we showed that cdk3 enhances epidermal growth factor-induced transformation of JB6 Cl41 cells and si-cdk3 suppresses Ras(G12V)/cdk3/ATF1-induced foci formation in NIH3T3 cells. These results clearly showed that the cdk3-ATF1 signaling axis is critical for cell proliferation and transformation. | 18,794,154 |
Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome. | Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment. The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI). After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)]. LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545. | 18,794,162 |
Eligibility of rheumatoid arthritis patients for anti-TNF-alpha therapy according to the 2005 recommendations of the French and British Societies for Rheumatology. | Several anti-TNF-alpha prescription guidelines in RA have been published, among which those issued by the British (BSR) and French (SFR) Societies for Rheumatology in 2005 are the most comprehensive. Objectives of the PRISME II survey were to assess and compare eligibility for anti-TNF-alpha therapy of RA patients consulting their usual rheumatologist according to (i) the SFR and BSR guidelines and (ii) the rheumatologist's opinion. PRISME II was a postal, cross-sectional, observational survey proposed to all office-based rheumatologists practising in France in 2005. Rheumatologists were to include three consecutive consulting anti-TNF-alpha-naïve RA patients. Disease activity was assessed using the disease activity score 28 (DAS28). Structural damage progression was estimated based on the reading by the usual rheumatologist. The factors determining eligibility in the rheumatologists' opinion were identified by a logistic regression analysis. Four hundred and thirty-four rheumatologists included 1132 patients. Ongoing RA structural progression was reported for 41% of the patients. According to the SFR and BSR criteria, 64 patients (7.0%) and 10 patients (0.9%), respectively, were eligible for anti-TNF-alpha therapy, while 10% were deemed eligible according to the rheumatologists' opinion. Determinants of eligibility according to the rheumatologists were: high disease activity (DAS28 >5.1), ongoing structural progression and elevated daily corticosteroid intake. These three determinants feature in the SFR guideline. The proportion of RA patients eligible for anti-TNF-alpha therapy varies greatly according to the BSR or SFR guidelines. In France, there is a remarkable convergence between rheumatologists' opinion and SFR guideline regarding the main factors to consider for initiation of an anti-TNF-alpha therapy. | 18,794,185 |
The efficacy of an internet-based cognitive-behavioral therapy intervention for child anxiety disorders. | To evaluate the efficacy of an Internet-based cognitive-behavioral therapy (CBT) approach to the treatment of child anxiety disorders. Seventy-three children with anxiety disorders, aged 7-12 years, and their parents were randomly assigned to either an Internet-based CBT (NET) or wait-list (WL) condition. Clinical diagnostic assessment and parent and child questionnaires were completed before and after treatment. The NET condition was reassessed at 6-month follow-up. At posttreatment assessment, children in the NET condition showed small but significantly greater reductions in anxiety symptoms and increases in functioning than WL participants. These improvements were enhanced during the 6-month follow-up period, with 75% of NET children free of their primary diagnosis. Internet delivery of CBT for child anxiety offers promise as a way of increasing access to treatment for this population. Future research is needed to examine ways to increase treatment compliance and further enhance the impact of treatment. | 18,794,187 |
In-transit lymph node metastases in breast cancer: a possible source of local recurrence after Sentinel Node procedure. | In-transit lymph node metastases are a common phenomenon in melanoma patients and have been increasingly recognised since the introduction of the Sentinel Node (SN) procedure. To which extent this also occurs in patients with breast cancer has not been studied yet. The aim of this study was therefore to explore the occurrence of in-transit lymph node metastases in patients with breast cancer. Afferent lymph vessels to the SN identified by blue dye were removed from 17 patients with breast cancer during a regular SN procedure. Three out of 17 patients showed a lymph node associated with the afferent lymph vessel. One of these lymph nodes showed a breast cancer macrometastasis, to be regarded as an in-transit metastasis. This metastasis would normally have been left in situ. In-transit lymph nodes associated with the afferent SN lymph vessels seem to occur in a significant proportion of patients with breast cancer. These lymph nodes may contain metastases, which are a potential source of local recurrence when left in situ. This finding generates the hypothesis that there may be an indication to remove these lymph vessels during the SN procedure. | 18,794,198 |
Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications. | The oestrogen receptor (ER) pathway is key for survival and progression in a significant proportion of breast cancers. The ER can be activated by oestrogen or activated due to "crosstalk" with growth factor receptor pathways. Activated ER signals through transcriptional and non-transcriptional mechanisms. Immunohistochemistry (IHC), in spite of the shortcomings, remains the method of choice as it provides for in situ assessment of ER expression within the tumour cells. This capability is lost in tissue grinding methods that assess oestrogen-binding activity or messenger RNAs in tumours. IHC is also not influenced by the presence of non-tumoural cells or low amounts of tumour cells within samples examined. It is clear that ER-positive tumours do not represent a single entity. Irrespective of the terminology used, low-grade ER-positive (also known as luminal A) tumours need to be differentiated from high-grade/highly proliferative ER-positive tumours. This can be done in a variety of ways including but not limited to analysis of FOXA1 and GATA-3 by IHC, and limited molecular profiling by Oncotype DX, MGH2-gene signature, intrinsic gene signature or MapQuant Dx. Several areas of ER biology are still poorly understood; these include: its function in the cytoplasm/plasma membrane, its role in the differentiation to proliferation switch, and pathways associated with resistance to hormonal therapy. A detailed understanding of these areas will permit better classification and a personalised approach to management of ER-positive breast cancers. | 18,794,199 |
What do case-control studies estimate? Survey of methods and assumptions in published case-control research. | To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate. | 18,794,220 |
Using "spinal shrinkage" as a trigger for motivating students to learn about obesity and adopt a healthy lifestyle. | Obesity is a global problem; however, relatively little attention is directed toward preparing and inspiring students of medicine and allied medical sciences to address this serious matter. Students are not routinely exposed to the assessment methods for obesity, its overall prevalence, causative factors, short- and long-term consequences, and its management by lifestyle modification. This physiology laboratory exercise involving students of medicine (n = 106) was developed to 1) introduce medical students to methods of obesity assessment and to differentiate between general and abdominal obesity, 2) generate an interest and sensitivity about obesity, and 3) stimulate thinking about modification of their lifestyle in relation to eating habits, weight control, and physical activity. Spinal shrinkage (the difference between the standing height of a person and his/her recumbent length) was used as an immediate observable parameter to demonstrate the effect of adiposity. Spinal shrinkage is recognized as an index of the compressive forces acting on the spine and is related to body mass index. A positive correlation (r = 0.365, P < 0.05) was observed between body mass index and spinal shrinkage. A questionnaire was used to assess student responses to this exercise. Students were motivated to engage in more physical activity (74%), adopt healthier eating (63%), and enhance their knowledge about obesity (67%). They expressed keen interest in the laboratory exercise and found the sessions enjoyable (91%). The laboratory exercise proved to be a success in motivating the students to actively learn and inquire about obesity and to adopt a healthier lifestyle. | 18,794,247 |
Association of IS1016 with the hia adhesin gene and biotypes V and I in invasive nontypeable Haemophilus influenzae. | A subset of invasive nontypeable Haemophilus influenzae (NTHI) strains has evidence of IS1016, an insertion element associated with division I H. influenzae capsule serotypes. We examined IS1016-positive invasive NTHI isolates collected as part of Active Bacterial Core Surveillance within the Georgia Emerging Infections Program for the presence or absence of hmw1 and hmw2 (two related adhesin genes that are common in NTHI but absent in encapsulated H. influenzae) and hia (homologue of hsf, an encapsulated H. influenzae adhesin gene). Isolates were serotyped using slide agglutination, confirmed as NTHI strains using PCR capsule typing, and biotyped. Two hundred twenty-nine invasive NTHI isolates collected between August 1998 and December 2006 were screened for IS1016; 22/229 (9.6%) were positive. Nineteen of 201 previously identified IS1016-positive invasive NTHI isolates collected between January 1989 and July 1998 were also examined. Forty-one IS1016-positive and 56 randomly selected IS1016-negative invasive NTHI strains were examined. The hia adhesin was present in 39 of 41 (95%) IS1016-positive NTHI strains and 1 of 56 (1.8%) IS1016-negative NTHI strains tested; hmw (hmw1, hmw2, or both) was present in 50 of 56 (89%) IS1016-negative NTHI isolates but in only 5 of 41 (12%; all hmw2) IS1016-positive NTHI isolates. IS1016-positive NTHI strains were more often biotype V (P < 0.001) or biotype I (P = 0.04) than IS1016-negative NTHI strains, which were most often biotype II. Pulsed-field gel electrophoresis revealed the expected genetic diversity of NTHI with some clustering based on IS1016, hmw or hia, and biotypes. A significant association of IS1016 with biotypes V and I and the presence of hia adhesins was found among invasive NTHI. IS1016-positive NTHI strains may represent a unique subset of NTHI strains, with characteristics more closely resembling those of encapsulated H. influenzae. | 18,794,287 |
Txt u ltr: using cellular phone technology to enhance a parenting intervention for families at risk for neglect. | One of the biggest challenges facing home visiting programs aimed at high-risk families is keeping families involved in the intervention. Cellular phones afford the opportunity for home visitors to maintain regular communication with parents between intervention visits and thus retain high-risk families in parenting interventions. The use of cellular phones may also increase the dosage of intervention provided to families and the fidelity with which parents implement the intervention, thus resulting in improved outcomes for parents and children. This brief report describes the development and initial testing of a parenting program, Planned Activities Training (PAT), which was enhanced through the use of cellular phones to promote the active engagement of parents. PAT is a five-session intervention aimed at improving parent-child interactions, increasing child engagement in daily activities, and reducing challenging child behaviors. To date, 19 parents have completed PAT and cell phone-enhanced PAT, and all have met the 90% correct mastery criterion and demonstrated improvements in their parenting behaviors. Parents have rated PAT and the text messaging and cellular phone call enhancements very positively. | 18,794,303 |
EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition. | EPB41L5 belongs to the band 4.1 superfamily. We investigate here the involvement of EPB41L5 in epithelial-mesenchymal transition (EMT) during mouse gastrulation. EPB41L5 expression is induced during TGFbeta-stimulated EMT, whereas silencing of EPB41L5 by siRNA inhibits this transition. In EPB41L5 mutants, cell-cell adhesion is enhanced, and EMT is greatly impaired during gastrulation. Moreover, cell attachment, spreading, and mobility are greatly reduced by EPB41L5 deficiency. Gene transcription regulation during EMT occurs normally at the mRNA level; EPB41L5 siRNA does not affect either the decrease in E-cadherin or the increase in integrin expression. However, at the protein level, the decrease in E-cadherin and increase in integrin are inhibited in both EPB41L5 siRNA-treated NMuMG cells and mutant mesoderm. We find that EPB41L5 binds p120ctn through its N-terminal FERM domain, inhibiting p120ctn-E-cadherin binding. EPB41L5 overexpression causes E-cadherin relocalization into Rab5-positive vesicles in epithelial cells. At the same time, EPB41L5 binds to paxillin through its C terminus, enhancing integrin/paxillin association, thereby stimulating focal adhesion formation. | 18,794,329 |
Orientation and structure of the Ndc80 complex on the microtubule lattice. | The four-subunit Ndc80 complex, comprised of Ndc80/Nuf2 and Spc24/Spc25 dimers, directly connects kinetochores to spindle microtubules. The complex is anchored to the kinetochore at the Spc24/25 end, and the Ndc80/Nuf2 dimer projects outward to bind to microtubules. Here, we use cryoelectron microscopy and helical image analysis to visualize the interaction of the Ndc80/Nuf2 dimer with microtubules. Our results, when combined with crystallography data, suggest that the globular domain of the Ndc80 subunit binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis. Such a binding mode, in which the Ndc80 complex interacts with sequential alpha/beta-tubulin heterodimers, may be important for stabilizing kinetochore-bound microtubules. Additionally, we define the binding of the Ndc80 complex relative to microtubule polarity, which reveals that the microtubule interaction surface is at a considerable distance from the opposite kinetochore-anchored end; this binding geometry may facilitate polymerization and depolymerization at kinetochore-attached microtubule ends. | 18,794,333 |
The Tsc1-Tsc2 complex influences neuronal polarity by modulating TORC1 activity and SAD levels. | Neuronal function depends on the specification of neuronal processes as axons or dendrites. In this issue of Genes & Development Choi and colleagues (2485-2495) show that without Tuberous Sclerosis Complex 1 (Tsc1) or Tsc2, molecules linked to the autosomal dominant disease tuberous sclerosis, an increase in the activity of the translational regulator Target of Rapamycin 1 (TORC1) causes neurons to have multiple axons and the translation of SAD kinase increases as well. Thus, in addition to the kinase LKB1, the Tsc1-Tsc2 complex, acting through TORC1, also modulates SAD to regulate axon formation. | 18,794,342 |
The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone. | The tailless (Tlx) gene encodes an orphan nuclear receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). The function of Tlx in neural stem cells of the adult SVZ remains largely unknown. We show here that in the SVZ of the adult brain Tlx is exclusively expressed in astrocyte-like B cells. An inducible mutation of the Tlx gene in the adult brain leads to complete loss of SVZ neurogenesis. Furthermore, analysis indicates that Tlx is required for the transition from radial glial cells to astrocyte-like neural stem cells. These findings demonstrate the crucial role of Tlx in the generation and maintenance of NSCs in the adult SVZ in vivo. | 18,794,344 |
Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. | The precise regulation of many alternative splicing (AS) events by specific splicing factors is essential to determine tissue types and developmental stages. However, the molecular basis of tissue-specific AS regulation and the properties of splicing regulatory networks (SRNs) are poorly understood. Here we comprehensively predict the targets of the brain- and muscle-specific splicing factor Fox-1 (A2BP1) and its paralog Fox-2 (RBM9) and systematically define the corresponding SRNs genome-wide. Fox-1/2 are conserved from worm to human, and specifically recognize the RNA element UGCAUG. We integrate Fox-1/2-binding specificity with phylogenetic conservation, splicing microarray data, and additional computational and experimental characterization. We predict thousands of Fox-1/2 targets with conserved binding sites, at a false discovery rate (FDR) of approximately 24%, including many validated experimentally, suggesting a surprisingly extensive SRN. The preferred position of the binding sites differs according to AS pattern, and determines either activation or repression of exon recognition by Fox-1/2. Many predicted targets are important for neuromuscular functions, and have been implicated in several genetic diseases. We also identified instances of binding site creation or loss in different vertebrate lineages and human populations, which likely reflect fine-tuning of gene expression regulation during evolution. | 18,794,351 |
A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression. | The H19/IGFf2 locus belongs to a large imprinted domain located on human chromosome 11p15.5 (homologue to mouse distal chromosome 7). The H19 gene is expressed from the maternal allele, while IGF2 is paternally expressed. Natural antisense transcripts and intergenic transcription have been involved in many aspects of eukaryotic gene expression, including genomic imprinting and RNA interference. However, apart from the identification of some IGF2 antisense transcripts, few data are available on that topic at the H19/IGF2 locus. We identify here a novel transcriptional activity at both the human and the mouse H19/IGF2 imprinted loci. This activity occurs antisense to the H19 gene and has the potential to produce a single 120-kb transcript that we called the 91H RNA. This nuclear and short-lived RNA is not imprinted in mouse but is expressed predominantly from the maternal allele in both mice and humans within the H19 gene region. Moreover, the transcript is stabilized in breast cancer cells and overexpressed in human breast tumors. Finally, knockdown experiments showed that, in humans, 91H, rather than affecting H19 expression, regulates IGF2 expression in trans. | 18,794,369 |
A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. | Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1alpha (PGC-1alpha) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1alpha in controlling the expression of CIDEA, an important regulatory factor in adipose cell function and obesity. Ectopically expressed CIDEA surrounded lipid droplets in brown adipocytes and induced the formation of lipid droplets in nonadipogenic cell lines. The expression and promoter activity of CIDEA was repressed by RIP140 and induced by PGC-1alpha, mediated through the binding of estrogen-related receptor alpha and NRF-1 to their cognate binding sites. Importantly, we demonstrate that RIP140 interacts directly with PGC-1alpha and suppresses its activity. The direct antagonism of PGC-1alpha by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways. | 18,794,372 |
Caspofungin-resistant Candida tropicalis strains causing breakthrough fungemia in patients at high risk for hematologic malignancies. | We identified three cases of C. tropicalis strains causing breakthrough fungemia in allogeneic stem cell recipients receiving caspofungin prophylaxis and treatment. Three genetically unrelated isolates with high echinocandin MICs were identified. Each strain carried a characteristic mutation conferring an amino acid substitution within Fks1p hot spot 1. | 18,794,386 |
Simultaneous measurement of beat-to-beat carotid diameter and pressure changes to assess arterial mechanical properties. | Use of local arterial distensibility measurements by change in carotid artery diameter divided by pulse pressure has limitations because blood pressure is often taken in a vessel distant or at a time different from where and when change in diameter is taken. In 92 subjects (23 to 91 years of age), carotid artery diameter was continuously measured ecographically, whereas blood pressure was continuously measured simultaneously tonometrically on the contralateral artery, the 2 signals being synchronized via 2 EKGs. Within each cardiac cycle, there was a linear relationship between the changes in vessel diameter and the changes in blood pressure during either the protomesosystole or the diastole after the dicrotic notch. The diastolic slope was displaced upward and steeper than the systolic slope, the pressure-diameter loop showing a hysteresis. Both slopes showed a high reproducibility when data were averaged over a several-second period. There were small differences between consecutive cardiac cycles, suggesting that modulation of arterial mechanical response to continuous changes in intravascular pressure may undergo physiological variations. In the 92 subjects, systolic and diastolic slopes correlated significantly with distensibility values obtained by Reneman formula and exhibited a close inverse relationship with each subject's age and systolic blood pressure, thereby showing the ability to reflect age- and pressure-dependent large artery stiffening. This method may allow precise assessment of man's arterial mechanical properties within each cardiac cycle. This highly dynamic assessment may help to collect information on properties of normal and altered large elastic arteries and the mechanisms involved in disease. | 18,794,405 |
The importance of auricular prostheses for speech recognition. | To examine the effects of an auricular prosthesis on sound levels at the entrance of the ear canal by measuring the auricular prosthesis transfer function (APTF) and to determine the effect of the prosthesis on speech recognition in noisy hearing conditions. Eight prostheses were used to measure the APTF. A microphone at the entrance of the ear canal measured sound pressure levels with the prosthesis present or absent while the head was rotated 360 degrees at 30 degrees increments. The Hearing in Noise Test was modified by the APTF to simulate the absence of an auricular prosthesis. Speech recognition was measured by testing 11 subjects with the unmodified Hearing in Noise Test and the modified Hearing in Noise Test. The APTF changed with the head's position relative to the speaker. The mean (SD) maximal gain provided by an auricular prosthesis was 8.1 (2.7) dB at 4.6 (1.0) kHz and 9.7 (1.7) dB at 11.5 (0.9) kHz at 0 degrees rotation. During speech testing, the auricular prosthesis improved the mean (SD) signal to noise ratio by 1.7 (1.7) dB at 0 degrees (P< .001), 0.9 (2.2) dB at 90 degrees (P=.04), and 0.5 (2.3) dB at 180 degrees (P=.52). The acoustic gain provided by an auricular prosthesis increases speech recognition in noisy environments. Auricular prostheses not only restore aesthetics but also improve hearing. | 18,794,410 |
Decreased bile duct injury rate during laparoscopic cholecystectomy in the era of the 80-hour resident workweek. | Considerable concern has been raised about the effects of restricted duty hours on surgical training. However, to our knowledge, the effect of the 80-hour resident workweek on operative outcomes after laparoscopic cholecystectomy has not been well studied. To compare the rates of bile duct injury and overall complications after laparoscopic cholecystectomy before and after the institution of the duty-hour restriction. Retrospective review of patient medical records to determine morbidity and mortality before (January 1, 2000, to June 30, 2003; period 1) and after (July 1, 2003, to June 30, 2006; period 2) implementation of duty hour limitations. Major public teaching hospital. A total of 2470 patients who had undergone laparoscopic cholecystectomy. Bile duct injury and overall complication rates as determined using multivariate analysis. Overall, 2470 laparoscopic cholecystectomy procedures were performed, including 1353 in period 1 and 1117 in period 2. In period 2, more patients had acute cholecystitis as the indication for surgery (49% vs 35% in period 1, P < .001), and a higher percentage of patients were male (22% vs 18%, P = .01). The incidence of bile duct injury and total complications decreased in period 2 from 1% to 0.4%(P = .04) and from 5% to 2% (P < .001), respectively. Mortality was unchanged. Multivariate analysis revealed that period 2 was protective for bile duct injury (odds ratio, 0.31; 95% confidence interval, 0.1-0.96; P = .04). For complications, both female sex (odds ratio, 0.62; 95% confidence interval, 0.38-0.9) and surgery during period 2 (odds ratio, 0.46; 95% confidence interval, 0.28-0.75) were protective, whereas older age (odds ratio, 1.03; 95% confidence interval, 1.02-1.05) was associated with complications. At a major public teaching hospital, the bile duct injury rate and the overall complication rate decreased after implementation of the 80-hour workweek. | 18,794,421 |
Nasal-air conditioning in patients with chronic rhinosinusitis and nasal polyposis. | To compare nasal-air conditioning in patients with chronic rhinosinusitis with nasal polyposis with healthy control subjects without nasal pathologic conditions, to investigate nasal-air conditioning after endoscopic sinus surgery with and without septoplasty and turbinoplasty 4 to 6 weeks after surgery, to examine the parameters of nasal patency and nasal geometry that possibly influence nasal-air conditioning before and after endonasal surgery, and to determine their relationship to nasal-air conditioning parameters. Prospective cohort study. Tertiary referral center. Twenty-five patients (median age, 51 years; age range, 20-74 years) having a diagnosis of chronic rhinosinusitis with nasal polyposis refractory to medical treatment and 22 healthy control subjects (median age, 25 years; age range, 18-52 years). Patients underwent endoscopic sinus surgery with or without septoplasty and turbinoplasty during 6 months and were followed up 4 to 6 weeks after surgery. Nasal-air conditioning was measured and acoustic rhinometry and active anterior rhinomanometry were performed before and after nasal surgery. Nasal airflow and nasal volume were significantly higher postoperatively than preoperatively. The preoperative heat increase and water gradient were lower in the patients compared with the controls. The postoperative heat increase was significantly higher than the preoperative values. The water gradient did not change after endonasal surgery. Nasal patency and volume were positively correlated with nasal heating, whereas nasal humidification showed a significant negative correlation with nasal volume. Patients with chronic rhinosinusitis with nasal polyposis seem to benefit from endoscopic sinus surgery with or without septoplasty and turbinoplasty because nasal heating is improved postoperatively. Four to 6 weeks after endonasal surgery, nasal humidification is neither improved nor worsened compared with preoperative values. | 18,794,436 |
Induction of collagen by estradiol: difference between sun-protected and photodamaged human skin in vivo. | To evaluate the effectiveness of topical estradiol in stimulating collagen I and III production in naturally aged and photoaged human skin of postmenopausal women and age-matched men. Vehicle-controlled treatment followed by biochemical and immunohistochemical analyses of skin biopsy specimens. Academic referral center. Seventy healthy volunteers (40 postmenopausal women with a mean age of 75 years, and 30 men with a mean age of 75 years) with photodamaged skin. Interventions Topical application of estradiol, 0.01%, 0.1%, 1%, or 2.5% or vehicle on aged or photoaged skin, with biopsy specimens taken after last treatment. De novo synthesis of collagen by quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Topical estradiol increased procollagen I and III messenger RNA and collagen I protein levels in sun-protected aged hip skin in postmenopausal women and, to a lesser extent, in age-matched men. Surprisingly, no significant changes in production were observed in women or men after 2-week estradiol treatment of photoaged forearm or face skin, despite similar expression of estrogen receptors (ER-alpha, ER-beta, and GPR30) in aged and photoaged skin. Estradiol treatment induced the estrogen-responsive gene GREB1, indicating that penetration of topical estradiol and genomic response to estrogen were similar in the 3 anatomic sites. Two-week topical estradiol treatment stimulates collagen production in sun-protected hip skin, but not in photoaged forearm or face skin, in postmenopausal women and aged-matched men. These findings suggest that menopause-associated estrogen decline is involved in reduced collagen production in sun-protected skin. Interestingly, alterations induced by long-term sun exposure hinder the ability of topical 2-week estradiol to stimulate collagen production in aged skin. clinicaltrials.gov Identifier: NCT00113100. | 18,794,456 |
Variation in care for recurrent nonmelanoma skin cancer in a university-based practice and a veterans affairs clinic. | To learn if treatment of recurrent nonmelanoma skin cancer (NMSC) varied in different practice settings. Prospective cohort study of consecutive patients with recurrent NMSC. A university-based dermatology practice and the dermatology clinic at the affiliated Veterans Affairs Medical Center (VAMC). Conventional therapies for NMSC were available at both sites. Patients All 191 patients diagnosed as having recurrent NMSC in 1999 and 2000 were included in the study. Data were collected from medical record review and surveys mailed to patients. Main Outcome Measure Performance of Mohs micrographic surgery (Mohs). Patients at the VAMC were older, less educated, poorer, and had more comorbid illnesses, but their tumors were similar to those of patients at the university-based practice. Treatment choices differed at the 2 sites: the proportions of tumors treated in the VAMC and university sites were 60% and 14%, respectively, for excisional surgery; and 24% and 61%, respectively, for Mohs (P < .001). In multivariate analyses adjusting for patient, tumor, and physician features that may have affected treatment choice, tumors treated at the university-based site remained significantly more likely to be treated with Mohs (odds ratio, 8.68 [95% confidence interval, 3.66-20.55]; P < .001). Substantial variation existed in the treatment of recurrent NMSC in different practice settings. This variation was not explained by measured clinical characteristics of the patients or the tumors. | 18,794,460 |
Site matters: winning the hearts and minds of patients in a cardiology clinic. | In medical care settings, mental health symptoms of depression and distress are associated with poor medical outcomes, yet they are often underrecognized. Authors sought to examine the effect of having immediate mental-health screening in the cardiology clinic. The Patient Health Questionnaire and the Impact of Event Scale were used to screen for depression and distress in 316 patients at an urban cardiology clinic. Because of poor follow-up rates, a psychiatrist was placed on the premises of the cardiology clinic to facilitate referrals. Placing a psychiatrist within the cardiology clinic significantly improved the rate of successful referrals. Because 45 patients (14%) endorsed suicidal thoughts, authors conclude that mental health screening programs should include an immediate evaluation by a clinician. | 18,794,506 |
Breast cancer and psychosocial factors: early stressful life events, social support, and well-being. | The allostasis theory postulates that stress causes the body to activate physiologic systems in order to maintain stability. The authors sought to examine the relationship between earlier stress and later development of breast cancer (BC). Authors correlated discrete and interactive relationships of stressful life events, social support, and well-being during childhood and adolescence with the occurrence of BC in adulthood among 300 women with primary BC and 305 matched control subjects. BC patients and control subjects reported similar childhood experiences. Yet, although childhood stressful life events were associated with reports of less family support and well being among the controls, those in the BC group who experienced high stress in early childhood actually expressed higher levels of family support and well-being than did those who had experienced lower levels of stress. These findings may reflect a tendency toward a repressive coping style among the BC group, which may be either a risk factor for the disease or a result of having it. | 18,794,509 |
Mania: psychiatric manifestations of the antiphospholipid syndrome. | Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by recurrent vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies. Central nervous system (CNS) involvement is a prominent feature of APS, and many neurological manifestations have been described in published reports. There are limited data on psychiatric syndromes occurring in association with APS, and there have been no previous reports of mania associated with APS. The authors present the case of a 31-year-old man who experienced an acute manic episode in association with APS. They review the literature on psychiatric manifestations of APS, discuss potential mechanisms of CNS pathogenesis, and consider diagnostic and treatment implications of the co-occurrence of APS and psychiatric symptoms. | 18,794,513 |
Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. | Prokaryote-eukaryote interactions are ubiquitous and have important medical and environmental significance. Despite this, a paucity of data exists on the mechanisms and pathogenic consequences of bacterial-fungal encounters within a living host. We used the nematode Caenorhabditis elegans as a substitute host to study the interactions between two ecologically related and clinically troublesome pathogens, the prokaryote, Acinetobacter baumannii, and the eukaryote, Candida albicans. After co-infecting C. elegans with these organisms, we observed that A. baumannii inhibits filamentation, a key virulence determinant of C. albicans. This antagonistic, cross-kingdom interaction led to attenuated virulence of C. albicans, as determined by improved nematode survival when infected with both pathogens. In vitro coinfection assays in planktonic and biofilm environments supported the inhibitory effects of A. baumannii toward C. albicans, further showing a predilection of A. baumannii for C. albicans filaments. Interestingly, we demonstrate a likely evolutionary defense by C. albicans against A. baumannii, whereby C. albicans inhibits A. baumannii growth once a quorum develops. This counteroffensive is at least partly mediated by the C. albicans quorum-sensing molecule farnesol. We used the C. elegans-A. baumannii-C. albicans coinfection model to screen an A. baumannii mutant library, leading to the identification of several mutants attenuated in their inhibitory activity toward C. albicans. These findings present an extension to the current paradigm of studying monomicrobial pathogenesis in C. elegans and by use of genetic manipulation, provides a whole-animal model system to investigate the complex dynamics of a polymicrobial infection. | 18,794,525 |
Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer. | To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer. One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA > or = 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%. The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04). The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine. | 18,794,543 |
Prognostic significance of disseminated tumor cells in the bone marrow of prostate cancer patients treated with neoadjuvant hormone treatment. | To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy. Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients' outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months. DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014). The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens. | 18,794,550 |
Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. | The American College of Physicians (ACP) developed this guideline to present the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis. Published literature on this topic was identified by using MEDLINE (1966 to December 2006), the ACP Journal Club database, the Cochrane Central Register of Controlled Trials (no date limits), the Cochrane Database of Systematic Reviews (no date limits), Web sites of the United Kingdom National Institute of Health and Clinical Excellence (no date limits), and the United Kingdom Health Technology Assessment Program (January 1998 to December 2006). Searches were limited to English-language publications and human studies. Keywords for search included terms for osteoporosis, osteopenia, low bone density, and the drugs listed in the key questions. This guideline grades the evidence and recommendations according to the ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that clinicians offer pharmacologic treatment to men and women who have known osteoporosis and to those who have experienced fragility fractures (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians consider pharmacologic treatment for men and women who are at risk for developing osteoporosis (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians choose among pharmacologic treatment options for osteoporosis in men and women on the basis of an assessment of risk and benefits in individual patients (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 4: ACP recommends further research to evaluate treatment of osteoporosis in men and women. | 18,794,560 |
PAI-1 and TAFI in inflammatory bowel disease: the yin and yang of the fibrinolytic system. | In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD. | 18,794,594 |
Prevalence and sociodemographic determinants of uninvestigated dyspepsia in the Czech Republic. | There are no data on the epidemiology of dyspepsia in Central Europe. The aim of this study was to evaluate the prevalence of uninvestigated dyspepsia in a representative sample of the Czech population. A total of 2509 persons, aged 5-100 years, randomly selected from 30 012 individuals in the general population, entered this multicentre, prospective, questionnaire-based epidemiological study. We found a 17% prevalence of long-lasting (>12 months) dyspeptic symptoms in the general population. Two subgroups were distinguished: (i) persons with dyspepsia as the only one long-lasting symptom and themselves feeling otherwise healthy (9%), mostly among younger patients (subgroup A); and (ii) patients with dyspepsia as part of the complex of previously recognized diseases (8%), mostly in older patients (subgroup B). The prevalence of dyspepsia was significantly higher among women. The excess cases of dyspepsia among the highly educated seemed to be cases of dyspepsia of subgroup A, and the higher prevalence of dyspepsia among the lower social classes was largely dyspepsia of subgroup B. Being a widow/widower had a significant effect on the risk of self-reported dyspepsia among 25-64-year-olds. No association between Helicobacter pylori infection and dyspepsia was found. The prevalence of uninvestigated dyspepsia in the Czech Republic is comparable with data from other European countries. Clearly distinct subgroups of dyspeptic patients exist that should be further studied. | 18,794,604 |
A delayed time of the peak tricuspid regurgitation signal: marker of right ventricular dysfunction. | Worsening degrees of tricuspid regurgitation (TR) have been associated with worse outcomes. We investigated the time it takes for the TR jet to attain its maximum peak (tmpTR) with measures of right ventricular (RV) function. Several echocardiographic variables of RV size and function and tmpTR corrected for heart rate were collected from 140 patients (mean age 57 +/- 20 years). Mean RV end systolic (15 +/- 9 cm) and end diastolic (25 +/- 9 cm) areas, RV fractional area change (44 +/- 19%), maximal tricuspid annular motion (1.98 +/- 0.71 cm), pulmonary artery systolic pressure (57 +/- 33 mm Hg) and tmpTR (248 +/- 75 ms). A negative correlation was seen between tmpTR and RV fractional area change (r = -0.74; P < 0.0001) and between tmpTR and maximal tricuspid annular excursion (r = -0.69; P < 0.0001). On a multiple stepwise linear regression analysis tmpTR was better than pulmonary artery systolic pressure in predicting RV dysfunction (P < 0.001). Receiver operating characteristic curve analysis demonstrated that a tmpTR value >240 ms identified RV systolic dysfunction (sensitivity 79% and specificity 94%, areas under the curves 0.923, P = 0.0001). The longest tmpTR values were seen in patients with both RV systolic dysfunction and pulmonary hypertension (310 +/- 30 ms, P < 0.0001). A delayed time to peak of the maximum TR jet correlates with RV dysfunction. Patients with normal RV function and no pulmonary hypertension had abnormal tmpTR values (243 +/- 57 ms) implying an underlying RV mechanical abnormality that requires further investigation. | 18,794,616 |
Cerebral vascular accident in a patient with reactive thrombocytosis: a rare cause of stroke. | Reactive thrombocytosis (RT) is usually a benign process and is not associated with thrombotic or hemorrhagic events We report a case of a young man who suffers a stroke caused by RT, which was secondary to splenectomy, iron deficiency, and infection. : Although rarely documented, RT can be the cause of a major vascular event. | 18,794,625 |
The association of Hashimoto disease and Congo red negative amyloidosis. | Systemic amyloidosis which is characterized by extracellular deposition of monoclonal immunoglobulin light chains in various organs may be difficult to diagnose at an early stage, especially when the Congo red stain is negative. We describe herein a case of Congo red negative primary amyloidosis associated with Hashimoto thyroiditis. The patient presented with multiple organ involvement suggestive of amyloidosis including heart failure, renal failure, and macroglossia. Serum and urine immunofixation studies were positive for monoclonal chains. Even though a biopsy taken from the enlarged tongue of the patient was negative when stained with Congo red, electron microscopy showed ultrastructural features of amyloid deposition. In conclusion, we are reporting a rare case of primary amyloidosis with a negative Congo red stain associated with Hashimoto thyroiditis. | 18,794,630 |
Australia and New Zealand survey of antimetabolite and steroid use in trabeculectomy surgery. | To assess the pattern of use of antimetabolites and steroids in trabeculectomy surgery among consultant ophthalmologists in Australia and New Zealand. A postal questionnaire of 25 questions regarding current glaucoma practices and antimetabolite and steroid use in trabeculectomy surgery was sent to all practicing Australian and New Zealand Fellows of the Royal Australia and New Zealand College of Ophthalmologists in July 2005. The second half of the survey consisted of questions on the number of trabeculectomies performed per year, topical steroid use, the type of antimetabolite used, and assessment of factors that may influence the decision to use them. The results were cross-tabulated according to state/country, years practicing, type of practice, and being a glaucoma subspecialist (GSS). The overall response rate was 78% (627 out of 808). Ninety-one percent stated that they managed glaucoma of which 65% stated that they perform trabeculectomy surgery and 16% considered themselves as a GSS. In 2004, 75% of ophthalmologists performed less than 10 trabeculectomies. Sixty-one percent used an antimetabolite in trabeculectomy surgery of which 5-fluorouracil was used 51% (intraoperatively) and 24% (postoperatively). Mitomycin C was used in 12% and 0.2 mg/mL was the most commonly used concentration for 2 or 3 minutes. Fifty-four percent used postoperative steroids in a primary trabeculectomy for 1 to 2 months with 48% of GSSs using it for 2 to 3 months. Forty-eight percent to 96% would use an antimetabolite in patients with risk factors for conjunctival scarring. This survey shows a wide range of the use of antimetabolites and steroids in trabeculectomy surgery with 5-fluorouracil being most commonly used. GSSs and young ophthalmologists would use antimetabolites more often and postoperative steroids for longer. This survey allows ophthalmologists to compare their own practices with those of their colleagues in Australia and the United Kingdom. | 18,794,674 |
Internal glaucoma drainage device tube fenestration for uncontrolled postoperative intraocular pressure. | To describe a novel approach to early postoperative intraocular pressure (IOP) control after glaucoma drainage device (GDD) implantation. Two patients with elevated IOP after GDD implantation underwent internal GDD tube fenestration using a 30-gauge needle to perforate the GDD tube. IOP was lowered in each case by over 50% without complication. Transanterior chamber internal GDD tube fenestration is a novel, straightforward approach to early IOP control after GDD implantation. This procedure adds to our armamentarium of methods for controlling IOP during the early postoperative period. | 18,794,687 |
Selective laser trabeculoplasty: a review. | The introduction of selective laser trabeculoplasty (SLT) has renewed interest in laser trabeculoplasty for the reduction of intraocular pressure (IOP) in eyes with glaucoma. This review was undertaken to address frequently raised issues pertinent to SLT in clinical practice. On the basis of the peer-reviewed medical literature, SLT demonstrates equivalent efficacy and comparable safety to argon laser trabeculoplasty, and is also equally as effective as topical medical therapy. SLT's safety profile includes mild and transient inflammation, ocular pain, and a small risk of moderate IOP elevations after the procedure. The mechanism of action of SLT is not known. SLT delivers less energy to the trabecular meshwork and generates less damage to angle tissues. Whether this renders SLT more repeatable than argon laser trabeculoplasty has not been evaluated in published data. SLT seems to be a safe and effective means of IOP reduction in eyes with glaucoma, and can reasonably be applied as primary or adjunctive therapy. | 18,794,688 |
Ostomy pouch wear time in the United States. | The purpose of this study was to determine average pouch wear times of persons with an ostomy living in the United States. In this national survey, subjects were identified by ostomy nurses and through ostomy support groups in the United States. Participants responding to a survey represented all 6 geographic regions of the United States identified by US Bureau of Census. Persons with colostomies, ileostomies, and urostomies were queried concerning their average pouch wear time. The mean wear time for ostomy pouches in the United States is 4.8 days. Persons with urostomies reported an average wear time of 5.02 days (SD = 1.74), those with ileostomies reported 5.01 days (SD = 2.25), and those with colostomies reported an average of 4.55 days (SD = 2.08). This study is the first of its kind to utilize a large, national sample to determine average wear time of ostomy pouches. Further research is needed to establish a benchmark for ostomy pouch wear time in the United States and to determine what factors affect wear time. | 18,794,702 |
The effects of time pressure and experience on nurses' risk assessment decisions: a signal detection analysis. | Time pressure and, occasionally, suboptimal assessment decisions are features of nursing in acute care. To explore the effect of generic and specialist clinical experience on the ability to detect the need to take action in acute care and the impact of time pressure on nurses' decision-making performance. Experienced acute care registered nurses (n = 241) were presented with 50 vignettes of real clinical risk assessments. Each vignette contained seven information cues. In response to these vignettes, nurses had to decide whether to intervene or not. The 26 vignettes were time limited and mixed randomly into the 50 cases. Signal detection analysis was used to establish nurses' performance, personal decision thresholds ([beta]), and their abilities (d') to distinguish a signal of clinical risk from the clinical noise of noncontributory information. Nurses had significantly lower d' and were significantly less likely to indicate intervening under time pressure. For ability-but not threshold-there was a significant interaction of time pressure and years of experience in acute care. With no time pressure, d' increased in line with years of experience. Under time pressure, there was no effect. Time pressure reduced nurses' ability to detect the need and the tendency to report intervening. Thus, there were more failures to report appropriate intervention under time pressure, and the positive effects of clinical experience were negated under time pressure. More and larger scale research on the effect on clinical outcomes of time pressured nursing choices is required. | 18,794,714 |
Reducing my risk of intrusion: an intention of old homebound women who live alone. | In assessing home safety for older persons, nurses have checked home security or assessed fear of crime but neglected to explore intentions to reduce the risk of intrusion. To describe the intentions of old homebound women relative to reducing the risk of intrusion. A descriptive phenomenological method was used. The 40 participants (aged 85-98 years, M = 89.6) met criteria for age, living alone, and homebound status. Over 18 months, a series of tape-recorded interviews was completed, focusing on perceptions about changes in feeling safe at home and precautions to prevent the need to reaching help quickly. Data analyzed were drawn from interviews with the 32 women who reported intentions to reduce intrusion risk. Feeling safe in-place was contextual to recognizing intrusion risk and intentions to reduce the risk. Most women denied a recent change in feeling safe but reported intentions to reduce intrusion risk. The nine women who reported feeling less safe referred to various personal-social situations as explanatory. The five components of the phenomenon were keeping watch here, keeping out of harm's way here, preventing theft and vandalism here, discouraging people who might want to get in here, and keeping intruders out of here. Each component phenomenon was the umbrella for a variety of specific intentions to reduce intrusion risk. Each woman was intending to reduce intrusion risk in unique ways. When conducting home safety assessments, nurses should explore intentions to reduce intrusion risk and use that information as a basis for individualized interventions to promote safety, rather than relying on generic suggestions such as locking the door. | 18,794,719 |
Genetic and gene expression studies implicate renin and endothelin-1 in edema caused by peroxisome proliferator-activated receptor gamma agonists. | Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists can cause peripheral edema in susceptible individuals. To investigate the mechanistic basis underlying this adverse event, we performed a candidate gene analysis of patients enrolled in clinical trials of muraglitazar, an investigational PPARalpha/gamma dual agonist, and developed a cell culture-based gene expression assay and nonhuman primate model of edema to study the edemagenic properties of PPARgamma agonists. A total of 213 single nucleotide polymorphisms (SNPs) in 63 genes were genotyped in 730 participants. Chi-square and logistic regression analyses were used to test for association with edema. Transcriptional responses to PPARgamma agonists were evaluated in Calu-6 cells using quantitative real-time PCR. Male Cynomolgus monkeys were treated with PPAR agonists and were evaluated for edema using MRI. SNPs in renin (rs2368564) and endothelin-1 (rs5370) were associated with reduced risk of edema (P=0.003 and P=0.028, respectively) and an SNP in beta1 adrenergic receptor (rs1801253) was associated with increased susceptibility to edema (P=0.034). Gene expression studies revealed that renin and endothelin-1 were regulated by PPARgamma in Calu-6 cells. A survey of 10 PPARgamma agonists further revealed that a compound's in vitro potency was correlated with its edemagenic potential leading to the prediction that one of three previously uncharacterized PPARgamma agonists would cause less edema. This prediction was validated in a nonhuman primate model of PPARgamma agonist-induced edema. Our results implicate a key role for renin and endothelin-1 in the edema caused by PPARgamma agonists and demonstrate how knowledge gained from pharmacogenetic studies can be applied in drug discovery. | 18,794,727 |
Preventable hospital-acquired conditions: the whys and wherefores. | The changes to the Centers for Medicare & Medicaid Services (CMS) Inpatient Prospective Payment System published in the Federal Register (, Vol. 72, No. 162) on August 22, 2007, introduced the term preventable "hospital-acquired conditions" (HACs). These printed rules and regulations came about through a provision in the Deficit Reduction Act of 2005 (Pub. No. 109-171) and required the Secretary of the Department of Health and Human Services to track and report on conditions considered to be high cost, high volume (or both); assigned a higher paying "diagnosis related group" (DRG) when present as a secondary diagnosis; and were thought to be reasonably preventable when evidence-based guidelines were employed. In order to comply with this mandate, the CMS, a federal agency within Health and Human Services, was assigned the task of choosing "preventable" HACs, also referred to as "serious preventable events," for which reporting and tracking would be conducted; with the added opportunity of reporting and tracking data regarding a patient's "present on admission" condition. These preventable HACs become of particular interest to hospitals on October 1, 2008. That is the day CMS begins freeing itself from paying hospitals for the targeted preventable HACs that afflict Medicare patients during their hospital stay and which were not present at the time of the patients' admission to the hospital. It is a form of pay-for-performance. | 18,794,745 |
In vitro disc pressure profiles below scoliosis fusion constructs. | Biomechanical human cadaveric study comparing straight and scoliotic spines with healthy and degenerated L4/5 discs. To describe the biomechanical environment of discs under various spinal alignments by measuring the coronal intradiscal pressure profiles. Abnormal loading of the lumbar discs in the concavity of scoliotic curves may accelerate disc degeneration, which may be related to pain. Eight intact human cadaver spines (T1-S1; mean donor age 47 years old) underwent radiographs, DEXA, and MRI and were graded for disc degeneration. Each specimen was instrumented in a normal (straight coronal) spinal alignment from T4-L4. Intradiscal pressure profiles for the L4/5 disc and resultant moments were obtained under axial follower loads up to 1500 N. Testing was repeated for bilateral 3-cm decompensation. Posterior instrumentation was used to induce scoliosis (thoracic and lumbar curve average = 25 degrees, fractional lumbosacral curve average = 5 degrees), and testing was repeated for all load states. MRI found 4 healthy (grade I and II) and 4 degenerated (grade III to V) L4/5 discs. Scoliosis and decompensation significantly increased coronal moments (P < 0.003). Disc pressures increased linearly with greater applied loads for all specimens. Healthy L4/5 discs exhibited uniform pressure profiles with normal spinal alignment and minimal effect with simulated scoliosis or decompensation. For degenerated discs, there was a relative pressure profile depression in the nucleus relative to the anulus region; with spinal malalignment, either due to scoliotic curvature, decompensation, or both, there was disc pressure profile asymmetry. The ratio of maximum intradiscal pressure at the concavity relative to the convexity was 1.1 (range, 1.0-1.2) for healthy discs and 3.6 (range, 2.2-4.4) for degenerated discs in the scoliotic specimens (P = 0.008). Disc pressure profilometry below long spinal constructs found asymmetric loading with the greatest loads at the concave inner anulus, especially in the presence of disc degeneration, scoliosis, and decompensation. For the degenerated cases, there was substantial disc pressure profile asymmetry despite only mildly severe scoliotic curvatures. These results suggest that scoliosis surgeons should minimize end-vertebra tilt, maximize lumbar curve, and balance correction at the time of surgical intervention. These results combined with prior animal studies suggest a compounding effect of asymmetric loading and progression of disc degeneration. | 18,794,754 |
Adolescent idiopathic scoliosis and exercising: is there truly a liaison? | Cross-sectional observational study. Evaluation and comparison of the prevalence of adolescent idiopathic scoliosis (AIS) among 2 groups of patients (athletes and nonathletes) to determine whether athletic activities are related to the development of AIS. The potential association between AIS and exercising remains uncertain. The latter has often been considered as a therapeutic means and a causative factor of the former. A group of 2387 adolescents (boys: 1177, girls: 1210, mean age: 13.4 years) was evaluated. All completed a questionnaire concerning personal, somatometric, and secondary sex characteristics, type, duration and character of daily-performed physical activities, and existing cases of AIS among relatives. Patients were classified into 2 groups according to their answers; "athletes" and "nonathletes." The groups were comparable as far as age, height, weight, onset of menstruation, family history of scoliosis, and side of handedness were concerned. Children underwent physical examination by 3 orthopedic surgeons who were unaware of their level of athletic activities. Children considered, by all, to be suspicious of suffering from scoliosis, underwent further radiographic evaluation. In 99 cases (athletes: 48, nonathletes: 51), AIS was radiographically confirmed (Cobb angle >10 degrees). No statistically significant difference was found between athlete and nonathlete adolescents (P = 0.842), athlete and nonathlete boys (P = 0.757), and athlete and nonathlete girls (P = 0.705), as far as the prevalence of AIS was concerned. The mean value of the Cobb angle of the main scoliotic curve was not statistically different between male athletes and nonathletes (P = 0.45) and female athletes and nonathletes (P = 0.707). With the Cobb threshold reset at 20 degrees, no statistically significant differences were detected either. Our results demonstrate that systematic exercising is probably not associated with the development of AIS. Actively participating in sports activities doesn't seem to affect the degree of the main scoliotic curve either. | 18,794,756 |
Influence of sacral morphology in developmental spondylolisthesis. | A radiographic study was conducted to investigate sacral morphology in a children and adolescent population with developmental L5-S1 spondylolisthesis. To determine the relationship between sacral morphology and developmental L5-S1 spondylolisthesis. The morphology of the adult sacrum has been recently shown to be abnormal in low grade spondylolisthesis. However, sacral morphology has never been evaluated in a pediatric population where remodeling and secondary changes are less pronounced. It remains unknown if these changes in sacral morphology are primary or secondary in developmental L5-S1 spondylolisthesis. The lateral standing radiographs of 131 subjects, aged 6 to 20 years old with developmental L5-S1 spondylolisthesis (91 low grade and 40 high grade) were analyzed with a dedicated software allowing to measure the following parameters, which were analyzed for each subject by the same individual and compared to a cohort of 120 subjects without any spinal pathology with similar age and sex distribution: the sacral table index (STI), sacral table angle (STA), sacral kyphosis (SK), S1 superior angle, S2 inferior angle, and grade of spondylolisthesis. Student t test was used to compare the parameters between the groups. This study demonstrated that STA is significantly smaller (P < 0.01) in children and adolescents with L5-S1 spondylolisthesis compared to a similar control group. Furthermore, STA is significantly smaller in high-grade spondylolisthesis when compared to subjects with low grade. There is also a significant difference in segmental sacral morphology (S1 and S2 anatomy) in the spondylolisthesis group. Increasing sacral kyphosis is also found to be significantly associated with spondylolisthesis. The sagittal sacral morphology is a constant anatomic variable specific to each individual and unaffected by the position of the patient in space. The anatomy of the sacrum in children and adolescents with L5-S1 spondylolisthesis is particular and different from a control group. This study suggests that sacral anatomy may have a direct influence on the progression of spondylolisthesis; a lower STA and higher sacral kyphosis may be 2 factors predisposing to vertebral slip in developmental spondylolisthesis. | 18,794,760 |
Isolation and characterization of phenolic compounds from the leaves of Salix matsudana. | A bioassay-guided in vitro screen has revealed that a 70% methanol extract of the leaves of Salix matsudana shows considerable inhibitory activity against cyclooxygenases (COX-1 and COX-2). A subsequent phytochemical study led to the isolation of a new flavonoid, matsudone A (1), together with five known flavonoids--luteolin (2), isoquercitrin (3), 7-methoxyflavone (4), luteolin 7-O-glucoside (5), 4',7-dihydroxyflavone (6)--and two phenolic glycosides, leonuriside A (7) and piceoside (8). Their structures were elucidated on the basis of extensive 1D- and 2D-NMR studies, high resolution ESI mass spectroscopic analyses and comparisons with literature data. The isolated compounds 1-8 were tested for their inhibitory activities against COX-1 and COX-2. Compounds 1, 5 and 6 were found to have potent inhibitory effect on COX-2 and compounds 3-5 exhibited moderate inhibition against COX-1. | 18,794,770 |
Chemical and enzymatic approaches to carbohydrate-derived spiroketals: di-D-fructose dianhydrides (DFAs). | Di-D-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucrose- and/ or D-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features has attracted considerable interest from the food industry. DFAs behave as low-caloric sweeteners and have proven to exert beneficial prebiotic nutritional functions, favouring the growth of Bifidobacterium spp. In the era of functional foods, investigation of the beneficial properties of DFAs has become an important issue. However, the complexity of the DFA mixtures formed during caramelization or roasting of carbohydrates by traditional procedures (up to 14 diastereomeric spiroketal cores) makes evaluation of their individual properties a difficult challenge. Great effort has gone into the development of efficient procedures to obtain DFAs in pure form at laboratory and industrial scale. This paper is devoted to review the recent advances in the stereoselective synthesis of DFAs by means of chemical and enzymatic approaches, their scope, limitations, and complementarities. | 18,794,777 |
Amifostine protection against mitomycin-induced chromosomal breakage in fanconi anaemia lymphocytes. | Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 +/- 4.0 - MMC vs 12.3 2.9 - AMF --> MMC) MN/1000CB, p < 0.01, one way ANOVA) as well as in FA patients (80.0 +/- 5.8 - MMC vs 40.1 +/- 5.8 - AMF --> MMC) MN/1000CB, p < 0.01, ANOVA). Release of ROS by peripheral blood mononuclear cells treated with AMF -> MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect. | 18,794,784 |
Uremic lung: new insights into a forgotten condition. | The high mortality rate of acute kidney injury (AKI) despite advances in dialysis led to a renewed appreciation of the impact of AKI on distant organ dysfunction. Mechanistic studies demonstrated that AKI induces increased lung vascular permeability, soluble and cellular inflammation, and dysregulated salt and water channels. AKI also affects the brain, heart, liver, bone marrow, and gastrointestinal tract. Klein et al. now demonstrate that interleukin-6 is a direct mediator of AKI-induced lung changes. | 18,794,816 |
Sparse odor representation and olfactory learning. | Sensory systems create neural representations of environmental stimuli and these representations can be associated with other stimuli through learning. Are spike patterns the neural representations that get directly associated with reinforcement during conditioning? In the moth Manduca sexta, we found that odor presentations that support associative conditioning elicited only one or two spikes on the odor's onset (and sometimes offset) in each of a small fraction of Kenyon cells. Using associative conditioning procedures that effectively induced learning and varying the timing of reinforcement relative to spiking in Kenyon cells, we found that odor-elicited spiking in these cells ended well before the reinforcement was delivered. Furthermore, increasing the temporal overlap between spiking in Kenyon cells and reinforcement presentation actually reduced the efficacy of learning. Thus, spikes in Kenyon cells do not constitute the odor representation that coincides with reinforcement, and Hebbian spike timing-dependent plasticity in Kenyon cells alone cannot underlie this learning. | 18,794,840 |
Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. | SRp38 is an atypical SR protein that functions as a general splicing repressor when dephosphorylated. We now show that phosphorylated SRp38 functions as a sequence-specific splicing activator. Unlike characterized splicing activators, SRp38 functions in the absence of other SR proteins but requires a cofactor for activity. SRp38 was able to induce formation of splicing complex A in the absence of the cofactor, but this factor was necessary for progression to complexes B and C. Mechanistically, SRp38 strengthens the ability of the U1 and U2 small nuclear ribonucleoproteins to stably recognize the pre-mRNA. Extending these findings, analysis of alternative splicing of pre-mRNA encoding the glutamate receptor B revealed that SRp38 alters its splicing pattern in a sequence-specific manner. Together, our data demonstrate that SRp38, in addition to its role as a splicing repressor, can function as an unusual sequence-specific splicing activator. | 18,794,844 |
Asymmetric caging in soft colloidal mixtures. | The long-standing observations that different amorphous materials exhibit a pronounced enhancement of viscosity and eventually vitrify on compression or cooling continue to fascinate and challenge scientists, on the ground of their physical origin and practical implications. Glass formation is a generic phenomenon, observed in physically quite distinct systems that encompass hard and soft particles. It is believed that a common underlying scenario, namely cage formation, drives dynamical arrest, especially at high concentrations. Here, we identify a novel, asymmetric glassy state in soft colloidal mixtures, which is characterized by strongly anisotropically distorted cages, bearing similarities to those of hard-sphere glasses under shear. The anisotropy is induced by the presence of soft additives. This phenomenon seems to be generic to soft colloids and its origins lie in the penetrability of the constituent particles. The resulting phase diagram for mixtures of soft particles is clearly distinct from that of hard-sphere mixtures and brings forward a rich variety of vitrified states that delineate an ergodic lake in the parameter space spanned by the size ratio between the two components and by the concentration of the additives. Thus, a new route opens for the rational design of soft particles with desired tunable rheological properties. | 18,794,859 |
Optogenetic analysis of synaptic function. | We introduce optogenetic investigation of neurotransmission (OptIoN) for time-resolved and quantitative assessment of synaptic function via behavioral and electrophysiological analyses. We photo-triggered release of acetylcholine or gamma-aminobutyric acid at Caenorhabditis elegans neuromuscular junctions using targeted expression of Chlamydomonas reinhardtii Channelrhodopsin-2. In intact Channelrhodopsin-2 transgenic worms, photostimulation instantly induced body elongation (for gamma-aminobutyric acid) or contraction (for acetylcholine), which we analyzed acutely, or during sustained activation with automated image analysis, to assess synaptic efficacy. In dissected worms, photostimulation evoked neurotransmitter-specific postsynaptic currents that could be triggered repeatedly and at various frequencies. Light-evoked behaviors and postsynaptic currents were significantly (P <or= 0.05) altered in mutants with pre- or postsynaptic defects, although the behavioral phenotypes did not unambiguously report on synaptic function in all cases tested. OptIoN facilitates the analysis of neurotransmission with high temporal precision, in a neurotransmitter-selective manner, possibly allowing future investigation of synaptic plasticity in C. elegans. | 18,794,862 |
CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. | Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies. | 18,794,900 |
Genetic co-transfer of CCR7 ligands enhances immunity and prolongs survival against virulent challenge of pseudorabies virus. | The CC chemokine receptor 7 (CCR7) and cognate CCR7 ligands, CCL19 and CCL21, help establish microenvironments in lymphoid tissue that can facilitate encounters between naive T cells and mature dendritic cells (DCs). This study was conducted to determine if CCR7 ligands can augment the immunogenicity of a DNA vaccine that expresses glycoprotein B (gB) of the pseudorabies virus (PrV). The genetic co-transfer of CCR7 ligands along with a PrV DNA vaccine increased the levels of serum PrV-specific immunoglobulin (Ig) G by 2- to 2.5-fold. In addition, the level of PrV-specific IgG2a isotype was significantly enhanced by co-injection of CCR7 ligand DNA, which indicates that CCR7 ligand biases the humoral immunity toward the Th1-type pattern. The co-injection of CCR7 ligand DNA consistently enhanced the level of Th1-type cytokines (IL-2 and IFN-gamma) produced by stimulated immune cells when compared with a group that was vaccinated with the PrV DNA vaccine. Also, the genetic co-transfer of CCR7 ligand DNAs with PrV DNA vaccine provided prolonged survival against a virulent challenge by PrV. Moreover, the co-administration of CCR7 ligand DNA increased the number of mature DCs into the secondary lymphoid tissues, which appeared to enhance the proliferation of PrV-immune CD4(+) T cells. Taken together, these findings indicate that CCR7 ligands are an attractive adjuvant for a PrV DNA vaccine that can offer protective immunity against the PrV. | 18,794,906 |
Designing pharmacogenetic projects in industry: practical design perspectives from the Industry Pharmacogenomics Working Group. | Pharmacogenetic association studies have the potential to identify variations in DNA sequence which impact drug response. Identifying these DNA variants can help to explain interindividual variability in drug response; this is the first step in personalizing dosing and treatment regimes to a patient's needs. There are many intricacies in the design and analysis of pharmacogenetic association studies, including having adequate power, selecting proper endpoints, detecting and correcting the effects of population stratification, modeling genetic and nongenetic covariates accurately, and validating the results. At this point there are no formal guidelines on the design and analysis of pharmacogenetic studies. The Industry Pharmacogenomics Working Group has initiated discussions regarding potential guidelines for pharmacogenetic study design and analyses (http://i-pwg.org) and the results from these discussions are presented in this paper. | 18,794,908 |
Symbiotic diversity in marine animals: the art of harnessing chemosynthesis. | Chemosynthetic symbioses between bacteria and marine invertebrates were discovered 30 years ago at hydrothermal vents on the Galapagos Rift. Remarkably, it took the discovery of these symbioses in the deep sea for scientists to realize that chemosynthetic symbioses occur worldwide in a wide range of habitats, including cold seeps, whale and wood falls, shallow-water coastal sediments and continental margins. The evolutionary success of these symbioses is evident from the wide range of animal groups that have established associations with chemosynthetic bacteria; at least seven animal phyla are known to host these symbionts. The diversity of the bacterial symbionts is equally high, and phylogenetic analyses have shown that these associations have evolved on multiple occasions by convergent evolution. This Review focuses on the diversity of chemosynthetic symbionts and their hosts, and examines the traits that have resulted in their evolutionary success. | 18,794,911 |
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