Biomedical subjects
G Smith
Publications and source records attributed to G Smith.
Determination of the nodal point position in the pseudophakic eye.
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The village that refused to die.
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The A to B approach to investing.
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A phase I evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early human immunodeficiency virus infection. Military Medical Consortium for Applied Retroviral Research.
BACKGROUND: Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens. METHODS: We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored. RESULTS: In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell proliferative responses to gp160. Response was associated with the CD4 cell count determined before vaccination (13 of 16 subjects [81 percent] with greater than 600 cells per milliliter responded, as compared with 6 of 14 [43 percent] with less than or equal to 600 cells per milliliter; P = 0.07) and with the number of injections administered (87 percent of subjects randomly assigned to receive six injections responded, as compared with 40 percent of those assigned to three injections; P = 0.02). Local reactions at the site of injection were mild. There were no adverse systemic reactions, including diminution of general in vitro or in vivo cellular immune function. After 10 months of follow-up, the mean CD4 count had not decreased in the 19 subjects who responded, but it had decreased by 7.3 percent in the 11 who did not respond. CONCLUSIONS: This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.
Assessment of malnutrition in elderly patients.
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GABAA-benzodiazepine receptors: demonstration of pharmacological subtypes in the brain.
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The GABAA receptor family in the mammalian brain.
The GABAA-benzodiazepine receptor protein from bovine brain was purified by affinity chromatography and the subunit composition examined by gel electrophoresis in sodium dodecyl sulfate. Protein staining revealed a doublet at 51-53 kDa, a band at 55 kDa, and a broad band at 57-59 kDa. The 51 and 53 kDa bands co-migrated with the alpha 1 and alpha 2 gene products identified by Western blotting with subtype-specific antibodies. These two bands were also photoaffinity labeled by [3H]flunitrazepam, as was a breakdown product at 44 kDa. Partial sequencing of proteolytic fragments of these polypeptides yielded sequences found in all alpha clones, and identified the benzodiazepine binding site within residues 8-297 and probably between 106-297 of alpha 1; the 44 kDa and 31 kDa bands yielded fragments containing alpha 3 sequence. The native alpha 3 polypeptide was identified with subtype-specific antibody at 57 kDa overlapping with the two major bands photolabeled with [3H]muscimol at 55 and 58 kDa. Antisera to a beta-selective peptide recognized four bands at 60, 58, 57 and 55 kDa. Thus, one can identify 6-8 distinct polypeptides with the possibility of another 4-6 in purified GABAA receptor proteins, depending on brain region, consistent with the family of gene products suggested by molecular cloning.
Electrical properties of axons within probst bundles of acallosal mice and callosi that have reformed upon glial-coated polymer implants.
Lesioning of the developing cerebral midline and corpus callosum of mice results in the formation of bilateral masses of axons known as Probst's longitudinal bundles. These ectopic axons were examined using an in vitro brain slice technique, and they were found to be functional and to have electrical properties that were similar to those of the unlesioned corpus callosum at a comparable age. When a nitrocellulose bridge is properly oriented at the site of the callosal lesion in neonates, the implant will support the migration of glia which, in turn, promote the redirection of callosal axons across the midline. These axons were also analyzed by in vitro brain slice techniques, and they were found to be functional and to have electrical properties that were similar to the unlesioned corpus callosum with respect to conduction velocity and chronaxie but dissimilar with respect to charge threshold and rheobase current.
Impact of acute alcohol intoxication on patterns of non-fatal trauma: cause-specific analysis of head injury effect.
The impact of alcohol on injury patterns was studied by using 14,920 injured men aged 15-64 years seen in an emergency room in Helsinki, Finland. Blood alcohol was estimated by clinical evaluation and breath test, and was coded into a three-grade intoxication code. Intoxication was recorded in 19.7 per cent. Head injury was more common among the intoxicated (64.1 per cent) than among the sober (17.6 per cent). The odds of head injury, if 1.0 among the sober, was 8.3 among the intoxicated. This head injury effect (HIE) was found in every major external cause category: falls 15.4, traffic 3.0, other unintentional injury 3.4 and assault 2.6. A major difference in HIE was found by hospitalization status: 2.1 for hospitalized and 9.8 for ambulatory patients. Alcohol seems to produce mostly low-energy events (like falls) resulting usually in minor, though potentially dangerous, head injury.
A study of the mortality and fecundity of Haemonchus contortus in sheep following experimental infections.
The regulation of the fecundity and mortality of H. contortus in sheep was examined using a series of mathematical models. Six-month-old Dorset crossbred lambs were infected once only with various doses of infective H. contortus larvae (500-20,000 larvae). Parasite mortality was found to be an increasing linear function of the magnitude of the initial infection over the range of doses examined. Parasite fecundity was found to remain constant over the intensity and duration of the infection. The average fecundity for H. contortus at the time of slaughter was found to be 7037 eggs per female worm per day. There was no evidence of time-dependent changes in fecundity or density-dependent regulation of fecundity.
The regulation of mortality and fecundity in Schistosoma mattheei following a single experimental infection in sheep.
The regulation of mortality and fecundity of Schistosoma mattheei in sheep was examined using a series of mathematical models applied to data culled from the literature. Parasite mortality (mu) was found to be an increasing linear function of the magnitude of the initial infection over the ranges of doses examined (200-91,000 cercariae) where mu = 9.78 x 10(-3) + 3.476 x 10(-7) infection dose. Parasite fecundity (lambda) was found to be inversely related to the duration of the infection. The best fit model for parasite fecundity was one in which fecundity decreased exponentially with time since initial infection, lambda = lambda 0e-delta(t-tau). There was no evidence for density-dependent regulation of fecundity.
Substance abuse and serious child mistreatment: prevalence, risk, and outcome in a court sample.
This study examined the prevalence and specific types of substance abuse in a sample of 206 cases of serious child abuse or neglect brought before a metropolitan juvenile court on care and protection petitions. In 43% of the cases, at least one of the parents had a documented problem with either alcohol or drugs, a figure which rose to 50% when alleged instances of substance abuse were included. Alcohol, cocaine, and heroin were the three most frequently mentioned abused substances. Parents with documented substance abuse were significantly more likely than nonsubstance-abusing parents to have been referred previously to child protective agencies, to be rated by court investigators as presenting high risk to their children, to reject court-ordered services, and to have their children permanently removed. When the two factors of court investigator high risk ratings and presence of parental substance abuse were combined, it was possible to obtain even higher levels of prediction of which parents would reject services and have their children permanently removed. Results suggest (1) the importance of increased screening, evaluation, and treatment of parental substance abuse in cases of serious child mistreatment; and (2) the possibility of adopting a predictive approach as to which families will be able to respond to court-ordered treatment requests and have their children returned.
Injuries from tire and wheel explosions during servicing.
STUDY OBJECTIVE: To evaluate injuries from tire and wheel explosions that occur during servicing. DESIGN: Retrospective analysis of all injury reports from the National Highway Traffic Safety Administration, the Occupational Safety and Health Administration, and the Insurance Institute for Highway Safety. RESULTS: For the period of 1978 through 1987, there were 694 reported injuries from explosions during tire servicing; 143 of them were fatal, resulting mainly from truck tires. Because the three data sources used different methods for case finding and covered different time periods, the actual number of such injuries was probably greater. Head injuries accounted for 78% of the deaths and 24% of nonfatal injuries. The proportion of injuries occurring during tire inflation declined from 51% in 1978 to 33% in 1987 (P less than .05). Fatal injuries involving single-piece rim wheels increased during the 1980s as multipiece rim wheels were phased out by the trucking industry. CONCLUSIONS: Exploding truck tires and wheel rims cause serious injuries. The use of safety cages during inflation as required by a 1980 Occupational Safety and Health Administration standard appears to have reduced injuries during truck tire inflation. The use of helmets during servicing may further reduce serious injuries.
Age-associated memory impairment diagnoses: problems of reliability and concerns for terminology.
Objective memory criteria for diagnosing age-associated memory impairment (AAMI), age-consistent memory impairment, and late-life forgetfulness (LLF) were applied to 523 cognitively normal older persons divided into 2 groups on the basis of the clinical memory assessment battery they received. Seventy-seven percent of Group 2 and 98% of Group 1 met the Crook et al. (1986) cognitive criteria for AAMI on at least 1 test. Rates based on individual tests varied from 7% to 96%. Objective-cognitive criteria for LLF were met by no members of Group 1 but by 31% of Group 2. Results suggest that, as proposed, the criteria for age-related diagnoses lack reliability. Concerns regarding the diagnosis of normal memory in older populations are considered.
Relationship between cefpirome clearance, serum creatinine, weight and age in patients treated for infection.
Cefpirome serum concentrations were measured by microbiological assay in 30 patients after five to nine days of treatment with 1 or 2 g bd for moderate to severe infection of presumed bacterial origin. Patients with serum creatinine (SCr) greater than 220 mumol/L were excluded. The age of patients ranged from 34-86 years. Creatinine clearance (Clcr) was calculated from age, sex, weight and SCr. The range of SCr was 63-220 mumol/L and the range of Clcr was 18-169 mL/min. The correlation coefficient with cefpirome clearance was 0.464 for SCr and 0.747 for Clcr. More than half of the patients with Clcr less than 50 mL/min had SCr within the normal range of 70-150 mumol/L. Mean cefpirome clearance in patients with Clcr 18-50 mL/min was 42.7 mL/min, which is very similar to the figure of 43.5 mL/min reported in a single dose volunteer study in patients with renal failure. Mean cefpirome clearance in patients with Clcr greater than 80 mL/min was 107.6 mL/min. In conclusion, these data on cefpirome clearance obtained after multiple dose treatment of patients with presumed bacterial infection are consistent with data previously obtained from single dose volunteer studies and support the currently recommended dose regimens. Clinicians should take account of age, weight and sex when estimating renal function from SCr.