APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Poliomyelitis outbreak in Natal/KwaZulu, South Africa, 1987-1988. 1. Epidemiology.

An epidemic of type 1 poliomyelitis occurred in Natal/KwaZulu in the eastern part of South Africa between December 1987 and November 1988. 412 poliomyelitis cases were reported, of whom 74% were younger than 5 years. The case-fatality rate was 8%. It is suggested that massive floods, experienced in the area 2 months earlier, triggered the outbreak.     

HELLP Syndrome: an Often Unrecognized Complication of Preeclampsia

We describe a case of preeclampsia with the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and highlight the delayed diagnosis due to its nonspecific presentation. This syndrome is associated with significant maternal and perinatal mortality and morbidity and we discuss the importance of early recognition of the condition, aggressive management and a multidisciplinary approach.     

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.     

Measurement of depression in dementia: Self vs clinician rating

The presence of depression was evaluated in a cross-section of 50 outpatients with dementia using the self-rated Geriatric Depression Scale and the clinician-rated Cornell Depression Scale. Impaired insight, as manifested by unawareness of dementia, correlated with dementia severity and discriminated a group of patients in whom the self-rated scale failed to show evidence of depression. Discrepancy between the two types of scales occurred among mildly as well as moderately demented patients when insight was impaired. Recognition of this discrepancy suggests that reliance on self-ratings may underestimate the presence and degree of depression among patients with dementia.     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

Identification of an extensive ζ-α globin gene deletion in a Chinese individual

We describe a novel alpha-thalassaemia-1 deletion that removes the entire zeta-alpha globin gene cluster. A Chinese couple were referred for counselling after two consecutive pregnancies ended with fetal hydrops. Gene mapping was used to demonstrate that the mother is heterozygous for the South-east Asia alpha-thalassaemia-1 deletion (zeta zeta zeta alpha alpha/zeta zeta--SEA), while the father carries an alpha-thalassaemia-1 deletion of more than 100 kilobases (zeta zeta alpha alpha/----). This newly discovered deletion extends for unknown distances 3' and 5' of the zeta-alpha globin gene cluster and has been designated (--HW).     

The Decline in Serum Albumin after Conversion to High Flux, High Efficiency Dialysis

Abstract: Hypoalbuminemia among chronic hemodialysis patients is recognized as a poor prognostic sign. We observed that many of our chronic patients had a progressive decrease in their plasma albumin concentrations after they were converted to high flux, high efficiency dialysis from conventional dialysis mode. This change occurred in the absence of changes in the KTIV and protein catabolic rate (per) normalized to body mass. When nitrogen losses were measured, we found no difference in the dialysate concentrations of urea, alpha amino nitrogen, uric acid, or total nitrogen when high flux polysulfone was compared with high efficiency Cuprophan. While urea was the predominant nitrogen solute in all dialysate samples, there were some with a large gap between total and urea nitrogen. Alpha amino nitrogen losses, expressed as leucine equivalents, were substantial, ranging from 8. 4 to 9. 8 g/3. 5 h dialysis treatment. We believe that the increased losses of nitrogen experienced by patients after their conversion to a more efficient method of dialysis and not compensated for by a spontaneous increased intake of protein led to the observed fall in plasma albumin. Both urea and amino acid nitrogen losses need to be accounted for when achievement of higher KTIV dialysis is pursued.