Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.     

Effect of positioning on oxygenation in single-lung transplant recipients.

BACKGROUND: Many benefits and adverse effects of positioning are related to changes in ventilation and perfusion. A number of unique factors related to the allograft make the effects of positioning difficult to determine in single-lung transplant recipients. OBJECTIVES: To determine the effect of 3 body positions (supine, lateral with allograft lung down, and lateral with native lung down) on oxygenation and blood flow in single-lung transplant recipients in the 24 hours immediately after surgery. METHODS: A quasi-experimental repeated-measures design with stratified assignment to 1 of 3 different sequencing patterns for turning group was used to study 15 transplant recipients, 9 with emphysema and 6 with fibrosis. Oxygenation, ventilation, and blood flow measures (heart rate, blood pressure) were assessed after each turn. The effect of ischemic reperfusion injury was also explored. RESULTS: The oxygenation, ventilation, and bloodflow variables did not differ significantly across group, diagnosis, or time. Oxygenation variables measured when the allograft lung was dependent did not differ significantly from such measurements obtained when the native lung was dependent. CONCLUSIONS: No single position maximizes oxygenation in the immediate postoperative period in single-lung transplant recipients. Although a single standard protocol for positioning cannot be supported, the study does support the idea that transplant recipients can be safely turned in the immediate postoperative period without compromising oxygenation or hemodynamic status.     

The avidity of specific IgM detected in primary rubella and reinfection

An IgM capture enzyme-linked immunosorbent assay for rubella-specific IgM was used to assess the avidity of specific IgM by comparing the results obtained with and without a mild protein denaturant in the washing fluid used after incubation of IgM with rubella haemagglutinating antigen. An avidity index (AI) was calculated with AIs less than 50% considered to indicate low avidity. Sera from recent primary rubella, rubella reinfection and from patients persistently reactive for specific IgM were tested. Urea and diethylamine (DEA) were compared as the protein denaturants. Twenty-six of 28 sera from cases of primary rubella gave an AI less than 50% with DEA, compared with 25 of 28 with urea. Seventeen of 20 sera from cases of reinfection gave an AI greater than 50% with DEA whereas only 14 of 20 had a similarly high avidity with urea. Eight of 10 sera from 4 cases of persistent specific IgM reactivity gave AIs greater than 50% with DEA, although this was reduced to 5 when urea was used. Thus a difference has been demonstrated between the avidity of specific IgM in primary infection from that demonstrated after a secondary antigenic challenge (reinfection). This may help in serologically distinguishing primary infection from reinfection.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

The effect of high-dose salmon calcitonin on bone mineral metabolism in the normal rat

Summary The paucity of information on the effect of long-term high-dose salmon calcitonin administration on normal bone mineral metabolism and histology prompted an investigation of the influence of high-dose synthetic calcitonin in the rat. Serum ionized calcium, osteocalcin or BGP (bone gla protein), and immunoreactive PTH were measured serially during calcitonin administration and bone histomorphometry analyzed at 6 weeks (after sacrifice). Daily injections of salmon calcitonin, 0.4 IU/100 g (group B) and 2 IU/100 g (group C), resulted in significant hypocalcemia at 4 hours for both experimental groups (P<0.004). Serium iPTH was significantly higher over the study period for both groups administered calcitonin. Serum BGP levels were significantly lower than controls during the study in group C (P<0.002) and to a lesser extent in group B (P<0.05). In group C, bone histomorphometry revealed increased resorption (onteoclast count), decreased trabecular bone volume, and decreased double-labeled tetracycline surface (bone formation). In group B an increase in osteoclast count but no alteration in bone formation was observed. To assess the role of PTH in the above findings, high-dose calcitonin was administered to parathyroidectomized rats. All of the above changes in bone histomorphometry were not observed in this group of animals. In conclusion, high doses of calcitonin promote hypocalcemia, secondary hyperparathyroidism, and osteoclastosis in the normal rat in a dose-dependent manner with very high-dose calcitonin impairing bone formation.