Investigation and treatment of urinary incontinence

Female urinary incontinence is a common but underreported condition. Initial investigation and treatment can in most cases be undertaken without urodynamic or other detailed tests. History by the use of validated symptom and quality of life questionnaires is key to the initial investigation. Initial treatment includes pelvic floor muscle training (PFMT) regardless of the type of incontinence; lifestyle interventions and bladder retraining, anticholinergics and serotonin/noradrenaline reuptake inhibitors (e.g. duloxetine) are also included depending on the type of symptoms. In mixed incontinence the predominant symptom should be treated first. When this initial treatment is ineffective, further investigation should be offered prior to specialised treatment. Urodynamics should be considered for all patients prior to surgery. Imaging and cystoscopy to exclude pathology, for example in elderly patients with an overactive bladder, are also necessary. Newer surgical interventions should be offered after careful consideration of the risk:benefit ratio for each individual woman and the amount of evidence that is currently available to support their use.     

Flow cytometric analysis of induced human graafian follicles. I. Demonstration and sorting of two luteinized cell populations.

STUDY OBJECTIVE: To test the hypothesis that induced human graafian follicles consist of different steroidogenic cell types on the basis of their light scatter characteristics as determined by flow cytometry. DESIGN: Cross-sectional, observational study. SETTING: Flow cytometry laboratory. PATIENTS: Thirty-six follicular aspirates from nine consecutive patients undergoing in vitro fertilization for tubal factor infertility were evaluated. RESULTS: Two distinct luteal cell populations were recovered. Both populations were positive by Oil Red O staining, suggesting the presence of intracellular lipid. Neither population stained positively for the presence of HLe-1/CD45, an antigen present on all human leukocytes. CONCLUSIONS: Cellular heterogeneity exists within the granulosa cell compartment.     

Failure of microchromatographic measurement of fetal hemoglobin in beta zero thalassemia-hereditary persistence of fetal hemoglobin.

We report microchromatographic measurement of fetal hemoglobin (HbF) proportions in a 36-year-old African-American multigravida woman. At 34 weeks she delivered a 630-g male infant who subsequently did well. Hemoglobin electrophoresis of the hemolysate revealed nearly 100% HbF without HbA, an extremely unusual naturally occurring sample. Family studies revealed a combination of hereditary persistence of fetal hemoglobin (HPFH) and beta zero-thalassemia minor. Southern blot technique confirmed heterozygous alpha 2 thalassemia and HPFH but failed to identify the beta thalassemic lesion. The absence of HbA and the very high amounts of HbF led us to measure HbF by several methods to confirm the accuracy of microchromatography of HbF at values approaching 100%. HPLC revealed a 14% F1 suggestive of microchromatographic underestimation due to glycated HbF. We conclude that cation-exchange microchromatography and the Betke method of alkali denaturation underestimate HbF values as they approach 100% and do not recommend these procedures in this rare situation.     

Lymphotoxin produced by human B- and T-cell lines appears in two distinct forms

Production and release of lymphotoxin (LT) was studied by metabolic labeling of human B- and T-cell lines with 14C-leucine and 35S-methionine. LT was immunoprecipitated with antiserum to LT and separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) followed by fluorography. Two molecular weight forms of LT with different rates of release were found both in cell supernatants and cell extracts. Monensin, a sodium ionophore, inhibited the release of LT. LT still appeared in two molecular weight forms after deglycosylation with N-glycanase. Treatment of cells with swainsonine followed by digestion of released LT with endoglycosidase H (endo H) demonstrated that the oligosaccharides were of the complex type. Subcellular fractionation of cells on Percoll density gradients demonstrated that intracellular LT is located to intermediate density fractions. No LT was found in the high density fractions corresponding to lysosomes. Phorbol 12-myristate 13-acetate induced production of tumor necrosis factor (TNF) in the B-lymphoblastoid cell line RPMI-1788. In conclusion, we have demonstrated the presence of two distinct molecular weight forms of LT, which contain N-linked oligosaccharides of the complex type.     

Serum procalcitonin levels in chronic hepatitis C patients under pegylated interferon-alpha plus ribavirin treatment.

OBJECTIVES: To evaluate the alterations of serum procalcitonin (PCT) levels in patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa) plus ribavirin (RIB) treatment and to correlate them with clinical and virological outcomes. STUDY DESIGN: Fifty-two consecutive patients (29 males, age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics) were evaluated for PCT levels at baseline and during the treatment course (at week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and again 6 months after completion of treatment. RESULTS: Two patients exhibited culture-proved bacterial infections during the treatment course. Thirty-six patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout the follow-up period except those two who exhibited bacterial infections during the treatment course. Virological responders exhibited significant decline of serum PCT levels over time compared to non-responders (p<0.001), even when adjusted for multiple baseline parameters (p=0.037). CONCLUSION: Serum PCT levels decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment, especially in the sustained virological responder group, while they elevate only when bacterial infections complicate the treatment course.     

Coexpression of the genes for platelet-derived growth factor and its receptor in human T-cell lines infected with HTLV-I

Several HTLV-I-infected T-cell lines express the two genes encoding platelet-derived growth factor (PDGF). Therefore, we examined the question of a possible self-stimulatory mechanism of proliferation involving PDGF in these cells. Using a nucleic acid probe and an antibody specific for the PDGF-B receptor (PDGFR-B), we examined four established human T-cell lines infected with HTLV-I, as well as several noninfected T-cell lines for expression of the PDGF-B receptor. Previous reports indicate that lymphocytes do not display receptors for PDGF; our results show that two noninfected T-cell lines (HUT-78, CCRF-HSB-2) expressed the canonical 5.5-kb PDGFR mRNA, and two HTLV-I-infected T-cell lines (C10/MJ, MT-2) expressed a novel PDGFR mRNA of 4.8 kb. Concomitantly, the cell lines expressing PDGFR mRNA also synthesize PDGFR proteins immunoprecipitated by the antibody to PDGFR-B. Differences were observed in the molecular weight of PDGFR molecules immunoprecipitated from uninfected and HTLV-infected T-cells. Immunofluorescence studies demonstrated that the PDGFR-B proteins are localized primarily on the cell external membrane. The results suggest that the HTLV-I-infected T-cells acquire an autostimulatory mechanism of cell proliferation that involves PDGF.     

Pet ownership and survival of European older adults

With pet ownership on the rise, millions of individuals are exposed to this environmental exposure. Although the subject has been largely studied, more evidence is needed to clarify the potential association of pet ownership with human health. The aim of this research is to study the potential association of pet exposure (any pet, cat, dog, bird, fish) with all-cause, cardiovascular and cancer mortality of older (≥ 50 years) European residents. To this end, a total of 23,274 participants from the Survey of Health Ageing and Retirement in Europe (SHARE) were employed (median follow-up 119 months). All-cause mortality (5163 events), as well as cardiovascular (CVD) (1832 events), and cancer mortality (1346 events) were examined using Cox Proportional Hazards models for their relation with pet exposure at baseline. Stratified analyses were also performed by gender and for single or multi-person households. No significant association was observed for any of the pets with all-cause mortality on the whole sample and the fully adjusted models. In stratified analyses, bird exposure significantly increased the risk of all-cause mortality in women [Hazard Ratio (HR)=1.23; 95% CI 1.04–1.44] as well as women living alone (HR=1.38; 95% CI 1.02–1.85). Cause-specific models revealed an increased risk of death for women bird owners for causes other than cancer and CVD (HR=1.40; 95% CI 1.05–1.99). In conclusion, bird ownership may be negatively associated with survival of older women in Europe.     

Autism as a disorder of prediction

A rich collection of empirical findings accumulated over the past three decades attests to the diversity of traits that constitute the autism phenotypes. It is unclear whether subsets of these traits share any underlying causality. This lack of a cohesive conceptualization of the disorder has complicated the search for broadly effective therapies, diagnostic markers, and neural/genetic correlates. In this paper, we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities. With compromised prediction skills, an individual with autism inhabits a seemingly “magical” world wherein events occur unexpectedly and without cause. Immersion in such a capricious environment can prove overwhelming and compromise one’s ability to effectively interact with it. If validated, this hypothesis has the potential of providing unifying insights into multiple aspects of autism, with attendant benefits for improving diagnosis and therapy.