Weight loss in obese subjects on a restricted diet given BRL 26830A, a new atypical beta adrenoceptor agonist

A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic beta adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3.35 MJ diet that was low in fat and high in fibre. Weight loss was 15.4 (SD 6.6) kg in subjects given BRL 26830A compared with 10.0 (5.9) kg in those given placebo (p = 0.02). The relative weight loss was 0.93 (0.39%) a week with BRL 26830A and 0.61 (0.38)% with placebo (p = 0.02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4.1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11.6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically. BRL 26830A may be a useful drug in the treatment of obesity.     

Morbidity in patients on l-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH

OBJECTIVE: Patients on L-thyroxine with a 'suppressed' TSH (< 0.05 mU/l) were compared to those in whom TSH was detectable but not elevated (0.05-4.0 mU/l), with regard to morbidity data. DESIGN: Biochemical data from Tayside Thyroid Register was matched to hospital admissions data obtained from Health Board Statistics. PATIENTS: The patients were identified from those registered on the computerized Tayside Register. MEASUREMENTS: Serum T4 and TSH assays, clinical assessment scores, and admission records with regard to ischaemic heart disease, overall fractures, fractured neck of femur and breast carcinoma. RESULTS: Over one year, 1180 patients on thyroxine replacement had clinical and biochemical assessment; 59% had a suppressed TSH and 38% 'normal' TSH. Patients with a suppressed TSH exhibited higher median serum thyroxine levels (146 nmol/l, range 77-252 vs 119 nmol/l, 58-224; P < 0.001). Patients under the age of 65 years on L-thyroxine had an increased risk of ischaemic heart disease compared to the general population (female 2.7 vs 0.7%, P < 0.001; male 6.4 vs 1.7%, P < 0.01), but the risk was no different between those with suppressed and normal TSH. There was no increase in risk for overall fracture, fractured neck of femur or breast carcinoma in those on thyroxine with suppressed or normal TSH. CONCLUSION: Patients under the age of 65 years on L-thyroxine had an increased risk of ischaemic heart disease. There was no excess of fractures in patients on L-thyroxine even if the TSH is suppressed.     

A case of Non-Hodgkin's lymphoma in a patient with Crohn's disease]

Although adenocarcinoma is a well known complication of chronic inflammatory bowel disease, primary gastrointestinal lymphoma occurring in Crohn's disease is rare. A 40-year-old man with 10 year-history of Crohn's disease had multiple longitudinal ulcerative lesions on descending colon in follow-up colonoscopic examination. Microscopic examination of proximal descending colon revealed peripheral T cell lymphoma and other site of the descending colon was consistent with Crohn's disease. The patient reached complete remission of malignant lymphoma after three cycles of combined chemotherapy. He has been well for 10 months with sulfasalazine maintenance therapy but was admitted to the hospital due to spontaneous bowel perforation of ascending colon. Right hemicolectomy was done, but the patient died of post-surgical recurrent mesenteric abscess and sepsis. To the best of our knowledge, this is the first case of Non-Hodgkin's lymphoma complicating Crohn's disease in Korea which was confirmed by immunohistochemical studies.     

Behandlung des hypoplastischen Linksherz-Syndroms

In contrast to other types of congenital heart defects, the treatment of hypoplastic left heart syndrome (HLHS) has become comparably successful only within the last decade. Postnatal management of circulatory disturbances of HLHS was previously often performed, similarly to other types of neonatal shock, without considering the peculiarities of postnatal hemodynamics. It is of overwhelming importance to limit pulmonary hyperperfusion by reducing systemic afterload and avoiding artificial respiration. The invention of selective hypothermic cerebral perfusion using the modified Blalock-Taussig shunt has decreased the need for long circulatory arrest times involving the brain, and promises a better neurological outcome. Postoperatively, sophisticated hemodynamic monitoring is mandatory to provide sufficient systemic oxygen delivery. α-blockers are usually given for strong afterload reduction. Hospital mortality is as low as 10–15% in centers experienced with the Norwood operation. The next surgical steps to create a serial systemic and pulmonary circulation involve superior cavopulmonary anastomosis performed as early as possible (4–6 months) and finally total cavopulmonary connection at an age of 3–4 years.     

The immunomodulatory effects of 3-monochloro-1,2-propanediol on murine splenocyte and peritoneal macrophage function in vitro.

3-Monochloro-1,2-propanediol (MCPD) is a well-known by-product of acid-hydrolyzed soy sauce during its manufacturing process. MCPD has been reported genotoxic in vitro, and reproductive toxicity and carcinogenicity in rats. To evaluate the immunomodulatory effect of MCPD on murine splenocyte and macrophage in vitro, we investigated splenocyte blastogenesis by concanavalin A (Con A), anti-CD3, and lipopolyssacharide (LPS), the production of cytokines from splenocyte, and the activity of mouse peritoneal macrophages. There was a significant decrease in lymphocyte blastogenesis to Con A or anti-CD3 at subtoxic dose of MCPD. A significant decrease in splenocyte blastogenesis to LPS was also observed. The production level of interferon (IFN)-gamma on splenocyte culture with Con A was significantly reduced at the higher concentration than 1.0mM of MCPD. The levels of interleukin (IL)-4 and IL-10 were also decreased at high concentrations of MCPD. There was a significant decrease in production of nitric oxide (NO) by peritoneal macrophages treated with MCPD. MCPD also inhibits tumor necrosis factor (TNF)-alpha production of stimulated macrophages. These results indicate that MCPD might be able to reduce the functionality of lymphocytes and peritoneal macrophages in vitro.     

Spontaneous resolution of prenatally diagnosed dural sinus thrombosis: a case report.

Fetal thrombosis of the dural sinus is an extremely rare congenital cerebrovascular condition that is potentially fatal. We report a case of dural sinus thrombosis diagnosed by prenatal ultrasonography and fetal magnetic resonance imaging (MRI) in the second trimester. The thrombosis showed partial resolution during pregnancy and resolved spontaneously after birth without neurological complications. This is the first report of spontaneous postnatal resolution, and may provide helpful information on the natural history and prenatal counseling of fetal thrombosis of the dural sinus.