Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy.

BACKGROUND: The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. METHODS: The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. RESULTS: In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. CONCLUSIONS: Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Peri-implantation glucocorticoid administration for assisted reproductive technology cycles.

BACKGROUND: In order to improve embryo implantation in in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles, the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intra-uterine environment by acting as immuno modulators to reduce the uterine NK cell count, normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation. OBJECTIVES: To investigate whether the administration of glucocorticoids around the time of implantation improves clinical outcomes in subfertile women undergoing IVF or ICSI, compared to no glucocorticoid administration. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group's trials register (February 2006), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2006), EMBASE (1976 to June 2006), CINAHL (1982 to June 2006) and Science Direct (1966 to June 2006) were searched. Reference lists of relevant articles and relevant conference proceedings were also hand searched. SELECTION CRITERIA: All randomised controlled trials (RCTs) addressing the research question were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility and quality of trials and extracted relevant data. MAIN RESULTS: Thirteen studies (1759 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported. AUTHORS' CONCLUSIONS: Overall, there is no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improves clinical outcome. The use of glucocorticoids in women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance. These findings are limited to the routine use of glucocorticoids and cannot be extrapolated to women with auto-antibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.

Medical equipment libraries: implementation, experience and user satisfaction.

The hospital-wide pooling and sharing of certain types of medical equipment can lead to both significant improvements in patient safety and financial advantages when compared with a department or ward-level equipment ownership system. In September 2003, a Medical Equipment Loan Service (MELS) was established, focusing initially on infusion pumps. The aims and expected benefits included; improving availability of equipment for both patients and clinical users, managing and reducing clinical risk, reducing equipment diversity, improving equipment management and reducing the overall cost of equipment provision. A user survey was carried out in 2005 and repeated in 2011. The results showed wide and continued satisfaction with the service. The process and difficulties of establishing the service and its development to include additional types of equipment are described. The benefits of managing medical equipment which is in widespread general use, through a MELS as part of a Clinical Engineering Department, are presented.

Increased incidence of postoperative infections associated with peritoneal dialysis in renal transplant recipients.

BACKGROUND: Infection is a frequent postoperative complication in renal transplant recipients. However, little information is available concerning the effect of pretransplantation dialysis modality on posttransplantation complications including infection. We therefore evaluated the effect of hemodialysis (HD) versus peritoneal dialysis (PD) on the incidence of postoperative infection as well as several other posttransplantation outcomes. METHODS: A retrospective analysis was performed using medical records covering the period 30 days after transplantation of 156 dialysis patients who underwent renal transplantation at a single center during a 22-month period. Of these patients, 103 received only HD, 32 received only PD, 13 received PD in the past and HD immediately before transplantation (PH/HD), and 8 received HD in the past and PD immediately before transplantation (HD/PD). The presence of culture-proven infection, types of infecting organisms, length of initial hospital stay, and incidence of rejection during the first 30 days after transplantation were determined for each patient. RESULTS: All groups were similar with regard to age, race, gender, underlying disease, donor type, incidence of delayed graft function, and perioperative antibiotic prophylaxis. There were more infectious complications within 30 days after transplantation in patients on PD just prior to transplantation (PD and HD/PD) than in HD patients (67.5% vs. 25.9%, P<0.00001). When types of infectious organisms were assessed, PD patients were found to have a greater incidence of infections with microorganisms that colonize human skin (P<0.0001). The median length of hospital stay was 3 days longer for PD patients and 6.5 days longer for HD/PD patients than for patients receiving HD (P=0.01 and 0.04), and PD and HD/PD patients were more likely to have an episode of rejection than HD patients (P=0.02). CONCLUSIONS: Renal replacement therapy with PD immediately before transplantation negatively affects outcome as compared with HD, predisposing patients to a greater incidence of postoperative infections and rejection and a longer hospital stay. Further study in a randomized controlled trial may help determine how adjustment of the dialysis method can optimize transplantation outcome.

Use of renal allografts from donors positive for hepatitis B core antibody confers minimal risk for subsequent development of clinical hepatitis B virus disease.

BACKGROUND: The risk associated with transplantation of renal allografts from hepatitis B virus core antibody-positive (HBcAb(+)), hepatitis B virus surface antigen-negative (HBsAg(-)) donors is not well defined. METHODS: Over 4 years, we performed 45 kidney transplants from IgG HBcAb(+), IgM HBcAb(-), HBsAg(-) donors into recipients with a history of prior hepatitis B virus (HBV) infection or reported vaccination. We examined HBV-related outcomes in these 45 patients, in comparison with 45 recipients of allografts from HBcAb(-) donors (matched for transplant type, date, and pretransplant HBV antibodies). We sought evidence for HBV transmission by testing posttransplant sera for the presence of HBcAb, hepatitis B virus surface antibody, and HBsAg. Additionally, we analyzed alanine aminotransferase profiles and allograft survival rates for all patients. RESULTS: No patient receiving an allograft from an HBcAb(+) donor developed clinical HBV infection. No patient receiving an allograft from an HBcAb(+) donor had HBsAg detected through retrospective testing of stored sera or through prospective routine clinical evaluation and care. However, among the HBcAb(+) kidney recipients, 27% developed new HBcAb and/or hepatitis B virus surface antibody after transplant; in contrast, only 4% of control patients developed new antibody responses (relative risk=4.94; confidence interval 1.07-22.83). Among the recipients of HBcAb(+) organs, 18% developed elevated transaminases after transplant, in comparison with 36% of the controls. No association was found between "seroconverter" status and elevated alanine aminotransferase profiles in either group. CONCLUSIONS: Transplantation of renal allografts from HBcAb(+), HBsAg(-) donors was not associated with clinically detectable HBV disease or antigenemia. However, recipients had a significantly increased risk of HBV seroconversion, consistent with exposure to HBV antigen. These results suggest that HBcAb(+) kidneys can be safely used if transplanted into appropriate recipients, but highlight the need for effective HBV vaccination and vaccine-response monitoring in potential recipients.

Anti-CD4 antibodies are associated with HIV-1 seroconversion and may be detectable before anti-HIV-1 antibodies. The Multicenter AIDS Cohort Study.

We examined the sera from 14 HIV-1 seroconverters for the presence of autoantibodies against CD4. Anti-CD4 antibodies were detected in the serum of 11 of 13 HIV-1-infected persons at the time of HIV-1 seroconversion. In 6 of 14 persons from whom a serum was obtained prior to HIV-1 seroconversion, anti-CD4 antibodies were found 90 to 540 days before antibodies to HIV-1 were detectable. In comparison, anti-CD4 antibodies were present in only 7 serum samples from 62 HIV-1 seronegative individuals, including 50 from a seronegative homosexual male cohort. These results suggest that anti-CD4 antibodies are generated in response to early HIV-1 infection and possibly could be used as a marker for HIV-1 infection in some infected persons who are seronegative for HIV-1.

Anti-CD4 anti-idiotype antibodies in volunteers immunized with rgp160 of HIV-1 or infected with HIV-1.

We examined the sera of volunteers vaccinated with recombinant gp160 of human immunodeficiency virus type 1 (HIV-1) and control volunteers for the presence of anti-(anti-gp160 idiotype) antibodies which antigenically mimic gp160 and, therefore, bind to CD4 on human cells. Anti-CD4 antibodies were detected in the sera of 3 of 5 rgp160 recipients and 1 of 5 controls by indirect immunofluorescence using CD4-transfected HeLa cells or enzyme-linked immunosorbent assay (ELISA) using recombinant soluble CD4 as the solid phase. The control volunteer who was positive subsequently developed antibodies to HIV-1 by Western blot analysis. The anti-CD4 antibodies detected in the sera of the rgp160 vaccinees and the control volunteer appeared to be anti-idiotypic in nature, reacting with a paratope expressed on goat anti-gp160 antibodies but not on antibodies from normal goat serum. Binding to either transfected CD4+ HeLa cells or blotted anti-gp160 serum could be inhibited by preincubating the anti-CD4 serum with soluble CD4, or preincubating the cells or blotted anti-gp160 serum with recombinant gp160. Anti-CD4 antibodies were initially detectable only after the antibody response to gp160 began to decrease in the vaccinees, and the HIV-1-infected volunteer mounted a detectable anti-HIV-1 antibody response only after a decline in the anti-CD4 antibodies in his serum. These data strongly suggest that anti-CD4 antibodies which are anti-idiotypic to a paratope expressed on anti-gp160 antibodies are generated in response to both vaccination with rgp160 and infection with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of interferon on 3T3-L1 cell differentiation.

Mouse 3T3-L1 fibroblasts, after attaining confluence, slowly differentiate functionally and morphologically into adipose cells. This conversion, characterized by a great accumulation of lipids, mostly triglycerides, is hastened by added insulin. The cells are relatively sensitive to the antiviral action of mouse fibroblast interferon (IF). Most cells treated with insulin in the presence of partially or highly purified interferon fail to differentiate. IF-treated cell cultures have far fewer adipose cells and much less lipid that replicate control cultures likewise stimulated to differentiate. The greatest differences are noted in the intracellular levels of triglycerides, cholesterol, and cholesterol esters, as well as in the incorporation of [14C]acetates into Folch-extractable lipids. Variously inactivated or mock IF preparations as well as several heterologous species interferons fail to inhibit 3T3-L1 differentiation. Thus, interferon appears to alter the program of events involved in the conversion of 3T3-L1 fibroblasts into adipose cells.

Identification of GPCMV infected cells in vitro and in vivo with a monoclonal antibody.

A monoclonal antibody was made which identifies a 160-180 kDa structural protein in guinea pig cytomegalovirus (GPCMV) infected cells by Western blot using non-reducing conditions. This protein was shown to be a virion structural protein by purification of GPCMV on a density viscosity gradient and Western blot analysis. Phosphoanacetic acid (PAA) experiments suggest that the protein is a late GPCMV protein. In vitro the monoclonal antibody labels a cytoplasmic protein in infected guinea pig embryo fibroblasts by 12 h postinfection. The monoclonal antibody also identifies GPCMV infected cells in vivo in paraffin embedded formalin fixed tissue.

Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis.

OBJECTIVES: A highly effective treatment for interstitial cystitis (IC) remains elusive. We determined whether sacral third nerve root (S3) percutaneous neurostimulation (PNS) might be effective in relieving symptoms of IC, as well as in normalizing urinary factors that are specifically altered in IC. METHODS: Six consecutive patients with symptoms and cystoscopic findings compatible with IC underwent 5 days of continuous S3 neurostimulation by way of leads placed percutaneously into the S3 foramen. Patients filled out voiding frequency diaries and pain and urgency questionnaires before PNS and at the end of PNS when the leads were removed. Urine specimens were collected at these two time points and measured for heparin-binding epidermal growth factor-like growth factor (HB-EGF) by enzyme-linked immunosorbent assay and for antiproliferative factor (APF) activity by (3)H-thymidine uptake by normal human bladder urothelial cells. RESULTS: S3 PNS significantly improved all measured parameters toward normal values. Voiding frequency decreased twofold from 23.1 +/- 4.6 to 10.6 +/- 4.0 voids daily during PNS (P = 0.0001). Pelvic pain on a scale of 1 to 10 decreased from 7.0 +/- 1.6 to 2.3 +/- 3.2 (P = 0.05). Urinary urgency on a scale of 1 to 10 decreased from 6.0 +/- 2.2 to 1.8 +/- 1.7 (P = 0. 02). Urinary HB-EGF concentration increased sevenfold from 1.5 +/- 2. 1 to 11.0 +/- 1.7 ng/mL (P <0.0001), and urinary APF activity decreased from -76.1% +/- 31% to -4.5% +/- 8.8% (P = 0.005). CONCLUSIONS: S3 PNS significantly decreased symptoms and normalized urinary HB-EGF and APF activity in patients with IC. These results suggest that permanent S3 PNS may be beneficial in treating IC.

Polymerase chain reaction amplification of bacterial 16s rRNA genes in prostate biopsies from men without chronic prostatitis.

OBJECTIVES: A previously reported study using nested polymerase chain reaction (PCR) analysis indicated the presence of DNA from a variety of prokaryotic microorganisms in 77% of transperineal prostate biopsies from patients with chronic nonbacterial prostatitis. Because that study did not include a control group, we investigated whether microbial DNA could also be found in transperineal prostate biopsies obtained from men who did not have a history of prostatitis. METHODS: Transperineal biopsies of both lobes of the prostate were obtained under ultrasound guidance from 9 patients with localized adenocarcinoma of the prostate. DNA was extracted from the prostatic tissue and two-round amplification performed using nested primers from a highly conserved region of the bacterial 16s rRNA gene. Amplified DNA was purified and sequenced, and sequences obtained were compared to bacterial rRNA genes recorded in GenBank. Results. Eleven of 18 biopsy specimens from 8 of 9 patients were positive for bacterial DNA by PCR. Sequence data indicated a predominant organism in 8 of 11 specimens, with greater than 95% homology to DNA from several different genera of bacteria, including Escherichia and Bacteroides. All 9 control samples from the instruments before biopsy were negative. CONCLUSIONS: The presence of bacterial 16s rRNA genes in prostatic tissue is not specific for chronic prostatitis and occurred in most of our patients with localized prostate cancer. Whether the presence of such bacteria is related to the development of prostatic diseases such as prostatitis or prostatic cancer will require carefully controlled trials, including appropriate control groups examined identically.

A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls.

OBJECTIVES: Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder of unknown etiology. We tested the hypothesis that a microorganism would be found at higher prevalence in urine or bladder tissue from women with IC than from control women. METHODS: Urine and bladder tissue were obtained at cystoscopy from 11 IC patients and 7 control subjects. These specimens were cultured for a variety of fastidious and nonfastidious bacteria, mycobacteria, fungi, and viruses. In addition, special staining techniques were used to examine biopsy specimens and cytospun urine, and tissue sections and outgrowths of explanted bladder cells were examined by electron microscopy. RESULTS: Cultures of urine from 6 of 11 IC patients grew five different bacteria (Corynebacterium sp. Klebsiella pneumoniae, Lactobacillus sp, Streptococcus constellatus, and Streptococcus morbillorum), human cytomegalovirus, or Torulopsis glabrata; one of these organisms (Lactobacillus sp) was found in urine from 2 patients. Although contamination by urethral organisms is possible, the prevalence of microorganisms in urine of IC patients (6 of 11) was significantly greater than in urine of control subjects (0 of 7) (P < 0.05). Acridine orange staining revealed rods with appropriate morphology in urine from 4 of the 5 IC patients who had positive bacterial cultures and yeastlike organisms in urine and bladder tissue specimens that grew Torulopsis. Additionally, rodlike organisms were seen in urine from 2 IC patients with negative bacterial cultures and cocci were seen in the urine of 1 control patient. Biopsy specimens from 2 IC patients grew Torulopsis sp or Lactobacillus sp, in agreement with the results of acridine orange staining and culture of urine from these patients; in contrast, specimens from 3 control subjects grew small numbers of Pseudomonas sp or Staphylococcus epidermidis, but no organisms were cultured from urine or seen in acridine orange-stained tissue smears. All other cultures and stains were negative. CONCLUSIONS: These data do not provide evidence that IC is associated with infection or colonization by a single microorganism. However, they do generate the hypothesis that the prevalence of microorganisms, especially bacteria at low concentrations, is greater in the urine of IC patients than of control subjects. If these results are confirmed by other controlled studies, the question of whether the presence of these organisms is a cause or a result of IC should be addressed.

A diagnostic in vitro urine assay for interstitial cystitis.

OBJECTIVES: A low molecular weight urine factor that inhibits the proliferation of normal bladder epithelial cells in vitro was previously shown to be present significantly more often in the urine of patients with interstitial cystitis (IC) than in the urine of asymptomatic age-, race-, and sex-matched control subjects. We sought to determine the specificity of this finding for IC by determining whether the urine of patients with other urogenital inflammatory disorders also contains a factor that inhibits bladder epithelial cell proliferation. METHODS: Urine was collected from women with IC, acute bacterial cystitis, or vulvovaginitis, as well as from asymptomatic control women. The proliferation of primary normal adult bladder epithelial cells was determined by measuring 3H-thymidine incorporation in vitro. RESULTS: Osmolality- and pH-corrected urine specimens from 50 (86%) of 58 women with IC significantly inhibited human bladder epithelial cell proliferation compared with 3 (8%) of 36 asymptomatic control women, 7 (12%) of 58 women with bacterial cystitis, and 0 (0%) of 12 women with vulvovaginitis (P < 0.001 for the comparison of mean percent change in 3H-thymidine incorporation with IC urine versus urine from each of the control groups). Optimal sensitivity and specificity values of 91.4% and 90.6%, respectively, were achievable at a cutoff of 25% inhibition of 3H-thymidine incorporation, using all three control groups. CONCLUSIONS: The measurement of urine antiproliferative activity may be a useful noninvasive means for diagnosing IC in women.

Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

The relation between immunoglobulin G antibodies to Chlamydia trachomatis and poor ovarian response to gonadotropin stimulation before in vitro fertilization.

OBJECTIVE: To determine whether a relation exists between previous exposure to Chlamydia trachomatis and impaired ovarian response to gonadotropin stimulation. DESIGN: Controlled clinical study. SETTING: Two university IVF centers. PATIENT(S): Two hundred forty-two patients receiving IVF treatment and 81 control patients. Ninety-four patients with a poor response to IVF, defined by cycle cancellation in response to a daily stimulation dose of 300 IU of FSH, and 148 patients with a good response were matched for age. Twenty-eight pregnant controls and 53 controls of proven fertility also were included. INTERVENTION(S): Serum samples were obtained from patients and controls. Serum levels of immunoglobulin (Ig) G antibodies to C. trachomatis were determined by ELISA. MAIN OUTCOME MEASURE(S): The prevalence of serum IgG antibodies to C. trachomatis in critically defined poor responders was compared with that of age-matched good responders. RESULT(S): A significantly higher proportion of poor responders had serum IgG antibodies to C. trachomatis compared with good responders (44.7% and 30.4%, respectively). Patients undergoing IVF had a significantly higher prevalence of IgG antibodies to C. trachomatis (36%) than did either pregnant or nonpregnant controls (12%). CONCLUSION(S): A significantly higher prevalence of serum IgG antibodies to C. trachomatis was observed in critically defined poor responders, suggesting a possible detrimental effect of C. trachomatis on subsequent ovarian function.

Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11beta-hydroxysteroid dehydrogenase RNA.

OBJECTIVE: To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11beta-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45(+), CD15(+) leukocytes was assessed semiquantitatively. DESIGN: Controlled study using semiquantitative assessment of 11beta-HSD mRNA. SETTING: University IVF center. PATIENT(S): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. INTERVENTION(S): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45(+), CD15(+) leukocytes from individual follicular fluid aspirates. MAIN OUTCOME MEASURES: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. RESULT(S): Periovulatory human oocytes; cumulus cells; CD45(+), CD15(+) leukocytes; and granulosa cells consistently express type 1 but not type 2 11beta-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11beta-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients. CONCLUSION(S): These studies of mRNA expression suggest that the enzymes present both in and around the periovulatory oocyte will favor a high-cortisol environment.

Triploid/diploid mosaicism (69XXY/46XX) presenting as severe early onset preeclampsia with a live birth: placental and cytogenetic features.

Triploid/diploid mosaicism was diagnosed following karyotyping of an infant with musculo-skeletal abnormalities delivered because of severe preeclampsia. An area of the placenta appeared unusual with histology suggestive of trophoblastic abnormality. The importance of detailed histopathological examination and ploidy and flow cytometry studies where diagnostic uncertainty exists are highlighted.

A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair.

Interstitial cystitis (IC) is a chronic bladder disease characterized by distinct bladder mucosal abnormalities, for which the etiology is unknown. Although the epidemiology of this disorder is similar to that of bacterial cystitis, prospective studies using sensitive culture techniques and polymerase chain reaction assay for a variety of microorganisms have failed to identify a specific infectious etiology for IC. We have identified a low-molecular-weight peptide in the urine of IC patients that inhibits the proliferation of normal bladder epithelial cells in vitro. We therefore propose a model of IC, in which this peptide inhibits bladder epithelial regeneration following damage (such as that caused by bacterial cystitis). The chronically damaged epithelium is prone to colonization with various microorganisms, and the resulting exposure to these microorganisms, other urinary antigens, and/or damaged epithelial cells prompts the low-level inflammatory response commonly seen in this disorder.