title
stringlengths
0
1.13k
abstract
stringlengths
1
15.7k
PMID
int64
22
36.5M
Critical analysis of the 4-hour A&E policys impact on elderly patients.
Government evaluations of the 4-hour waiting time policy show an overall improvement in accident and emergency (A&E) waiting times. However, the audit results shadow the policy's impact on age groups, which make it difficult to determine the policy's impact on older people, who are the largest and most vulnerable service users. Literature suggests that the policy has benefited the younger populace more than the older user group, who experience difficulties in other areas of the health system, both upstream through inappropriate ward admissions, incomplete assessments, poor care, and bed-access blocks while being held in clinical decision units as well as downstream, where ambulance staff are managing stacked patients outside A&E departments, causing ambulance delays to more vulnerable older patients in communities. While patient flow through A&E has improved, the upstream-downstream effect has disrupted patient flow through the remaining health system and communities, which has resulted in increased dissatisfaction and poor care mainly among the elderly population. This article examines the problems experienced by the elderly in A&E prior to the policy's introduction and its subsequent impact on older people following implementation, in order to determine whether the policy has improved or further deteriorated care towards this group.
18,946,398
[Alveolo-interstitial pneumonia due to Temozolamide].
Temozolomide is an alkylating agent approved for treatment of glioblastoma in association with radiotherapy. We report the case of a 56 year old woman presenting with alveolo-interstitial pneumonia after treatment with Temozolomide. Initially she received induction treatment with Temozolomide and concomitant radiotherapy for bifocal high grade glioblastoma. A month later she received, as scheduled, the first course of Temozolomide maintenance chemotherapy. Grade II dyspnoea developed a few days later. High resolution computed tomography showed alveolo-interstitial opacities with basal predominance, associated with alveolar nodules. Broncho-alveolar lavage showed a lymphocytosis. No bacteria were isolated from microbiological samples. A final diagnosis of drug-induced pneumonia was based on the time sequence and absence of other causes. There is little literature concerning the pulmonary toxicity of Temozolomide. However, our case report of drug-induced pneumonia and similar observations in the databases of regional pharmacovigilance centres suggest that this side effect should be included in the summary of product characteristics.
18,946,417
New devices and techniques for airway management.
Innovation over the past 25 years in the field of the airway management has led to the proliferation of new and improved techniques and devices. It is important to emphasize that the definition of a failed airway must include the inability to maintain acceptable oxygenation and not only the evidence of unsuccessful laryngoscopy and impossible intubation. We must ask ourselves: is it always necessary to intubate? Is it necessary in all patients? Our answer is absolutely ''no." Patients' oxygenation is the absolute priority, where the choice of whether or not to intubate represents only a technical problem. The existing literature primarily supports the use of the classic laryngeal mask airway (LMA) for providing effective ventilation and oxygenation; it suggests the use of the intubating LMA as an important rescue device and the use of the Combitube as a well-established emergency airway. The role in managing complex airway problems of many new extraglottic devices has not yet been completely investigated and will likely be better defined in the coming years. The videolaryngoscopes seem to be an interesting and promising option in the field of airway management. Furthermore, the applicability of associated techniques could represent an efficacious strategy to overcome the limitations of the single device by strengthening their capabilities and chances of successful airway management. To date there is no technique found to be effective in every case or that can solve all airway problems. It is not the latest device or the latest technique that can solve an airway management problem, but the operator's experience and skill with the device and technique that he knows best and uses daily.
18,946,431
Fixed drug eruptions due to cotrimoxazole.
This prospective study on Fixed Drug Eruption (FDE) was carried out between January 2003 to December 2006 in Dermatology department of Mymensingh Medical College Hospital & private chambers. This study was carried out with an objective to see the specific site of involvement and other clinical parameters in FDE due to cotrimoxazole. In each case, a detailed history was taken and a thorough physical examination was done by at least one dermatologist. Patients with suspected FDE, who had consented, were included in the study. Oral re-challenge test was done in each case after written or verbal consent of the patient or legal guardian. For oral re-challenge, usually half of the usual therapeutic dose of the suspected drug (s) was given first and reactions were observed and if no reaction, then full therapeutic dose was given and then again reactions were observed. In case of no reaction to one drug, the next drug was tested after 2 to 7 days. Age & sex distribution, number of attacks of FDE, number of lesions, distribution of sites of involvement were determined in each case of FDE. All informations were recorded in pre-tested data sheet. Among 93 patients of suspected FDE, 61 patients were confirmed as FDE with identified causes, of which 36 cases were due to cotrimoxazole (59.02%). Age range of patients was from 5 years to 65 years with mean of 24.92 years. Male was predominantly affected (M:F=6.2:1). In 50% cases presenting attack was the 2nd attack. Rest 50% had 3 to more than 10 attacks. Number of lesions was: 2-5 lesions in 50%, solitary lesion in 16.67%, 6-10 lesions in 13.89% and more than 10 lesions in 19.44% cases. Sites of involvement in cases of FDE due to cotrimoxazole (n=36) were as follows: lips 58.33%, genitalia 33.33%, oral 13.89%, trunk 38.89%, limbs 55.56%, hands 16.67%, feet 19.44%, face 19.44% and conjunctiva 2.78%.
18,946,439
Effects of deep heat therapy on the patients with chronic low back pain.
A randomized clinical trial was conducted in the Department of Physical Medicine & Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from 1st April 2006 to 31st March 2007. A total of 102 patients of Chronic LBP were included in the study. Out of them, 42 (41.2%) were male and 60 (58.8%) were female and male: female ratio was 1:1.43. The mean age of the patients was 42.22+/-8.07 years. They were divided randomly into two groups by the way of lottery for the clinical trial. Group A was treated with short wave diathermy (SWD) and non steroidal anti inflammatory drugs (NSAID) and Group B was treated with placebo SWD and NSAID. After treatment the result was compared and student's 't' test was done to see the level of significance. There was significant improvement after treatment in both the group (P=0). In comparison between two groups, it was found that there was no significant improvement in pre-treatment, after 1st week and after 2nd week. Improvement was found in Group A than Group B after 3rd week (P=0.05). And the improvement was gradually increased in Group A in comparison to Group B. Finally, it was found that there was significant improvement in Group A than Group B after 6th week (P=0). From the present study, it may be concluded that both the treatment (NSAID and SWD) is effective for the treatment of Chronic LBP. But the patient may be more benefited if SWD is used as an adjunct to NSAID.
18,946,448
Clinical profile, management and outcome of lupus.
Systemic Lupus Erythematosus (SLE) is a disease of many faces and great mimicry. Women of child bearing ages are the potential candidates for this disease though it may occur in any age and sex group and the clinical manifestations do not vary with sex differentiation. Etiology of SLE is still to be defined and it has a prevalence of 27.7/100,000 population with higher rate of incidence in Asian and African women. This is a prospective study done from January, 2002 to December, 2006. The objective of the study was to observe the clinical profile and outcome of patients suffering from SLE. 33 patients were diagnosed following the ARA criteria. All the patients were investigated with ANA, anti ds-DNA antibody, routine blood and urine examination and follow up was done following SLE Disease Activity Index (SLEDAI) scoring system along with routine blood and urine examination. Mean age at presentation was 27.3 years with a standard deviation of 12.5. Among them, constitutional symptoms were present in 91% of the patients, hematological features were also present in 91% of patients where anemia was almost universal, one patient was suffering from autoimmune hemolytic anemia and 4 patients had thrombocytopenia. Mild leucopenia and lymphopenia was also observed in 33% patients. 60% patients show an ESR higher than 100 mm in 1st hour. Musculoskeletal and cutenous features were present in 81% and 75% cases respectively. 36% patients had some degree of renal involvement at the time of diagnosis. 6% patients had severe neuropsychiatric features. After appropriate management 52% patients leading a normal life with medication, 30% patients had a fluctuating course, 9% patients died and 9% lost follow up. Outcome was better in the patients who were diagnosed and treated early.
18,946,454
Crosstalk between small GTPases and polarity proteins in cell polarization.
Cell polarization is crucial for the development of multicellular organisms, and aberrant cell polarization contributes to various diseases, including cancer. How cell polarity is established and how it is maintained remain fascinating questions. Conserved proteins of the partitioning defective (PAR), Scribble and Crumbs complexes guide the establishment of cell polarity in various organisms. Moreover, GTPases that regulate actin cytoskeletal dynamics have been implicated in cell polarization. Recent findings provide insights into polarization mechanisms and show intriguing crosstalk between small GTPases and members of polarity complexes in regulating cell polarization in different cellular contexts and cell types.
18,946,474
From cells to organs: building polarized tissue.
How do animal cells assemble into tissues and organs? A diverse array of tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. Conserved design principles underlying this diversity are emerging from studies of model organisms and tissues. We discuss how conserved polarity complexes, signalling networks, transcription factors, membrane-trafficking pathways, mechanisms for forming lumens in tubes and other hollow structures, and transitions between different types of polarity, such as between epithelial and mesenchymal cells, are used in similar and iterative manners to build all tissues.
18,946,477
Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration.
Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), and Dab1 are the main components of the Reelin signalling cascade. Reelin is the sole ligand defined so far in signalling through this pathway. Postnatal migration of neuronal precursors from the subventricular zone (SVZ) to the olfactory bulb (OB), however, depends on ApoER2 and Dab1, but functions independently of Reelin. Here, we show that thrombospondin-1 (THBS-1) is a novel physiological ligand for ApoER2 and VLDLR. THBS-1 is present in the SVZ and along the entire rostral migratory stream (RMS). It binds to ApoER2 and VLDLR and induces phosphorylation of Dab1. In contrast to Reelin, it does not induce Dab1 degradation or Akt phosphorylation, but stabilizes neuronal precursor chains derived from subventricular explants. Lack of THBS-1 results in anatomical abnormalities of the RMS and leads to a reduction of postnatal neuronal precursors entering the OB.
18,946,489
Long-lasting molecular changes in human skin after repetitive in situ UV irradiation.
It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at > or = 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at > or = 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.
18,946,495
Towards systems biology of heterosis: a hypothesis about molecular network structure applied for the Arabidopsis metabolome.
We propose a network structure-based model for heterosis, and investigate it relying on metabolite profiles from Arabidopsis. A simple feed-forward two-layer network model (the Steinbuch matrix) is used in our conceptual approach. It allows for directly relating structural network properties with biological function. Interpreting heterosis as increased adaptability, our model predicts that the biological networks involved show increasing connectivity of regulatory interactions. A detailed analysis of metabolite profile data reveals that the increasing-connectivity prediction is true for graphical Gaussian models in our data from early development. This mirrors properties of observed heterotic Arabidopsis phenotypes. Furthermore, the model predicts a limit for increasing hybrid vigor with increasing heterozygosity--a known phenomenon in the literature.
18,946,548
Short-term effects of irbesartan treatment on microalbuminuria in patients with normotensive type 2 diabetes.
To observe the short-term effects of irbesartan treatment on microalbuminuria in patients with normotensive type 2 diabetes. A total of 40 normotensive type 2 diabetes patients (mean age 55.1+/-11.4 years) who had microalbuminuria were included in this non-comparative and prospective research study. The study took place in Ege University Hospital, Bornova-Izmir, Turkey, between January 2005 and April 2005. Patients were treated with irbesartan 300mg/day for 3 months. Physical examination, medical history, systolic and diastolic blood pressure levels, microalbuminuria, diabetes markers fasting and non-fasting blood glucose, glycosylated hemoglobin [HbA1c], lipid profile, creatinine and urea were obtained at baseline and after 3 months of irbesartan treatment. The primary assessment criterion was the change in microalbuminuria. The mean microalbuminuria level at baseline was 110.8+/-93.1mg/24 hours. It significantly decreased to 45.6+/-62.5mg/24 hours at the end of 3 months of irbesartan treatment (p<0.001). When patients were stratified according to the change in the microalbuminuria status after treatment, 90% of them either returned to normo albuminuria or their microalbuminuria decreased. Both diastolic and systolic blood pressures, fasting and non-fasting blood glucose, and HbA1c were found to be significantly decreased after 3 months of irbesartan treatment compared to pre-treatment values. The positive effect of irbesartan on microalbuminuria occurs independently from HbA1c, fasting blood glucose, and blood pressures. The short-term treatment of irbesartan is effective to decrease microalbuminuria in normotensive type 2 diabetes patients, independent of its antihypertensive effect. There is a need for multicenter prospective studies to investigate this further.
18,946,564
Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.
In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.
18,946,603
Beneficial effects of Annona squamosa extract in streptozotocin-induced diabetic rats.
The present study investigated the possible therapeutic effects of Annona squamosa (A. squamosa) extract on certain biochemical markers in streptozotocin (STZ)-induced diabetes mellitus in rats. The effects of an aqueous extract of A. squamosa leaves on blood glucose, insulin, C-peptide, albumin, albumin/globulin ratio, urea, uric acid and creatinine and the activities of diagnostic marker enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase were examined in the plasma, liver and kidney tissues of control and experimental groups. Oral administration of A. squamosa (300 mg/kg) aqueous extract to diabetic rats for 30 days significantly reduced blood glucose, urea, uric acid and creatinine, but increased the activities of insulin, C-peptide, albumin, albumin/globulin ratio and restored all marker enzymes to near control levels. The present results shown that A. squamosa extract has an antihyperglycaemic effect and consequently may alleviate liver and renal damage associated with STZ-induced diabetes mellitus in rats.
18,946,614
Blistering erysipelas: not a rare entity.
Soft tissue infections are common, but erysipelas, especially its blistering feature, is an under-recognised entity. There have been few reports of blistering erysipelas. We aim to describe the clinical characteristics, management and the risk factors for erysipelas in 20 patients admitted in a tertiary hospital in Singapore. A chart review of all cases of erysipelas, diagnosed by experienced dermatologists and admitted to the Singapore General Hospital during the period January 2006 to August 2006, was conducted. There were 20 patients (11 male, nine female) with an average age of 62.2 (range 31-86) years. The most commonly-involved site was the leg (75 percent), followed by the arm (15 percent) and face (ten percent). The clinical characteristics were well dermarcated (50 percent), erythema (100 percent) and oedema (85 percent), and bullae and vesicles formation (80 percent). Most presented with no pain (40 percent) and minimal signs of systemic toxicity. There was no positive blood culture, but the swab on the blistering erysipelas yielded positive cultures in 67 percent. The most common predisposing factor was disruption in the skin barrier (65 percent), followed by venous insufficiency (20 percent) and lymphoedema (25 percent). All patients received empirical antibiotics, most commonly penicillin and cloxacillin (65 percent), for an average duration of 20.65 (10-41) days, and with local care, there was complete resolution. In our experience, erysipelas is a clinically distinct entity and commonly presents with bullae or vesicles. It has favourable prognosis, and rarely develops any complication with timely and appropriate therapy.
18,946,616
Anatomical variations of the thyroid gland: possible surgical implications.
The organogenesis of the thyroid gland in humans is often disturbed, leading to a variety of morphological variations of the gland, such as hypoplasia, ectopy, hemiagenesis and agenesis. As the morphological variations are usually diagnosed incidentally during examination for other thyroid gland diseases, the true incidence is therefore uncertain. This study was structured to investigate the gross anatomical features of the thyroid gland in 105 (88 male and 17 female) cadavers from the coastal belt of southern India, an endemic goitre region. The pyramidal lobe was present in 61 (58 percent) male cadavers, and 52 (49.5 percent) cadavers showed the presence of the levator glandulae thyroideae. 33 percent of the specimens studied showed agenesis of the isthmus. However, the accessory thyroid tissue was found in only one cadaver. This study highlights the various developmental anomalies of the thyroid gland, which forms a cornerstone to safe and effective surgery.
18,946,620
Clinics in diagnostic imaging (124). Multiple enchondromatosis in Ollier disease.
A three-year-old girl presented with slow-growing swellings at the left foot and upper right humerus. Radiographs show multiple enchondromas in both feet, proximal humeri and scapulae, as well as at multiple sites in the hands, distal forearm bones and pelvis, in keeping with multiple enchondromatosis in Ollier disease. The clinical presentation and imaging features of enchondromas and the different types of enchondromatosis are discussed.
18,946,621
Iron transport in Francisella in the absence of a recognizable TonB protein still requires energy generated by the proton motive force.
The mechanism of iron transport in Francisella is still a puzzle since none of the sequenced Francisella strains appears to encode a TonB protein, the energy transducer of the proton motive force necessary to act on the bacterial outer membrane siderophore receptor to allow the internalization of iron. In this work we demonstrate using kinetic experiments of radioactive Fe(3+) utilization, that iron uptake in Francisella novicida, although with no recognizable TonB protein, is indeed dependent on energy generated by the proton motive force. Moreover, mutants of a predicted outer membrane receptor still transport iron and are sensitive to the iron dependent antimicrobial compound streptonigrin. Our studies suggest that alternative pathways to internalize iron might exist in Francisella.
18,946,633
Human BDNF isoforms are differentially expressed in cocaine addicts and are sorted to the regulated secretory pathway independent of the Met66 substitution.
Differential BDNF gene (BDNF) promoter use leads to protein isoforms differing by 8 or 15 N-terminal residues (BDNF1 and BDNF2) whose regulation and function are not completely understood versus the well-known 247-aa BDNF "short" form. To describe how BDNF isoform levels were regulated by chronic drug use, we measured BDNF isoform-specific mRNA levels in different human brain regions from cocaine addicts relative to age, race, and gender-matched controls. The cocaine group had threefold higher levels of exon 4-specific (BDNF Short) mRNAs in cerebellum versus controls (P < 0.01). In cortex, exon 4 and exon 1-specific BDNF mRNA levels (BDNF1) were significantly reduced in the cocaine group relative to controls (40%, P < 0.01). We also tested the hypothesis that the signal peptides of isoforms BDNF1 and BDNF2 confer different functional properties and determined if the functional Val66Met polymorphism influenced these functions. In contrast to transfected AtT-20 cells producing BDNF Short, regulated secretion of BDNF1 or BDNF2 was not affected by the Met66 substitution. Hippocampal neurons producing BDNF1 or BDNF2 on either the Val66 or Met66 background were similarly distributed in dendrites and had similar colocalization patterns with the secretory granule marker Sec II. This pattern differed from neurons producing BDNF Short Met66, which had impaired trafficking. Together, these findings support a mechanism by which variant BDNF proteins can overcome the functional defect of the Met66 substitution and suggest how functional differences in BDNF may impact brain responses in disease.
18,946,637
[Identification of lung architecture using HRCT].
The pulmonary interstitium is divided into different compartments, with the secondary pulmonary lobule representing the smallest subunit surrounded by connective tissue. Identification of the lobular architecture is a prerequisite for categorizing the broad spectrum of pulmonary interstitial diseases into distinct patterns. High-resolution computed tomography (HRCT) patterns comprise reticular and nodular opacities, ground-glass opacities, and consolidation. Air trapping and emphysema are associated with decreased pulmonary attenuation. The features of these patterns are derived from the anatomic basis and are linked with typical differential diagnoses, although the nonspecificity of the different patterns should be kept in mind. A main objective is to focus on mixed patterns.
18,946,649
[From end-organ disease to a classifiable bladder pain syndrome: paradigm shift in the understanding of urological pain syndromes exemplified by the condition currently called interstitial cystitis].
Growing clinical and scientific data imply that the condition currently called interstitial cystitis is not just a mere bladder end-organ disease but that the symptoms perceived to be related to the bladder are rather one aspect of a complex pelvic pain syndrome. The term bladder pain syndrome/interstitial cystitis (BPS/IC) suggested by the European Society for the Study of IC/PBS (ESSIC) for this condition is currently the only one strictly consistent with the taxonomy guidelines of the European Association of Urology and the International Association for the Study of Pain. BPS would be diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom such as persistent urge to void or urinary frequency. Confusable diseases as the cause of the symptoms must be excluded. Classification of BPS types might be performed according to findings at cystoscopy with hydrodistention and morphologic findings in bladder biopsies. The end-organ condition interstitial cystitis has thus become a chronic pain syndrome with a predominantly neurovisceral pathophysiology. In daily practice, therapeutic approaches aiming at both the peripheral bladder urothelium and central nervous targets should be combined. A multimodal treatment strategy, such as the combination of tricyclic antidepressants with instillation therapy, still appears reasonable and justified.
18,946,652
Acute tryptophan depletion and self-injurious behavior in aggressive patients and healthy volunteers.
An association between serotonin (5-HT) activity and self-injurious (i.e., self-aggressive) behavior across the spectrum of lethality (from self-mutilation through completed suicide) is a well-replicated finding. Studies to date, however, have relied on nonexperimental designs to examine this relationship, limiting the causal inferences that can be drawn about the role of 5-HT in self-aggressive behavior. Examine the effect of experimentally altered 5-HT activity (via dietary tryptophan depletion) on self-aggressive behavior among adults with and without intermittent explosive disorder (IED). Individuals with a marked history of aggression, such as those with IED, are characterized by compromised 5-HT and heightened risk for self-aggression, making this a population of interest for examining the proposed relations. IED patients (n = 16) and healthy controls (n = 16) received a tryptophan depletion and a placebo drink on separate days at least 1 week apart. Self-aggressive behavior was assessed on both study days using a well-validated laboratory-based behavioral assessment with self-aggression defined as the intensity of shock self-administered. Tryptophan depletion facilitated selection of more intense shocks, on average, in both groups. Patients with IED were also more self-aggressive overall than healthy volunteers. No IED by drink condition interactions were found. Experimentally lowered 5-HT bioavailability enhances overall self-injurious behavior irrespective of aggression history.
18,946,662
Element-tagged immunoassay with inductively coupled plasma mass spectrometry for multianalyte detection.
The multianalyte immunoassay approach is currently attracting increasing attention due to its high sample throughput, short assay time, low sample consumption and reduced overall cost per assay. This paper reviews progress in the field of multianalyte immunoassays using inductively coupled plasma mass spectrometry, as well as applications of this approach in different fields. Examples related to the combination of protein microarray technology with the multitag approach of the immunoassay ICP-MS method and to the use of ICP-MS in the field of imaging are described. A novel strategy that involves tagging antibodies for ICP-MS detection in sensitive multitag bioassays is also presented. Finally, the outlook for this promising technique is discussed.
18,946,666
A novel medium for the isolation of N-acylhomoserine lactone-degrading bacteria.
A novel chemically defined medium, named KG medium, supplemented with N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), an acylhomoserine lactone (AHL) used as signalling molecules in Gram-negative bacterial cell-to-cell communication, as the sole source of carbon and nitrogen, was designed and successfully used for the enrichment and isolation of AHL-degrading bacteria. A 3-oxo-C6-HSL-degrading bacterium, 13sw7, was isolated from sewage after six enrichment transfers in the 3-oxo-C6-HSL-containing KG medium. On the basis of the almost complete 16S ribosomal DNA sequence, isolate 13sw7 was clustered with unculturable beta-proteobacteria. This study indicates that the AHL-containing KG medium is effective in isolating AHL-degrading bacteria, including those previously considered unculturable, from environmental sources. To the best of our knowledge, this is the first documentation of the isolation of an AHL-degrading proteobacterium from sewage.
18,946,694
Evolution in biological and nonbiological systems under different mechanisms of generation and inheritance.
The majority of definitions of life and evolution include the notion that part of an organism has to be copied to its offspring and that this includes some form of coded information. This article presents the thesis that this conception is too restrictive and that evolution can occur in systems in which there is no copy of information between generations. For that purpose, this article introduces a new set of concepts and a theoretical framework that is designed to be equally applicable to the study of the evolution of biological and nonbiological systems. In contrast to some theoretical approaches in evolution, like neo-Darwinism, the approach presented here is not focused on the transmission and change of hereditary information that can be copied (like in the case of DNA). Instead, multiple mechanisms by which a system can generate offspring (with and without copying) and by which information in it affects the structure and evolution of its offspring are considered. The first part of this article describes in detail these new concepts. The second part of this article discusses how these concepts are directly applicable to the diversity of systems that can evolve. The third part introduces hypotheses concerning (1) how different mechanisms of generation and inheritance can arise from each other during evolution, and (2) how the existence of several inheritance mechanisms in an organism can affect its evolution.
18,946,696
Wear analysis in THA utilizing oxidized zirconium and crosslinked polyethylene.
Oxidized zirconium, a material with a ceramic surface on a metal substrate, and highly cross-linked polyethylene are two materials developed to reduce wear. We measured in vivo femoral head penetration in patients with these advanced bearings. We hypothesized the linear wear rates would be lower than those published for cobalt-chrome and standard polyethylene. We retrospectively reviewed a select series of 56 THAs in a relatively young, active patient population utilizing oxidized zirconium femoral heads and highly cross-linked polyethylene acetabular liners. Femoral head penetration was determined using the Martell computerized edge-detection method. All patients were available for 2-year clinical and radiographic followup. True linear wear was 4 microm/year (95% confidence intervals, +/- 59 microm/year). The early wear rates in this cohort of relatively young, active patients were low and we believe justify the continued study of these alternative bearing surfaces. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
18,946,711
Relapsing polychondritis--case series from South India.
Relapsing polychondritis (RP) is a rare recurring inflammatory disorder with variable clinical course. It has been described mainly in Caucasian population. Reports from other ethnic groups are few. We report seven cases of relapsing polychondritis in south Indian population. In between 1995 and 2008, seven patients fulfilling the McAdam-Damiani-Levine criteria for diagnosis of relapsing polychondritis were identified. Records pertaining to these patients were studied and clinical presentation, course, and treatment offered were analyzed retrospectively. The female-to-male ratio in our series was 2.5:1. The age of onset of symptoms ranged from 28 to 54 years, with a mean of 40.2 years. An average of 20 months, ranging from 3 months to 6 years, elapsed before the patient presented to us seeking a diagnosis. Various structural involvement in our series were as follows: pinna in four (57%), nasal cartilage in five (71%), joints in three (43%), eyes in three (43%), laryngotracheal tree in three (43%), inner ear in one (14.3%), skin in one (14.3%), and heart in one (14.3%). Associated autoimmune diseases were present in four (57%) patients in the form of one of the following in each: vasculitis, autoimmune hemolytic anemia, hypothyroidism, and rheumatoid arthritis. All seven patients received prednisolone with three of them requiring additional immunosuppressants. There was no mortality amongst the four patients who had remained on follow-up at the time of this report. Although RP is an uncommon disorder, clinicians should be aware of the manifestations so as to initiate prompt treatment and prevent complications. Our series reports less frequent auricular cartilage and skin involvement and an exceptional case of basal cell carcinoma, although the other manifestations were similar to that seen in Caucasian and other Asian populations.
18,946,713
A tale of three acaropathogenic fungi in Israel: Hirsutella, Meira and Acaromyces.
We review published and unpublished studies conducted in Israel with six acaropathogenic fungi, assayed in order to control the citrus rust mite, Phyllocoptruta oleivora (Ashmead) (CRM). Hirsutella thompsonii Fisher was introduced twice, killed 80-90% of the exposed mites, but due to its requirements for near-saturation humidities was deemed unsuitable for local outdoors conditions. Hirsutella kirchneri (Rostrup) Minter et al. and Hirsutella necatrix Minter et al. were also introduced and assayed against CRM and spider mites, but their efficacy was unsatisfactory. Three indigenous fungi found to be associated with mites, Meira geulakonigii, Meira argovae and Acaromyces ingoldii--all three recently described by Boekhout, Gerson, Scorzetti & Sztejnberg--were assayed against several mites. Meira geulakonigii killed 80-90% of several spider mites and of the CRM, and caused some mortality of Iphiseius degenerans (Berlese), one out of three phytoseiid predators assayed. Mortality was not due to parasitization; extracts from the media in which the fungi had developed caused considerable mite death, suggesting that it was a result of fungal toxins. Data from a field study indicated that spraying blastoconidia of M. geulakonigii on grapefruits infested by CRM significantly reduced pest-incurred damage from 23 to 13%. Applying qRT-PCR methodology indicated that M. geulakonigii was endophytic within sealed grapefruit flowers and in the flavedo of the fruits' peel. Neither in the laboratory nor in the field was any evidence ever obtained that this fungus damaged the plants, leading us to hypothesize that M. geulakonigii serves as a "body guard" of grapefruits (and perhaps other plants as well). All three fungi suffered very little mortality after being exposed to various insecticides and acaricides that are in current local use (with the exception of sulfur). The ability of M. geulakonigii to reduce mite numbers without affecting the host plant, the minimal fungal effect on some predatory mites, its endophytic nature along with the apparent tolerance of M. geulakonigii to many insecticides and acaricides, suggest that this fungus could be suitable for integrated pest management (IPM) program.
18,946,714
Technical feasibility of transperineal MR-guided prostate interventions in a low-field open MRI unit: canine study.
Magnetic resonance imaging (MRI) provides superior visualization of the prostate, its substructure, surrounding tissues, and, most important, focal lesions or cancer. The purpose of our canine study was to demonstrate the feasibility of a low-field (0.35 T) transperineal system that enables precise MR image guidance of prostate interventions. The canines were placed in the right lateral decubitus position. Template reconstruction, trajectory planning, contouring were based on T2-weighted FSE images. For image guidance and target confirmation, fast gradient spoiled-echo (FSPGR) sequence was used. MR compatible coaxial needles were manually inserted through the perineum to the base of the prostate. After satisfactory position was confirmed, brachytherapy catheters were placed through the coaxial needles. The mean deviation of the needle displacements was 2.9 mm with a median value of 2.7 mm. 97% of the errors were less than 4.0 mm. The needle placement accuracy was modelled by the Rayleigh distribution with a sigma value of 2.3 mm. Visual confirmation of needle placements was demonstrated on pathology tissue slices. The time needed for each step was: anaesthesia - 15 min, setup and positioning - 15 min, initial imaging - 15 min, template registration, projection - 15 min, contouring, trajectory planning, insertion of 12 needles - 60 min Based on our canine experiences our method seems to be a promising approach for performing feasible, accurate, reliable and high-quality prostate MR guidance within a reasonable time span.
18,946,728
Low doses of cholestyramine in the treatment of hyperthyroidism.
The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis. Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism. In a prospective, randomized, double-blind, placebo-controlled trial, 45 patients with newly diagnosed hyperthyroid Graves' disease were randomly assigned into the following treatment protocols: group I, cholestyramine 2 g BID, methimazole and propranolol; group II, cholestyramine 1 g BID, methimazole and propranolol; group III, placebo powder, methimazole and propranolol. The fixed dose of methimazole (30 mg/d) and propranolol (40 mg/d) was used. The study period was 4 weeks. Serum total triiodothyronine and free thyroxin were measured at baseline, and at the ends of the second and the fourth week of the study. The serum thyroid hormone levels decreased more rapidly and to a greater extent in the cholestyramine-treated groups. All of the patients in group I had achieved euthyroid state at the end of the study. We conclude that low dose of cholestyramine is an effective and well-tolerated adjunctive agent in the treatment of hyperthyroid Graves' disease.
18,946,743
Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers.
Breast cancer is a hormone-dependent tumor. Most breast cancer cells have an androgen receptor (AR), but the clinical value of AR expression is unclear. AR expression was evaluated in 227 primary breast cancers using immunohistochemistry. The relation of AR expression to clinicopathological factors and biomarkers was analyzed. AR expression was assessed semiquantitatively, and tumors with more than 10% of stained cells were regarded as positive. The AR-positive rate was higher in smaller tumors (P=0.045), tumors with negative lymph node metastasis (P=0.045), scirrhous-type tumors (P<0.0001), tumors of low histological grade (P=0.0001), and p53-negative tumors (P = 0.0097). Although AR had no relation to menopausal status, 79% of cases of high AR expression (>50% stained cells) were in postmenopausal women. AR was related to estrogen receptor (ER; P=0.027) and progesterone receptor (PR; P=0.016) expression, but showed no relation to human epidermal growth factor receptor type 2 (Her2) expression. Regarding the coexpression of these receptors, 18 of the 42 cases of triple-negative (ER/PR/Her2-negative) tumors (43%) were AR-positive. AR expression is related to low malignancy in breast cancer. The assessment of AR expression may lead to new treatment strategies for breast cancer, especially in postmenopausal women and in women with tumors that show triple negativity for hormone receptors.
18,946,753
Congenital vulvar lymphangioma circumscriptum.
Lymphangioma circumscriptum (LC) is a defect of lymphatic channels in the deep dermis and subcutaneous layers, characterized by grouped vesicles. This disorder rarely occurs in vulvar sites. We present a rare case of LC in a 72-year-old patient who presented with a vulvar mass and ipsilateral leg edema.
18,946,758
A single mutation at lysine 241 alters expression and trafficking of the D2 dopamine receptor.
Ubiquitination of G protein-coupled receptors has been identified to regulate receptor signal transduction including agonist-induced internalization and sorting of internalized receptor for degradation or for recycling. Using co-immunoprecipitation and immunoblot analysis, I found that the membrane-associated D(2) dopamine receptor (DAR) is mono-ubiquitinated in the absence of an agonist following heterologous expression in human embryonic kidney cells (HEK293). By using site-directed mutagenesis, this report shows that the loss of lysine-241, K241A D(2) DAR reduced the amount of membrane-associated D(2) DAR. It is of interest that the K241A D(2) DAR also had a distinctly different ubiquitination pattern than the wild-type D(2) DAR. It is important to note that the ubiquitinated mutant D(2) DAR was degraded through ubiquitin-proteasome pathway. These data provide the factual evidence that a loss of lysine-241 of the D(2) DAR affects receptor ubiquitination and renders the protein susceptible to the proteasomal degradation.
18,946,766
Biological specificity of visceral adipose tissue and therapeutic intervention.
With excess energy storage, obesity develops, leading to increased risk for type 2 diabetes and cardiovascular diseases. The distribution of body fat appears to be even more important than the total amount of fat. Abdominal and, in particular, visceral adiposity is strongly linked to insulin resistance, type 2 diabetes, hypertension, dyslipidaemia, sleep apnea, and other complications of obesity. Visceral adiposity, manifested as a high waist circumference, is now accepted as a major component of the metabolic syndrome. However, the biological mechanisms underlying the adverse impact of visceral fat accumulation remain to be established. This review will focus on the analysis of the biological specificity of adipose tissue located in the abdominal region, and will explore intervention strategies targeting the impaired function of the visceral adipocyte as potential therapies for the cardio-metabolic outcomes of patients with the metabolic syndrome.
18,946,788
The development of an instrument for evaluating clinical teachers: involving stakeholders to determine content validity.
Research indicates that the quality of supervision strongly influences the learning of medical students in clinical practice. Clinical teachers need feedback to improve their supervisory skills. The available instruments either lack a clear theoretical framework or are not suitable for providing feedback to individual teachers. We developed an evaluation instrument based on the 'cognitive apprenticeship model'. The aim was to estimate the content validity of the developed instrument. Item relevance was rated on a five-point scale (1 = highly irrelevant, 5 = highly relevant) by three groups of stakeholders in undergraduate clinical teaching: educationalists (N = 12), doctors (N = 16) and students (N = 12). Additionally, stakeholders commented on content, wording and omission of items. The items were generally rated as very relevant (Mean = 4.3, SD = 0.38, response = 95%) and any differences between the stakeholder groups were small. The results led to elimination of 4 items, rewording of 13 items and addition of 1 item. The cognitive apprenticeship model appears to offer a useful framework for the development of an evaluation instrument aimed at providing feedback to individual clinical teachers on the quality of student supervision. Further studies in larger populations will have to establish the instrument's statistical validity and generalizability.
18,946,815
Advances in automatic, manual and microwave-assisted solid-phase peptide synthesis.
Solid-phase strategies speed up the production of both short- and long-sequence peptides compared with solution methodologies. Therefore, solid-phase peptide synthesis (SPPS), proposed by Merrifield in the early 1960s, contributed to the 'Peptide Revolution' in the fields of diagnostics, and drug and vaccine development. Since then, peptide chemistry research has aimed to optimize these synthetic procedures, focusing on areas such as amide bond formation (the coupling step), solid supports and automation. Particular attention was devoted to the environmental impact of SPPS: the requirement for large amounts of organic solvents meant high costs for industrial peptide manufacturing that needed to be reduced. SPPS, alone or in hybrid technologies, has become strategic for the production of peptides as active pharmaceutical ingredients on a commercial scale.
18,946,841
Aryl-aryl crosss-couplings that avoid the preparation of haloaromatics.
Advances in the development of cross-coupling protocols that avoid haloaromatics are reviewed. Most of the reports that are discussed appeared in the literature within the past 2 years and describe either alternatives to halogenated electrophiles or halogen-free preparations of the organometallic partners. However, while this review is not limited to cross-couplings that are entirely free of haloaromatics, coverage of the topic is largely restricted to reactions affording new aryl-aryl, aryl-heteroaryl and heteroaryl-heteroaryl carbon-carbon bonds during the cross-coupling event.
18,946,848
Sirolimus-eluting and paclitaxel-eluting stents for the treatment of coronary bifurcations.
The aim of the study was to compare the outcomes of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stent implantation in coronary bifurcations treated with either a 1-stent or 2-stent strategy. The study used a retrospective cohort analysis of consecutive de novo bifurcations, excluding left main, treated with SES or PES between April 2003 and June 2005. We identified 170 bifurcations in 161 patients treated with SES and 119 bifurcations in 112 patients treated with PES. During a median follow-up of 1,061 days (interquartile range 814-1,314), 43 patients (26.7%) in the SES group and 28 (25.0%) in the PES group had a major adverse cardiac event (P = .78). The angiographic restenosis rate per bifurcation was 20.9% and 25.9%, respectively (P = .41). There was no difference overall in the occurrence of target lesion revascularization (TLR) per bifurcation, 22 with SES (12.9%) and 18 with PES (15.1%), P = .61. The TLR rate was similar for SES and PES in bifurcations treated with 1 stent (6.7% vs 11.4%, P = .40) and in bifurcations treated with both branch stenting (20.0% vs 20.4%, P =1.0). In this cohort, the long-term clinical outcomes appear similar overall between SES and PES in the treatment of coronary bifurcations irrespective of whether a 1-stent or 2-stent strategy was used.
18,946,894
Samuel A. Levine and the history of grading systolic murmurs.
Murmurs were described first by Laennec in 1819, after which the significance of a murmur became a matter of debate. By the late 19th century, many physicians regarded systolic murmurs as "organic," whereas others believed that they were often "functional." Samuel Levine became a central figure in separating functional from organic systolic murmurs. Freeman and Levine's 1933 study of 1,000 "noncardiac" subjects determined the frequency, cause, and significance of systolic murmurs. Murmurs were rated on a scale of 1 to 6 grades of intensity. Approximately 20% of their patients had grade 1 or 2 systolic murmurs. Hypertension, fever, tachycardia, and anemia were common factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or anemia. Thus, louder systolic murmurs were found to be a significant finding, as were the cause, location, and effects of posture. They concluded that systolic murmurs often have an explanation and that their grade can be useful in the diagnosis and prognosis. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. Levine's system of grading a systolic murmur is valuable and persists into the 21st century.
18,946,930
Transfusion management using a remote-controlled, automated blood storage.
Generally, the safety of transfusion terapies for patients depends in part on the distribution of the blood products. The prevention of adverse events can be aided by technological means, which, besides improving the traceability of the process, make errors less likely. In this context, the latest frontier in automation and computerisation is the remote-controlled, automated refrigerator for blood storage. Computer cross-matching is an efficient and safe method for assigning blood components, based on Information Technology applied to typing and screening. This method can be extended to the management of an automated blood refrigerator, the programme of which is interfaced with the Transfusion Service's information system. The connection we made in our Service between EmoNet and Hemosafe enables real-time, remote-controlled management of the following aspects of blood component distribution: a) release of autologous and allogeneic units already allocated to a patient, b) release of available units, which can be allocated by remote-control to known patients, in the presence of a valid computer cross-match, c) release of O-negative units of blood for emergencies. Our system combines an information database, which enables computer cross-matching, with an automated refrigerator for blood storage with controlled access managed remotely by the Transfusion Service. The effectiveness and safety of the system were validated during the 4 months of its routine use in the Transfusion Service's outpatient department. The safety and efficiency of the distribution of blood products can and must be increased by the use of technological innovations. With the EmoNet/Hemosafe system, the responsibility for the remote-controlled distribution of red blood cell concentrates remains with the chief of the Transfusion Services, through the use of automated computer procedures and supported by continuous training of technicians and nursing staff.
18,946,954
[Study of expression of beta-III tubulin in human eye tissues during prenatal development].
Expression of beta-III tubulin, a marker protein of early neuronal cells, was studied by molecular genetic and immunochemical techniques. The study was performed with human eyes in the 8.5th to 27-28th weeks of prenatal development. Expression of beta-III tubulin was detected immunochemically in the retina and lens fibers in the 8.5 to 22-23 weeks of development. PCR revealed a high level of expression of the gene for beta-III tubulin in the retina of 9.5-week embryos. The level of expression of this gene remained high until the 18th week of prenatal development, slightly decreased to the 24th week, and became negligible in 27- to 28-week embryos. In the 15th to 24th weeks of prenatal development, the level of expression of this gene in the lens was very low and became undetectable in 27- to 28-week embryos. The results of PCR analysis are consistent with immunochemical data.
18,946,987
Iodine deficiency in 2007: global progress since 2003.
Iodine deficiency is a global public health problem, and estimates of the extent of the problem were last produced in 2003. To provide updated global estimates of the magnitude of iodine deficiency in 2007, to assess progress since 2003, and to provide information on gaps in the data available. Recently published, nationally representative data on urinary iodine (UI) in school-age children collected between 1997 and 2006 were used to update country estimates of iodine nutrition. These estimates, alongside the 2003 estimates for the remaining countries without new data, were used to generate updated global and regional estimates of iodine nutrition. The median UI was used to classify countries according to the public health significance of their iodine nutrition status. Progress was measured by comparing current prevalence figures with those from 2003. The data available for pregnant women by year of survey were also assessed. New UI data in school-age children were available for 41 countries, representing 45.4% of the world's school-age children. These data, along with previous country estimates for 89 countries, are the basis for the estimates and represent 91.1% of this population group. An estimated 31.5% of school-age children (266 million) have insufficient iodine intake. In the general population, 2 billion people have insufficient iodine intake. The number of countries where iodine deficiency is a public health problem is 47. Progress has been made: 12 countries have progressed to optimal iodine status, and the percentage ofschool-age children at risk of iodine deficiency has decreased by 5%. However, iodine intake is more than adequate, or even excessive, in 34 countries: an increase from 27 in 2003. There are insufficient data to estimate the global prevalence of iodine deficiency in pregnant women. Global progress in controlling iodine deficiency has been made since 2003, but efforts need to be accelerated in order to eliminate this debilitating health issue that affects almost one in three individuals globally. Surveillance systems need to be strengthened to monitor both low and excessive intakes of iodine.
18,947,032
Simulation model of the impact of biofortification on the absorption of adequate amounts of zinc and iron among Mexican women and preschool children.
Biofortification is an agricultural process that attempts to increase the iron and zinc content of staple food crops. Improving the absorption of zinc and iron could contribute to reducing the high rates of deficiency of these micronutrients in developing-country settings. To simulate the effects of biofortification of staple food crops (maize, wheat, rice, and beans) on the absorption of zinc and iron among women and children in Mexico. We analyzed dietary data from the 1999 Mexican National Nutrition Survey. On the basis of the intake of the four staple food crops and the increase in zinc and iron content that could be achieved by conventional breeding in the short term, the prevalence of inadequacy in the amounts of absorbed zinc and iron was determined. The mean increase in the amounts of absorbed zinc and iron was compared according to rural and urban residence and according to region of the country. In rural areas, simulated biofortification of maize resulted in a reduction in the prevalence of absorption of inadequate amounts of zinc of 47% in children and 56% in women but had no effect on the prevalence of absorption of inadequate amounts of iron. The increase in zinc absorption was greater in rural populations and in the Central and Southern regions (p < .05). Biofortification of maize could significantly improve zinc absorption among children and women in Mexico living in areas most vulnerable to zinc deficiency. Studies of the biological impact of biofortified maize on zinc status are warranted.
18,947,033
Prostate cancer hope.
A new drug has the potential to improve treatment for men with prostate cancer.
18,947,077
Retrospective clinical and molecular analysis of conditioned laboratory dogs (Canis familiaris) with serologic reactions to Ehrlichia canis, Borrelia burgdorferi, and Rickettsia rickettsii.
Dogs are susceptible to different tickborne infections, including members of the Anaplasmataceae (Ehrlichia canis, E. ewingii, E. chaffeensis, Anaplasma phagocytophilum, A. platys), Borrelia burgdorferi, and Rickettsia rickettsii. These diseases can manifest with clinical signs including fever, anorexia, malaise, lameness, rash, and bleeding episodes; however, these signs are nonpathognomonic, and infections can occur in the absence of clinical signs. Hematologic abnormalities can include leukopenia, thrombocytopenia, hyperproteinemia and hypergammaglobulinemia. In biomedical research, diseases such as canine monocytic ehrlichiosis, Lyme disease, and Rocky Mountain spotted fever may cause morbidity among exposed dogs and confound research results. Random-source dogs are susceptible to these diseases because of their increased risk of arthropod exposure. Nonpurpose bred, randomly selected conditioned dogs (n = 21) were examined; blood samples were taken for hematology, biochemistry analysis, tickborne pathogen serology, and PCR. Of these, 2 dogs (10% of the population) presented with illness characterized by fever, malaise, lameness, or hemostatic abnormalities, and 15 (71%) had antibodies to one or more tickborne pathogens. No specific hematologic or biochemical differences were apparent between seronegative dogs and seropositive dogs reactive to all 3 pathogens. E. canis and B. burgdorferi PCR of tissues and blood were negative for all dogs. PCR amplification of several Ehrlichia and Anaplasma genes yielded no positive samples. From this cohort of dogs, serologic and molecular results indicate prior exposure without active infection or clinical disease. Exposure to and potential for infection with these bacteria and other pathogens may contribute to blood and tissue alterations that could confound experiments and lead to misinterpretation of data in canine models.
18,947,166
Diagnosis and treatment of pulmonary arterial hypertension and atrial fibrillation in an adult chimpanzee (Pan troglodytes).
This report describes the diagnosis and treatment of pulmonary arterial hypertension (PAH) in an adult male captive chimpanzee. Although cardiovascular disease in general is common in human and great apes, diagnosis and treatment of PAH in nonhuman primates are uncommon. In the case we present, the adult chimpanzee was diagnosed with an arrhythmia during an annual physical examination and later with PAH during a scheduled cardiovascular evaluation. PAH can either be primary or secondary and can lead to right ventricular overload and heart failure. This description is the first case study of pulmonary arterial hypertension in a great ape species.
18,947,173
Structural and photophysical characterization of multichromophoric pyridylporphyrin-rhenium(i) conjugates.
Four porphyrin-Re(I) conjugates, in which a pyridylporphyrin chromophore is directly coordinated to the electron-acceptor fragment [ fac-Re(CO) 3(bipy)] (+), were prepared: the dimeric and pentameric compounds [ fac-Re(CO) 3(bipy)(4'MPyP)](CF 3SO 3) ( 1) (4'MPyP = 4'-monopyridylporphyrin) and [ fac-{Re(CO) 3(bipy)} 4(mu-4'TPyP)](CF 3SO 3) 4 ( 2) (4'TPyP = 4'-tetrapyridylporphyrin), and the corresponding compounds with 3' rather than 4' porphyrins, [ fac-Re(CO) 3(bipy)(3'MPyP)](CF 3SO 3) ( 3) and [ fac-{Re(CO) 3(bipy)} 4(mu-3'TPyP)](CF 3SO 3) 4 ( 4). These adducts proved to be very stable in solution and were also structurally characterized in the solid state by X-ray crystallography. A detailed photophysical study was performed on the zincated adducts of the conjugates 1- 3, labeled 5, 6, and 7, respectively. In all adducts the typical fluorescence of the zinc-porphyrin unit was reduced in intensity and lifetime by the presence of the peripheral rhenium-bipy fragment(s) (heavy-atom effect). For the dyads 5 and 7 the photoinduced charge transfer process from the zinc-porphyrin to the Re(I)-bipy unit is only slightly exoergonic. Ultrafast spectroscopy experiments showed no evidence for electron transfer quenching in the dyads as such, whereas the addition of pyridine (that binds axially to zinc and thus affects the porphyrin redox potential) led to a moderately efficient photoinduced electron transfer process. In perspective, an appropriate functionalization of the bipy ligand and/or of the porphyrin chromophore might improve the thermodynamics and, thus the efficiency, of the photoinduced electron transfer process.
18,947,175
Simultaneous detection of pH changes and histamine release from oxyntic glands in isolated stomach.
Real-time simultaneous detection of changes in pH and levels of histamine over the oxyntic glands of guinea pig stomach have been investigated. An iridium oxide pH microelectrode was used in a potentiometric mode to record the pH decrease associated with acid secretion when the sensor approached the isolated tissue. A boron-doped diamond (BDD) microelectrode was used in an amperometric mode to detect histamine when the electrode was placed over the tissue. Both sensors provided stable and reproducible responses that were qualitatively consistent with the signaling mechanism for acid secretion at the stomach. Simultaneous measurements in the presence of pharmacological treatments produced significant variations in the signals obtained by both sensors. As the H2 receptor antagonist cimetidine was perfused to the tissue, histamine levels increased that produced an increase in the signal of the BDD electrode whereas the pH sensor recorded a decrease in acid secretion as expected. Addition of acetylcholine (ACh) stimulated additional acid secretion detected with the pH microelectrode whereas the BDD sensor recorded the histamine levels decreasing significantly. This result shows that the primary influence of ACh is directly on the parietal cell receptors rather then the ECL cell receptors of the oxyntic glands. These results highlight the power of this simultaneous detection technique in the monitoring and diagnosis of physiological significant signaling mechanisms and pathways.
18,947,199
Optically active supramolecular complexes of water-soluble achiral polythiophenes and folic acid: spectroscopic studies and sensing applications.
Optically active supramolecular complexes of water-soluble achiral polythiophene (PT) derivatives, PMTPA or PMTEA (Chart 1), and folic acid have been prepared; and the complex formation processes have been studied by absorption, emission, and circular dichroism (CD) spectroscopies. The complexes exhibited unique split-type induced CDs in the pi-pi* transition region of PTs, indicating that the molecular chirality of the glutamic acid moiety in folic acid was expressed in PT backbones. The influences of temperature, solvent composition, and the structures of the inducing molecules on the chirality induction to PTs were also investigated, and a possible mechanism for the formation of chiral superstructures was proposed. Furthermore, it was found that, upon addition of folic acid into aqueous solution of PTs (PMTPA or PMTEA), a dramatic color change from yellow to purple along with the emission quenching of PT derivatives was observed. PMTEA, having one fewer carbon in the hydrophobic side chain relative to PMTPA, showed better selectivity toward folic acid sensing over ATP because of its higher solubility in water and the appropriate hydrophilic/hydrophobic balance in the complex. Therefore, it can be applied as a colorimetric and fluorescent probe for detecting folic acid with high selectivity and sensitivity. Besides naked-eye detection of folic acid, the detection limit can be extended to be 10 (-8) M by using fluorometry and PMTEA as the probing molecule.
18,947,207
Water-in-model oil emulsions studied by small-angle neutron scattering: interfacial film thickness and composition.
The ever-increasing worldwide demand for energy has led to the upgrading of heavy crude oil and asphaltene-rich feedstocks becoming viable refining options for the petroleum industry. Traditional problems associated with these feedstocks, particularly stable water-in-petroleum emulsions, are drawing increasing attention. Despite considerable research on the interfacial assembly of asphaltenes, resins, and naphthenic acids, much about the resulting interfacial films is not well understood. Here, we describe the use of small-angle neutron scattering (SANS) to elucidate interfacial film properties from model emulsion systems. Modeling the SANS data with both a polydisperse core/shell form factor as well as a thin sheet approximation, we have deduced the film thickness and the asphaltenic composition within the stabilizing interfacial films of water-in-model oil emulsions prepared in toluene, decalin, and 1-methylnaphthalene. Film thicknesses were found to be 100-110 A with little deviation among the three solvents. By contrast, asphaltene composition in the film varied significantly, with decalin leading to the most asphaltene-rich films (30% by volume of the film), while emulsions made in toluene and methylnaphthalene resulted in lower asphaltenic contents (12-15%). Through centrifugation and dilatational rheology, we found that trends of decreasing water resolution (i.e., increasing emulsion stability) and increasing long-time dilatational elasticity corresponded with increasing asphaltene composition in the film. In addition to the asphaltenic composition of the films, here we also deduce the film solvent and water content. Our analyses indicate that 1:1 (O/W) emulsions prepared with 3% (w/w) asphaltenes in toluene and 1 wt % NaCl aqueous solutions at pH 7 and pH 10 resulted in 80-90 A thick films, interfacial areas around 2600-3100 cm (2)/mL, and films that were roughly 25% (v/v) asphaltenic, 60-70% toluene, and 8-12% water. The increased asphaltene and water film composition at pH 10 versus pH 7, along with unique dynamic interfacial tension profiles, suggested that the protonation state of carboxylic moieties within asphaltenes impacts the final film properties. This was further supported when we characterized similar asphaltenic emulsions that also contained 9-anthracence carboxylic acid (ACA). Addition of this aromatic acid led to slightly thinner films (70-80 A) that were characteristically more aqueous (up to 20% by volume) and 5-6% (v/v) ACA. This unique in situ characterization (deduced entirely from SANS data from emulsion samples) of the entire film composition calls for further investigation regarding the role this film-based water plays in emulsion stability.
18,947,210
Analytic calculations of vibrational hyperpolarizabilities in the atomic orbital basis.
We present an analytic scheme for the calculation of pure vibrational contributions to linear and nonlinear optical properties such as the polarizability and the first and second hyperpolarizabilities. The formalism is fully expressed in terms of a perturbation- and time-dependent atomic orbital basis, using the elements of the density matrix in the atomic orbital basis as the basic variables. We calculate perturbed densities up to third order with respect to the electric field in accordance with the n + 1 rule, and the approach is therefore applicable for the calculation of pure vibrational contributions involving all vibrational coordinates in large molecular complexes. In the case of static electric fields, we therefore only need to calculate 19 response equations, independent of the size of the molecule. If we can determine the molecular energy and force field, the calculation of pure vibrational contributions to the nonlinear optical properties of the molecule is therefore a rather straightforward task. We illustrate the implementation by calculating pure vibrational contributions to the first and second hyperpolarizabilities of molecules containing up to 66 atoms using basis sets of good quality.
18,947,217
Bonded exciplex formation: electronic and stereoelectronic effects.
As recently proposed, the singlet-excited states of several cyanoaromatics react with pyridine via bonded-exciplex formation, a novel concept in photochemical charge transfer reactions. Presented here are electronic and steric effects on the quenching rate constants, which provide valuable support for the model. Additionally, excited-state quenching in poly(vinylpyridine) is strongly inhibited both relative to that in neat pyridine and also to conventional exciplex formation in polymers, consistent with a restrictive orientational requirement for the formation of bonded exciplexes. Examples of competing reactions to form both conventional and bonded exciplexes are presented, which illustrate the delicate balance between these two processes when their reaction energetics are similar. Experimental and computational evidence is provided for the formation of a bonded exciplex in the reaction of the singlet excited state of 2,6,9,10-tetracyanoanthracene (TCA) with an oxygen-substituted donor, dioxane, thus expanding the scope of bonded exciplexes.
18,947,220
Dialkylphosphates (DAPs) in fruits and vegetables may confound biomonitoring in organophosphorus insecticide exposure and risk assessment.
Trace residues of organophosphorus (OP) pesticides are associated with fruits and vegetables that have been sprayed with those OP pesticides to guard against insect pests. Human dietary exposure to these OP pesticides is commonly estimated by measuring the amount of OP metabolites in urine, assuming a stoichiometric relationship between a metabolite and its parent insecticide. Dialkylphosphates (DAPs) are the OP metabolites that are most often used as markers in such biomonitoring studies. However, abiotic hydrolysis, photolysis, and plant metabolism can convert OP chemicals (OP residues) to DAP residues on or in the fruits and vegetables. To evaluate the extent of these conversions, OPs and DAPs were measured in 153 produce samples. These samples from 2 lots were known to contain OP insecticide residues based on routine monitoring by California producers and shippers. A total of 12 OPs were quantified, including mevinphos, naled, acephate, methamidophos, oxidemeton-methyl, azinphos-methyl, dimethoate, malathion, methidathion, phosmet, chlorpyrifos, and diazinon. All OP insecticide residues were below their respective residue tolerances in 2002-2004. A total of 91 of 153 samples (60%) contained more DAP residues than parent OPs. The mean mole fractions [DAPs/(DAPs + OPs)] for the first and second lots of produce were 0.62 and 0.50, respectively, and the corresponding geometric means were 0.55 and 0.34. The corresponding mean mole ratios (DAPs/OP) were 7.1 and 3.4, with geometric means of 2.1 and 0.9. Any preformed DAPs ingested in the diet that are excreted in urine may inflate the estimated absorbed OP insecticide doses in occupational and environmental studies. In subsequent prospective studies, time-dependent production of dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) in strawberries and leaves following malathion sprays occurred concomitant with the disappearance of the parent insecticide and its oxon. DAPs are more persistent in plants and produce at routinely measured levels than their parent OP insecticides.
18,947,233
Update on oral cyanocobalamin (vitamin B12) treatment in elderly patients.
The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Prospective randomized studies (n=3), a systematic review by the Cochrane group (n=1) and prospective studies in a well defined population (n=5) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature does not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment. This review confirms the previously reported efficacy of oral cobalamin treatment in elderly patients. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections.
18,947,260
Use of flowable composites for orthodontic bracket bonding.
To test the bonding characteristics of four flowable composites for orthodontic bracket bonding. Metal brackets were bonded to acid-etched human enamel using four flowable composites (Grandio Flow, GF; UniFil Flow, UF; UniFil LoFlo Plus, UL; and DenFil Flow, DF), an orthodontic bonding system (Transbond XT, TX), and a restorative composite (Filtek Z250, FZ). After 24 hours of storage in water at 37 degrees C, a shear bond strength (SBS) test was performed. After debonding, the adhesive remnant index (ARI) was assessed. In addition, the flow and flexural strength of the materials were examined. The SBS for the flowable composites ranged between 7.2 and 8.3 MPa, and TX showed a significantly higher value (mean 10.9 MPa). The flowable composites also demonstrated a significantly superior flowability, yet inferior flexural strength (except for DF) than TX and FZ. Two flowable composites (GF and UL) produced significantly higher ARI scores than TX and FZ, which represented a larger resin remnant on the enamel surfaces after debonding. When considering the SBS and ARI scores obtained in this study, flowable composites with no intermediate bonding resin could be conveniently applied for orthodontic bracket bonding.
18,947,267
Occlusal hypofunction induces atrophic changes in rat gingiva.
To clarify the influence of occlusal hypofunction on the integrity of gingival tissue and gingival extracellular matrix biosynthesis. Thirteen-week-old male Wistar rats were divided into two groups. To eliminate occlusal forces, all the right maxillary molars were extracted in the hypofunctional group. The control group was anesthetized but not subjected to surgery. The rats were killed at 2 and 4 weeks after the procedure, and the lower right second molars were prepared for histological analysis. To investigate the effect of occlusal hypofunction on collagen biosynthesis, the expression of connective tissue growth factor (CTGF) and lysyl oxidase (LOX) was determined by immunohistochemistry as well as histological examination by hematoxylin and eosin staining. Disorientation of the collagen fibers, proliferation of the connective tissue fibroblasts, and enlargement of epithelial intercellular gaps were observed in gingival tissue of rat molars with experimental occlusal hypofunction. Immunohistochemically, the expression of CTGF and LOX was increased significantly (P < .05) in the hypofunctional group. These results suggest that occlusal hypofunction can affect the structural integrity and the expression of CTGF and LOX in gingival tissue.
18,947,276
Primary myelofibrosis: update on definition, pathogenesis, and treatment.
Primary myelofibrosis (PMF) is a clonal stem cell disorder that manifests clinically as anemia, splenomegaly due to extramedullary hematopoiesis, leukoerythroblastosis, and constitutional symptoms, which are the clinical hallmarks of PMF. Within the past three years it has been determined that a single, recurrent, somatic mutation in the gene encoding the cytoplasmic tyrosine kinase Janus kinase 2 (JAK2) occurs in the majority of patients with PMF, and more recently, activating mutations in the gene encoding the thrombopoietin receptor MPL have also been identified in a subset of PMF patients. These discoveries have yielded important insights into the pathogenesis of PMF and have brought about the first opportunity for rationally targeted therapy for this disorder. Here we present an updated review of the pathogenesis, definition, and treatment of PMF in light of the discovery of JAK2 and MPL mutations, as well as other recent work in the myeloproliferative neoplasm field.
18,947,294
Biomarkers for prostate cancer.
The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer.
18,947,298
Polycystic kidney disease.
A number of inherited disorders result in renal cyst development. The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2. The PKD1 protein, polycystin-1, is a large receptor-like protein, whereas polycystin-2 is a transient receptor potential channel. The polycystin complex localizes to primary cilia and may act as a mechanosensor essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. Elucidation of defective cellular processes has highlighted potential therapies, some of which are now being tested in clinical trials. ARPKD is the neonatal form of PKD and is associated with enlarged kidneys and biliary dysgenesis. The disease phenotype is highly variable, ranging from neonatal death to later presentation with minimal kidney disease. ARPKD is caused by mutation in PKHD1, and two truncating mutations are associated with neonatal lethality. The ARPKD protein, fibrocystin, is localized to cilia/basal body and complexes with polycystin-2. Rare, syndromic forms of PKD also include defects of the eye, central nervous system, digits, and/or neural tube and highlight the role of cilia and pathways such as Wnt and Hh in their pathogenesis.
18,947,299
Transcriptome alterations due to physiological normoxic (2% O2) culture of human embryonic stem cells.
Human embryonic stem cells (hESCs) hold great promise therapeutically. In order to deliver on this promise the correct defined conditions for long-term propagation must first be established. Researchers have now provided reports describing the benefits of culturing hESCs in physiologically approximate levels of oxygen. These physiological values fall in the range of 2 to 5% O2. Benefits include reduced spontaneous differentiation, enhanced chromosomal stability and increased clonality. The aim of our study was to examine the transcriptional consequences of culturing hESCs in physiological normoxia (2% O2) using microarray technology. Three karyoptically normal hESC lines (H1, H9 and RH1) were examined. At the initiation of this experiment, established hESC lines were redesignated as passage (p) 0 in 21% O2, then bifurcated into 21% O2 and 2% O2, and maintained for a further ten passages at which time samples were again collected. RNA was extracted from all sample points and subjected to microarray analysis using the Affymetrix U133 Plus 2.0 platform. Bioinformatic analysis was performed using dChip and GoStat. We performed grouped analyses of gene expression of early (p0) versus late (p10) air-cultured cells. This revealed relative stability with six (air p0 baseline vs p10 experimental) and one (air p10 baseline vs p0 experimental) gene(s) displaying both greater than twofold and statistically significant upregulation. Conversely, we identified 302 gene upregulations and 56 downregulations when comparing 21% O(2) (p0p10) with 2% O2 (p10). These significantly upregulated changes clustered into 82 over-represented and 9 under-represented ontology terms. These terms were indicative of signaling pathways, developmental potential and metabolism. Hierarchical clustering indicated a trend for 2% O2 cultured cells to cluster collectively with reduced heterogeneity when compared with 21% O2 cultured cells. The gene changes associated with 2% O2 culture may be predictive of novel cellular requirements for stable self-renewal, maintenance of pluripotency, and a reduction of hESC-line heterogeneity.
18,947,306
Ophthalmic imaging today: an ophthalmic photographer's viewpoint - a review.
Ophthalmic imaging has changed dramatically since the 1960s with increasingly complex technologies now available. Arguably, the greatest changes have been the development of the digital camera and the speed, processing power and storage of electronic data. Already, ophthalmic practices in many major institutions overseas have paperless medium storage and electronically generated reporting from all equipment that use a computer interface. It is hard to remember the widespread use of photographic film with its attendant costs, or even to remember the days before optical coherence tomography (OCT). These latest technical improvements in ophthalmic imaging are now standard in large Australian institutions and becoming more widespread in smaller private practices. The technicians that operate and maintain this ever-increasing plethora of gadgetry have seen their work practices change from the darkroom to the complexities of data-based imaging and storage. It is a fitting time to examine the contemporary state of ophthalmic imaging and what lies on the horizon as we move towards 2020.
18,947,332
Looking while unhappy: mood-congruent gaze in young adults, positive gaze in older adults.
Recent findings that older adults gaze toward positively valenced stimuli and away from negatively valenced stimuli have been interpreted as part of their attempts to achieve the goal of feeling good. However, the idea that older adults use gaze to regulate mood, and that their gaze does not simply reflect mood, stands in contrast to evidence of mood-congruent processing in young adults. No previous study has directly linked age-related positive gaze preferences to mood regulation. In this eye-tracking study, older and younger adults in a range of moods viewed synthetic face pairs varying in valence. Younger adults demonstrated mood-congruent gaze, looking more at positive faces when in a good mood and at negative faces when in a bad mood. Older adults displayed mood-incongruent positive gaze, looking toward positive and away from negative faces when in a bad mood. This finding suggests that in older adults, gaze does not reflect mood, but rather is used to regulate it.
18,947,348
Individual differences in delay discounting: relation to intelligence, working memory, and anterior prefrontal cortex.
Lower delay discounting (better self-control) is linked to higher intelligence, but the basis of this relation is uncertain. To investigate the potential role of working memory (WM) processes, we assessed delay discounting, intelligence (g), WM (span tasks, 3-back task), and WM-related neural activity (using functional magnetic resonance imaging) in 103 healthy adults. Delay discounting was negatively correlated with g and WM. WM explained no variance in delay discounting beyond that explained by g, which suggests that processes through which WM relates to delay discounting are shared by g. WM-related neural activity in left anterior prefrontal cortex (Brodmann's area 10) covaried with g, r= .26, and delay discounting, r=-.40, and partially mediated the relation between g and delay discounting. Overall, the results suggest that delay discounting is associated with intelligence in part because of processes instantiated in anterior prefrontal cortex, a region known to support the integration of diverse information.
18,947,356
Vascular involvement in rheumatic diseases: 'vascular rheumatology'.
The vasculature plays a crucial role in inflammation, angiogenesis, and atherosclerosis associated with the pathogenesis of inflammatory rheumatic diseases, hence the term 'vascular rheumatology'. The endothelium lining the blood vessels becomes activated during the inflammatory process, resulting in the production of several mediators, the expression of endothelial adhesion molecules, and increased vascular permeability (leakage). All of this enables the extravasation of inflammatory cells into the interstitial matrix. The endothelial adhesion and transendothelial migration of leukocytes is a well-regulated sequence of events that involves many adhesion molecules and chemokines. Primarily selectins, integrins, and members of the immunoglobulin family of adhesion receptors are involved in leukocyte 'tethering', 'rolling', activation, and transmigration. There is a perpetuation of angiogenesis, the formation of new capillaries from pre-existing vessels, as well as that of vasculogenesis, the generation of new blood vessels in arthritis and connective tissue diseases. Several soluble and cell-bound angiogenic mediators produced mainly by monocytes/macrophages and endothelial cells stimulate neovascularization. On the other hand, endogenous angiogenesis inhibitors and exogenously administered angiostatic compounds may downregulate the process of capillary formation. Rheumatoid arthritis as well as systemic lupus erythematosus, scleroderma, the antiphospholipid syndrome, and systemic vasculitides have been associated with accelerated atherosclerosis and high cardiovascular risk leading to increased mortality. Apart from traditional risk factors such as smoking, obesity, hypertension, dyslipidemia, and diabetes, inflammatory risk factors, including C-reactive protein, homocysteine, folate deficiency, lipoprotein (a), anti-phospholipid antibodies, antibodies to oxidized low-density lipoprotein, and heat shock proteins, are all involved in atherosclerosis underlying inflammatory rheumatic diseases. Targeting of adhesion molecules, chemokines, and angiogenesis by administering nonspecific immunosuppressive drugs as well as monoclonal antibodies or small molecular compounds inhibiting the action of a single mediator may control inflammation and prevent tissue destruction. Vasoprotective agents may help to prevent premature atherosclerosis and cardiovascular disease.
18,947,376
Hemostasis and ageing.
On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role.
18,947,391
Chlamydia trachomatis diversity viewed as a tissue-specific coevolutionary arms race.
The genomes of pathogens are thought to have evolved under selective pressure provided by the host in a coevolutionary arms race (the 'Red Queen's Hypothesis'). Traditionally, adaptation by pathogens is thought to rely not on whole chromosome dynamics but on gain/loss of specific genes, yielding differential abilities to infect distinct tissues. Thus, it is not known whether distinct host organs differently shape the genome of the same pathogen. We tested this hypothesis using Chlamydia trachomatis as model species, looking at 15 serovars that infect different organs: eyes, genitalia and lymph nodes. We analyzed over 51,000 base pairs from all serovars using various phylogenetic approaches and a non-phylogenetic indel-based algorithm to study the evolution of individual and concatenated loci. This survey comprised about 33% of all single nucleotide polymorphisms in C. trachomatis chromosomes. We present a model in which genome evolution indeed correlates with the cell type (epithelial versus lymph cells) and organ (eyes versus genitalia) that a serovar infects, illustrating an adaptation to physiologically distinct niches, and discarding genetic drift as the dominant evolutionary driving force. We show that radiation of serovars occurred primarily by accumulation of single nucleotide polymorphisms in intergenomic regions, housekeeping genes, and genes encoding hypothetical and cell envelope proteins. Furthermore, serovar evolution also correlates with ecological success, as the two most successful serovars showed a parallel evolution. We identified a single nucleotide polymorphism-based tissue-specific arms race for strains in the same species, reflecting global chromosomal dynamics. Studying such tissue-specific arms race scenarios is crucial for understanding pathogen-host interactions during the course of infectious diseases, in order to dissect pathogen biology and develop preventive and therapeutic strategies.
18,947,394
Comparing the xylose reductase/xylitol dehydrogenase and xylose isomerase pathways in arabinose and xylose fermenting Saccharomyces cerevisiae strains.
Ethanolic fermentation of lignocellulosic biomass is a sustainable option for the production of bioethanol. This process would greatly benefit from recombinant Saccharomyces cerevisiae strains also able to ferment, besides the hexose sugar fraction, the pentose sugars, arabinose and xylose. Different pathways can be introduced in S. cerevisiae to provide arabinose and xylose utilisation. In this study, the bacterial arabinose isomerase pathway was combined with two different xylose utilisation pathways: the xylose reductase/xylitol dehydrogenase and xylose isomerase pathways, respectively, in genetically identical strains. The strains were compared with respect to aerobic growth in arabinose and xylose batch culture and in anaerobic batch fermentation of a mixture of glucose, arabinose and xylose. The specific aerobic arabinose growth rate was identical, 0.03 h-1, for the xylose reductase/xylitol dehydrogenase and xylose isomerase strain. The xylose reductase/xylitol dehydrogenase strain displayed higher aerobic growth rate on xylose, 0.14 h-1, and higher specific xylose consumption rate in anaerobic batch fermentation, 0.09 g (g cells)-1 h-1 than the xylose isomerase strain, which only reached 0.03 h-1 and 0.02 g (g cells)-1h-1, respectively. Whereas the xylose reductase/xylitol dehydrogenase strain produced higher ethanol yield on total sugars, 0.23 g g-1 compared with 0.18 g g-1 for the xylose isomerase strain, the xylose isomerase strain achieved higher ethanol yield on consumed sugars, 0.41 g g-1 compared with 0.32 g g-1 for the xylose reductase/xylitol dehydrogenase strain. Anaerobic fermentation of a mixture of glucose, arabinose and xylose resulted in higher final ethanol concentration, 14.7 g l-1 for the xylose reductase/xylitol dehydrogenase strain compared with 11.8 g l-1 for the xylose isomerase strain, and in higher specific ethanol productivity, 0.024 g (g cells)-1 h-1 compared with 0.01 g (g cells)-1 h-1 for the xylose reductase/xylitol dehydrogenase strain and the xylose isomerase strain, respectively. The combination of the xylose reductase/xylitol dehydrogenase pathway and the bacterial arabinose isomerase pathway resulted in both higher pentose sugar uptake and higher overall ethanol production than the combination of the xylose isomerase pathway and the bacterial arabinose isomerase pathway. Moreover, the flux through the bacterial arabinose pathway did not increase when combined with the xylose isomerase pathway. This suggests that the low activity of the bacterial arabinose pathway cannot be ascribed to arabitol formation via the xylose reductase enzyme.
18,947,407
Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene.
Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance. Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations. We identified a c.1868T>C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals. We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.
18,947,413
Replantation of multiple digits and hand amputations: four case reports.
This study reports four cases of hand avulsion at the proximal wrist level and multiple digits amputation were received in plastic and hand surgery unit during the year 2007-2008. All patients were male labors between 22-30 years old, and the amputation due to machine injuries. Successful replantation were achieved, after a period of follow up with occupational therapy all patients regain good functional and cosmetic results. This study proves the strong indication of replantation of multiple digits & hand amputations.
18,947,423
Analysis of differential gene-regulatory responses to zinc in human intestinal and placental cell lines.
Transcriptomic studies are useful for elucidating molecular mechanisms through which changes in nutrient availability produce pleiotropic effects on whole-body and tissue physiology. To further the knowledge of gene-regulatory effects of Zn on tissues important for adult and fetal Zn nutrition, we analysed the responses of human intestinal Caco-2 and placental JAR cells to changes in Zn supply. Analysis of oligonucleotide microarrays demonstrated that, despite the analogous roles of the two tissues in nutrient transfer, different genes respond to changes in Zn availability in intestinal cells compared with placental cells. A number of Fe- and Cu-related genes were identified as targets for regulation by Zn, revealing potential mechanisms underlying reported dietary interactions between Zn and other metals. We established that there are fundamental differences in Zn-regulated transcriptional control in Caco-2 compared with JAR cells. We demonstrated that Zn-induced transcriptional activation of the metallothionein 2A promoter occurs over different, and physiologically relevant, concentration ranges in Caco-2 and JAR cells, indicating that these cell lines sense changes in the extracellular Zn concentration over different ranges. Also, we established that mRNA levels of the Zn-responsive metal response element binding transcription factor (MTF)-1, and its homologue MTF-2, are regulated by Zn in Caco-2 but not JAR cells, which may in part underlie differential gene responses to Zn in intestinal and placental cells. The present study identified a number of novel molecular targets that may underlie symptoms associated with deficient or excessive Zn supply and highlighted the necessity of taking account of cell- and tissue-specific processes when investigating Zn-regulated gene expression in mammals.
18,947,441
Methicillin-resistant Staphylococcus aureus in people living and working in pig farms.
We compared the prevalence of human and animal methicillin-resistant Staphylococcus aureus (MRSA) at pig farms in The Netherlands, and related this to individual and farm-level characteristics. More than half of the farms investigated (28/50) had MRSA in pigs or stable dust and about one third (15/50) of person(s) were identified as MRSA carriers. Human carriage was found only on farms with MRSA-positive pigs or dust. MRSA strains in human samples were the same spa-type as found in pigs and all were not typable by pulsed-field gel electrophoresis (NT-MRSA). Multivariate analyses showed that risk factors for human MRSA carriage were: working in pig stables (OR 40, 95% CI 8-209) and the presence of sows and finishing pigs (OR 9, 95% CI 3-30). Veterinary sample collectors sampling the pigs showed transient MRSA carriage only during the day of the farm visit. Working in pig stables with MRSA-positive pigs poses a high risk for acquiring MRSA, increasingly so when contact with live pigs is more intensive or long lasting.
18,947,444
Post-release evaluation of Eretmocerus hayati Zolnerowich and Rose in Australia.
Bemisia tabaci biotype B is a significant pest of agriculture world-wide. It was first detected in Australia in 1994. Assessments of the potential of parasitoids already present in Australia to control this pest indicated that two species of Eretmocerus and 11 species of Encarsia were present, but they did not exert sufficient control with a combined average of 5.0+/-0.3% apparent parasitism of 4th instars. Further, only 25% of samples containing biotype B had parasitised individuals present. The surveys also identified that fewer B biotype were being parasitised compared with the Australian indigenous biotype. Overall, Er. mundus was the most abundant parasitoid prior to the introduction. Previous research indicated that Er. hayati offered the best prospects for Australia and, in October 2004, the first releases were made. Since then, levels of apparent parasitism have averaged 29.3+/-0.1% of 4th instars with only 24% of collections having no parasitism present. Eretmocerus hayati contributed 85% of the overall apparent parasitism. In addition, host plants of the whitefly with low or no parasitism prior to the release have had an order of magnitude increase in levels of parasitism. This study covers the establishment of the case to introduce Er. hayati and the post-release establishment period November 2004-March 2008.
18,947,454
Uni-centric localization of Castleman's disease treated with laparoscopic and traditional approach. Report of two cases.
Castleman's disease (CD) is a rare lymphoproliferative disorder. Clinically CD has been subdivided in two forms: uni-centric and multicentric. The uni-centric type is limited to a single anatomic lymph-node-bearing region. The present report describes two cases of uni-centric CD: the first was an abdominal localization treated with a laparoscopic approach; the second was a submaxillary localization treated with a classical approach. In case 1 the laparoscopic approach permitted to reach diagnosis, not clear after diagnostic imaging procedures, and enabled a total and excellent resolution of the pathology because our patient, after eight months of follow up, has had no evidence of recurrence of the disease. In case 2 we want to highlight that CD should be considered in the differential diagnosis of a solitary neck mass and that the surgical treatment is diagnostic and curative at the same time.
18,947,460
[Related factors in the development of anemia in preterm infants].
To investigate the related perinatal factors in the development of anemia of prematurity by a case-control study. The medical data of 165 preterm infants admitted to the department of neonatology in Peking University Third Hospital from January 2005 to December 2006 were retrospectively reviewed. The infants were classified into two groups: anemia and non-anemia (control). The factors associated with anemia of prematurity were identified. Sixty-three preterm infants (38.1%) had anemia. The gestational age (32.5+/-2.0 weeks vs 33.7+/-1.9 weeks) and birth weight (1682.7+/-393.9 g vs 2041.1+/-510.1 g) of the anemia group were significantly lower than those of the control group (P<0.01). The blood loss from laboratory testing (12.4+/-6.5 mL/kg vs 6.6+/-3.6 mL/kg) and the duration of hospital stay (25.6+/-14.2 days vs 14.1+/-8.7 days) of the anemia group were significantly higher than those of the control group (P<0.01). More critically ill patients (33.3%) were noted in the anemia group compared with in the control group (9.8%) (P<0.01). In the anemia group, 44.4% of the mothers had preeclampsia but only 28.4% in the control group (P<0.05). Multiple factor logistic regression analysis revealed that the blood loss from laboratory testing was the only independent high-risk factor for anemia of prematurity. Compared with the preterm infants whose blood loss from laboratory testing was < 5 mL/kg, the OR values of the preterm infants whose blood loss was 5-10, 10-15 and > or = 15 mL/kg was 1.737 (95% CI: 0.699-4.316, P>0.05), 4.141 (95% CI: 1.573-10.905, P<0.01) and 32.267 (95% CI: 8.053-129.287, P<0.01), respectively. Anemia of prematurity is associated with gestational age, birth weight, duration of hospital stay, illness severity and maternal preeclampsia. The blood loss from laboratory testing is an independent risk-factor in the development of anemia of prematurity.
18,947,476
[Assessment of the young rat model of visceral hypersensitivity by measuring electrical discharge of external oblique].
To study the value of measuring electrical discharge of external oblique in assessment of young rat model of visceral hypersensitivity. Eight-day-old neonatal Sprague-Dawley rats were randomly assigned to two groups: an experimental group and a control group (n=16 each). Rats in the experimental group were subjected to mechanical colorectal irritation daily for 7 consecutive days, while the rats in the control group did not received colorectal irritation treatment. On the 6th week of their lives, the spike amplitude of external oblique were measured to evaluate the bowel sensitivity. When the colorectal distention (CRD) pressure was 30 and 45 mmHg, the 95% confidence interval of the spike amplitude in the experimental group was significantly higher than that in the control group (P<0.01). When the CRD pressure were 60 and 75 mmHg, the 95% confidence interval of the spike amplitude in female rats was significantly higher than that in males (P<0.05). The electrical discharge of external oblique confirmed that chronic colorectal irritation in neonatal rats can result in a chronic visceral hypersensitivity in the juvenile stage, with gender differences. Electrophysiological assessment is a quantitative test, and can objectively reflect visceral sensibility of pain.
18,947,489
Trends in influenza vaccination coverage rates in the United Kingdom over six seasons from 2001-2 to 2006-7.
In order to understand motivations and barriers to vaccination, and to identify people's intentions to get vaccinated for season 2007-8, influenza vaccination coverage was assessed in the United Kingdom (UK) from 2001 to 2007. Between 2001 and 2007 representative household surveys were performed by telephone interview with 12,143 individuals aged 16 or older. The overall influenza vaccination coverage rate dropped non-significantly from 25.9% in 2005-6 to 25.0% in 2006-7 (p=0.510). In the elderly (>/=65 years) the rate decreased from 78.1% to 65.3% (p=0.001), and the odds ratio of being vaccinated compared to those not belonging to any of the risk groups targeted by vaccination decreased from 36.6 to 19.9. Healthcare workers and chronically ill persons had odds ratios of 2.0 and 15.5, respectively. The most important reason for getting vaccinated was a recommendation by the family doctor or nurse, and this was also perceived as the major encouraging factor for vaccination. No recommendation from the family doctor was the main reason for not getting vaccinated. A total of 38.4% of the respondents intended to get immunised against influenza in 2007-8. From 2001 to 2006 a slightly increasing trend (p for trend across seasons <0.0001) in vaccination coverage was observed in the UK, but in 2006-7 the rates returned to the level of 2004-5. Less media attention to the threat of avian influenza after 2005 may have contributed to the recent decrease of vaccination rates.
18,947,523
National seasonal influenza vaccination survey in Europe, 2008.
A cross-sectional survey was undertaken with the European Union (EU) Member States and Norway and Iceland to describe seasonal influenza immunisation in the 2006-7 season, in particular to identify country-specific recommendations for risk groups, obtain vaccine uptake information and allow comparison with global recommendations. A standardised questionnaire was completed electronically by each country's project gatekeeper. Of the 29 countries surveyed, 28 recommended seasonal influenza vaccination for older age groups (22 for those aged > 65 years), and in one country vaccine was recommended for all age groups. All countries recommended vaccinating patients with chronic pulmonary and cardiovascular diseases and most countries advised to immunise patients with haematologic or metabolic disorders (n=28), immunologic disorders (n=27) and renal disease (n=27), as well as residents of long-term care facilities (n=24). Most countries recommended vaccination for staff in hospitals (n=25), long-term care facilities (n=25) and outpatient clinics (n=23), and one-third had such recommendations for workers in essential (n=10), military (n=10) and veterinary services (n=10) and poultry industry (n=13). Eight countries recommended vaccine for pregnant women; and five advised to vaccinate children (with age limits ranging from 6 months to 5 years). Twenty countries measured influenza vaccine uptake among those aged > 65 years (range 1.8%-82.1%), seven reported uptake in healthcare workers (range 14%-48%) and seven assessed coverage in persons with underlying medical conditions (range 27.6%-75.2%). The data provided by this study can assist EU states to assess and compare their influenza vaccination programme performance with other countries. The information provides a comprehensive overview of policies and programmes and their outcomes and can be used to inform joint discussions on how the national policies in the EU might be standardised in the future to achieve optimal coverage. Annual surveys could be used to monitor changes in these national policies.
18,947,524
Evaluation of urinary and faecal continent stomas.
To evaluate the outcome and complications of urinary and faecal continent catheterizable stomas. Retrospective record review of all patients operated on in our institution within the last 6 years. Fifty-five children received 63 stomas. The mean age at operation was 9.2 years and the mean follow-up period was 2.8 years. The diagnoses were: neurogenic bladder (n=22), bladder or cloacal exstrophy (n=20), anorectal malformation (n=6), persistent cloaca (n=3), Hirschsprung's disease (n=2), posterior urethral valves (n=1) and prune belly syndrome (n=1). There were 35 urinary stomas and 28 faecal stomas. Eight patients received both stomas. Both the appendix and a transverse tubularized intestinal segment (Yang-Monti technique) were used; in some cases a caecal flap was created. In three patients the appendix was divided and used to construct two stomas. The implantation of urinary stomas was into the native bladder in 24 patients and into the intestinal segment of an augmented bladder in 11 cases. The location of the stoma was umbilical in 20 cases, right lower quadrant of the abdomen in 35, neo-umbilicus in five and left lower quadrant in three. When an extra-umbilical location was chosen skin flaps were used. Excellent cosmetic and functional results were achieved in 53 (84.2%) of the 63 stomas, which are continent and easy to catheterize. Two had acceptable results with minor problems. There were eight re-operations (12.6% of stomas, 14.5% of patients). The reasons for the re-operations were difficult catheterization in two, incontinence in three, and mucosal prolapse in three patients in whom skin flaps were not used. Of the eight re-operations, seven were in urinary stomas and one in a faecal stoma. Urinary incontinence was attributed to shortening of the intravesical tunnel. No difference in results was observed between the different techniques used, with the exception that cutaneous anastomosis without skin flaps had to be revised because of prolapse, and two out of three incontinent channels had been constructed with tubularized ileum. Catheterizable continent urinary and faecal stomas achieve the objectives of urinary and faecal continence and independence in most patients with a low complication rate.
18,947,542
Differences in embryogenesis of epispadias, exstrophy-epispadias complex and hypospadias.
Minor variants of a spectrum of anomalies are usually more common than the major variants. Penile epispadias is rare compared with the relatively more common exstrophy-epispadias complex, but it has been assumed that the former is simply a lesser form of the latter. This assumption is challenged and an alternative explanation is proposed for the embryogenesis of isolated epispadias. Descriptions of the normal and abnormal development of the cloaca, the cloacal membrane, the external genitalia, the pubis, and in particular the tail were studied. The tail was found to begin its elongation at about 21 days of development, when it overlies the cloacal membrane; it then impacts upon the body stalk and turns aside to lie upon the ventral abdominal wall. By 8 weeks all 10 tail segments have undergone apoptosis. The tail may briefly compress and separate the merging second sacral pair of mesodermal streams that sever the cloacal-allantoic connection and form part of the phallus. These streams then come together to form the phallus behind the allantoic connection which then lies on the dorsal slope of the epispadiac penis. If the compression by the tail occurs after the first paired streams have met and formed the penis, the next pair that form the inner genital folds and penile urethra may be held apart by compression of the tail creating extreme forms of hypospadias on the ventral slope of the penis. This tail compression theory may explain the rarity of epispadias compared to the relatively more common exstrophy-epispadias complex.
18,947,553
Continent urinary diversion with a urachal remnant.
The Mitrofanoff procedure, first described in 1980, has been widely adopted for pediatric continent urinary diversion to increase patient independence and continence, decrease morbidity and infections, and preserve renal function. Although this principle employs the appendix primarily, numerous other tissue conduits have been described. We report a unique use of a urachal remnant as a continent conduit resulting in less morbidity by maintaining the integrity of the native urinary bladder, while maintaining patient continence and allowing easy and successful catheterization.
18,947,570
A case of bilateral prenatal testicular torsion: Ultrasonographic features, histopathological findings and management.
The aim of this study was to demonstrate the ultrasonographic features of prenatal bilateral torsion of the testis, and its histological correlation and management. A newborn presented at delivery with both testes enlarged, swollen and tender. Prenatal ultrasound (US) showed enlarged, hyperechoic testes. Colour Doppler US examination was performed. US revealed both testes to be heterogeneous. Colour Doppler US did not reveal any flow signal. On inguinal exploration both testes appeared necrotic. Histology showed recognizable seminiferous tubules and Leydig cells. We believe that both testes should be left in situ after bilateral detorsion even if their macroscopic appearance is necrotic.
18,947,572
Surgical treatment of neuropathic urinary incontinence in 2005. When, what, and how?
We present our current opinions on the surgical treatment of urinary incontinence in children with spina bifida. The age of treatment, preferred treatment modalities and results are discussed. We emphasize the importance of initiating treatment for incontinence at an early age as well as the use of effective surgical techniques.
18,947,575
Anterior urethral valve associated with posterior urethral valves.
The association of anterior urethral valve (AUV) with posterior urethral valve (PUV) is rare. A 7-month-old infant was presented at a district hospital with episodes of acute pyelonephritis. He was treated medically and a voiding cystourethrogram (VCUG) confirmed bilateral vesico-urethral reflux. The presence of concomitant AUV and PUV was not recognized. He underwent several surgical procedures, which failed. He had reflux recurrence following two antireflux procedures. He had urinary retention after each operation, which was managed by vesicostomy and perineal urethrostomy. At the age of 3.5 years, he was referred to our paediatric urology clinic. Noticing the AUV and PUV in the past VCUG, the valves were fulgurated. Urodynamic study before and 3 months after valve ablation showed a high voiding pressure. VCUG 6 months following ablation showed no reflux, but several uroflowmetric studies showed a staccato and interrupted pattern. Empirical treatment with an alpha-blocker was started. One year after treatment, a repeat VCUG showed no reflux. Uroflowmetry and urodynamic studies returned to normal. The perineal urethrostomy was closed. The child was asymptomatic after 9 months of follow up.
18,947,585
Conservative management of overactive bladder in children: evaluation of clinical and urodynamic results.
Overactive bladder in children may indicate serious anatomic as well as functional changes in both the lower and upper urinary tracts. In order to prevent such problems, these patients should be diagnosed quickly and treated appropriately. In this study, children with diurnal and nocturnal enuresis symptoms (without any underlying neurological pathology) were evaluated and the long-term follow-up results are discussed. Between 2001 and 2004, 95 children with an average age of 8.1 years (1-13 years), referring with complaints of diurnal incontinence, nocturnal enuresis and recurrent urinary tract infections, were included in the study. Apart from conventional evaluation and ultrasonographic and urodynamic examinations, voiding cysto-urethrography was performed in children with upper tract changes. Seventy-three children (76.8%) completely responded to medical treatment, in 12 children (12.6%) the clinical status has been significantly improved, and in the remaining 10 children (10.5%) conservative management was unsuccessful. Of the children demonstrating complete response or significant improvement, 18 children (18.9%) continued to be under medication during 3-22 months of follow up with a mean maintenance period of 7.4 months. Average time to resolution in all groups was 2.6 years (0.2-3.8 years). Conservative therapy (especially oral anticholinergic agents) in children with overactive bladder is effective when applied appropriately (especially in patients with evident detrusor instability) with adequate follow up. Taking the effect of behavioural factors into account, biofeedback training programs in addition to medical treatment should solve the problem in the majority of cases.
18,947,592
The effect of indwelling catheter on OH-proline in the urethral wound: an experimental study.
To investigate the effect of catheterization on urethral wound healing by measuring OH-proline. Eighteen male New Zealand albino rabbits were divided equally into three groups. In the control group, urethral tissue samples were taken from the ventral penile surface. In group II, the ventral penile surface was incised and primarily repaired by 6/0 polydioxanone. In group III, the incised urethra was repaired by 6/0 polydioxanone and a urethral catheter was inserted. Tissue samples were taken on the 20th postoperative day in groups II and III. Tissue OH-proline levels were measured by the method of Bergman and Loxley. The Kruskal-Wallis statistical test was used for evaluation. OH-proline values as microg/mg dry tissue were 16.43+/-2.68 in the control group, 14.47+/-1.82 in group II and 14.63+/-0.63 in group III. There was no significant difference between the three groups (P>0.05). Use of a urethral catheter does not appear to have a direct effect on collagen synthesis in wound healing.
18,947,605
Testicular germ cell tumors in children: management and outcome in a series of 20 patients.
Testicular germ cell tumors occurring during childhood are extremely rare. This study reports the clinical presentation, pathological diagnosis, treatment methods and outcome in a series of 20 boys, aged between 3.5 months and 16 years (median: 1.5 years; 19 were prepubertal), who were treated between 1963 and 2003. Histologically, mature teratoma was present in seven, immature teratoma in four and yolk sac tumor in nine. Nineteen patients were stage I; only one patient was stage IV. Of the 11 teratomas, 10 were treated by orchiectomy and one by testis-sparing tumor excision only. All 11 patients have survived and show no evidence of disease between 10 and 28 years after surgery. The nine patients with yolk sac tumor were managed by orchiectomy, in two plus retroperitoneal lymphadenectomy, and in eight plus chemotherapy. One patient is in remission for 10 months, seven are alive with no evidence of disease for 5.5-23 years, and one patient died from a T-cell acute lymphoblastic leukemia, 2 years after the end of treatment of the testicular tumor. A gradual switch towards less invasive treatment has been observed over the years. This study confirms the excellent cure rates obtained in children with testicular germ cell tumor, provided diagnosis is prompt and treatment accurate.
18,947,609
Ureteropelvic junction obstruction unmasked after correction of vesicoureteral reflux using endoscopic treatment with Deflux.
A case of intermittent ureteropelvic junction obstruction unmasked after correction of vesicoureteral reflux using endoscopic treatment with Deflux is presented. The difficulty in diagnosis and making treatment decisions for patients with coexisting ureteropelvic junction obstruction and vesicoureteral reflux is discussed.
18,947,611
Collagen prolyl 4-hydroxylase is up-regulated in an acute bladder outlet obstruction.
Compliance is primarily related to extracellular matrix deposition, and prolyl 4-hydroxylase (P4Hs) plays a critical role in the synthesis of the matrix. To study the alteration of P4Hs, under the influence of variable hydrostatic pressure, a novel pressure device was used to expose human bladder smooth muscle cells (HBSMC) and fibroblasts (HBF) to pressures in the physiologic range. We then studied acute obstructed porcine bladder tissues to see if changes can also be seen after in-vitro obstruction. HBSMC and HBF were exposed to pressures at 0, 20 and 40 cmH(2)O for up to 72 h. In-vivo studies were carried out next, using six normal (control) and five obstructed porcine bladders. Pigs were exposed to a consistent hydrostatic pressure of < or =20 cm for 24 h after ligation of the urethra. We used 2-DE to compare protein profiling of HBSMC under normal and increased pressures. Other analyses were used to detect molecular alteration and altered expression of mRNA for P4Hs. We identified 437 proteins from 476 spots (91.8%) obtained from HBSMC that were differentially expressed under normal and increased pressures. Under increased pressure, 48 unique proteins were significantly increased or decreased, and a prominent protein regulating extracellular matrix synthesis highly correlated with P4Hs. The exposure of both HBSMC and HBF to a sustained hydrostatic pressure resulted in the increased expression of P4Hs in a time- and pressure-dependent manner. In vivo, P4Hs expression was also significantly increased in the obstructed group. P4Hs is up-regulated, in the human bladder, time and pressure dependently. The alteration of P4Hs over a short period may significantly influence the synthesis of extracellular matrix in vivo and lead to decreased compliance. Our results also support the concept that bladder outlet obstruction, with resultant pressures of 40 cmH(2)O or less, results in molecular changes consistent with decreased compliance.
18,947,616
The role of renal resistive index measures in the diagnostic work up of congenital hydronephrosis.
To evaluate the role of renal resistive index (RI) measures in the diagnostic work up of congenital hydronephrosis. Seventeen neonatal pigs were randomized to either left-sided partial unilateral ureteral obstruction (n=12) or sham operation (n=5) at 2 weeks of age. Serial investigations including B-mode ultrasound, RI measures and combined clearance/renographic evaluations were performed at 4, 12 and 24 weeks of age under light sedation. Results were analysed statistically, and receiver operating characteristic (ROC) curves were generated in order to evaluate the diagnostic efficacy of RI. In all, 15 animals completed the study protocol. In the obstructed group, hydronephrosis and significant compromise of renal function developed on the subject side, whereas sham-operated pigs had stable renal morphology and function throughout the study. There were however no significant differences in RI or DeltaRI between the two groups at any age, or between right and left RIs in the obstructed group at any point. RI and DeltaRI had no prognostic or diagnostic value as judged by ROC curve analysis. RI and DeltaRI were not affected by partial unilateral ureteral obstruction induced in the immature neonatal porcine kidney. The results of this study do not support the clinical use of Doppler ultrasound studies in the diagnostic work up of congenital hydronephrosis.
18,947,629
Retroperitoneal laparoscopic nephrectomy in children: at last the gold standard?
We analyzed our experience with retroperitoneal laparoscopic nephrectomy giving special attention to the learning curve, morbidity, and feasibility in a teaching institution. Between 1996 and 2004, we performed 104 laparoscopic nephrectomies in 88 children. Only four were performed via the transperitoneal approach, the others being via the retroperitoneal approach; the files of the latter were analyzed. Mean age was 5 years (20 days-15 years). Main indications were pretransplant nephrectomy for arterial hypertension, nephrotic syndrome or uremic hemolytic syndrome (51%), non-functioning kidney secondary to obstruction, reflux or ectopic ureter (38%), and multicystic dysplastic kidney (11%). Bilateral nephrectomy was performed in 13 children. The lateral retroperitoneal approach was feasible in all cases even for those who had previous renal surgery. Conversion was not needed in any patient. No significant blood loss was observed. Mean operative time was 97 min (range 44-240) for unilateral nephrectomy; 46 nephrectomies were done in less than 90 min. In bilateral cases the mean operative time was 260 min (range 160-390). The operative time was less than 4 h in seven bilateral cases. Postoperative course was uneventful. Hospital stay was 1.9 days (range 1-3) for urological indications and 5 days (range 3-7) for patients with terminal renal disease. The procedure was initially performed by one surgeon, but was then expanded to other surgeons of the team, and safely taught to residents and fellows. The procedure is safe, the learning curve is reasonable, teaching is feasible, operating time becomes with experience closer to open surgery without morbidity, and cosmetic results are excellent. This procedure may be considered as the gold standard for nephrectomy in children.
18,947,636
Urinary urea excretion in idiopathic hypercalciuria of children.
In adults, it is well known that high protein intake may increase the risk of nephrolithiasis through increased urinary calcium excretion and other mechanisms. We aimed to assess the role of protein intake on urinary calcium excretion in children with idiopathic hypercalciuria (HC). The 24-h urinary urea excretion as a reflection of protein intake was evaluated in 65 children with HC and in 76 normocalciuric control children. All of them were on a free diet and did not receive any specific drug. Urinary urea excretion was 18.9+/-6.6 (SD) mmol/kg/day in the HC group and 14.2+/-4.9 in controls (P<0.0001). Urinary urea excretion significantly decreased with age, as well as with body weight and height gain in both groups. Calcium excretion significantly increased with increasing sodium and urea excretion in the HC but not the control group. There was a significant (P=0.005) interaction between urinary sodium and urea excretion in the rising calciuria of the HC group. Multiple regression analysis showed that, in the HC group, variations in urinary urea explained 11.4% of the entire variability of urinary calcium excretion, whereas adding the urinary sodium effect increased this relation only to 16%. Children with HC have a higher dietary protein intake than normocalciuric children. The decrease in urea excretion with increasing age and body mass may reflect the relatively higher protein intake of young growing individuals. Salt and protein have a cumulative effect on rising calcium excretion in HC children, but the role of protein intake is outstanding.
18,947,649
Biofeedback therapy in the treatment of bladder overactivity, vesico-ureteral reflux and urinary tract infection.
Voiding disorders are commonly encountered in paediatric urology practice. Urinary incontinence often leads to the impairment of self-esteem but can also cause renal damage, when recurrent urinary tract infection (UTI) or vesico-ureteral reflux (VUR) exists. The aim of this study was to assess the efficacy of a biofeedback training program in children with a long history of voiding disorders. Between 1998 and 2002, 60 children with voiding disorders without neuropathic disease, aged 5-14, were treated. There were 48 girls and 12 boys. The main symptoms were daytime incontinence for 90%, urge syndrome for 78%, and night-time incontinence for 60%. UTIs were noted in 62% of the children, for 37% of them in association with a VUR. Ten weekly sessions were planned for all the children. They were given instructions on toilet behaviour and posture, and pelvic floor training. They had to supervise their voiding frequency and liquid intake at home using a chart. Biofeedback procedure used surface perineal electrodes. The exercises focused on relaxation of the perineum. The first results were recorded 6 months after the last session: 96% of the children with daytime incontinence and 83% of the children with night-time incontinence were cured or improved; 84% of the children were free from infection and VUR was cured in 50% of cases. After a mean follow-up of 21 months, 8% of the children with daytime incontinence and 33% with night-time incontinence relapsed, with a significant difference between primary and secondary enuresis. A breakthrough UTI was observed in 19% of cases. This non-invasive training program was effective in the treatment of daytime incontinence, UTI and VUR. There was an improvement in secondary but not primary enuresis. To prevent relapse, additional support sessions seem to be necessary.
18,947,650
Significance of age-specific creatinine levels at presentation in posterior urethral valve patients.
Determination of prognostic factors is of great importance in decision making on therapies and informing parents about the probable outcome of disease. The present study aims to evaluate and assess the prognostic factors in posterior urethral valve (PUV) patients. The data of 68 patients treated between 1996 and 2004 were evaluated retrospectively. The mean age at diagnosis was 36.4 months. The serum creatinine levels were standardized using the age-specific creatinine reference (ASCR) levels. The age at diagnosis, clinical presentation, initial serum creatinine, method of treatment, presence of vesicoureteral reflux (VUR) and hydroureteronephrosis (HUN), all of which may effect the prognosis, were evaluated. The analysis revealed that, of the 36 patients whose initial serum creatinine levels were within ASCR, only one (2.8%) had a final serum creatinine higher than ASCR values. In contrast, of the 32 patients whose initial serum creatinine levels were not within ASCR, 19 (59.4%) had final serum creatinine levels higher than ASCR (P<0.001). The distribution of final serum creatinine according to treatment method, presence of UTI before treatment and age at diagnosis was not statistically significant; however, the difference in distribution for initial serum creatinine (P<0.001), mode of clinical presentation (0.016), presence of HUN (0.019) and state of VUR (0.037) before treatment was statistically significant. Final outcome with regard to renal function in PUV patients is affected by bilateral VUR and most significantly by serum creatinine levels higher than ASCR.
18,947,654
An exceptional case of urogenital sinus associated with a scrotal pouch and duplicate urethra in a female child.
We report the case of an unusual genitourinary anomaly in a 5-year-old patient. The malformation consisted of a para-anal persistent urogenital sinus in a 46XX patient associated with a scrotum-like structure in the presumed clitoral location. A duplicate urethra arising from the anterior aspect of the bladder neck drained into the scrotal pouch. Two hemivaginas drained into the urogenital sinus. The patient was totally continent through the urogenital sinus but the duplicate urethra was incontinent. No hormonal problems were encountered. The girl underwent total urogenital sinus mobilization, scrotal pouch ablation, and duplicate urethra resection.
18,947,664
Collecting duct carcinoma arising from multicystic dysplastic kidney disease.
Malignancy arising from a multicystic dysplastic kidney (MCDK) is rare. Most reports are of Wilms' tumor and clear-cell renal cell carcinoma arising from a previously unrecognized MCDK. To our knowledge, no reports have described collecting duct carcinoma arising from MCDK.
18,947,667
Extensive skin bridging with glans epithelium replacement by penile shaft skin following newborn circumcision.
Extensive skin bridging with replacement of glans epithelium by shaft skin is an unusual complication of newborn circumcision not previously described. Patients with extensive skin bridges and replacement of at least 50% of glans epithelium with shaft skin underwent lysis of the bridges and excision of displaced skin. Fibrin glue was used to coat the raw glans surface, and urinary diversion was provided for 1 week. Six boys aged 2-15 years underwent the procedure. In each the glans healed with a smooth, cosmetically normal appearance. There were no complications. Skin bridges after newborn circumcision can be associated with unsightly replacement of normal glans epithelium by shaft skin. Correction involves division of the skin bridges and excision of all abnormal skin with a coating of fibrin glue over the raw surface. Glans epithelium subsequently recovers the glans, restoring a normal appearance.
18,947,680
Vesicoureteric reflux and tumor necrosis factor-alpha gene polymorphism.
To determine the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphism in promoting renal scarring among patients with vesicoureteric reflux (VUR). This genetic variant involves a guanosine to adenine transition at position -308, and this single-base polymorphism is associated with increased transcription of the TNF-alpha gene. Recent studies suggest that the TNF-alpha gene may be associated with predisposition to renal scarring. A total of 195 (51.8% females) patients with VUR demonstrated by voiding cystourethrogram were recruited, 126 of them with reflux nephropathy diagnosed by dimercaptosuccinic scan. The control group included 266 healthy individuals. Genotyping was performed by polymerase chain reaction and digestion with a restriction enzyme. Allele frequencies of -308G and -308A were 83.8% and 16.2%, respectively in patients with VUR and 88.9% and 11.1%, respectively in controls (P<0.05). No differences were found in genotype distribution related to presence/absence of renal scars. There was no relationship between TNF-alpha genotype and grade of VUR or the presence of proteinuria. Our data suggest that the TNF-alpha AA genotype is not associated with reflux nephropathy. The TNF-alpha-308A allele could be related to a higher susceptibility to VUR.
18,947,693
Ibuprofen-induced papillary necrosis causing bilateral ureteric obstruction.
Ibuprofen, a non-steroidal anti-inflammatory drug, is the mainstay in the management of pain and fever in children. In most children, ibuprofen is well tolerated and does not produce significant adverse effects. We report a case of acute papillary necrosis causing bilateral ureteric obstruction induced by ibuprofen.
18,947,702
Treatment of vesicoureteral reflux in children using stabilized non-animal hyaluronic acid/dextranomer gel (NASHA/DX): a long-term observational study.
Vesicoureteral reflux (VUR) can be treated with open surgery, antibiotic therapy or endoscopic injection. A goal in children is to reduce the incidence of febrile urinary tract infections (UTIs). The present long-term observational study investigated outcomes and experiences of endoscopic treatment with stabilized non-animal hyaluronic acid/dextranomer, NASHA/Dx. Children treated with NASHA/Dx between 1993 and 1998 were sent a questionnaire by mail in 2005. Patients included in the study (n=231) had VUR grade III-V before treatment and grade 0-II afterwards. Patients completed 21 questions, with parental assistance if required. The questionnaire assessed clinical outcome, and the attitudes of both patients and their parents to their experiences of treatment with NASHA/Dx gel. Patients reporting UTI after treatment were contacted and their records analyzed. Questionnaires were completed by 179 eligible patients. Most (72%) received a single injection of NASHA/Dx gel, and all experienced febrile UTI before treatment. After treatment, 45 patients (25%) experienced UTI; 25 of these reported fever. Patient records and telephone interviews revealed no evidence of febrile UTI in 19 cases; febrile UTI was confirmed in six cases, an incidence of 3.4%. When asked about the worst aspect of VUR treatment, 9% indicated treatment with NASHA/Dx compared to 19% for medication and 72% for voiding cystourethrogram (VCUG); parent-rated responses were 19%, 24% and 57%, respectively. Endoscopic treatment with NASHA/Dx gel was associated with a low number of febrile UTIs following treatment, viewed positively and considered less bothersome than medication or VCUG. These findings support this treatment as a primary intervention for VUR.
18,947,708
Can urodynamic studies be dispensed with in the initial urologic management of children with meningomyelocele? A study of 30 cases and review of the literature.
To identify whether a relationship exists between information gathered from voiding patterns, neurological status and radiological findings, and the actual dysfunction seen on cystometry in children with spina bifida. Thirty consecutive children with spina bifida underwent clinical evaluation, urinary tract imaging and cystometry. The clinical and radiological data were correlated with actual bladder dysfunction. Cystometry was abnormal in 87% with overactive detrusor in 77%. Seventeen patients (57%) had significant residual urine of whom all had neurological or voiding abnormalities. Irrespective of radiological findings (abnormal in 53%), 90% of these patients had detrusor overactivity and 10% an underactive detrusor. In the group with insignificant residual urine (n=13), upper tract was abnormal in six (46%) of which four had neurological/voiding abnormalities and detrusor overactivity. The other two patients with normal neurologic status and voiding pattern had normal cystometry, but their upper tract damage was inexplicable. Of the patients with insignificant residual urine and normal upper tracts (n=7), four had neurologic/voiding abnormalities, three with an overactive detrusor and one underactive detrusor, and of the other three, one had an overactive detrusor. Patients with significant residual urine can be presumed to have detrusor overactivity and may be initially managed with clean intermittent catheterization and bladder relaxants. Cystometry is indicated if upper tract shows deterioration. In patients with insignificant residual urine and abnormal clinical evaluation or radiology, detrusor overactivity can be presumed and urodynamic studies deferred. Patients with insignificant residual urine, normal radiology but abnormal clinical findings must undergo initial cystometry.
18,947,734