Androgen dependent stimulation of aromatase activity in genital skin fibroblasts from normals and patients with androgen insensitivity

OBJECTIVE: To measure the effect of androgens or aromatase activity as an index of androgen responsiveness in patients with androgen insensitivity. DESIGN: Genital skin fibroblasts were established in culture using primary skin explants obtained from normal males at the time of circumcision and from androgen insensitive patients who had surgery either for gonadectomy (complete androgen insensitivity syndrome) or for reconstruction of the external genitalia (partial androgen insensitivity syndrome). PATIENTS: Foreskin samples were obtained at the time of circumcision in 27 normal males. Scrotal or labia majora skin was obtained at the time of surgery from 14 patients with the complete and 22 with the partial forms of the androgen insensitivity syndrome. MEASUREMENTS: Basal and stimulated levels of aromatase activity were measured in genital skin fibroblasts following preincubation with natural and synthetic, nonmetabolizable androgens. RESULTS: Following a 48-hour preincubation with testosterone or dihydrotestosterone, there was a five to six-fold stimulation of aromatase activity in normal fibroblasts. Mibolerone, a synthetic androgen, produced similar results. The stimulatory effect was blocked by anti-androgens. Seven patients with partial androgen insensitivity, of whom four were either receptor deficient or showed a qualitative defect in androgen binding, had reduced mibolerone induced stimulation of aromatase activity. All ten patients with receptor negative complete androgen insensitivity had an absent response. There was no aromatase induction in a further three patients with complete androgen insensitivity who were receptor positive. Two siblings in the latter group had an exon deletion encoding for part of the DNA binding domain of the androgen receptor. CONCLUSIONS: Androgens stimulate aromatase activity in genital skin fibroblasts from normals. The response is mediated via the androgen receptor and can be decreased or absent in patients with the androgen insensitivity syndrome. This may be a useful in-vitro marker of androgen responsiveness in such patients.     

Histology as a prognostic factor in early gastric cancer.

Of 431 patients with gastric cancer observed in our institution, 23 (5.3%) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology.     

Factors associated with levels of physical activity at work and during leisure time]

Factors associated with levels of physical activity at work and during leisure time were analyzed among 577 subjects who had been selected as population controls for a case-control study by random selection from telephone directories. The intensity of physical activity at work was inversely associated with body mass index, the proportion of professionals & managers, consumption of western style breakfast, coffee, butter/margarine, and whisky; and positively associated with rice intake. Frequency of physical activities during leisure time was positively associated with consumption of vegetables, fruits, mushrooms, milk, cheese and coffee, and moderation in eating; and inversely associated with rice intake and the prevalence of gastrointestinal symptoms and medication. The association of physical activity with these factors should be considered in studying its relationship to disease risk.     

Treatment options in multiple chemical sensitivity.

The essential features of treatment for chemical sensitivity are: 1) Encouraging the provision of clean air, food, water, and surroundings. 2) Identifying substances to which the patient is sensitive, with subsequent a) enhanced avoidance, or b) specific immunotherapy to reduce the patient's reactivity to those substances. 3) Assessing and enhancing the patient's nutritional status to maximize the body's ability to detoxify and to minimize the free-radical production and oxidative stress of xenobiotics. 4) Addressing concurrent problems such as infections, immunosuppression, and other medical conditions in an appropriate fashion. 5) Evaluating the patient's psychologic status and addressing any social and emotional problems in a compassionate manner. The author believes that multiple chemical sensitivity is a real condition with documented physiologic abnormalities. It is not a functional or psychologic illness or a belief system of the patient. Second, this condition is diagnosable and treatable by various means. These treatment options not only make common sense but usually result in significant improvement for these unfortunate patients, who deserve the very best efforts of their health care providers.     

A prolonged outbreak of ornithosis in duck processors.

In 1985 an outbreak of ornithosis affected 13 of 80 (16%) workers in a duck-processing plant. New employees were three times more likely to become cases than established employees. The highest attack rate was in those on the production line. Following the outbreak, an occupational health scheme was set up to monitor the health of new recruits to the company. Serological evidence of recent infection was demonstrated in 18 of 37 (49%) new employees tested in the first 3 months of employment. Five (14%) also had clinical evidence of ornithosis. Veterinary investigation of the ducks demonstrated a high proportion with asymptomatic chlamydial infection. It is suggested that ornithosis may be more common in duck processors than is currently supposed. Strategies to reduce occupational risks are discussed.     

The relation of the accumulation of cadmium in human placenta to the intake of high-fibre grains and maternal iron status.

Exposure to cadmium via the diet is known to depend to a large extent on the intake of cereal grains, particularly the high-fibre fractions of wheat. Subjects with low iron status absorb more cadmium than those with better iron status. The purpose of the present study was to determine to what extent cadmium accumulation in human placenta is affected by the intake of grain fibre and maternal iron status during pregnancy. Thirty-nine pregnant women participated in the study. In each trimester the women were requested to complete a dietary history and to allow blood samples to be taken for haemoglobin, serum ferritin and serum thiocyanate determinations, the latter as a marker for smoking. At delivery the whole placenta was taken for the determination of the cadmium concentration. The 32 women who had serum thiocyanate levels less than 70 mumol/l, who had completed at least one dietary history and from whom a blood sample was obtained in the third trimester, were included in the final statistical analyses. In the group of women who consumed less than the median intake of grain fibre and had more than 15 micrograms ferritin/l serum in the third trimester, the placenta cadmium concentration was nearly half that in the placentae of women who had consumed more grain fibre or had lower iron status in late pregnancy.     

Two-color analysis of lymphocyte subpopulations in patients with nephrotic syndrome due to membranous nephropathy.

Two-color flow cytometry was carried out to determine the correlation between cell-mediated immunity and the levels of proteinuria in 30 patients with membranous nephropathy. Lymphocyte subpopulations were measured by two-color flow cytometry using various monoclonal antibodies of the Leu series. Clinically, the patients were divided into four stages as follows: 1. untreated nephrotic stage, 2. prednisolone (PSL) treated nephrotic stage, 3. persistent proteinuric stage (incomplete remission, ICR) and 4. complete remission (CR). Two-color flow cytometry showed a significant decrease in Leu 2a+15+ (suppressor T) cells and relative increase in Leu 3a+8+ (suppressor inducer T) cells in the untreated nephrotic stage. The mean Leu 3a+8-/Leu 2a+15+ (helper/suppressor) cell ratio was normalized in the persistent proteinuric stage or complete remission after treatment with PSL. Patients with membranous nephropathy showed a significant elevation of Leu 2a+DR+ cells after treatment with PSL. The abnormalities of suppressor T cells and suppressor inducer T cells in the peripheral blood appear to reflect the levels of proteinuria in patients with membranous nephropathy. It was concluded that PSL might stimulate Leu 2a positive cells and then increase the number of Leu 2a+15+ cells in the peripheral blood of patients with membranous nephropathy.     

Premalignant lesions and nonsquamous malignancy of the penis and carcinoma of the scrotum.

Premalignant lesions of the penis include cutaneous horn, balanitis xerotica obliterans, and leukoplakia. The true incidence of progression of each of these to squamous-cell carcinoma is unknown. Bowenoid papulosis, erythroplasia of Queyrat, and Bowen's disease are histologically identical to in situ carcinoma. Although the first is consistently benign, the latter two regularly evolve into invasive cancer. Malignant scrotal lesions include squamous-cell carcinoma, liposarcoma, leiomyosarcoma, basal-cell carcinoma, extramammary Paget's disease, erythroplasia of Queyrat, malignant melanoma, and metastases. Hemangioma can be confused with carcinoma.