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Biomedical subjects

C M Bates

Publications and source records attributed to C M Bates.

At least 19 recordsLinked to original sources

Success of a nurse led community based genitourinary medicine clinic for young people in Liverpool: review of the first year.

OBJECTIVES: To assess the outcome and workload of a community based, nurse led comprehensive sexual health and contraceptive service for clients aged less than 25. METHODS: Review of appointment diaries and clinic records of clients who attended the Brook genitourinary medicine (GUM) clinic. The workload, case mix, and achievement of national targets in the first year of the service were compared with those for the same age group of clients attending the nearby hospital based GUM clinic. A limited client satisfaction questionnaire was carried out 8 months after the clinic opened. RESULTS: 1061/1700 (62.4%) clients (185, 17.4% male) attended booked appointments. Chlamydia trachomatis was detected in 16.1% of women and 20.5% of men at Brook (p<0.05), where 22.6% of women and 50% of men had at least one sexually transmitted infection (p<0.001). HIV testing was offered to 98.5% of clients. 60.7% of all identified contacts attended a clinic for testing and/or treatment. Client responses to a questionnaire about the service were very favourable. Only 2.3% of Brook GUM clients needed referral to a physician. CONCLUSIONS: Nurse led community based GUM services, such as the one provided at the Merseyside Brook Centre, appeal to young people and our success should encourage others to consider similar ventures.

Adolescent↗

Lichen sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory disorder of the skin and mucosa, presenting to genitourinary physicians and dermatologists. It affects both sexes and all age groups. Although the exact aetiology is uncertain, genetic predisposition, infections and autoimmune factors have been implicated in its pathogenesis. Symptoms include pruritus and soreness, but asymptomatic presentations are not uncommon. The classical clinical picture is of atrophic white plaques in the anogenital region. Histopathology is specific with basal cell degeneration, upper dermal oedema, homogenization of collagen and a chronic inflammatory infiltrate. Short courses of potent topical corticosteroids form the mainstay of treatment. The condition tends to be remitting and relapsing, with spontaneous regressions reported in a few. In men, the term balanitis xerotica obliterans is sometimes used to describe late and severe LS of the penis. Scarring and progression to squamous cell carcinomas can occur in chronic LS, resulting in significant morbidity. A multidisciplinary approach to care and the need for long-term monitoring cannot be overemphasized.

Carcinoma, Squamous Cell↗

Vulvodynia--new and more effective approaches to therapy.

Two cases are described of treatment-resistant vulvodynia that responded well to gabapentin. Gabapentin, an anti-epileptic drug, has been used in the treatment of neuropathic pain such as diabetic neuropathy and post-herpetic neuralgia. However, there has been little experience of its use in the relief of symptoms in vulvodynia and we add our observations to the one report of its use in these circumstances that has been published so far.

Acetates↗

Molluscum contagiosum--a novel presentation.

A case history is described of an HIV-seropositive man who presented with a swelling on the right cheek and a history of disseminated molluscum contagiosum. Electron microscopy of the abscess aspirate showed pox virions indicative of molluscum contagiosum. This is an unusual presentation of molluscum contagiosum and the authors review the literature of other presentations.

AIDS-Related Opportunistic Infections↗

Role of N-myc in the developing mouse kidney.

N-myc is a transcription factor expressed in the developing metanephric kidney and other organs. In mice, complete disruption of the N-myc gene results in fetal death on the first day of renal organogenesis. In addition to the null N-myc allele, others have generated a hypomorphic N-myc allele. In this study, combinations of these mutant genes were used to demonstrate that reduction in N-myc protein levels correlate with fewer developing glomeruli and collecting ducts in embryonic kidney explants. Histological sections revealed that the mutant kidneys were hypoplastic with normal developing structures. The data indicate that the hypoplasia is due to a reduction in proliferation rather than an increase in apoptosis. Thus, N-myc loss causes a decrease in numbers of ureteric bud tips and developing glomeruli in explants and hypoplastic kidneys in vivo, in a dose-dependent manner.

Animals↗

Identification of risk factors in blood donors found to have HIV infection.

To ascertain whether current screening procedures for human immunodeficiency virus (HIV) infected blood can be improved, a study of blood donors found by Mersey and North Wales Blood Centre to be HIV positive was made. In total 22 donors were identified, of which 16 were referred to the Department of Genito-Urinary Medicine (GUM) in Liverpool. Most (9/16) should have been excluded from donating because of recognized risk factors. However, in 7 cases no such identifiable factors were found. Although the risk of transfusion transmitted infection is small, there is an argument for testing donated blood for HIV RNA by nucleic acid technology.

Adult↗

Acute vision loss in children with autosomal recessive polycystic kidney disease.

Patients with autosomal recessive polycystic kidney disease (ARPKD) often present with renal insufficiency and hypertension. We present two children with ARPKD and end-stage renal disease who developed anterior ischemic optic neuropathy and vision loss. Anterior ischemic optic neuropathy occurs rarely in children and has never been reported in children with ARPKD or end-stage renal disease. Both of our patients were chronically hypotensive and anemic, which are known risk factors for ischemic optic neuropathy.

Anemia↗

Characterization of human proximal tubular cells after hypoxic preconditioning: constitutive and hypoxia-induced expression of heat shock proteins HSP70 (A, B, and C), HSC70, and HSP90.

In animal models of cardiac or cerebral ischemic preconditioning, induction of heat shock proteins (HSPs), especially HSP70, correlates with protection from subsequent injury. The extent of HSP70 induction after stress correlates inversely with initial HSP70 levels. Primate cells, unlike nonprimate cells, express high basal levels of HSP70; thus, primate cells may respond differently to preconditioning than nonprimate cells. We have demonstrated that exposing cultured human proximal tubular epithelial cells (PTEC) to 12 h of hypoxia followed by a 24-h recovery period (hypoxic preconditioning) induces resistance to subsequent hypoxic injury. Herein, we characterize the expression of HSP70, HSP90, and heat shock cognate-70 (HSC70) in PTEC under basal conditions and after hypoxic preconditioning. By Northern blot analysis, we demonstrate that hypoxic preconditioning of PTEC increases mRNA for HSP70 > HSP90 > HSC70. With reverse transcription and polymerase chain reaction, mRNA transcripts from three different HSP70 genes (HSP70 A, B, and C) were detected in unstressed PTEC. Transcripts from these genes were also detected in freshly isolated human renal cortex, indicating that all three genes are expressed in vivo. By Western blot analysis, we demonstrate that PTEC express high basal levels of HSP70, HSC70, and HSP90. Hypoxic preconditioning did not lead to a significant increase in protein content of any of these HSPs, despite increased mRNA levels. This suggests that HSP accumulation cannot account for the development of cytoresistance after hypoxic preconditioning in PTEC. However, high basal expression of HSP70 in human PTEC may contribute to their innate resistance for hypoxia.

Base Sequence↗

Insulin receptor-related receptor expression in non-A intercalated cells in the kidney.

Insulin receptor- related receptor (IRR) is a novel receptor tyrosine kinase in the insulin receptor family. Previous studies have demonstrated that the mammalian organ with the highest level of IRR mRNA is the kidney. By in situ hybridization, kidney expression of IRR transcript is only in the distal nephron and the collecting ducts; however, the specific cellular distribution of IRR is unknown. The purpose of this study was to examine IRR protein expression in the adult mouse kidney using immunohistochemical techniques. IRR was specifically present in a subset of cells in the connecting tubule, the initial collecting tubule, and the cortical collecting duct. IRR protein is detected in cells that express vacuolar H+-ATPase and carbonic anhydrase 2, but not in cells that express band 3 (anion exchanger 1). In the cortical collecting duct, the IRR positive cells are likely B intercalated cells. In the connecting tubule and the initial collecting tubule, the cells are B cells and/or non-A non-B cells. Thus, IRR is a specific marker for non-A intercalated cells in the kidney.

Animals↗

Cystic fibrosis presenting with hypokalemia and metabolic alkalosis in a previously healthy adolescent.

Cystic fibrosis (CF) is an exocrine disease affecting multiple organ systems. Patients with CF usually present with respiratory or gastrointestinal abnormalities. This study presents a case of a previously healthy 17-yr-old man who was diagnosed with CF after presenting with metabolic alkalosis and hypokalemia. The defect associated with CF is in the cystic fibrosis transmembrane regulator (CFTR), which acts primarily as a chloride channel. Partially functional CFTR may be associated with less severe pulmonary and gastrointestinal manifestations, as in the case presented. Dysfunctional CFTR in the sweat ducts of CF patients are responsible for excessive chloride and sodium losses, especially in warm weather. Hypokalemia seen with heat stress is secondary to sweat as well as renal potassium wasting. Metabolic alkalosis is maintained by the excessive sweat sodium chloride losses which leads to extracellular fluid (ECF) volume contraction and chloride depletion. Generation of alkalosis may be related to dysfunctional CFTR in the kidney, but is most likely secondary to hypokalemia with ECF volume contraction. Finally, one must consider CF when confronted with hypokalemia and alkalosis in a previously healthy patient.

Acidosis↗

Susceptibility of human proximal tubular cells to hypoxia: effect of hypoxic preconditioning and comparison to glomerular cells.

In animals models, exposure of the brain, heart, or kidneys to sublethal ischemia induces tolerance for subsequent ischemia. However, the ability of human renal cells to undergo hypoxic preconditioning has not been evaluated. In addition, it is unclear if renal ischemic preconditioning induces resistance at the cellular level, or if preconditioning is a result of altered postischemic hemodynamics or the azotemic environment. In this study, we tested the ability of cultured human proximal tubular epithelial cells (PTEC) to undergo hypoxic preconditioning at the cellular level. Hypoxia was induced by incubating cells in an anaerobic incubator in glucose-free buffer (combined oxygen-glucose deprivation; COGD). Cell injury was assessed by lactate dehydrogenase (LDH) efflux, release of arachidonic acid metabolites, and light microscopy. PTEC preconditioned with 12 h of COGD and a 24-h recovery period had less LDH efflux than control PTEC after subsequent exposure to 20 h of COGD (15.0 +/- 2.5% vs. 44.0 +/- 3.4%, p < 0.05). Preconditioned PTEC also retained relatively normal morphology and had less release of arachidonic acid metabolites than control PTEC. Because renal ischemia is characterized predominately by tubular injury with relative sparing of the glomerulus, we determined if PTEC are more susceptible to hypoxic injury than glomerular cells. For further comparison, we also assessed the susceptibility to hypoxia of the porcine tubular epithelial cell line LLC-PK1. After exposure to 18 h of COGD, LDH efflux from PTEC (25.5 +/- 3.3%, mean +/- SEM) was lower than from LLC-PK1 cells (47.6 +/- 4.0%; p < 0.01), but not mesangial cells (22.7 +/- 5.0%) or glomerular endothelial cells (38.2 +/- 6.2%). In conclusion, we have demonstrated that cultured PTEC are as resistant to hypoxic injury as glomerular cells, and that PTEC attain cytoresistance after hypoxic preconditioning. Characterization of the molecular changes that occur in human PTEC after hypoxic preconditioning may reveal innate survival mechanisms that can be manipulated to promote protection from renal ischemia in patients.

Animals↗

HIV medicine: drug side effects and interactions.

The drugs used in HIV medicine often have toxic side effects; additionally, the risk of drug interactions is high because of the frequent necessity to prescribe multiple drugs. This article covers common or important drug side effects and interactions.

AIDS-Related Opportunistic Infections↗

Evaluation of 4 commercial test kits for parvovirus B19-specific IgM.

Four commercial test kits for parvovirus B19 IgM were evaluated by testing 491 sera assembled into 7 panels. The serum panels were designed to assess sensitivity and specificity of the commercial assays and to reflect the various clinical settings in which acute B19 infection forms part of the differential diagnosis. A mu-capture radioimmunoassay (MACRIA) was used as the reference test. With respect to MACRIA, the commercial B19 IgM assays showed an overall sensitivity of 70.1-84.1% and specificity of 92.2 to 97.4%. Assay performance varied in different clinical situations. In sera from adults with acute B19 arthropathy, all 4 assays were 100% sensitive, but in children with fifth disease, the sensitivity ranged from 44.1 to 88.6%. The sensitivity of all 4 assays was also low when testing samples collected more than 6 weeks after onset of symptoms and in women with B19-associated embryopathy. Specificity was greater than 97% in healthy blood donors, but varied from 70.9 to 83.3% in patients acutely infected with other viruses, including rubella. Although the IgM test kits here evaluated may be usefully introduced for B19 diagnosis in certain settings, knowledge of their limitations will be important when results have been interpreted.

Acute Disease↗

Effect of extracellular calcium on survival of human proximal tubular cells exposed to hypoxia.

Removal of extracellular calcium has been demonstrated to improve membrane integrity of rodent myocytes, astrocytes, and renal tubular cells injured by hypoxia. In this study, the effect of extracellular calcium on long-term survival of cultured human proximal tubular epithelial cells (PTEC) subjected to hypoxia was evaluated. In addition, the effect of extracellular calcium on release of arachidonic acid metabolites (AAM) was assessed during and after hypoxia. To induce hypoxic injury, PTEC were incubated in an anaerobic chamber in glucose-free buffer (combined oxygen/glucose deprivation, COGD). Long-term survival was assessed by measuring lactate dehydrogenase (LDH) efflux during COGD and after an additional 24-h "recovery" period (in routine culture medium in 95% air/5% CO2). To determine if extracellular calcium influenced AAM release from membrane phospholipids, cells were preincubated with [3H]arachidonic acid and the release of AAM was measured during COGD and recovery. With this model system, PTEC exhibited minimal LDH efflux during < or = 12 h COGD, but LDH efflux increased to 73.9 +/- 4.7% by 24 h COGD. With 12-18 h of COGD, the extent of LDH efflux was greater during recovery than during COGD, indicating that, for human PTEC, the extent of membrane damage does not become fully evident by LDH efflux for hours after hypoxia. PTEC exposed to 24 h of COGD in the absence of extracellular calcium exhibited strikingly less LDH efflux during COGD than cells incubated in the presence of extracellular calcium, suggesting that extracellular calcium contributes to membrane damage during COGD. However, upon reexposure of PTEC to extracellular calcium, LDH efflux rapidly increased to control levels. Furthermore, despite allowing cells to recover in oxygen or oxygen and glucose before exposure to calcium-containing medium, a rapid increase in LDH efflux could not be avoided. These results suggest that COGD induces an irreversible injury that ultimately leads to loss of membrane integrity whether or not extracellular calcium is present; however, extracellular calcium accelerates the loss of membrane integrity caused by hypoxia. Extracellular calcium did not alter AAM release, indicating that the effect of extracellular calcium on membrane damage (as indicated by LDH efflux) was not mediated by an increased activity of phospholipases (such as phospholipase A2) that are involved in the release of AAM.

Arachidonic Acid↗

Lipid alterations following impact spinal cord injury in the rat.

A computer-controlled impactor was used to produce a severe spinal cord injury in the rat thoracic spinal cord. Cords were rapidly frozen in situ at 5, 15, 30, and 60 min and 6, 12, and 24 h postinjury. Control cords were noninjured cords from animals having undergone a laminectomy and allowed to recover for 90 min postlaminectomy. The cords were assayed for alterations in lipid metabolism. Specifically, there were rapid increases in prostaglandin F2 alpha and thromboxane, with a peak increase in thromboxane levels at 30 min. Prostaglandin F2 alpha levels peaked at 15 min with levels remaining nearly constant for 12 h. There were no detectable changes in phospholipid levels, although diacylglycerol levels and free fatty acid levels were increased. Total free fatty acids were increased at 12 and 24 h postinjury by 2.3- and 3.2-fold over control levels, respectively. Arachidonic acid levels were not significantly elevated at early time points, however, these early time points correspond to elevated eicosanoid synthesis and this may account for the lack of early detectable increases in arachidonic acid. After 6 h postinjury, arachidonic acid levels were 20-fold greater than control levels and remained elevated at 24 h. There were minimal decreases in cholesterol and no decrease in either choline or ethanolamine plasmalogen levels. These results suggest a rapid turnover of arachidonic acid following spinal cord injury with a concomitant increase in vasoconstrictive eicosanoid synthesis. The lack of changes in major membrane constituents suggests the mechanisms may not involve general membrane degradation, but an over-stimulation of phospholipase A2-linked membrane receptors.

Animals↗

The management of patients with inflammatory smear results in general practice.

OBJECT: To ascertain the management of inflammatory smear results by general practitioners. DESIGN: Postal questionnaire survey. SUBJECTS: All 200 general practitioners on Wirral Family Health Services Authority list as principals in 1990 and 1991. MAIN OUTCOME MEASURES: Answers to questions covering a variety of aspects concerning the management of inflammatory smear results in general practice. RESULTS: One hundred and thirteen (57%) replied. Ninety per cent have facilities to test for Trichomonas vaginalis and Candida albicans. Sixty eight per cent were able to test for Chlamydia trachomatis. A high vaginal swab (HVS) was the commonest swab taken (88%); 31% of doctors included a swab for Chlamydia trachomatis. Of doctors who gave treatment without microbiological confirmation 74% gave metronidazole and 64% gave tetracycline or erythromycin. Eighty five per cent repeat smears are undertaken within three months. Ninety seven per cent of doctors said more detailed information would be helpful on the cytology report. One hundred per cent of doctors referred to a gynaecologist of colposcopy was advised. Male sexual partners were advised to attend the Department of Genitourinary Medicine by 12% of doctors (70% do not refer to either their general practitioner or genitourinary department). CONCLUSION: Most patients with inflammatory smear results are managed by their general practitioner without reference to specialist services. Many patients are not investigated for infection but treatment often includes medication which covers the most likely or potentially serious genital pathogens. More detailed advice given with the cytology report on further management or a local protocol would be helpful to aid management in this difficult area. If recommendations for referral of certain groups of patients to genitourinary departments were implemented the present workload of the department would be increased.

Cervix Uteri↗