Structure-activity relationship of quinazolinedione inhibitors of calcium-independent phosphodiesterase.

A series of quinazolinediones and azaquinazolinediones is described which possess potent inhibitory activity toward the calcium-independent phosphodiesterase enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to animal models predictive of chronic diseases such as depression and inflammation. These results support the hypothesis that inhibition of CaIPDE may lead to useful activity in such chronic diseases.

Mucoepidermoid bronchial adenoma in a 6-year-old girl: a case report and review of the literature.

A rare case of a mucoepidermoid bronchial adenoma discovered in a 6-year-old girl with recurrent pneumonia is presented. A review of the literature suggests that less than 15 cases in the pediatric age group have been reported. Although primary lung carcinomas are rare in children, this case illustrates that recurrent lobar pneumonia in children should be aggressively investigated and that the proper therapy is conservative surgical resection.

Landry Guillain-Barré Strohl syndrome in pregnancy: report of three cases treated with plasmapheresis.

Landry Guillain-Barré Strohl syndrome complicating pregnancy is a rare occurrence, with only 31 cases previously reported in the obstetric literature. Cytomegalovirus as a potential etiologic agent has been documented in only two of these cases. In the past, symptomatic treatment of pregnant patients with severe and progressive symptoms has been associated with an unacceptably high rate of maternal morbidity and mortality. Recent studies have shown convincingly that plasmapheresis is the treatment of choice for nonpregnant patients acutely ill with Guillain-Barré syndrome, but data regarding its use in pregnancy are limited. We report three patients, two of whom had positive cytomegalovirus titers, in whom aggressive plasmapheresis prevented the need for ventilatory support and its inherent increase in maternal morbidity and mortality.

Muscle strength and fatigue during isokinetic exercise in individuals with multiple sclerosis.

PURPOSE: To compare muscle strength and muscle fatigue of the knee extensors and flexors in individuals with multiple sclerosis (MS) and non-MS control subjects and to evaluate the reliability of muscle strength and muscle fatigue testing in these individuals. METHODS: Thirty individuals (13 women and 2 men for both MS and control groups), age (mean +/- SD) 38.8 +/- 10 for MS and 33.1 +/- 7.6 yr for controls, participated in this investigation. Peak torque was measured on two occasions separated by approximately 7 d at 30, 60, 90, 120, 180 degrees.s(-1) with 2 min of recovery between each bout. The nondominant leg was tested followed by the dominant leg after 10 min of recovery. Subjects then performed three bouts of 30 flexions and extensions of the dominant leg at 180 degrees.s(-1) with 1 min of recovery between bouts. RESULTS: The reliability of muscle torque was very high for individuals with MS (only 1 of 20 measurements with an ICC below 0.900). Total work was also highly reliable for MS, but the Fatigue Index (work during the last 15 contractions/work during the first 15 contractions) x 100 was not. Peak torque adjusted for age, body mass, and fat free mass (measured by whole body plethysmography; the Bod Pod; Life Measurement Instruments; Concord, CA) was significantly greater for controls than for MS for three of four lower body muscle groups tested. For the muscle fatigue test (3 bouts of 30 knee extensions and flexions at 180 degrees.s(-1)), the Fatigue Index was greater (less fatigue) for the knee extensors for controls than MS for the third bout. For flexion, the Fatigue Index was greater for controls than MS over the three bouts (group effect). Total work was significantly greater for controls than MS for the flexors (group effect) and approached significance for the extensors. CONCLUSIONS: Individuals with MS were weaker than controls when data were adjusted for age, body mass, and fat free mass. This latter finding (force relative to age and fat free mass) suggests that there is a reduced ability to activate muscle mass in MS and/or the muscle mass of individuals with MS is of lower quality (i.e., reduced force/unit muscle mass) than controls.

Coexistence of ectopic rhythms and periodic EEG pattern in anoxic encephalopathy.

In this paper, we reported unique EEG patterns in two patients with anoxic encephalopathy. In the patient with a longer survival, the early EEG showed: suppression-burst pattern and theta pattern coma during quiet states; and quasi-periodic, generalized, epileptiform discharges associated with alpha-theta pattern coma during periods of arousal. A second EEG showed a disappearance of suppression-burst pattern and alpha coma. A third EEG demonstrated a disappearance of quasi-periodic epileptiform discharges. Such distinct evolution of the electroencephalogram was associated clinically with increased responsiveness despite a fatal course of illness. The second patient who had a more dramatic course, had an EEG immediately preceding death, which showed a combination of periodic pattern and theta pattern coma.

Blepharospasm associated with olivopontocerebellar atrophy.

We report two cases of cranial dystonia (blepharospasm) associated with olivopontocerebellar atrophy (OPCA). The pathophysiology of blepharospasm appears to involve an increased excitability of the interneurons of the blink and corneal reflexes. It is hypothesized that blepharospasm associated with OPCA might be due to rostral brainstem lesions disrupting central dopaminergic and cholinergic pathways, resulting in disinhibition of brainstem reflexes or denervation supersensitivity of the facial nuclear complex.

Effects of dazmegrel, piroxicam and cyclophosphamide on the NZB/W model of SLE.

To investigate the potential importance of prostaglandins and thromboxane in systemic lupus erythematosus (SLE), the effects of a nonsteroidal antiinflammatory drug (piroxicam) and a thromboxane synthetase inhibitor (dazmegrel) were examined on survival, proteinuria, food consumption, body weight, and peripheral lymphocyte subset distribution in the NZB/W model of autoimmune lupus disease. The effect of an immunosuppressant (cyclophosphamide) known to be effective in the treatment of murine lupus on these parameters was also examined. Cyclophosphamide at 25 mg/kg ip weekly prolonged survival, inhibited proteinuria and prevented the characteristic decline in peripheral T cells and the relative increase in B cells seen in NZB/W lupus disease while having no apparent effect on body weight or food consumption. Neither dazmegrel at 50 or 200 mg/kg/day in the diet nor piroxicam at 2 mg/kg/day in the diet had any significant effects on these parameters.

Antiarrhythmic response to intravenously administered magnesium after cardiac surgery.

We evaluated the antiarrhythmic response to magnesium given intravenously to 40 patients who had had elective cardiopulmonary bypass for the surgical treatment of acquired cardiac disease. All 40 patients were found to have hypomagnesemia postoperatively as defined by a serum magnesium level of less than 1.8 mg/dL. The ventricular arrhythmias of these patients were categorized by a modified Lown grade classification. Magnesium sulfate (16 mEq, [2000 mg]) was administered, and the patients were reclassified according to their rate of ventricular ectopia. All arrhythmias of a higher grade responded to the treatment with a marked reduction in ventricular ectopia and were reclassified to a lower grade. This study supports the routine administration of magnesium sulfate, at a dose of 16 mEq, in postoperative cardiac patients who are hypomagnesemic.