Wallace P. Ritchie

Parathyroid Carcinoma in a Chronic Hemodialysis Patient

G. Gopal Krishna, MD, Section of Nephrology, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140 (USA) Dear Sir, Hyperparathyroidism and parathyroid hyperplasia invariably accompany chronic renal failure [1]. However, parathyroid carcinoma rarely occurs in this setting. Indeed, our survey of the English language literature revealed only one patient developing this lesion during chronic renal failure [2]. We report a second patient manifesting such an association. A 64-year-old white female developed end-stage renal disease in 1976 secondary to idiopathic chronic interstitial nephritis. Her serum calcium at that time was 9 mg/dl (1.97 mmol/l), phosphorus 7.9 mg/dl (2.55 mmol/l) with a normal albumin concentration. Despite therapy with phosphate-binding agents, serum phosphate levels remained greater than 6 mg/dl (1.94 mmol/l). Over the next several years she developed multiple bone fractures (ribs, ankle and hip) from severe secondary hyperparathyroidism. Beginning in September 1983, serum calcium levels ranged from 10 to 11 mg/dl (2.50–2.74 mmol/l). Parathyroid hormone (PTH) levels (C-terminal assay) in February 1985 were greater than 10,000 pg/ml (normal 0–340 pg/ml). At parathyroidectomy in May 1985, the two inferior glands were hyperplastic while both superior glands revealed malignant changes with infiltration of adjacent thyroid tissue (fig. 1). Immunoperoxidase studies using monoclonal antibodies, positive for PTH and negative for thyroglobulin, confirmed that the tumor indeed originated from parathyroid tissue. No metastatic foci were identified in the seven paratracheal lymph nodes resected. As of June 1988 the patient is in a stable condition with no clinical evidence of metastatic disease. Parathyroid carcinoma is a rare cause of hyperparathyroidism, accounting for only 1–3% of patients with

Isoproterenol-induced gastric mucosal protection from bile acid: Role of endogenous prostaglandins

Topical isoproterenol is a potent protective agent against bile acid-induced gastric mucosal injury in hypotensive and normotensive rats. This study was undertaken to ascertain what role endogenous prostaglandins and gastric mucosal blood flow play in isoproterenol-induced protection. Accordingly, anesthetized, fasted rats were given the cyclooxygenase inhibitor, indomethacin (5 mg/kg subcutaneously), 30 min prior to topical pretreatment with 3 ml of intragastric saline, isoproterenol (3 μM), or 16,16-dimethyl prostaglandin E2 (3 μM) for 15 min. Gastric injury was induced with topical 5 mM acidified taurocholate and damage assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology of the gastric epithelium. In a separate set of experiments, the effects of topical isoproterenol on gastric mucosal blood flow (laser Doppler flowmetry) and luminal PGE2 concentrations (125I radioimmunoassay) were examined. Pretreatment with topical isoproterenol or 16,16-dimethyl prostaglandin E2 significantly decreased bile acid-induced net luminal ion fluxes and DNA accumulation, suggesting mucosal protection. The protective effect of isoproterenol, but not 16,16-dimethyl prostaglandin E2, was negated by indomethacin (corroborated by histology). Further, isoproterenol did not significantly alter gastric mucosal blood flow, but did augment luminal PGE2 concentrations, an effect also abolished by indomethacin. Thus, isoproterenol appears to protect the gastric mucosa from the damaging effects of bile acid through a mechanism that requires the synthesis and release of cytoprotective endogenous prostaglandins.

Bleeding gastric or duodenal ulcer

Of the estimated 4 000 000 people in the USA with peptic ulcer disease, about 100 000 bleed each year. The attendant mortality rate has remained relatively constant at 6–10% during the past 30 years, despite numerous advances in therapy. Predictors of increased chance of death from an episode of ulcer haemorrhage include an age of over 60 years, multiple organ system disease, transfusion of 5 or more units of whole blood or its equivalent, the recent stress of operation, trauma or sepsis, and the performance of emergency surgery to control haemorrhage (in these patients mortality rates range from 15 to 25%). The mortality rate in patients undergoing emergency surgery is twice as high for bleeding gastric ulcer as it is for bleeding duodenal ulcer.

Prostaglandins. A surgeon's perspective.

Stress ulcers are multiple, superficial erosions of the proximal stomach that develop in the setting of severe physiological stress. Evidence suggests that the mechanism of cytoprotection may be impaired in settings conducive to their development. The two most critical elements in the pathogenesis of the disease are the presence of some luminal acid and some degree of associated mucosal ischemia. The probable endpoint is reduction of intramucosal pH below acceptable physiological limits. In the absence of effective prophylaxis, 30% of patients with stress ulcer disease will develop hemorrhage of life-threatening severity--acute hemorrhagic gastritis--a condition difficult to treat both nonoperatively and operatively. Mortality remains high irrespective of the capacity to control hemorrhage. Prevention is the best treatment. Both H2- receptor antagonists and intragastric titration with antacids have been proposed in prophylaxis. Current evidence suggests that each is equally efficacious for moderately ill patients. However, for the severely ill, antacid titration is superior to cimetidine. A small group of critically ill patients are not effectively treated by either modality. It seems likely that prostaglandins may prove efficacious in this patient population.