Metabolic complications of obesity. Pathophysiologic considerations.

Given a specific research interest in human fatty acid metabolism, this article focuses primarily on the evidence surrounding the hypothesis that dysregulation of the fuel release function of fat cells (lipolysis) is an important contributing factor to the health hazards of obesity.

Hepatolithiasis (intrahepatic stone) during octreotide therapy for acromegaly: a case report.

We report a case of hepatolithiasis (intrahepatic stone) complicated by gram-negative sepsis in a 37 year old male with acromegaly being treated with octreotide. As a child, he had suffered a traumatic injury to his liver requiring the surgical repair of a laceration. This is the first reported case of hepatolithiasis during octreotide therapy. Gallstones and bile sludge are common side effects of octreotide therapy but rarely become symptomatic or require treatment. Hepatolithiasis is uncommon in western countries but is quite prevalent in East Asia and is often associated with a predisposing condition that causes intrahepatic bile stasis (eg. bile duct stricture). In addition to its known effect on gallbladder stasis, octreotide alters bile acid composition and may thus hasten intrahepatic sludge and stone formation. Extra caution should be taken in using octreotide or its long-acting analog in patients otherwise predisposed to intrahepatic bile stasis.

Preliminary comparison of the endoscopic transnasal vs the sublabial transseptal approach for clinically nonfunctioning pituitary macroadenomas.

OBJECTIVE: To assess the advantages and disadvantages of an endoscopic transnasal approach to pituitary surgery for a select group of clinically nonfunctioning macroadenomas and to compare results of this approach with the sublabial transseptal approach at a single institution. PATIENTS AND METHODS: We retrospectively reviewed the records of 26 patients with clinically nonfunctioning pituitary macroadenomas approached endoscopically and 44 matched control patients with the same tumors approached sublabially between January 1, 1995, and October 31, 1997. RESULTS: At baseline, the groups were not significantly different for age, sex distribution, number of comorbid conditions, visual field defects, degree of anterior pituitary insufficiency, or preoperative assessment of tumor volume or invasiveness. Mean (SD) operative times were significantly reduced in the endoscopic group vs the sublabial group: 2.7 (0.7) hours vs 3.4 (0.9) hours (P < .001). Postoperative assessment of surgical resection and postoperative alterations of anterior pituitary function or visual fields were not significantly different between groups, and complication rates were similar in both groups. CONCLUSION: This endoscopic transnasal approach to pituitary resection results in significantly shorter operative time without compromising the extent of tumor resection. The distinct disadvantage of this approach is an off-center view of the sella and a diminished working channel to the sella turcica. For these reasons, the endoscopic approach or its variation is an alternative to the sublabial approach but should be considered only by experienced pituitary neurosurgeons.

Hyperkalemic renal tubular acidosis induced by trimethoprim/sulfamethoxazole in an AIDS patient.

A patient with the acquired immunodeficiency syndrome (AIDS) and sickle cell anemia presented to the University of Wisconsin Hospital on two separate occasions with pneumocystis carinii pneumonia (PCP). On both occasions he was treated with high-dose intravenous trimethoprim/sulfamethoxazole (TMP/SMX). Several days into each treatment course he developed hyperkalemia and systemic acidosis consistent with hyperkalemic renal tubular acidosis (RTA). The abnormalities resolved in the first instance with the addition of amphotericin B while continuing TMP/SMX, and in the second upon discontinuation of the TMP/SMX. While an increasing number of cases with TMP/SMX-induced hyperkalemia have been reported, hyperkalemic RTA is an uncommon complication of TMP/SMX therapy, occurring in patients with predisposing factors for acidosis such as aldosterone defects, medullary dysfunction and renal insufficiency.

Receptor-specific activity of heteromeric thyrotropin (TSH) analogs: development of synthetic TSH antagonists.

In an attempt to create potent and specific inhibitors of the interaction of thyrotropin (thyroid-stimulating hormone [TSH]) with its receptor, we designed a series of 18 synthetic peptides containing sequences of both alpha and beta subunits that were shown previously to interact with the TSH receptor. These "heteromeric" peptide analogs included amino acid residues from alpha 26-46, beta 31-52, beta 88-95 and beta 101-112 that were arranged variously and were separated from each other by artificial amino acid spacers. Each peptide was tested for its ability to interact with the TSH receptor in a radio-receptor assay (TSH-RRA) using porcine thyroid membranes and a bio-assay for TSH using FRTL-5 cells. Twelve of the 18 peptides showed binding activity in the TSH-RRA. None of the analogs demonstrated thyroid stimulatory activity, but five inhibited TSH bioactivity and were, thus, pure antagonists, the most potent possessing EC50 values in the 3-5 microM range. Specificity of the antagonists was tested by measuring their ability to inhibit hCG binding to ovarian membranes, hCG-stimulated progesterone production in MA-10 rat Leydig tumor cells and FSH binding to testicular membranes. Only those peptides that included the alpha-subunit sequence CFSR or CCFSR exhibited binding activity for the heterologous receptors, and that activity was 10-fold lower than in the TSH assays. None of the heteromeric peptides showed activity in the hCG bioassays, further demonstrating their specificity as TSH antagonists. These studies illustrate the utility of a synthetic peptide approach in the development of analogs of peptide hormones. Future alterations that significantly enhance the potency of these antagonists may result in substances with clinical efficacy in diseases such as Graves' disease and differentiated thyroid cancer that involve the thyrotropin receptor.