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This randomized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy. When delayed hypersensitivity to phenytoin developed, the patient was switched to phenobarbital. The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations. There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups (p = 0.75). The time between injury and seizures did not significantly differ between the two groups. The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures. It cannot be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy. The finding that no patient with a phenytoin plasma concentration of 12 microgram/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy, and should be studied further. Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study, or other currently available or newly developed drugs, can prevent the occurrence of posttraumatic epilepsy.

A randomized double-blind placebo-controlled study was carried out to determine whether phenytoin administered soon after injury lessens the incidence of epilepsy in the 1st week after severe head trauma. In this study, 244 patients were randomized into either a phenytoin or placebo group. The patients in the phenytoin group were administered phenytoin intravenously or intramuscularly within 24 hours of hospital admission. Patients in the placebo group received intravenous or intramuscular diluent. The patients were switched from parenterally administered phenytoin or placebo as soon as oral doses could be tolerated. Over 78% of the phenytoin patients had plasma concentrations of at least 10 micrograms/ml at 1, 3, and 7 days after injury. There was no significant difference in the percentage of patients having early seizures in the treated and placebo groups (p = 0.99). There was no significant difference in the interval from injury to first seizure between the treated and placebo groups (p = 0.41). The early administration of phenytoin did not lessen the occurrence of seizures in the 1st week after head injury. Since the effectiveness of seizure prophylaxis has not been established, the authors suggest that anticonvulsant drugs be administered only after an early seizure has occurred.

The relationship between Glasgow Coma Scale (GSC) scores obtained during the 1st week after head injury and outcome at 1 year was analyzed in 170 patients. Seventy-two of 76 patients with initial GCS scores of 3 or 4 lived, and only one had a favorable outcome. Favorable and unfavorable outcomes were almost equally divided when the initial GCS scores were in the intermediate range of 5, 6, or 7. No patients with an initial GCS score in this intermediate range that subsequently worsened had a favorable outcome, while over 80% of those improving to a score higher than 7 had a favorable outcome. Only 12% of those persisting with a score of 5, 6, or 7 for 1 week had favorable outcome. Outcome predictions using the multiple logistic model were made for this intermediate group of patients based on GCS scores and data on midline shift derived from computerized tomography (CT). The patients with initial scores of 5, 6, or 7 with midline shifts of less than 4.1 mm on initial CT scanning had a significantly higher favorable outcome rate compared with patients with a larger shift. However, outcome prediction made by combining shift data and initial GCS scores are not significantly more accurate than predictions based solely on initial GCS scores. Combining 48-hour GCS scores and shift data significantly improves predictive accuracy based only on coma scores. The data obtained by combining GCS scores at 72 hours and 1 week and shift data is marginally significant for improving accuracy of outcome predictions. It is concluded that GCS scores and shift data are highly accurate indicators of outcome in head-injured patients.

Starlings (Sturnum vulgaris) collected in 1973 at 51 sites throughout the continental United States were analyzed for mercury, lead, cadmium, arsenic, and selenium. All samples contained detectable levels of these elements. In general, residues were low: mercury residues ranged from less than 0.01 to 0.20 ppm; lead, from less than 0.10 to 3.20 ppm; cadmium, from less than 0.05 to 0.20 ppm; arsenic, from less than 0.05 to 1.40 ppm; and selenium, from 0.10 to 1.10 ppm. There was a significant overall decline in mercury and lead residues in starlings since 1971, and a significant increase in arsenic residues. Lead residues were significantly higher in starlings from urban areas than from rural areas.

The concentration of antibiotic in cerebrospinal fluid was measured during treatment of seven children with infected ventricular shunts. Antibiotics were administered via the ventricular shunt or through an external ventricular drain. 53 CSF samples were obtained 7-19 h after antibiotic administration. Wide variation in cerebrospinal fluid antibiotic concentration occurred from patient to patient following either route of administration. For optimal management of shunt infections, we recommend periodic assessment of antibiotic concentration or activity in ventricular fluid and determination of the minimum inhibitory concentration of antibiotic required for each pathogen.

Leucocyte migration inhibition in response to ubiquitous antigens was studied in 104 patients as an in vitro indicator of cell-mediated immunity. Patients with cerebral glioma, benign intracranial tumours, and subarachnoid haemorrhage demonstrated impaired inhibition of leucocyte migration compared with control subjects. The greatest impairment occurred in patients with subarachnoid haemorrhage, while the least impairment was seen in patients with glioma. Significant rises in inhibition of leucocyte migration in response to antigen preparations from glioma and normal brain were seen in the early post-operative period in patients with glioma and subarachnoid haemorrhage. Impaired cellular immunity, together with sensitivity of lymphocytes to brain-derived antigens, are features of cerebral disease in general and not specific for glioma.

This prospective randomized controlled clinical trial compares the effects of early parenteral nutrition and traditional delayed enteral nutrition upon the outcome of head-injured patients. Thirty-eight head-injured patients were randomly assigned to receive total parenteral nutrition (TPN) or standard enteral nutrition (SEN). Clinical and nutritional data were collected on all patients until death or for 18 days of hospitalization. Survival and functional recovery were monitored in survivors for 1 year. Of the 38 patients, 18 were randomized to the SEN group and 20 to the TPN group. Demographically, the two groups of patients were similar on admission. There was no significant difference in the severity of head injury between the two groups as measured by the Glasgow Coma Scale (p = 0.52). The outcome for the two groups was quite different, with eight of the 18 SEN patients dying within 18 days of injury, whereas no patient in the TPN group died within this period (p less than 0.0001). The basis for the improved survival in the TPN patients appears to be improved nutrition. The TPN patients had a more positive nitrogen balance (p less than 0.06), and a higher serum albumin level and total lymphocyte count. More adequate nutritional status may have improved the patients' immunocompetence, resulting in decreased susceptibility to sepsis. The data from this study strongly support the favorable effect of early TPN on survival from head injury.

As part of the National Pesticide Monitoring Program, the Fish and Wildlife Service, U.S. Department of Interior, analyzed selected fish samples from 100 monitoring stations for residues of mercury, arsenic, lead, cadmium, or selenium in 1971-73. At most stations, detectable residues of all metals were present in more than 95 percent of the composite samples. Fishes with mercury residues exceeding 0.5 mg/kg wet weight in the whole fish were mainly predators. Fishes with residues of arsenic, lead, cadmium, and selenium exceeding 0.5 mg/kg included predatory and nonpredatory species. The number of composite samples in which residues of these elements exceeded 0.5 mg/kg decreased from 1971 to 1973, whereas the percentage of samples with detectable residues increased slightly. Only selected samples were analyzed in 1973; therefore, these figures should be used only cautiously as trend data. Species of fish collected varied considerably between geographic regions but were similar from year to year within each region.