Obesity: determinants and therapeutic initiatives.

There are several possible determinants of obesity, including impaired thermogenesis and the differential utilization of fuels in different tissues. Whereas hypometabolism may initiate obesity in some people, once obese, individuals tend to manifest a higher resting metabolic rate because of their greater fat-free mass, exhibit an impaired thermic response to food, and expend more calories than lean individuals for equivalent amounts of activity. As a result, over a 24-h period, obese people generally expend more energy than lean people. A second determinant of obesity is related to fuel utilization and suggests that those predisposed to be obese may have an innate insulin resistance in muscle, leading to decreased uptake, oxidation, and storage of glucose in this tissue. As a result, the glucose is shunted to adipose tissue, where it is stored. With regard to treatment of obesity, emphasis on increased energy expenditure through the inclusion of reasonable amounts of activity is essential. However, this must always be combined with restraint in caloric intake.     

Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.     

Relative incidence of Crohn's disease and ulcerative colitis in six Melbourne hospitals

Information on the relative incidence of Crohn's disease and ulcerative colitis was obtained by a prospective investigation at six Melbourne teaching hospitals. One hundred and eleven patients who presented with chronic inflammatory bowel diseases between 1980-1981 were admitted to the study. Forty (36%) patients were diagnosed as having Crohn's disease and 63 (57%) patients as having ulcerative colitis. The type of chronic inflammatory bowel disease could not be determined in eight (7%) patients. These findings suggest that the relative frequency of Crohn's disease and ulcerative colitis in Melbourne hospitals is within the range that is reported for northern Europe and the United States.     

Estrogen and progesterone production by granulosa cell monolayers derived from in vitro fertilization procedures: lack of evidence for modulation by androgen

The role(s) of androgens in the steroidogenic regulation of human granulosa cell production of estrogen and progesterone during monolayer culture was studied. These cells were exposed in vivo to human menopausal gonadotropin and hCG gonadotropin with or without clomiphene citrate. Steroid production rates were compared between cells cultured in control medium and those cultured in medium containing a nonaromatizable androgen [dihydrotestosterone (DHT)] or an aromatizable androgen [androstenedione (A'D)]. Some cultures received A'D from 3-12 days; other cultures received DHT alone for 3, 6, or 9 days before the addition of A'D for 3 days. The effect on steroid production during the culture interval before the addition of A'D also was evaluated. Exposure to A'D increased estrogen production over 50-fold compared with that in control cells or those treated with DHT (P less than 0.001). DHT also failed to alter estrogen production when A'D was added to cultures. Furthermore, the delay in introducing A'D to the cultures for up to 9 days did not decrease subsequent estrogen production compared with that in cultures continually exposed to A'D or DHT plus A'D. Progesterone production was substantial for at least 12 days of culture and was unaffected by the presence of androgen. These results do not confirm previous studies using murine or porcine granulosa cells, which suggested that androgen receptor-dependent mechanisms were involved in increasing estrogen and/or progesterone production in vitro. Rather, they indicate that androgen may not be required to maintain aromatase capability per se in human granulosa-luteal cells previously exposed to ovulation-inducing quantities of gonadotropin.     

Phase II study of iproplatin in metastatic breast carcinoma

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.