Blinded clinical evaluation of positron emission tomography for diagnosis of probable Alzheimer's disease.

We evaluated the sensitivity and specificity of positron emission tomography for diagnosis of probable Alzheimer's disease under conditions similar to those encountered in the routine clinical practice of nuclear medicine. We obtained tomographic images of regional cerebral blood flow from three groups of subjects: (1) 13 subjects, ages 69 to 84, who had probable Alzheimer's disease diagnosed by validated clinical criteria; (2) 15 subjects, ages 57 to 77, who had Parkinson's disease without dementia; and (3) 11 subjects, ages 65 to 83, who were normal. Three blinded reviewers, who had not previously seen the images, categorized them as normal, bilateral temporoparietal flow defects typical of Alzheimer's disease, or other abnormality. Consensus interpretation demonstrated sensitivity of 0.38 (5/13) and specificity of 0.88 (23/26) for identifying patients with probable Alzheimer's disease. Thus, the criterion of bilateral temporoparietal reduction in cerebral blood flow used in this study did not have sufficient sensitivity to be of clinical value. While other criteria may be developed to improve diagnostic accuracy, clinical utility can be established only by testing for validity in patients with a full spectrum of complicating neurologic and psychiatric conditions for whom diagnosis is uncertain and who are then followed longitudinally to determine clinical outcome or pathologic findings.     

Lack of control of liver gluconeogenesis in cholestatic rats with reduced portal blood flow.

Previous studies indicated a role for ischemia in the metabolic changes induced by cholestasis. Liver pyruvate kinase is a key enzyme for the concurrent control of glycolysis and gluconeogenesis. In this experiment the control of pyruvate kinase activity was investigated in cholestatic rats. Pyruvate kinase kinetics changed from a sigmoidal type in sham-operated rats to a hyperbolic type in obstructed rats. The change in the enzymatic kinetics paralleled the reduction in the portal blood flow, which reached 50% of the control value 7 days after obstruction. Dibutyryl cyclic AMP (5 mumol/kg body wt) plus theophylline 0.1 mmol/L failed to inactivate the enzyme when injected into the portal veins of rats whose livers were obstructed 7 days before. Both the kinetics changes and the lack of phosphorylation control are compatible with ischemia.     

Aminophylline in the emergency department. Maximizing safety and efficacy

An experimental technique designed to predict theophylline doses needed to attain therapeutic theophylline concentrations in 43 emergency department (ED) patients was compared with a standard conventional regimen in 46 ED patients. The experimental protocol utilized a computer-assisted dosage prediction program that incorporated baseline theophylline concentration rapidly obtained using a bedside assay. The standard protocol used conventional loading and infusion rates, as well as an estimate of time of last theophylline dose based on patient history. Plasma theophylline concentrations, estimated 1 and 6 hours after commencement of aminophylline therapy in each regimen, were compared. The experimental protocol was equally rapid but much more accurate in achieving targeted theophylline concentrations. Experimental dosage prediction was associated with a higher proportion of theophylline concentrations in the therapeutic range at 1 (81 percent vs 26 percent; p less than 0.001) and 6 hours (91 percent vs 37 percent; p less than 0.001). There was a trend toward fewer toxic concentrations recorded at 1 (0 percent vs 7 percent; p = 0.27) and 6 hours (0 percent vs 10 percent; p = 0.08). This protocol, which was performed quickly and without difficulty by residents in a busy hospital ED, offers an opportunity to improve the efficacy and decrease the toxicity of theophylline use in asthma emergencies.     

Comparative study of the morphological changes in lymphocytes of elderly individuals and centenarians.

The number of white blood cells, the morphological changes of the peripheral lymphocytes and some immunological variables were examined in 118 centenarians and in 499 healthy subjects of 60-89 years of age. There was no change in the absolute number of leucocytes, lymphocytes, or T or B cells with age. The occurrence of a myelin-like structure in the mitochondria and the presence of lipofuscin in the cytoplasm of lymphocytes increased with age and showed a correlation with the absolute number of T cells. A correlation could be observed between the absolute number of B cells, serum IgG level and the presence of antinuclear factor.     

A randomized trial of plasmapheresis and subsequent pulse cyclophosphamide in severe lupus: design of the LPSG trial.

A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feed-back between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial.     

Antiphospholipid antibodies in pre-eclamptic women: relation to growth retardation and neonatal outcome.

The significance of antiphospholipid antibodies in pre-eclamptic women has not been thoroughly elucidated. The purpose of this study was to determine the proportion of pre-eclamptic women who were antiphospholipid antibody positive, and to elucidate the significance of these antibodies regarding growth retardation and neonatal outcome. Positive levels of anticephalin antibodies, which are antiphospholipid antibodies, were detected in 7 (19%) out of 37 pre-eclamptic women, as compared with none of 40 in a control group of normotensive women at similar stage of pregnancy (p = 0.004). The birthweight percentiles of the neonates of anticephalin antibody positive women were significantly lower than those of the neonates of anticephalin antibody negative women (p = 0.018). Four of 7 infants of anticephalin antibody positive women were growth retarded (less than 2.5th percentile). This was a significantly larger proportion than that for anticephalin antibody negative women (3/30) (p = 0.004). The 95% confidence interval for the difference between the two proportions was 0.10 to 0.85. Two of the 7 neonates of anticephalin antibody positive women died during the neonatal period, compared with none of the 30 neonates of anticephalin antibody negative women (p = 0.003). Thus, our study suggests that positive levels of anticephalin antibodies in pre-eclamptic women increase the risk for growth retardation and neonatal death.     

Leiomyosarcoma of the mouth floor and oropharynx]

Leiomyosarcomas arise rarely in the head and neck. We report a 41-year-old woman with an extremely rare leiomyosarcoma of the floor of the mouth extending to the oropharynx. This article stresses the value of imaging methods such as CT, MRI and ultrasound for preoperative diagnosis, and emphasises histopathological findings. The therapeutic principles and prognostic factors of leiomyosarcomas are illustrated on the basis of this case.