Mild traumatic brain injury in an insured population: subjective complaints and return to employment

The great majority of traumatic brain injury (TBI) is of mild severity, with Glasgow Coma Scores (GCS) of 13-15, post-traumatic amnesia of less than 48 hours and brief, if any, hospitalization. All mild TBI admissions to hospital were provided with education in the form of a brief interview and a brochure on minor head trauma from the National Head Injury Foundation. Seventy-seven insured individuals with mild TBI were contacted by phone between 1 and 3 months post-injury to determine the frequency and severity of post-traumatic symptoms and the rate of return to work (RTW). Twenty-six per cent of those contacted had subjective complaints; 88% had returned to work or school; 16% of those returning did so with some symptoms. Only 45% of symptomatic individuals sought medical consultation for their condition when offered. Education about post-traumatic symptoms from the onset may provide sufficient reassurance to most individuals that future use of medical services is seen as unnecessary. Rate of RTW is relatively higher than reported in previous studies of mild TBI.     

Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT₂ receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence. Received: 30 April 1996/Final version: 3 July 1996     

Two Novel Pyrrolopyrimidine Lipid Peroxidation Inhibitors U-101033E and U-104067F Protect Facial Motor Neurons Following Neonatal Axotomy

Recent reports suggest that oxygen radical-induced lipid peroxidation plays a role in the retrograde degeneration of motor neurons following facial nerve axotomy in the neonatal rat. The purpose of the present study was to explore this notion further by testing the neuroprotective properties of two novel brain-penetrating, lipid peroxidation inhibitors, U-101033E and U-104067F, in this model of neuronal degeneration. In Experiment 1, 14-day-old rats were pretreated with 3, 10, or 30 mg/kg U-101033E (po) 10 min before right facial nerve axotomy (Day 0) and then posttreated once a day from Day 1 to Day 6, and once every other day from Day 8 to Day 21. Rats were sacrificed 21 days postaxotomy and surviving cholinergic cell bodies were identified using choline acetyltransferase immunocytochemistry. Both 10 and 30 mg/kg U-101033E significantly enhanced motor neuron survival, with survival rates of 65.9–88.9% being noted in comparison to 51.7–62% survival in vehicle controls (P ≤ 0.05). Experiment 2 demonstrated a significant neuroprotective effect of 10 and 30 mg/kg U-104067F using the same dosing schedule. Experiment 3 was designed to test whether shorter periods of drug exposure (e.g., 5 or 7 days) would be sufficient to preserve motor neurons in rats treated with 10 mg/kg U-101033E. The results suggested that as little as 5 days of drug treatment is sufficient to enhance motor neuron survival. Finally, Experiment 4 demonstrated an 18–19% increase in motor neuron survival in rats treated with 10 and 30 mg/kg U-104067F for 5 consecutive days postaxotomy. Taken together, the attenuation of motor neuron degeneration by the two pyrrolopyrimidine lipid peroxidation inhibitors, U-101033E and U-104067F, lends support to the notion that lipid peroxidation contributes to the pathogenesis of axotomy-induced neurodegeneration.     

Comparison of gas-liquid chromatography and EMIT assay for serum valproic acid

We describe a simple direct extraction method for the gas-liquid chromatography determination of serum valproic acid. The working range for the assay is 2-180 mg/L and our within-run precision was 5.8 and 4.3% at the 40 and 90 mg/L concentrations respectively. Hemolyzed and lipemic sera as well as samples from patients with hyperbilirubinemia and from patients with decreased renal function were put through the assay and no interfering peaks were noted. Interference occurred when teflon-lined screw caps were used during the extraction step. The method was proven to be accurate by linear regression analysis of samples containing weighed-in amounts of valproic acid. The above assay was compared to an enzyme immunoassay technique (EMIT). The working range for the latter is 10-150 mg/L and the with-run precision was 10.8 and 5.9% and 90 mg/L concentration respectively. Samples were run by both the gas-liquid chromatograph and enzyme immunoassay methods and gave very similar results over the range 16-139 mg/L.     

Phagocytosis of light- and dark-adapted rod outer segments by cultured RPE cells: a reassessment

Rod outer segments (ROS) isolated from adult rat retinas are phagocytized by cultured rat retinal pigment epithelial (RPE) cells. Using a double immunofluorescent labeling procedure, we have compared the binding and ingestion of ROS isolated at different times of the day. After 2 hr of incubation, approximately 98% of the ROS are ingested, while 2% are still attached to the RPE cell surface, irrespective of the time of day or lighting conditions under which the ROS are isolated. These findings differ from those reported earlier, using a radioactive method for quantitating ROS phagocytosis (Hall, 1978).     

Vitamin D-independent expression of chick brain calbindin-D28K.

A combination of calbindin-D28K-specific cDNA probes and polyclonal antisera were used to investigate expression of the calbindin-D28K in the vitamin D-deficient avian brain in vivo in response to pharmacological doses of the vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Serum calcium levels were stimulated (2-fold) and intestinal calbindin-D28K expression (between 10- and 30-fold) by 1,25(OH)2D3 (6.5 nmol/animal) after 12 h. In marked contrast, steady-state whole brain levels of calbindin-D28K as judged by enzyme-linked immunoassay (ELISA) remained constant. Northern gel analysis revealed that three species of calbindin-D28K mRNA (2.0, 2.6 and 3.1 kb) were present a priori in the vitamin D-deficient chick brain and that administration of pharmacological doses (6.5 nmol/animal) of 1,25(OH)2D3 failed to influence their relative abundance. Separate but parallel dot blot hybridization analyses also confirmed that brain calbindin-D28K-mRNA levels were not influenced by 1,25(OH)2D3. These experiments demonstrate at the molecular level that, in contrast to the intestine, the gene encoding calbindin-D28K in the brain is regulated by mechanism(s) or factors which are independent of vitamin D status.