AlphaB-crystallin immunolocalization yields new insights into inclusion body myositis

OBJECTIVE: To study the expression of the small heat shock protein, alphaB-crystallin (alphaBC), in inclusion body myositis (IBM). BACKGROUND: In humans, alphaBC is constitutively expressed in the eye lens, muscle, and heart, but not in lymphoid tissues. Induced expression of alphaBC occurs under metabolic stress, in virus-infected lymphocytes, and in degenerative brain lesions, including neurofibrillary tangles and senile plaques in AD. The previously reported pathologic similarities between AD and IBM prompted us to study alphaBC expression in IBM. METHODS: Immunolocalization of alphaBC in muscle of 11 patients with IBM, 50 patients with other muscle diseases, and 4 controls; and quantitative analysis of the frequency of fibers with 1) increased alphaBC expression in IBM and polymyositis and 2) structural abnormality (vacuolated, non-necrotic and invaded by mononuclear cells, Congo red-positive, SMI-31 positive, and ubiquitin positive) in IBM. RESULTS: We detected enhanced expression of alphaBC not only in all structurally abnormal IBM fibers, but also, and with severalfold higher frequency, in IBM fibers without significant structural abnormality (X fibers) (p values in paired t-tests < 0.001). We also found enhanced alphaBC in abnormal fibers in other diseases; X fibers, however, were extremely sparse or absent, except in two atypical cases of polymyositis refractory to immunotherapy. CONCLUSION: That the X fibers are much more frequent than the structurally abnormal fibers in IBM points to a pathogenic stressor acting upstream to the development of structural abnormalities. The identification of this stressor is now of paramount importance for deciphering the enigma of IBM.     

Cystic lesions of the pineal region – MRI and pathology

Pineal lesions are rare. Tumours in this location comprise 0.4–1 % of intracranial tumours. They grow mainly as solid-mass lesions, and cystic tumours are not common. On MRI, a cystic configuration is associated usually with non-neoplastic pineal lesions rather than with a tumour, but analysis does not allow cystic pineal tumours to be distinguished from glial cysts with certainty. We compared neuroradiological and pathological data from 13 cystic pineal lesions, analysing preoperative MRI. Formalin-fixed, paraffin-embedded surgical specimens were stained routinely and immunocytochemically, using the streptavidin-biotin-complex method. Histology revealed six pineocytomas, four glial cysts, an arachnoid cyst, a low-grade astrocytoma and a teratoma. Signal characteristics of pineocytomas were similar in many respects to those of glial pineal cysts. Histomorphological analysis allowed unambiguous discrimination between pineocytomas and glial pineal cysts. Received: 19 July 1999/Accepted: 3 September 1999     

Are single fractions of radiotherapy suitable for plantar fasciitis?

The use of radiotherapy for plantar fasciitis has never been reported in Australasia and is scarcely found in the English language medical literature, but it is commonly used in Europe, especially in Germany. In Europe, treatment courses consisting of multiple small fractions have been associated with high levels of pain relief. In the present report, the use of single fractions or radiotherapy was evaluated by reviewing seven consecutive patients referred for treatment and by applying objective and subjective criteria for pain relief. One patient died of unrelated causes soon after treatment and one declined to receive radiotherapy. Four patients each received a single dose of 8 Gy resulting in complete pain relief. One patient was treated with 8 Gy and 12 weeks later was retreated achieving partial pain relief. A follow‐up interview was conducted after a mean of 15.6 months, ranging from 1.5 to 30 months. No acute or late effects occurred; however, the possibility that delayed effects may yet occur, particularly carcinogenesis, cannot be excluded. Radiotherapy for this common condition should be investigated further as it might be safer and more effective than other methods currently in use.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Correlation between basic fibroblast growth factor immunostaining of stromal cells and stromelysin-3 mRNA expression in human breast carcinoma.

We examined the localization of basic fibroblast growth factor (bFGF) in a series of human breast carcinomas using immunohistochemistry. Staining was observed in tumour cells in 15 out of 54 (28%) tumours and in the adjacent stroma in 34 out of 54 (63%) tumours examined. No correlation was observed between positive staining of these two compartments. The relationship between bFGF staining and expression of the metalloprotease stromelysin-3, and between bFGF and microvessel density, was examined. A statistically significant correlation (P < 0.003) was observed between bFGF staining of the stromal compartment and high expression of stromelysin-3 (ST-3; MMP-11) metalloprotease mRNA by stromal cells. In contrast, no correlation was observed between bFGF and intratumour microvessel density (IMD). These results raise the possibility that bFGF may be involved in the induction of stromelysin-3 mRNA expression in breast cancer stroma.     

Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.

Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.     

Survival for rectal cancer patients and international comparisons.

BACKGROUND: Population-based cancer registry data are important because they reflect routine care, present long-term follow-up, can show differences in treatment, outcomes and health care over time, and can be used for comparisons between regions and countries. PATIENTS AND METHODS: Details of all cancer patients in the Munich region are recorded by the Munich Cancer Registry. Rectal cancer patients with an invasive primary tumor diagnosed between 1996 and 1998 were included in this analysis (n=936). Observed and relative survival are presented. Observed survival was also investigated with a Cox proportional hazards regression model. RESULTS: Median follow-up time of survivors was 5.7 years. Five-year relative survival for the whole sample was 62.2%. International Union Against Cancer (UICC) stage was the most important prognostic factor in the multivariate analysis. Compared with the 1992-1999 Surveillance Epidemiology and End Results (SEER) data (62.4%), relative survival for each disease stage and the whole sample were very similar. In comparison with other European registries, Munich patients had slightly higher survival rates per stage (for example, 5-year relative survival in UICC III was 58.3% in Munich, 54.6% in South East Netherlands, 33.3% in Modena and 47.4% in Cote d'Or); however, more patients in Munich were in higher disease stages with worse prognoses, indicating poorer early detection. CONCLUSIONS: These results indicate that treatment of rectal cancer in Munich is good, but early detection could be improved. Cancer registries should publish their population-based stage data to ensure quality of care and provide regular feedback to health-care workers and decision makers. Comparisons between countries without stage data should be conducted cautiously.