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Biomedical subjects

A Heath

Publications and source records attributed to A Heath.

At least 55 records · Page 3Linked to original sources
PubMed1995

GIP and GLP-1(7-36)amide secretion in response to intraduodenal infusions of nutrients in pigs.

Investigation of nutrient stimulation of two gut hormones GIP (glucose dependent insulotropic polypeptide) and GLP-1(7-36)amide (the active truncated form of glucagon-like peptide-1) is made difficult by the differential control of gastric emptying. Direct nutrient infusion into the duodenum was therefore carried out on three female pigs. The infusates consisted of saline (0.85 g or 1.7 g/100 ml); glucose (20 g or 40 g/100 ml); fat (30 g or 60 g/500 ml) and glucose/fat (20 g and 30 g or 40 g and 60 g per 1000 ml). Plasma glucose levels were elevated as expected by glucose or glucose/fat infusions, and they were not affected by the presence of fat in the infusate. Insulin secretion was stimulated in the presence of glucose or glucose/fat. Plasma triacylglycerol was elevated following fat and glucose/fat infusions. The greatest stimulus for GIP secretion was glucose/fat (P < 0.05); fat alone was a poor stimulus for GIP secretion, but glucose was a potent stimulus. GLP-1(7-36)amide was moderately stimulated by glucose and markedly stimulated by fat and glucose/fat infusions (P < 0.05). We conclude that, in pigs, dual nutrient infusion of glucose/fat is a strong stimulus for both GIP and GLP-1(7-36)amide secretion. The hormones therefore have the potential to play an important physiological role, both in the stimulation of insulin secretion and in adipose tissue metabolism in pigs.

Analysis of Variance↗
PubMed1995

Similar patterns of simian immunodeficiency virus env sequences are found in the blood and lymphoid tissues of chronically infected macaques.

Two cynomolgus macaques were infected with a genetically complex challenge stock of simian immunodeficiency virus (SIVmac251-32H). One animal developed SIV-induced disease and was sacrificed at 16 months postinfection. The second remained healthy until it too was sacrificed at 20 months postinfection. The polymerase chain reaction (PCR) was used to amplify env gp120-coding sequences from provirus present in samples of blood, spleen, and inguinal lymph node taken from both animals on the day of sacrifice. The proviral burden present in each of the tissue samples was also determined using a quantitative PCR assay. The proviral burdens in the blood, spleen, and inguinal lymph node of the healthy animal (I225) were similar. This was not the case for animal I227, in which the burden in the inguinal lymph node was much higher than for blood or spleen. Phenogram analysis of the hypervariable V1 region of env revealed that the diversity of nucleotide sequences recovered from each tissue of both macaques were similar and overlapping. Some selected amino acid differences were observed that were specific for a tissue or one of the macaques. However, the results do not suggest that the overall evolution of env in provirus populations recovered from lymphoid tissues is distinct from that recovered from the blood.

Amino Acid Sequence↗
PubMed1995

Creating care partnerships with long-distance caregivers.

Primary family caregivers cannot always physically be there to care for aging relatives; they may live in another state or even another country. By developing a care partnership, however, with a provider and the older relative, long-distance caregivers can be assured that relatives get the care they need from qualified and effective providers.

Aged↗
PubMed1994

Perceived support and adjustment to stress in a general population sample of female twins.

The stress-buffering effect of perceived support is explored in a large panel survey of adult female twins. The analysis begins by documenting a significant interaction between perceived support and acute stress in predicting DSM-III-R major depression. Various hypotheses are investigated to explain this interaction. These include the possibilities that the interaction is due to a stress-buffering effect of perceived support which is mediated by received support, that perceived support promotes either the increased use or the increased effectiveness of certain coping strategies, or that there is some underlying genetic factor that affects both the perception of support and adjustment to stress. No evidence was found for any of these hypotheses. The paper closes with a discussion of directions for future research aimed at explaining the interaction between perceived support and acute stress.

Adaptation, Psychological↗
PubMed1994

Primary plasma antioxidants in adult respiratory distress syndrome patients: changes in iron-oxidizing, iron-binding, and free radical-scavenging proteins.

Ten adult patients (three male, age range, 15 to 67 years) with established ARDS were studied for serial changes in the proteinaceous antioxidant activities of their plasma. All had LISs in excess of 2.5 on admission to the study. Blood samples were taken as soon as possible after the diagnosis of ARDS, and from 10 patients at risk of developing ARDS. These were compared with healthy control subjects. Deoxyribose, phospholipids, and DNA were used as markers of damage in reactions generating inorganic and organic oxygen radicals and an oxo-iron species. The ability of plasma to inhibit such damage was expressed as antioxidant activity. This study does not address the clinical problem of why certain "at risk" patients develop ARDS, but rather the question of why some patients with established ARDS are better able than others to survive the disease. ARDS patients had transferrin levels that were significantly lower (1.76 +/- 0.13 gm/L) than those of normal controls (2.91 +/- 0.12 gm/L, p < 0.001), which decreased the ability of their plasma to protect phospholipid membranes and DNA against iron-stimulated free radical damage. The iron-oxidizing antioxidant properties of plasma were mainly dependent on the protein ceruloplasmin, concentrations of which were significantly higher in ARDS patients (0.387 +/- 0.04 gm/L) than in healthy controls (0.265 +/- 0.03 gm/L, p = < 0.05) or patients at risk of ARDS (0.24 +/- 0.04 gm/L, p = < 0.05). The iron-oxidizing (ferroxidase) antioxidant activities of plasma from ARDS patients, however, were similar to those of both control groups. Measurement of plasma ferroxidase activities confirmed that although more ceruloplasmin was present in the plasma of ARDS patients, enzyme activities were comparable to those of both control groups, which was suggestive of a loss of ceruloplasmin ferroxidase activity. Scavenging and radical-stimulating properties of plasma (devoid of iron-binding and iron-oxidizing properties) was partly dependent on protein thiol groups, which were lower in ARDS patients and in patients at risk of developing ARDS. Serial sample analysis revealed that ARDS patients showed substantial daily variations in biochemical parameters, implying that single time-point sampling may be unsuitable when studying these patients.

Adolescent↗
PubMed1993

A twin study of recent life events and difficulties.

OBJECTIVES: To examine the role of genetic and familial-environmental factors in the origin of stressful life events. DESIGN: Self-report questionnaires describing stressful life events in the last year. PARTICIPANTS: Both members of 2315 twin paris ascertained from the population-based Virginia Twin Registry. RESULTS: Life events were modestly but significantly correlated in twin pairs, and correlations in monozygotic (MZ) twins consistently exceeded those in dizygotic (DZ) twins. For total life events, the best-fitting twin model indicated that familial-environmental and genetic factors each accounted for around 20% of the total variance. Individual life events could be best divided into "network events" (directly affecting individuals in the respondent's social-network) where twin resemblance was due solely to the familial environment, and "personal" events (directly affecting the response) where most twin resemblance was the result of genetic factors. CONCLUSIONS: While neither genes nor familial environment is likely to directly produce life events, personal and social factors that predispose to life events are substantially influenced by an individual's genetic and family background. These results, which suggest that stressful life events reflect more than random influences, may have important implications for our understanding of the relationship between stressful life events and psychopathology.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗