A new technique for examining intestinal biopsies

A new technique for measuring changes in the architecture of the small intestinal mucosa is described using a modification of the technique of television image analysis to measure the areas occupied by the surface and crypt epithelium in proximal jejunal biopsies. The ratios of these two areas to each other were then calculated. In 12 control mucosae, the mean ratio (+/-SD) was 2.27 +/- 0.41. In 12 untreated flat mucosae, by contrast, the mean ratio was only 0.24 +/- 0.07. This ten-fold difference, which was highly significant (p < 0.001), was greater than that for any similar measurements previously reported. This technique is intended for the measurement of changes in the mucosa too small for existing techniques to detect reliably rather than for the diagnosis of coeliac disease.     

Postinfarction angina: results of early revascularization

To assess the efficacy of surgical revascularization for postinfarction angina within 30 days of acute infarction, the clinical course of 103 patients treated surgically from January 1979 to July 1982 was reviewed. There were 84 men (82%) and 19 women (18%) with a mean age of 58 years (range 34 to 80). Group A (11 patients) underwent surgery within 24 hours of infarction, Group B (21 patients) within 7 days and Group C (71 patients) within 30 days. Eighty-four patients (82%) had subendocardial infarctions and 19 patients (18%) had transmural infarction. Transmural infarction was more common in patients in Group A (36%) than in those in either Group B (19%) or Group C (15%). There were two deaths, both in Group C (1.9%), within 30 days of surgery. The use of intraaortic balloon or inotropic support and the occurrence of major arrhythmias or perioperative infarction was noted in 30 patients (29%) (64% in Group A, 33% in Group B and 18% in Group C). The average time in the intensive care unit was 3.2 days, with an average total hospital stay after surgery of 8.3 days. Late follow-up (mean 15.4 months, range 1 to 39) is complete for 97 patients (97%). There were no late myocardial infarctions and 93 patients (96%) were essentially free of angina. The only late death (1.0%) was caused by septicemia from delayed sternal wound infection. This study suggests that myocardial revascularization within the first 30 days after myocardial infarction can be accomplished with an acceptable operative mortality in selected patients with postinfarction angina refractory to medical management.     

Epidemiology of hyperuricemia in an ambulatory elderly population

The relationship of serum uric acid concentration to age and sex was assessed in 1,701 participants in a geriatric multiphasic screening clinic. Included were 1,067 women and 634 men. The mean uric acid level for men was 6.35 mg/100 ml compared to 5.44 mg/100 ml for women. No statistically significant increases in serum uric acid between age groups were apparent, except for women over 84 years of age. The mean serum urate concentrations found in this geriatric study are higher than those reported for other population groups, suggesting a higher normal value for the elderly.     

Hexose-6-phosphate dehydrogenase contributes to skeletal muscle homeostasis independent of 11β-hydroxysteroid dehydrogenase type 1

Glucose-6-phosphate (G6P) metabolism by the enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the sarcoplasmic reticulum lumen generates nicotinamide adenine dinucleotide phosphate (reduced) to provide the redox potential for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to activate glucocorticoid (GC). H6PDH knockout (KO) mice have a switch in 11β-HSD1 activity, resulting in GC inactivation and hypothalamic-pituitary-adrenal axis activation. Importantly, H6PDHKO mice develop a type II fiber myopathy with abnormalities in glucose metabolism and activation of the unfolded protein response (UPR). GCs play important roles in muscle physiology, and therefore, we have examined the importance of 11β-HSD1 and GC metabolism in mediating aspects of the H6PDHKO myopathy. To achieve this, we examined 11β-HSD1/H6PDH double-KO (DKO) mice, in which 11β-HSD1 mediated GC inactivation is negated. In contrast to H6PDHKO mice, DKO mice GC metabolism and hypothalamic-pituitary-adrenal axis set point is similar to that observed in 11β-HSD1KO mice. Critically, in contrast to 11β-HSD1KO mice, DKO mice phenocopy the salient features of the H6PDHKO, displaying reduced body mass, muscle atrophy, and vacuolation of type II fiber-rich muscle, fasting hypoglycemia, increased muscle glycogen deposition, and elevated expression of UPR genes. We propose that muscle G6P metabolism through H6PDH may be as important as changes in the redox environment when considering the mechanism underlying the activation of the UPR and the ensuing myopathy in H6PDHKO and DKO mice. These data are consistent with an 11β-HSD1-independent function for H6PDH in which sarcoplasmic reticulum G6P metabolism and nicotinamide adenine dinucleotide phosphate-(oxidized)/nicotinamide adenine dinucleotide phosphate (reduced) redox status are important for maintaining muscle homeostasis.     

Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF-I remain uncertain. The West Midlands Pituitary database contains details of 419 patients (241 female) with acromegaly. Serum IGF-I data from the Regional Endocrine Laboratory were available for 360 patients (86%). At diagnosis, mean age was 47 yr (range, 12-84) and mean duration of follow-up was 13 yr (0.5-48). Sixty-one percent were treated by surgery and 39% by nonsurgical means. Radiotherapy was used alone or as adjuvant therapy in 50%. All patients were registered with the Office of National Statistics to obtain information on deaths. At the date of analysis (31 December 2001), 95 of the 419 patients had died (43 males), giving a standardized mortality ratio of 1.26 [confidence interval (CI), 1.03-1.54; P = 0.046]. After controlling for age and sex, data indicated that mortality was increased in subjects with posttreatment GH levels more than 2 micro g/liter, compared with those with levels less than 2 micro g/liter [ratio of mortality rates (RR), 1.55 (range, 0.97-2.50); P = 0.068]. By contrast, a much smaller increase was observed for subjects with elevated posttreatment IGF-I levels compared with those with normal levels [RR, 1.20 (range, 0.71-2.03); P = 0.50]. Treatment with radiotherapy was associated with increased mortality [RR, 1.67 (range, 1.09-2.56); P = 0.018], with cerebrovascular disease the predominant cause of death [standardized mortality ratio, 4.42 (range, 2.71-7.22); P = 0.005]. These results confirm the increased mortality in acromegaly and suggest that reduction of GH levels to less than 2 micro g/liter is beneficial in terms of improving long-term outcome. The sole use of IGF-I as a marker for effective treatment of acromegaly is not justified by this data. This study also highlights the potential deleterious effect of radiotherapy.     

Clinical review 16: Parathyroid hormone-related proteins: coming of age in the 1990s

The last 3 yr have yielded a fertile harvest of new information on the HHM clinical syndrome and on the novel peptide hormone family responsible for the syndrome. Whereas the clinical riddle enshrouding the HHM syndrome first posed in the early 1940s appears to have been largely solved, a whole new field, concerning the physiological role(s) of PTHRP has opened. The field has evolved rapidly and provides an example of fruitful clinical investigation: the original problem was a clinical one (the HHM syndrome); understanding the clinical disorder led to pursuit of the problem in the laboratory (adenylate cyclase assays, protein purification, molecular cloning, PTHRP synthesis); and observations made in the laboratory have rapidly yielded clinical fruits (PTHRP immunoassays) and opened a new window on normal physiology.