Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use

Studies have shown that oral contraceptive use may protect against pelvic inflammatory disease (PID), but it is not known whether oral contraceptives protect against the disease among women already infected with Chlamydia trachomatis or Neisseria gonorrhoeae. The relationship between oral contraceptive use and PID was analyzed in a case-control study of 141 women with verified PID and 739 randomly selected, sexually active women with no clinical evidence of the disease. Case and control subjects were stratified on the basis of infection with C trachomatis, N gonorrhoeae, or neither organism. Among women infected with C trachomatis alone, those with PID were less likely than control subjects to use oral contraceptives. The association was significant when oral contraceptive use was compared with nonuse (odds ratio, 0.22; 95% confidence interval, 0.08 to 0.64) and with noncontraception (odds ratio, 0.17; 95% confidence interval, 0.06 to 0.53) and remained so after adjusting for potential confounding variables by logistic regression analysis. Among women infected with N gonorrhoeae alone, no association was found between use of oral contraceptives and PID. These data suggest that oral contraceptive use protects against symptomatic PID among women infected with C trachomatis but not among those infected with N gonorrhoeae.     

The effect of toremifene therapy on serum immunoglobulin levels in breast cancer.

Estrogens and anti-estrogens enhance the number of immunoglobulin (Ig)-secreting cells in pokeweed mitogen (PWM)-stimulated lymphocyte cultures. Lymphocytes from patients who have received anti-estrogen therapy show similar enhancement of Ig-secreting cells after PWM stimulation. In this study the effect of anti-estrogen (toremifene) therapy on serum immunoglobulin (IgA, IgM, IgG) levels in breast cancer patients was investigated. Serum Ig levels were followed up to two years after or during the therapy. An unexpected finding was that the Ig levels decreased during the follow-up period. This decrease was seen in patients who responded to the therapy as well as in those who did not.     

Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts

OBJECTIVES

The purpose of this study was to provide clinical and anatomical characteristics as well as genetic background of a malignant arrhythmogenic disorder.

BACKGROUND

An inherited autosomally dominant cardiac syndrome causing stress-induced polymorphic ventricular tachycardia and syncope in the absence of structural myocardial changes was detected in two families.

METHODS

Two unrelated families with six victims of sudden death and 51 living members were evaluated. Resting and exercise electrocardiograms (ECG), echocardiography, magnetic resonance imaging (MRI), cineangiography, microscopic examination of endomyocardial biopsies and a drug testing with a class IC antiarrhythmic agent flecainide were performed. A genetic linkage analysis was carried out to map the gene locus.

RESULTS

Of the 24 affected individuals, 10 had succumbed with six cases of sudden death, and 14 survivors showed evidence of disease. Exercise stress test induced ventricular bigeminy or polymorphic ventricular tachycardia in affected individuals. Three children initially examined before 10 years of age developed arrhythmias during a four-year follow-up. Resting ECGs were normal in affected subjects except a slight prolongation of the QT intervals adjusted for heart rate (QTc) (430 ± 18 vs. 409 ± 19 ms, affected vs. nonaffected, p < 0.01). Administration of flecainide did not induce ECG abnormalities encountered in familial idiopathic ventricular fibrillation. Ventricular volumes, contractility and wall measurements were normal by echocardiography, right ventricular cineangiography and MRI. Histopathological examination showed no fibrosis or fatty infiltration. The cumulative cardiac mortality by the age of 30 years was 31%. The disease locus was assigned to chromosome 1q42–q43, with a maximal pairwise lod score of 4.74 in the two families combined. Only one heterozygous carrier was clinically unaffected suggesting high disease penetrance in adulthood.

CONCLUSIONS

A distinct cardiac disorder linked to chromosome 1q42–q43 causes exercise-induced polymorphic ventricular tachycardia in structurally normal hearts and is highly malignant. Delayed clinical manifestation necessitates repeated exercise electrocardiography to assure diagnosis in young individuals of the families.     

Induction of Proliferation in Isolated Guinea Pig Gastric Epithelium During Restitution After Superficial Injury

Immediate repair of the gastrointestinalepithelium after superficial injury is calledrestitution. It is based on the migration of thesurviving mucoid neck cells over the area of injury. Theinvolvement of growth factors in the process has beenrecently documented. They are known to enhance theprocess (ie, EGF, FGF, TGF-) and to activate thebasolateral Na⁺-H⁺-antiport (EGF).They may exert their effect by activating intracellular tyrosinekinases or by inducing chemotaxis. Yet, their precisemechanism of action in the process is unknown. The aimof the present study was to investigate the effect of modulation of the signal transductionpathway on the occurrence of proliferative mucoid neckand foveolar cells in guinea pig gastric epithelium.Therefore guinea pig gastric epithelium was mounted in Ussing chambers in vitro and perfused 4 hrafter superficial injury with 1.25 M NaCl. The potentialdifference over the epithelium and tissue resistancewere recorded simultaneously. The tissue was exposed either to cycloheximide, genistein, or to4-phorbol myristate 13-acetate (PMA) during the 4-hrrecovery, and the expression of proliferative cells wasassessed by staining the tissue for proliferative cells (Ki-67). The mean proliferative index oftissues subjected to NaCl injury was significantlyhigher than that of uninjured control tissues after 4 hrof restitution. Inhibition of the signaling pathway with genistein decreased the proliferative indexsignificantly, while its stimulation with phorbolmyristate increased it. Both electrophysiologic andmorphologic restitution were sensitive to genistein, but not to PMA or cycloheximide. Superficialepithelial injury results in a significantly increasedoccurrence of proliferative cells in isolated guinea piggastric epithelium. This endogenous activation of the tissue is sensitive to inhibition bytyrosine kinases and to stimulation by protein kinases.Electrophysiologic and morphologic recovery are alsoaffected by the modulation of the signaling pathway. This suggests that it is involved in theimmediate repair process.     

Interactions between human papillomavirus and other sexually transmitted agents in the etiology of cervical cancer

The interplay between human papillomavirus, notably type 16, and HIV in cervical carcinogenesis leads to persistent infection and cervical neoplasia by destruction of the afferent arm (Langerhans cells) of the host immune system. The joint effect takes place at the early stages of squamous intraepithelial lesions and has severe consequences if left untreated. The recent increase of cervical cancer mortality in young women in developed countries may well be a result of the HIV epidemic. Infection with Chlamydia trachomatis is associated with cervical squamous cell carcinoma but not with cervical adenocarcinoma, and the association remains after adjusting for human papillomavirus 16. Joint effects of C. trachomatis and the human papillomaviruses have not been studied at the population level but indirect evidence from epidemiological studies suggests that the interaction might be different (synergistic versus antagonistic) at different stages (cervical intraepithelial neoplasia versus invasive cervical cancer) of cervical carcino-genesis. Concomitant exposure to human papillomaviruses 6 or 11 and human papillomavirus type 16 has not been shown to result in excess risk of cervical squamous cell carcinoma. This antagonistic joint effect was also discovered between human papillomavirus types 18 and 16, as well as 33 and 16. Herpes simplex virus type 2 antibodies are associated with a modest risk of cervical cancer, which is not surprising since the presence of herpes simplex virus antibodies reflects risk-taking sexual behaviour. However, no excess risk remains after adjustment for human papillomavirus type 16, and no interaction between these two viruses has been found in epidemiological studies. Evidence of interaction between human papillomavirus type 16 and the other members of the herpesvirus family is still at an experimental level and difficult to judge. Little progress has been made in the most promising experimental association between the oncogenic human papillomaviruses and adeno-associated viruses. In addition to the well established interaction between human papillomaviruses and HIV, intriguing interactions are emerging between the human papillomaviruses and C. trachomatis, as well as between the different human papillomavirus types.     

Clinical presentation and outcome of listeriosis in patients with and without immunosuppressive therapy.

Seventy-four cases of systemic listeriosis occurring from 1971 to 1989 in the greater Helsinki area in Finland are reviewed with a special interest in the effect of preceding immunosuppressive therapy on the clinical presentation. Of these patients, 66% had an underlying disease, most commonly malignancy, diabetes mellitus, or renal transplantation, and 43% had received immunosuppressive therapy within 1 week before onset of listeriosis. Bacteremia and central nervous system infections (both in 43% of cases) were the most common clinical entities. The percentage of patients with meningitis was not greater among immunosuppressed patients (13/32, 41%) than among patients with underlying diseases not treated with immunosuppressive agents (9/16, 56%) or among previously healthy nonpregnant hosts (7/11, 64%). Immunosuppressed patients did not die more frequently than did those with underlying diseases not treated with immunosuppressive therapy (case fatality rate, 29% vs. 38%, respectively). However, all previously healthy non-neonatal patients survived, whereas 32% (15/47) of those with any kind of underlying disease succumbed.     

Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis

To define and quantitate histologic changes in the endometrium that best correlate with documented upper genital tract infection (UGTI) and laparoscopically diagnosed acute salpingitis, we studied endometrial biopsy specimens from 69 consecutive patients with clinically suspected acute pelvic inflammatory disease (PID) who underwent microbiological evaluation for UGTI and laparoscopic examination for acute salpingitis. Both UGTI and acute laparoscopically confirmed salpingitis were present in 37 patients (54%), UGTI without salpingitis in 1 (1%), salpingitis without UGTI in 11 (16%), and neither UGTI nor salpingitis in 20 (29%). Chlamydia trachomatis or Neisseria gonorrhoeae UGTI was found in 34 women, Escherichia coli in two patients, Peptococcus magnus in one woman, and with Streptococcus agalactiae in one woman. The following features were correlated both with UGTI and with salpingitis: presence of any neutrophils in the endometrial surface epithelium; neutrophils within gland lumens; dense subepithelial stromal lymphocytic infiltration; any stromal plasma cells; and germinal centers containing transformed lymphocytes. The simultaneous presence of five or more neutrophils per X 400 field in endometrial surface epithelium, together with one or more plasma cell per X 120 field in endometrial stroma, was the best predictor of UGTI plus salpingitis. This combination had a sensitivity of 92% and a specificity of 87% for predicting the diagnosis of both UGTI and laparoscopically confirmable acute salpingitis. Prospective studies are needed to assess the usefulness of these criteria.     

Binding of progestins to the glucocorticoid receptor: Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes

A number of physiological and synthetic progestins were tested for their ability to compete with [³H]dexamethasone for the binding to the glucocorticoid receptor of human mononuclear leukocytes and their ability to elicit glucocorticoid-like effects on the same cells. As compared to the reference compound dexamethasone (relative receptor binding affinity defined as 100%), two potent synthetic progestins with a pregnane-type structure, megestrol acetate and medroxyprogesterone acetate, were found to display a considerable binding affinity towards the receptor (46 and 42%, respectively). The relative binding affinity of the naturally occurring ligand, cortisol, to the receptor was clearly lower (25%). The effective binding of medroxyprogesterone acetate to the glucocorticoid receptor was confirmed by direct binding studies utilizing a tritiated derivative of this steroid. No evidence for the existence of a specific progesterone receptor in human mononuclear leukocytes was obtained as judged by the results of competition experiments where a progesterone receptor-specific ligand [³H]Org 2058 was used. Medroxyprogesterone acetate and megestrol acetate also induced glucocorticoid-like effects on the lymphocyte functions. These included inhibition of the proliferative responses to the T-cell mitogens concanavalin A and phytohaemagglutinin and an enhanced accumulation of immunoglobulin secreting cells in pokeweed mitogen-stimulated cultures. The progestin effect appears to be mediated through a radiosensitive (suppressor) subpopulation of T lymphocytes. In contrast, the synthetic progestins related structurally to 19-nortestosterone, norethisterone and d-norgestrel, were virtually devoid of binding affinity towards the glucocorticoid receptor nor did they measurably influence the in vitro lymphocyte functions. These studies demonstrate that certain progestins in common clinical use probably possess inherent glucocorticoid activity and suggest that side effects attributable to this character (e.g. suppression of the pituitary-adrenal axis) might be expected when these compounds are used in pharmacological doses.     

Intrauterine contraceptive device use in patients with acute salpingitis

The frequency of intrauterine contraceptive device (IUD) use among 144 hospitalized women with acute salpingitis was compared with that of 229 control women, who were symptomless sexual partners of men examined for non-gonococcal urethritis. The relative risk for salpingitis was higher for IUD than in the group of basal level of disease (p < 0.02). This was mostly caused by the high relative risk in the women with no deliveries. Oral contraceptives showed a contrary picture, the relative risk was significantly lower than on the basal level (p < 0.01). Non-gonococcal and gonococcal infections were equally represented in salpingitis patients with IUDs. The severity of the infection in IUD users did not differ from that of non-IUD users.