Macular recovery time, diabetic retinopathy, and clinical variables after 7 years of improved glycemic control.

Effects of long-term improved glucose control on neurosensory retinal function are investigated. Changes in macular recovery of nyctometry (photostress) are assessed in 45 insulin-dependent diabetic patients between study start and after 7 years prospective follow-up (the Oslo Study). Intensified insulin treatment improved glycosylated hemoglobin (HbA1) from 11.7 +/- 2.2% at start to a 7-year cumulative mean of 9.5 +/- 1.5% (p less than 0.0001). Improved macular recovery performance was observed in patients with 7-year mean HbA1 below 10%, compared to a worsening in those above 10% (p less than 0.001-0.02), and non-proliferative retinopathy progressed less in those with HbA1 below 10%, than in those above (p less than 0.01). Macular recovery at study start did not predict progression or outcome of retinopathy 7 years later. Intraocular pressure fell during the 7 years (p less than 0.001) and was cross-sectionally negatively correlated to macular recovery at the 7-year end-point (p less than 0.001-0.002). Macular recovery was not related to age, duration of diabetes, systemic blood pressure, or urinary albumin excretion level. The study indicates that severity of retinopathy, glycemic control and intraocular pressure are interesting covariants to neurosensory dysfunction in diabetes. Furthermore, the study suggests a critical level of long-term blood glucose or retinopathy, or both, above which neurosensory function of macular recovery is significantly reduced.     

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.