Effect of aminoglycosides on the disposition of thyroid hormones and thyroglobulin.

Our study was designed to confirm the potential effects of three aminoglycosides on the disposition of thyroid hormones. Twenty-seven patients diagnosed with either cellulitis (n = 19), chronic osteitis (n = 4), or an abscess (n = 4) were selected. Thirteen patients received tobramycin, 60 to 100 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; seven patients received netilmicin, 40 to 120 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; and seven patients received either cloxacillin, 1.5 gm iv q. 4 h., or cefoperazone, 2 to 4 gm iv q. 12 h. for at least 7 days. Another group of six normal subjects received neomycin, 0.5 gm po q. 6 h. for 7 days. All these subjects had normal thyroid function before antibiotic dosing and none had thyroid function abnormalities. Tobramycin and cloxacillin/cefoperazone did not influence thyroid function. Netilmicin decreased the total serum concentrations of triiodothyronine (T3) from 114 +/- 9 to 75 +/- 7 ng/dl (P less than 0.01), probably because of increased clearance, as the T3 free fraction increased from 0.43% +/- 0.02% to 0.49% +/- 0.02% (P less than 0.05). Thyroxine (T4) and reverse T3 (rT3) levels were not affected. Neomycin decreased T3 levels from 104 +/- 8 to 92 +/- 7 ng/dl (P less than 0.05) and the serum concentrations of thyroglobulin from 17.3 +/- 2.0 to 11.7 +/- 2.0 ng/ml (P less than 0.001). Because T4 and rT3 levels did not change, our results suggest that neomycin may have directly affected the gland. We conclude that some aminoglycosides can alter the disposition of thyroid hormones.

Evidence for a defect of antibody-dependent cellular cytotoxic (ADCC) effector function and anti-HIV gp120/41-specific ADCC-mediating antibody titres in HIV-infected individuals.

Antibody-dependent cellular cytotoxicity (ADCC) is an important antiviral effector mechanism. However, its role, as well as the functional integrity of the ADCC-effector cells in HIV infections, is not well understood. For studying gp120/41-specific ADCC, we recently developed a virus-free target cell system, using a natural killer (NK) cell activity-resistant human lymphoid cell line of B lineage, which was transfected with the env gene of the human immunodeficiency virus type 1 (HIV-1); gp120/41-expressing cell clones were thus selected. In this study, these gp120/41-expressing cloned cells were used as targets in a gp120/41-specific ADCC assay for (a) examining the functional integrity of ADCC-effector cells from HIV-seropositive individuals, and (b) titrating the sera of these individuals for gp120/41-specific, ADCC-mediating antibodies. Our data indicate for the first time that the percentage of sera positive for ADCC-mediating antibodies to gp120/41 is higher in individuals with CD4 counts < or = 400 and > or = 200/mm3. The individuals with CD4 counts < 200/mm3 were found to have the lowest titers of these antibodies in their sera. The ADCC-effector function of the peripheral blood mononuclear cells (PBMC) of HIV-infected individuals was significantly (p < 0.05) reduced as compared to the PBMC from healthy, HIV-seronegative individuals. Further, human recombinant IL2 and interferon-gamma were found to exert a significant (p < 0.05) enhancing effect on ADCC mediated by PBMC from these HIV-infected individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional factors in the aetiology of multiple sclerosis: a case-control study in Montreal, Canada.

BACKGROUND: It has been suggested that nutrition and food patterns, particularly high consumption of animal fat and low intake of fish products, may play a role in the aetiology of multiple sclerosis (MS). METHODS: The relation between nutritional factors and MS was studied among 197 incident cases and 202 frequency matched controls in metropolitan Montreal during 1992-1995. Dietary information was collected by employing a 164-item food frequency questionnaire in a face-to-face interview. RESULTS: An inverse association was observed between high body mass index (BMI) and the risk of MS, with an odds ratio (OR) of 0.76 (95% confidence interval [CI]: 0.61-0.95), per 5-unit increase in BMI, both sexes combined. In addition, taller women showed a greater risk for MS; the OR per 10 cm increase in height was 1.58 (95% CI: 1.06-2.35). In continuous variable analyses, using the difference between the lowest and highest quartile of intake as a unit, a positive association was observed with energy and animal fat intake. The OR per 897 kcal increase was 2.03 (95% CI: 1.13-3.67) and 1.99 (95% CI: 1.12-3.54) per 33 g of animal fat intake above the baseline. A significant protective effect was observed with other nutrients, including vegetable protein, dietary fibre, cereal fibre, vitamin C, thiamin, riboflavin, calcium, and potassium. Similar trends were seen for males and females when analysed separately. With respect to specific foods (as opposed to nutrients), a higher intake of fruit juices was inversely associated with risk (OR = 0.82; 95% CI: 0.74-0.92). A protective effect was also observed with cereal/breads intake for all cases combined (OR = 0.62; 95% CI: 0.40-0.97) and for fish among women only; pork/hot dogs (OR = 1.24; 95% CI: 1.02-1.51) and sweets/candy (OR = 1.29; 95% CI: 1.07-1.55) were positively associated with risk. CONCLUSION: The study generally supports a protective role for components commonly found in plants (fruit/vegetables and grains) and an increased risk with high energy and animal food intake.

Dental amalgam and multiple sclerosis: a case-control study in Montreal, Canada.

BACKGROUND: The aetiology of multiple sclerosis (MS) remains poorly understood. Dental amalgams containing mercury have recently been suggested as a possible risk factor for MS. METHODS: In a case-control study conducted between 1991 and 1994, we interviewed a total of 143 MS patients and 128 controls, to obtain information on socio-demographic characteristics and the number of dental amalgams and the time since installation based on dentists' records. RESULTS: Neither the number nor the duration of exposure to amalgams supported an increased risk of MS. After adjustment for age, sex, smoking, and education those who had more than 15 fillings had an odds ratio (OR) of 2.57 (95% CI: 0.78-8.54) compared to those who had none; for individuals whose first amalgam was inserted more than 15 years prior to the study, we found an OR of 1.34 (95% CI: 0.38-4.72). CONCLUSIONS: Although a suggestive elevated risk was found for those individuals with a large number of dental amalgams, and for a long period of time, the difference between cases and controls was not statistically significant.

In-vitro anti-chlamydial activities of free and liposomal tetracycline and doxycycline.

The purpose of this study was to evaluate the anti-chlamydial activities in vitro of liposome-encapsulated doxycycline (Dox) and tetracycline (Tet) in comparison with free Dox and Tet. Dox and Tet encapsulated in cationic (CAL), anionic (ANL) and neutral (NTL) liposomes by sonication, were quantified by high-performance liquid chromatography. Anti-chlamydial activities were determined by addition of serial dilutions of antibiotics (MIC 0.12-0.007 mg/L; MBC 4-0.25 mg/L) to HeLa 229 cell monolayers inoculated with Chlamydia trachomatis L2/434/Bu (10(3) ifu/well). After incubation for 72 h at 37 degrees C, chlamydial inclusions were stained by the May-Grünwald Giemsa method to establish MICs. MBCs were determined in chlamydial agent-free medium after second passages. Dox-encapsulation efficiencies were 28.6 SEM 6.4% in cationic (CAL-Dox), 49.1 SEM 6.7% in anionic (ANL-Dox) and 21.0 SEM 0.8% in neutral (NTL-Dox) liposomes. Tet-encapsulation efficiencies were 3.5 SEM 0.3% in anionic (ANL-Tet) and 2.2 SEM 0.6% in neutral (NTL-Tet) liposomes; no Tet was detected in cationic (CAL-Tet) liposomes. MIC values were 0.06 mg/L for Dox, 0.12 mg/L for Tet, 0.03 mg/L for CAL-Dox, NTL-Dox and NTL-Tet, and 0.01 mg/L for ANL-Dox and ANL-Tet. MBCs were 4 mg/L for Tet, 0.5 mg/L for CAL-Dox and NTL-Dox, and 1 mg/L for Dox, ANL-Dox, ANL-Tet, NTL-Tet and NTL-Tet. For MICs, the relative increase in anti-chlamydial activity observed with liposomal formulations compared to the corresponding free antibiotic ranged from 2- to 6-fold with Dox and from 4- to 10-fold with Tet. For MBCs, the relative increases in anti-chlamydial activity were 2- and 4-fold with liposome-encapsulated Dox and Tet, respectively. Dox was better encapsulated than Tet in all liposomes. Liposome-encapsulated drugs showed greater anti-chlamydial activities than their free forms; thus, these drug formulations have potential in the treatment of chlamydial infections.

Efficient entrapment of amikacin and teicoplanin in liposomes.

A higher encapsulation rate was obtained using the dehydration-rehydration method compared with the reverse-phase evaporation technique in negative multilamellar vesicles with amikacin (AMK) (45% versus 15%; P < 0.05) and teicoplanin (TCP) (34% versus 25%; P < 0.05). The addition of 250 mM sucrose to AMK- or TCP-containing liposomes without prior drying prevented a significant decrease in antibiotic content in unilamellar and multilamellar vesicles over a 3-month period at -70 degrees C.

The role of laparoscopy in acute pelvic infections.

54 patients presented by history, physical examination and laboratory tests with suspected pelvic inflammatory disease (PID). The use of laparoscopy as a diagnostic tool proved in 13 cases (24%) that the presumptive diagnosis was incorrect. Bacteriological studies revealed chlamydial infection in 21 of 41 cases, in 6 cases only at laparoscopy in the pelvic cavity, gonococcal in 9 of 41 cases; mycoplasmas were identified in 15 cases, being the only pathogen in 7. In 9 cases, no recognized pathogens were isolated. Polymicrobism was frequent. Follow-up studies identified 5 cases of treatment failure; 2 of Gonococcus and 3 of Chlamydia, and detected 3 cases of Chlamydia which had not been identified initially. We discuss the use of laparoscopy in the diagnosis and for follow-up and treatment of PIDs.

An etiologic survey of clinical factors in cervical intraepithelial neoplasia: a transverse retrospective study.

In this retrospective survey 235 patients were studied: 123 patients with cervical intraepithelial neoplasia (CIN) and 112 controls. Fourteen epidemiologic variables were reviewed. The stepwise logistic multiple regression analysis demonstrated that age at first sexual contact was the variable most related to CIN appearance, followed by the occupation of the husband. School attendance and socioeconomic indices of the patients' fathers, husbands or partners were lower in the CIN group, as shown in the descriptive analysis. Age at first pregnancy was also found to be lower among CIN patients. Promiscuity and contraception did not seem to play a significant role in the incidence of neoplastic disease. A carcinogenic model is proposed.

[Intestinal schistosomiasis. Early hepatic involvement with portal hypertension: study of 5 cases]. / Schistosomiase intestinale. Précocité de l'atteinte hépatique avec hypertension portale: étude de cinq cas.

Pathological and hemodynamic investigations were performed in 5 canadian patients who had been infected by Schistosoma mansoni four months before in Martinique. Mononuclear cell infiltration of portal tracts was disclosed in all 5 patients; it was associated with eosinophilic infiltration in 3, hepatocellular necrosis in 3, granulomas in 2 and fibrosis in 2. Presinusoidal portal hypertension was demonstrated in 4 out of the 5 patients. These observations suggest that histological changes are constant at this stage after infestation by S. mansoni and could be responsible for the early development of portal hypertension which is classically a late feature of the disease.

[The sexual needs of homosexual HIV seropositive men]. / Les besoins sexuels des hommes homosexuels séropositifs au VIH.

A two-step study was conducted to identify the sexual needs of a group of seropositive homosexual men. At first, there was an interview with 30 men which aimed to define their objectives of sexual health. This was followed by a questionnaire distributed among 88 seropositive men and 173 seronegative men, who evaluated the objectives stated in the first step. The statistical analysis of collected data allowed for the identification and narrowing down of four major needs: being in good health, being in love, being sexual and, to a lesser degree, being secure. Results are discussed and point to the role played by the biological, psychological and sociological uneasiness in the context of the difficulties that seropositive homosexual men have in satisfying their sexual needs. This evaluation can prove useful in the planning and the implementation of sexological services for HIV-positive persons.

Prevalence of and risk factors for sexually-transmitted infections in hidden female sex workers.

OBJECTIVES: We wanted to determine the age-specific prevalence of selected sexually transmitted infections while assessing the risk factors among hidden female sex workers (HFSW). METHODS: One hundred HFSW over 15 years of age were recruited in an impoverished area of Antananarivo, Madagascar. After oral informed consent, blood and endocervical swabs were tested for specific antigens, antibodies, and pathogens using molecular, serologic, and microscopic examinations. A risk factor analysis was conducted with odds ratios and 95% confidence intervals. RESULTS: Thirty-two percent, 27, 12, and 7% of HFSW were infected respectively with Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis. Specific antibodies against, syphilis were detected in 11%. None were HIV-positive. The main factors associated with STI were: young age, being married, lower education level, early age for first intercourse, and a history of genital infection.

Sustained interleukin-6 and interleukin-8 expression following infection with Chlamydia trachomatis serovar L2 in a HeLa/THP-1 cell co-culture model.

Chlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-beta (IL-1beta), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factor-alpha (TNF-alpha)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1beta expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-alpha synthesis was down regulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1beta, IL-6, IL-8 and TNF-alpha expression was reduced, whereas the synthesis of IL-10 and IL-12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.

Toxoplasmosis and the compromised host.

A high percentage of population shows antibodies to Toxoplasma gondii yet clinical manifestations of primary infestations are rare. Congenital and secondary forms (chorioretinitis) are serious medical conditions. An outburst in a compromised host is always serious and may be fatal. Therefore, patients subjected to immunosuppressive therapy or with pathologic immune suppression should be clinically and serologically screened and, when toxoplasmosis is diagnosed, treated for the entire period of immunosuppression.

Analysis of long-term viral expression in CEM cells persistently infected with non syncytium-inducing HIV-1 strains.

CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains obtained from AIDS patients or seropositive individuals. The surviving cells were followed for several months in the persistently infected cultures designated 65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light and electron microscopy, immunofluorescence, reverse transcriptase assay, polymerase chain reaction amplification (PCR), nucleic acid hybridization and flow cytometry. The virus isolates induced relatively few syncytia and other cytopathic effects in the corresponding cell lines and the number of cells positive for virus expression never rose above 44%. Distinct peaks of antigen-positive cells were obtained, coincident with high levels of reverse transcriptase activity. The cultures were strongly resistant to superinfection by laboratory strain Lai, with the exception of 65870/CEM which expressed HIV antigens in up to 15% of the cells for a few days. However, cell lysis was minimal in all cases. After long-term cultivation of the three cultures, no antigen-positive cells were detected and no trace of virus expression could be observed. The remaining cells consisted entirely of CD4-negative cells. PCR analyses indicated that cells harboring a provirus were progressively eliminated from the cultures, leaving only virus-free cells. In this system, cells carrying a latent provirus survive for a limited period of time before virus activation induces cell lysis. These results suggest that at least three types of cells exist in the CEM cell line: CD4-positive cells which are rapidly killed by the virus, a second type harboring a latent viral genome after the infection and which grow normally until activation of the resident genome by external or internal signal(s), and a third type which represents rare CD4-negative cells present in the initial CEM population and which are selected for by the NSI isolates. This is the first study documenting specific interactions between NSI strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell culture.