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PubMedDate not supplied

Epidemiologic and clinical characteristics of pelvic inflammatory disease associated with Mycoplasma hominis, Chlamydia trachomatis, and Neisseria gonorrhoeae.

We studied selected epidemiologic, clinical, serologic, and microbiologic findings and their interrelationships among 57 women with acute pelvic inflammatory disease (PID). Cervical cultures positive for Neisseria gonorrhoeae alone and for both N. gonorrhoeae and Chlamydia trachomatis were associated with young age, nulliparity, and use of birth-control pills. Positive serologic findings for C. trachomatis were associated with the isolation of C. trachomatis and/or N. gonorrhoeae from the cervix and predicted the presence of a pelvic mass. High levels of antibody to Mycoplasma hominis were associated with increasing age and parity, and predicted a low concentration of C-reactive protein (CRP), a long hospital stay, and a high convalescent-phase erythrocyte sedimentation rate (ESR). Women with recurrent PID had higher titers of antibody to C. trachomatis than those with primary PID. The use of an intrauterine contraceptive device predicted high CRP, high acute-phase ESR, long hospital stay, and was frequently associated with positive serologic tests for M. hominis. These results demonstrate that the clinical picture of PID depends not only on the microorganisms involved but also on many epidemiologic factors such as age, contraceptive method, and parity.

Acute Disease↗
PubMed1994

Clinical and microbiological characteristics of symptomatic vulvovaginal candidiasis in HIV-seropositive women.

OBJECTIVES: To evaluate the clinical and microbiological characteristics of symptomatic vaginal candidiasis in Human Immunodeficiency Virus (HIV)-seropositive women attending a gynaecologic outpatient clinic for sexually transmitted diseases (STDs). DESIGN: Vaginal, rectal and oral specimens from cases and controls were cultured for Candida spp. SUBJECTS: Eighty-four consecutive HIV-seropositive and 384 HIV-seronegative women with clinical signs of vulvovaginitis. SETTING: A gynaecological out-patient clinic in Pavia, Italy. RESULTS: The overall prevalence of vaginal candidiasis was 61.9% (52/84) in the cases and 32.3% (124/384; p < .001) in the controls. After adjustment by logistic regression analysis for confounding factors (age at first intercourse, lifetime sex partners, new partner/s in the last 6 months, type of contraceptive used), HIV-seropositive patients were at higher risk for both Candida albicans (odds ratio = 2.5; 95% confidence interval 1.31-4.69; p = 0.006) and Torulopsis glabrata vaginitis (OR = 3.5; 95% CI = 1.05-11.60; p = 0.04) than controls. HIV-seropositive subjects had also increased rates of oral and rectal colonisation with Candida spp. Finally, the time to recurrence of vaginal infection was significantly shorter in HIV-seropositive patients than controls and was correlated with the severity of HIV-induced immunodepression. CONCLUSIONS: Vulvovaginal candidiasis is very common in HIV-seropositive women and its prevalence is correlated with the immunological status of the host. These patients have higher frequencies of Torulopsis glabrata vaginal infection and are more prone to recurrence than HIV-seronegative controls.

AIDS-Related Opportunistic Infections↗
PubMed2006

Prasterone.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of prasterone are discussed. SUMMARY: Prasterone is a proprietary synthetic dehydroepiandrosterone product under investigation for use in women with systemic lupus erythematosus (SLE) who are taking glucocorticoids. Initial trials investigated prasterone as a treatment to improve disease activity and symptoms in women with mild to moderate SLE. The Food and Drug Administration (FDA) did not approve prasterone's labeling for these indications. Subsequent trials have focused on prasterone as a treatment to limit bone loss in women who have SLE. A study was conducted to assess bone mineral density in patients who had been taking glucocorticoids for six months or longer. The patients in the prasterone group showed an increase in bone mineral density, while the placebo group demonstrated a loss. The most common adverse effects of prasterone therapy were acne and hirsutism. Hematuria, hypertension, and serum creatinine concentration increases have also occurred. Interactions of prasterone potentially exist with 5-alpha reductase inhibitors and additive or antagonistic effects could possibly occur with androgens, estrogens, oral contraceptives, and progestins. In clinical trials, oral prasterone dosages of 100-200 mg/day were administered. These dosages have resulted in supraphysiological hormone levels. CONCLUSION: FDA has granted orphan drug status for the prevention of loss of bone mineral density in SLE patients taking glucocorticoids. FDA is requesting additional Phase III trial data for the treatment of SLE and the prevention of loss of bone mineral density.

Adjuvants, Immunologic↗
PubMed1999

Role of medical history in brain tumour development. Results from the international adult brain tumour study.

In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40-12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49-0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61-0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.

Adult↗
PubMedDate not supplied

A voluntary serosurvey and behavioral risk assessment for human immunodeficiency virus infection among college students.

The authors conducted a voluntary serosurvey and educational campaign among 3394 undergraduate students attending the University of Maryland at College Park to determine the prevalence of and risk factors for human immunodeficiency virus type 1 (HIV-1) infection. Two students were seropositive (0.06%, 95% confidence interval 0-0.15%). Both were homosexual men with multiple sexual partners. Despite the low prevalence of infection, potential risk factors for transmission of HIV-1 were common, as assessed by a self-administered anonymous questionnaire. These included a previous sexually transmitted disease (12.6%), male homosexual intercourse (4.8% of men), heterosexual anal intercourse (25.3%), heterosexual intercourse with a person at risk (an HIV-1 infected person, a bisexual man, a parenteral drug user, a female prostitute, or a hemophiliac) (5.2%), multiple sexual partners (21% reported 10 or more lifetime partners), and intravenous drug use (1.3%). Assessment of the efficacy of our program by comparing responses on pre- and post-test questionnaires showed gains in knowledge about heterosexual transmission of HIV-1 and an increase in the reported frequency of condom use 1-2 months after participating in the survey. The authors conclude that HIV-1 infections are occurring among college students but in our study group remain confined to persons with known high-risk behavior; however, practices that may support transmission are common, and programs designed to diminish these behaviors among college students are needed.

Adolescent↗
PubMed1990

Cells adherent to copper-bearing intrauterine contraceptive devices determined by monoclonal antibodies.

The presence of nucleated cells adherent to copper-bearing IUDs removed from successful IUD users, as well as from those IUD users with accidental pregnancy, was determined by a panel of monoclonal antibodies. A significant decrease in the percentage of CD3+ cells-mature T lymphocytes was found in the cell population adherent to IUDs removed from pregnant compared to non-pregnant uteri (43 +/- 2.6 vs 34 +/- 1.5). Among these cells, the percentage of CD4+ cells was increased (from 22.9 +/- 1.9 to 30.4 +/- 2.0), and CD8+ was decreased (from 23 +/- 0.9 to 10.8 +/- 1.2). The percentage of HLA-DR+ cells was also decreased (from 24.3 +/- 1.7 to 16.7 +/- 1.8). B4+ cells (B lymphocytes) were present in a similar percentage on IUDs removed from pregnant as well as from non-pregnant uteri. Thus, the uterine cavity in the presence of an IUD, contains a consistent population of immunologically competent cells. The question still remains, whether the change in the number of nucleated cells present in the uterine cavity with an IUD could contribute to its antifertility effect.

Adhesiveness↗
PubMed2005

Sympathetic and T helper (Th)2 bias may ameliorate uterine fibroids, independent of sex steroids.

We propose that inadequate sympathetic bias and Th2 bias in the uterine environment contributes to the formation of fibroids, independent of the sex steroid status. We also propose that fibroids represent a modern maladaptation that partly results from decreasing exposure to seminal fluid, which contains catecholalmines, transforming growth factor beta1 (TGFbeta1), aldosterone, prostaglandins, and other factors that shift the uterine environment to sympathetic and T helper (Th)2 bias. Lower risk of fibroids is associated with pre-menarche, post-menopause, pregnancy, exposure to contraceptives, smoking, earlier age of first pregnancy, shorter interval since last pregnancy, higher parity, and non-obesity. These associations are currently attributed to alterations of sex steroids. However, the association may also be explained by the observation that pre-menarche, post-menopause, pregnancy, and smoking represent periods of sympathetic and Th2 bias. Furthermore, use of contraceptives, early age of first pregnancy, short interval since last pregnancy, high parity, abnormal pap smear, and non-obesity may represent surrogates for increased sexual activity and increased exposure to seminal fluid. Catecholalmines, aldosterone, TGF, and prostaglandins are among the seminal fluid components that promote sympathetic and Th2 bias. Vasectomized copulations protect against fibroids, an observation that undermines the steroid hypothesis and supports our hypothesis. The putative mechanism of action of uterine artery embolization (UAE) for fibroid treatment is starvation of blood supply, but the extensive collaterals that protect uterine perfusion would presumably also buffer against fibroid hypoperfusion. Instead, the sympathetic and Th2 responses to UAE-related ischemia may contribute to fibroid regression. A potential explanation for the association of fibroids with intrauterine devices may be a Th1 cell-mediated immune response to the foreign body, which may also enhance the contraceptive effect. Novel methods of preventing and treating fibroids by promoting sympathetic and Th2 shift through natural, pharmacologic, and neuromodulatory means are envisioned. Fibroids are likely a modern dysfunction given the high Darwinian fitness cost of fibroid-related infertility, and may be attributable to reduced intercourse frequency. Fibroids have been observed among animals in captivity that are presumably reproductively isolated.

Female↗
PubMed1998

Endometriosis. The case for early, aggressive treatment.

While the debate rages on regarding how metabolic and immunologic changes fit into the pathophysiology of endometriosis, the clinician must nonetheless make decisions regarding treatment. This article examines the relevant literature, with particular emphasis on immunologic aspects, nonclassic, early and deep disease as well as data on progression, recurrence and effects of treatment, to propose innovations in the management of early-stage disease. All symptomatic early-stage disease should be treated aggressively--even after conservative surgical resection of all apparent endometriosis, adjunct medical treatment in the form of a gonadotropin-releasing hormone agonist should be strongly considered.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Antisperm antibody: a monkey wrench in conception/magic bullet of contraception?

Antisperm antibodies can cause infertility by interacting with spermatozoa through immunoglobulin binding protein thereby blocking their penetrance of cervical mucus and/or by interfering with sperm-egg interaction. However, these antibodies appear not to be cytotoxic to embryos since a high implantation rate and consequently high pregnancy rate were achieved by IVF-ET treatment of women with antisperm antibodies. Also the finding that these antibodies do not appear to cause any deleterious clinical symptoms and have yet be associated with infertility suggested that sperm antigens are promising candidates in the development of immunocontraceptives. Some synthetic peptides corresponding to segments of human sperm antigens have effectively induced infertility in female rats when administered as an immunogen. Different peptides, adjuvants and routes of administration should be studied to determine the optimum conditions for inducing high antisperm antibody titers in the host. Moreover, identification of various steps and factors that are involved in regulating the production of antisperm antibodies such as immunoglobulin binding factor may open new paths in the treatment of immunological infertility and at the same time lead to a more effective immunocontraceptive.

Animals↗
PubMed1995

Dose effects of the gonadotropin-releasing hormone antagonist, Nal-Glu, combined with testosterone enanthate on gonadotropin levels in normal men.

OBJECTIVE: To test the hypothesis that over a 4-week treatment period, Nal-Glu GnRH antagonist ([AcD2Nal1, D4ClPhe2, D3Pal3, Arg5, DGlu6 [AA], DAla10] GnRH) at a dose of 200 micrograms/kg per day SC would suppress levels of immunologically active and biologically active LH and FSH more completely than a dose of 100 micrograms/kg per day. DESIGN: Placebo controlled clinical study. SETTING: A university community. SUBJECTS: Thirty normal male volunteers. INTERVENTIONS: We administered Nal-Glu at doses of 0, 100, and 200 micrograms/kg body weight per day in combination with T enanthate, 50 mg IM weekly, to separate groups of men (9 or 10 men per group) for 4 weeks. RESULTS: Serum levels of immunologically active and biologically active gonadotropins were suppressed similarly in both groups of men who received Nal-Glu; this suppression was significantly greater than in the men who received placebo + T. Local side effects were more severe in the Nal-Glu 200 micrograms/kg per day group. CONCLUSIONS: Administration of Nal-Glu in combination with T suppresses gonadotropins more completely than does T alone, but at doses > 100 micrograms/kg, gonadotropins are not suppressed additionally with larger doses of Nal-Glu. Subjects experienced greater local discomfort and side effects with the higher dosage. These findings suggest that dosages of Nal-Glu of > 100 micrograms/kg per day may have no advantage over the 100-micrograms/kg dose in a male contraceptive regimen.

Adult↗
PubMed2004

Nevirapine in the treatment of HIV.

Nevirapine (Viramune, Boehringer Ingelheim Ltd) is the first marketed non-nucleoside reverse transcriptase inhibitor. As with any antiretroviral drug, nevirapine should always be used as part of a fully suppressive regimen. Clinical studies have shown that nevirapine-containing regimens may accomplish durable virological and immunological responses in approximately half of all antiretroviral-naive patients. It can also be successfully used as a component of salvage therapies and as a part of a strategy to simplify protease inhibitor-containing regimens. Nevirapine has a beneficial effect on the lipid profile in both treatment-naive and -experienced patients. Nevirapine also has an important role in preventing mother-to-child transmission of HIV. It is usually well-tolerated with rash and liver toxicity being the most frequently reported adverse events. Nevirapine interacts with cytochrome P450 enzymes both as a substrate and as an inducer. For this reason, therapeutic drug monitoring should be recommended whenever nevirapine is used with protease inhibitors, methadone (Methadose, Rosemont Pharmaceuticals Ltd), oral contraceptives, rifampicin (Rifadin, Aventis Pharma) and other potentially interacting drugs. Nevirapine-resistant mutations are common to the non-nucleoside reverse transcriptase inhibitor family and they include K103N, V106A, Y181C, Y188C and G190A. A better understanding of the nevirapine profile will certainly contribute to ensuring that its clinical application becomes more effective and beneficial.

Animals↗
PubMed1997

Interactions between steroid hormones and viral oncogenes in the pathogenesis of cervical cancer.

Steroid hormones are frequently prescribed as anticontraceptive drugs to young women. Persistent papillomavirus infections particularly with high risk virus types are very common in younger women and were shown to be the strongest risk factor for the later development of cervical cancer. Steroid hormones interfere with persistent papillomavirus infections on various levels. They enhance the expression level of two viral genes, E6 and E7, which are required for the oncogenic activities of high risk papillomaviruses. In addition, they interfere with cellular gene functions involved in cell cycle regulation and programmed cell death, for example through inhibition of p53-mediated transcriptional transactivation of genes involved in cell cycle arrest and apoptosis. Furthermore, steroids inhibit the immunologically mediated resolution of minor HPV-induced cervical lesions, particularly through inhibition of major histocompatibility class I and class II antigen expression. These observations point to potent cocarcinogenic effects of steroid hormones in persistently papillomavirus infected individuals by enhancing the transforming activities of viral oncogenes and interfering with the efficient resolution of virus infected lesions. The clinical significance of these experimental observations requires careful analysis in prospective trials.

Apoptosis↗
PubMed1995

A strategy for identifying candidate sperm antigens for immunocontraception: isolation of human testis cDNA clones using polyclonal antisera directed against hamster acrosomal membrane preparation.

Components of the mammalian sperm acrosome that have been conserved during evolution are probably essential for fertilization and are therefore potential antigens for the development of an immunocontraceptive vaccine. In order to identify such protein components, a series of specific polyclonal antisera were generated by immunizing rabbits with purified acrosomal membrane fractions from hamster epididymal spermatozoa. Antisera were finally selected using immunological and in-vitro fertilization assays, and used to then screen a human testis lambda gt11 cDNA library. As a result of this screening over 70 clones were identified, selected and purified. The cDNAs were amplified by polymerase chain reaction (PCR) and the inserts characterized by restriction enzyme digestion and oligonucleotide probing techniques. The functional activity beta-galactosidase fusion proteins expressed by these clones (HA5-2, HA6-2 and HB4-1) inhibited significantly fertilization and reduced spermatozoa binding compared to controls. To date, sequence data has been obtained from HB4-1 (1.75 kb). The first 1132 nucleotides displayed > 96% homology to human testis-specific lactate dehydrogenase (LDH-C4) gene, the product of which is a known candidate antigen for a contraceptive vaccine. This finding suggests that a strategy involving the screening across species for conserved moieties of the mammalian acrosome may be useful for identifying candidate antigens for immunocontraception.

Acrosome↗
PubMed1976

In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay.

A sensitive bioassay for serum LH and hCG has been developed by utilization of the testosterone response of collagenase-dispersed rat Leydig cells to gonadotropic stimulation in vitro. Testosterone production by dispersed interstitial cells is stimulated by human, ovine, bovine, porcine, rat and rabbit LH, and by hCG and pregnant mare serum gonadotropin. The rat testis interstitial cell assay gives parallel dose-response curves for all steroidogenic gonadotropins tested, and thus permits cross-species comparison of the intrinsic biological activities of native and modified gonadotropins. The sensitivity of the rat interstitial cell bioassay is equal to or higher than that of radioimmunoassay, with detection limits of 50 muU for hMG and 20 muU for hCG. The optimum conditions for bioassay of serum gonadotropins were provided by incubation of dispersed interstitial cells in the presence of 1-methyl 3-isobutyl xanthine with the addition of gonadotropin-free serum or 5% BSA to ensure a constant proportion of serum protein in all assay samples and standards. Assays performed under these conditions gave parallel dose-response curves and identical maximum responses to both standards and serum samples containing endogenous LH or hCG. All responses to human gonadotropin standards and serum samples in the bioassay were abolished by incubation in the presence of antisera to LH or hCG. This sensitive and specific method permits bioassay of basal levels of LH in male and female serum, and of the higher gonadotropin levels in postmenopausal and pregnant subjects after appropriate dilution of the serum samples. For normal men and women, serum samples of 25-100 mul are employed, while volumes of 1-20 mul are adequate for assay of LH in postmenopausal or hypogonadal subjects. Serum LH values in hypopituitary and oral contraceptive-treated subjects were usually undetectable, while LH levels in normal subjects were always measurable with good precision. The within-assay coefficient of variation for measurement of a normal male plasma pool (30 mU/ml) was +/- 10%, and the between-assay variation was +/- 15%. The precision of the assay (lambda) was 0.035 +/- 0.015 (n = 72). In 42 normal females, the bio: immuno (B:I) ratio for serum LH was 1.20 +/- 0.40 (SD), and no consistent change in ratio was observed throughout the menstrual cycle. By contrast, significantly higher B:I ratios were observed in normal males (2.5 +/- 0.4), postmenopausal females (2.6 +/- 0.6) and patients with Turner's syndrome (2.6 +/- 0.6). These findings suggest that the LH circulating in normal female plasma is similar in biological and immunological activity to hMG, whereas the LH present in normal male plasma and in states of increased gonadotropin secretion has a relatively higher biological activity. The rat interstitial cell bioassay provides for the first time a practical and precise assay for measurement of the biologically active LH levels in serum of normal biologically active LH levels in serum of normal human subjects.

Animals↗
PubMed1983

An increase in high-molecular weight renin substrate associated with estrogenic hypertension.

We have previously reported that estrogens have the potential to induce new forms of renin substrate in addition to elevating the major circulating form of this protein. One of these estrogen-induced forms had a molecular weight in excess of 150,000. In this study we have compared the plasma concentration of the high-molecular-weight renin substrate in normotensive women receiving estrogen therapy and women with estrogenic hypertension. A statistically significant elevation of this protein was associated with estrogenic hypertension and normotensive pregnant women at term. This form of renin substrate differed from the major form with respect to electrophoretic mobility, isoelectric point, and immunologic cross-reactivity. In addition, kinetic analysis indicated that this high-molecular-weight substrate has a significantly higher affinity for the enzyme renin than the major circulating form (Km = 1800 +/- 290 versus 3520 +/- 260 ng angiotensin I equivalents/ml). These results suggest that in addition to renin substrate concentration, substrate composition may play an important role in blood pressure regulation.

Adult↗
PubMed1997

Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?

The major histocompatibility complex (MHC) is an immunologically important group of genes that appears to be under natural as well as sexual selection. Several hypotheses suggest that certain MHC-allele combinations (usually heterozygous ones) are superior under selective pressure by pathogens. This could influence mate choice in a way that preferences function to create MHC-heterozygous offspring, or that they function to create specific allele combinations that are beneficial under the current environmental conditions through their complementary or epistatic effects. To test these hypotheses, we asked 121 men and women to score the odours of six T-shirts, worn by two women and four men. Their scorings of pleasantness correlated negatively with the degree of MHC similarity between smeller and T-shirt-wearer in men and women who were not using the contraceptive pill (but not in Pill-users). Depending on the T-shirt-wearer, the amount of variance in the scorings of odour pleasantness that was explained by the degree of MHC similarity (r2) varied between nearly 0 and 23%. There was no apparent effect of gender in this correlation: the highest r2 was actually reached with one of the male odours sniffed by male smellers. Men and women who were reminded of their own mate/ex-mate when sniffing a T-shirt had significantly fewer MHC-alleles in common with this T-shirt-wearer than expected by chance. This suggests that the MHC or linked genes influence human mate choice. We found no significant effect when we tested for an influence of the MHC on odour preferences after the degree of similarity between T-shirt-wearer and smeller was statistically controlled for. This suggests that in our study populations the MHC influences body odour preferences mainly, if not exclusively, by the degree of similarity or dissimilarity. The observed preferences would increase heterozygosity in the progeny. They do not seem to aim for more specific MHC combinations.

Adult↗
PubMed2005

Immunocontraceptive approaches in females.

In the female reproductive system, there are multiple points, where immunointerception is feasible. Among these, the most promising are those that interfere immunologically at the level of sperm-egg interaction or neutralize human chorionic gonadotropin (hCG), which is required for the establishment and maintenance of pregnancy. Immunization studies in various animal models including non-human primates with zona pellucida (ZP) glycoproteins have demonstrated curtailment of fertility. To circumvent the ovarian pathology often observed following immunization with ZP glycoproteins, synthetic peptides devoid of 'oophoritogenic' T cell epitopes as immunogens have been proposed. Though of utility for controlling wildlife populations, its application in humans will have to wait till the safety of ZP glycoprotein vaccine is established beyond doubt. Clinical trials in women have established that immunocontraceptive vaccine based on Beta-subunit of hCG inhibits fertility. To make it a practical proposition, novel strategies have to be adopted to increase its immunogenicity so that 'contraceptive' antibody titers are achieved in near to 100% recipients.

Animals↗