Report of a collaborative study to assess the determination of glycoprotein antigen content of rabies vaccines for human use.
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Animals↗
Biomedical subjects
A Heath
Publications and source records attributed to A Heath.
Social support, depressed mood, and adjustment to stress: a genetic epidemiologic investigation.
A survey of 821 same-sex female twin pairs from a population-based registry assessed 8 dimensions of social support and social integration. Twin analyses documented significant common environmental influences on 5 of these 8 measures and significant genetic influences on 5 of the 8. A decomposition of the multiplicative association between support and a measure of stressful life experiences in predicting depressed mood--an association typically interpreted as providing evidence for a stress-buffering effect of social support--shows clearly that it is the environmental and genetic factors that cause support, rather than support itself, that buffer the effects of stress on mood in most cases. We discuss the implications of this result for future research on the relationship between social support and psychopathology.
Adaptation, Psychological↗
Population sequence analysis of a simian immunodeficiency virus (32H reisolate of SIVmac251): a virus stock used for international vaccine studies.
The virus structural genes gag and env (both gp120 and gp41 regions) of the 32H isolate of SIVmac251 were amplified using the polymerase chain reaction (PCR). The proviral template used in the PCR was DNA isolated from cells used to prepare several experimental SIV vaccines, which have been tested in simians, and a standard challenge stock of virus, which has been used in international collaborative studies. The PCR products were cloned and the nucleotide sequences of several clones were determined for each gene. From a comparison of the sequences obtained the predominant amino acid sequences of gag and env were predicted and the degree of sequence heterogeneity was determined. Conserved and more variable regions of each protein were identified. The gp120 region of env was more heterogeneous than gag or the transmembrane protein of env (gp41). Within gp120, sequence variability was concentrated to specific regions equivalent to the V1, V2, and, to a lesser extent, the C1 regions identified for human immunodeficiency virus type 1 (HIV-1). In contrast the region equivalent to the hypervariable "V3-loop" of HIV-1 was highly conserved. The implications of the data is discussed in relation to the ability of this virus stock to prepare effective vaccines against SIV.
Amino Acid Sequence↗
Restriction of serum antibody reactivity to the V3 neutralizing domain of HIV gp120 with progression to AIDS.
OBJECTIVE: To identify epitopes on HIV-1 gp120 that correlate with disease resistance and/or prognostic indication. DESIGN: The identification of epitopes on HIV-1 gp120 was determined by testing the reactivity by immunoblotting of anti-HIV-positive human sera against partially cleaved Chinese hamster ovary (CHO) cell-derived recombinant gp120. Cleavage of recombinant gp120 occurs in the V3 loop region resulting in 70 and 50K cleavage bands if the protein is subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Antibodies reactive with the 120 Mr band alone on immunoblotting indicate that binding is restricted to this cleavage site. Reactivity to either of the cleavage products is independent of gp120 cleavage and indicates that binding occurs in sites other than the V3 cleavage region. METHODS: A panel of anti-HIV-positive human sera was tested for virus neutralizing activity and reactivity by immunoblotting against CHO cell-derived gp120. RESULTS: All sera reacted with the uncleaved from of gp120 but reacted either weakly or did not react with its cleavage products. There was a statistically significant correlation between serum reactivity to cleavage products and clinical stage of disease [Centers for Disease Control (CDC) criteria]. Sera of asymptomatic individuals (CDC stage II/III) were more likely to recognize either one or both of the cleavage products compared with sera from patients presenting with symptoms of disease (CDC stage IV). Furthermore, sera reacting with either one or both of the cleavage products were more likely to have higher neutralizing antibody titres than those that were unreactive. CONCLUSIONS: There is a restriction of serum antibody reactivity (when tested by immunoblotting) to the V3 loop with progression to disease. Raised neutralizing antibody titres may be dependent on regions outside the V3 cleavage site.
Acquired Immunodeficiency Syndrome↗
Predicting severity of tricyclic antidepressant overdose.
The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.
Adolescent↗
Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics.
The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration.
Amitriptyline↗
Amitriptyline and amitriptyline metabolites in blood and cerebrospinal fluid following human overdose.
The toxicokinetics of amitriptyline were studied in nine patients admitted to hospital in Matthew-Lawson Coma Scale grade III-IV after an estimated ingestion of 1-5 g amitriptyline. Gastric lavage was performed and 50 g activated charcoal were given orally. Venous blood samples were taken on admission and at 1, 2, 4, 8, and 24 h, and in some patients at 36 and 48 h after admission. Arterial blood samples were taken at 1, 4, 8, and 24 h after admission. Lumbar punctures were performed 1 h after admission in 8 patients and again 4 h later in 5 patients. A urine sample was screened for other drugs. The bound and unbound fraction of amitriptyline and its metabolites nortriptyline, E and Z forms of 10-OH-amitriptyline and nortriptyline were analyzed in plasma, whole blood, red blood cells, and cerebrospinal fluid using an HPLC technique. The T1/2 alpha and T1/2 beta for amitriptyline were 1.5 - 3.1 and 15 - 43 h respectively. The rate of elimination of amitriptyline was not dose-dependent. The arteriovenous differences in the total amitriptyline+nortriptyline concentration were maximal in patients admitted soon after intake of drugs. Amitriptyline concentrations in cerebrospinal fluid were quantitatively similar to the unbound amitriptyline concentration in blood. The highest cerebrospinal fluid amitriptyline concentration was 506 nmol/L. There were large individual differences in plasma, blood and cerebrospinal fluid concentrations between different individuals. Repeated quantitative analysis of amitriptyline and its metabolites is unlikely to contribute to the clinical management of most patients with amitriptyline overdose.
Adult↗
Stable lyophilized reagents for the serum ferritin assay.
Two monoclonal antibodies to human ferritin, including one that was coupled to horseradish peroxidase, were lyophilized. These reagents show little loss of activity on reconstitution and demonstrate acceptable stability in the accelerated degradation test. When applied in a simple ELISA for the assay of serum ferritin along with the WHO standard for serum ferritin (80/602) they provide a robust assay with standardized reagents which is potentially suitable for use as a reference assay.
Antibodies, Monoclonal↗
The genetic epidemiology of bulimia nervosa.
OBJECTIVE: The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD: Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS: Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS: The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.
Adolescent↗
Chronic neuropsychological and neurological impairment following acute exposure to a solvent mixture of toluene and methyl ethyl ketone (MEK).
A 38 year-old laborer experienced solvent intoxication during each of two spray paintings of a dump truck and other heavy equipment in an enclosed, unventilated garage. The paint base consisted primarily of toluene and methyl ethyl ketone. Nausea, headaches, dizziness, respiratory difficulty and other symptoms began after exposures. Over the next several days he developed impaired concentration, memory loss and cerebellar signs including an intention tremor, gait ataxia and dysarthria. MRI of the brain and EGG early in the work-up were normal, although later MRIs demonstrated fluid collection over the left parietal area. Examination by a toxicologist and neurologist revealed likely toxic encephalopathy with dementia and cerebellar ataxia. Three formal neuropsychological assessments over 2 1/2 years quantified cognitive, motor and behavioral changes. Despite similar findings in chronic exposure to these solvents, lasting sequelae following acute exposure have not been widely reported.
Adult↗
Report of a collaborative study for assessing the potency of hepatitis B vaccines.
A collaborative study was carried out to examine the suitability of a hepatitis B vaccine derived from plasma as an immunogenicity reference for vaccines produced by recombinant DNA technology in yeast. The use of a plasma derived vaccine as reference appeared satisfactory, although the use of homologous reference improved agreement in potency estimates. The use of a recombinant standard did not however improve agreement for a recombinant vaccine produced by a different manufacturer. The variation in the dilution of vaccine required to induce antibodies in 50% of test animals and in potency estimates varied widely between laboratories (25-fold and 10-fold respectively). However this was similar to the variation found in a previous collaborative study.
Animals↗
High dose atropine in organophosphorus poisoning.
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Antidotes↗
Measuring effectiveness in infection control.
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Cross Infection↗
Self-poisoning treated in the ICU.
This retrospective study compares number and type of self-poisonings admitted to the intensive care units (ICU) at Sahlgren's Hospital, Gothenburg, during 1972 and 1976. The total number of patients requiring intensive care was unchanged, but a change in the pattern of self-poisoning was seen. In 1976 the number of patients requiring intensive care following acute alcohol intoxication had increased, whereas the number of barbiturate and methaqualone poisonings decreased. Tricyclic antidepressants formed the largest group in both years. Fewer patients needed endotracheal intubation and IPPV in 1976 than in 1972. Also, fewer complications were seen, and the death rate among ICU-treated patients decreased. In the Gothenburg area barbiturates accounted for one half of all deaths due to self-poisoning and tricyclic antidepressants for one fifth. Any expected decrease in intensive care as a result of fewer barbiturate and methaqualone poisonings was obscured by an increase in severe alcohol intoxication.
Alcoholic Intoxication↗
Psychiatric drug treatment in children.
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Adolescent↗
[Severe metabolic alkalosis--treatment with hydrochloric acid].
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Aged↗
Anticonvulsants and thyroid function.
Serum total and free thyroid hormone concentrations were estimated in 42 patients with epilepsy taking anticonvulsants (phenytoin, phenobarbitone, and carbamazepine either singly or in combination). There was a significant reduction in total thyroxine (TT4), free thyroxine (FT4), and free triiodothyronine (FT3) in the treated group compared with controls. Free hormone concentrations were lower than total hormone concentrations, suggesting that increased clearance of thyroid hormones occurs in patients receiving anticonvulsants. Detailed analysis indicated that phenytoin had a significant depressant effect on TT4, FT4, FT3, and reverse T3 (rT3). Phenobarbitone and carbamazepine had no significant main effects, but there were significant interactions between phenytoin and carbamazepine for TT4 and FT4. phenobarbitone and carbamazepine for FT3, and phenytoin and phenobarbitone for rT3.
Adolescent↗