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Biomedical subjects

K Hart

Publications and source records attributed to K Hart.

At least 19 recordsLinked to original sources

Cognitive characteristics of adolescent suicide attempters.

The present study examined the relationship among psychiatric diagnosis, depression, attributional style, and hopelessness among 69 adolescent suicide attempters and 40 psychiatrically hospitalized adolescent controls. Contrary to predictions, the suicide attempters were more likely than the nonsuicidal group to attribute good events to global causes. No differences in attributional style were found across the depressed versus nondepressed subjects. However, there was a modest relationship between depression and attributional style. Results suggest that maladaptive cognitive characteristics are present in adolescent clinical samples but may be less specific to suicide attempters than is often suggested.

Adolescent

Familial pulmonary hypertension in association with an abnormal hemoglobin. Insights into the pathogenesis of primary pulmonary hypertension.

A kindred with a familial hemoglobinopathy and familial primary pulmonary hypertension with autosomal dominant transmission has been identified. Affected family members were obvious from their cyanosis due to a reduced affinity for oxygen by the hemoglobin variant. The mother and one child had clinical pulmonary hypertension, whereas two siblings had cyanosis and preclinical pulmonary vascular disease as evidenced by abnormal perfusion lung scans and elevated levels of fibrinopeptide A in the face of normal pulmonary hemodynamics. In one, pulmonary hypertension could be induced with exercise. The studies on this family support the hypothesis that primary pulmonary hypertension may be initiated by abnormalities of the pulmonary vascular bed that predispose to in situ thrombosis. The possible common genetic transmission of the two diseases offers the speculation that the gene that confers predisposition to pulmonary hypertension may be located near the gene responsible for beta globulin.

Beta-Globulins

The effects of phenylephrine on right ventricular performance in patients with pulmonary hypertension.

Pulmonary hypertension causes right ventricular ischemia and failure as a result of increased afterload combined with reduced coronary blood flow. Increasing coronary driving pressure by raising aortic pressure with phenylephrine has been shown to reverse right ventricular ischemia from pulmonary hypertension in animals. Since vasodilators often fail to reduce afterload, we tested whether raising the coronary driving pressure would improve right ventricular function in man. Ten patients with pulmonary hypertension had hemodynamics and right ventricular coronary driving pressure measured before and 10 minutes after a steady state was reached with a phenylephrine infusion titrated to raise aortic pressure by 25 percent. Phenylephrine caused a significant (p less than .01) increase in mean aortic pressure (84 to 108 mm Hg) and right ventricular coronary driving pressure (46 to 69 mm Hg). In response, there was a significant (p less than .01) rise in mean pulmonary artery pressure (58 to 67 mm Hg), right ventricular end-diastolic pressure (10 to 16 mm Hg) and wedge pressure (5 to 9 mm Hg), and an insignificant fall in cardiac output (3.26 to 3.09 L/min) and pulmonary artery O2 saturation (57 to 49 percent). Although phenylephrine increased right ventricular coronary driving pressure, it worsened right ventricular function as manifest by a rise in end-diastolic pressure and fall in cardiac output. Any benefit of raising right ventricular coronary driving pressure may have been offset by alpha vasoconstriction of right ventricular coronary blood flow and/or pulmonary arterial vasoconstriction. Phenylephrine does not appear to be a useful therapy of right ventricular failure from pulmonary hypertension in patients who fail vasodilators.

Adult

Social skills and depression in adolescent suicide attempters.

The relationship among depression, social skills, and suicidal behavior was examined in a sample of 41 adolescents hospitalized in a general medical setting following a suicide attempt. These subjects were compared to 40 nonsuicidal psychiatrically hospitalized adolescents. Level of depression, assessed using the Children's Depression Inventory (CDI), and social skills, assessed via the Matson Evaluation of Social Skills with Youngsters (MESSY), were evaluated for all subjects. The suicide attempters and psychiatrically hospitalized patients were not found to differ on either the CDI or MESSY. However, multiple regression analyses revealed the factor scores of the MESSY to be related to depression in both patient groups. The data provide support for the relationship between social skills and depression. Results are also discussed in terms of the similarities between adolescent suicide attempters and nonsuicidal psychiatrically disturbed adolescents.

Adolescent

A method for generating hybrids containing nonselected fragments of human chromosomes.

We have used an irradiation and fusion technique to generate somatic cell hybrids that contain human chromosomal fragments. As a model system, a human-hamster hybrid containing a single human X chromosome was gamma-irradiated and fused with a rodent line. Hybrids were obtained without imposing direct selection for human material. Analysis of 29 clones by in situ hybridization and Southern blotting revealed that human fragments were incorporated into the hybrid cell genomes in most lines. Like chromosome-mediated gene transfer (CMGT)-generated hybrids, these hybrids contained multiple human fragments and retained alphoid centromeric sequences with a high frequency. However, unlike the CMGT, human fragments (apart from alphoid sequences) of less than 10(7) bp showed no evidence for rearrangements. This technique provides a method for constructing hybrids that contain a limited number of small human fragments derived exclusively from any chromosome of choice without the need to impose selection. Such hybrids provide a valuable resource for high-resolution mapping over short distances and for the isolation of disease and other loci mapped genetically.

Animals

Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy.

Cloned cDNA sequences representing exons from the Duchenne/Becker muscular dystrophy (DMD/BMD) gene were used for deletion screening in a population of 287 males males affected with DMD or BMD. The clinical phenotypes of affected boys were classified into three clinical severity groups based on the age at which ambulation was lost. Boys in group 1 had DMD, losing ambulation before their 13th birthday; those in group 2 had disease of intermediate severity, losing ambulation between the ages of 13 and 16 years; and boys in group 3 had BMD, being ambulant beyond 16 years. A fourth group consisted of patients too young to be classified. Clinical group allocation was made without previous knowledge of the DNA results. A gene deletion was found in 124 cases where the clinical severity group of the affected boy was known. The extent of the deletions was delineated using cDNA probes. There were 74 different deletions. Fifty-five of these were unique to individual patients, but the other 19 were found in at least two unrelated patients. The different clinical groups showed generally similar distributions of deletions, and the number of exon bands deleted (that is, deletion size) was independent of phenotype. Some specific deletion types, however, correlated with the clinical severity of the disease. Deletion of exons containing HindIII fragments 33 and 34 and 33 to 35 were associated with BMD and were not found in patients with DMD. Deletions 3 to 7 occurred in four patients with the intermediate phenotype and one patient with BMD. Other shared deletions were associated with DMD, although in four cases patients with disease of intermediate severity apparently shared the same deletion with boys with DMD. The range of phenotypes observed, and the overlap at the genetic level between severe and intermediate and mild and intermediate forms of dystrophy, emphasizes the essential continuity of the clinical spectrum of DMD/BMD. There were no characteristic deletions found in boys with mental retardation or short stature which differed from deletions in affected boys without these features.

Adolescent

The prevalence of pulmonary hypertension in the United States. Adult population estimates obtained from measurements of chest roentgenograms from the NHANES II Survey.

Because a definitive diagnosis of pulmonary hypertension requires cardiac catheterization, there have been no data on the prevalence of pulmonary hypertension in the general population. The diameter of the right descending pulmonary artery, as measured from chest roentgenograms, has been used by clinicians as a noninvasive indicator of pulmonary hypertension. Chest roentgenograms from the Second National Health and Nutrition Examination Survey, a sample survey of the US civilian noninstitutional population, were used in conjunction with estimates of sensitivity and specificity of this technique determined from patients who underwent right heart catheterization to estimate the prevalence of pulmonary hypertension (mean pulmonary artery pressure greater than 20 mm Hg at rest) in the US population aged 25 years and older. The prevalence is estimated to be very low in the population at large, primarily because of the low prevalence in women of all ages. The prevalence in men is 13.4 percent above age 34, and increases to 28.2 percent above age 64. Thus, in elderly men, pulmonary hypertension is relatively common and may have an important impact in the management of this age group.

Adult

Prediction of the effects of mild head injury: a message about the Kennard Principle.

We surveyed assumptions with regard to the relation between age and outcome of head injury (a.k.a. the "Kennard Principle"). Two groups (N = 120) of practicing clinicians were sent background information about a mild to moderate head injury in which only the age of the patient varied and were asked to predict likely outcome (degree of impairment). Predicted outcome differed significantly, with an adolescent case judged much more likely to have serious impairment than a child case. Implications of the (mis)application of the Kennard Principle are discussed.

Adolescent

The application of linkage analysis to genetic counselling in families with Duchenne or Becker muscular dystrophy.

A total of 278 families of probands with Duchenne or Becker muscular dystrophy has been ascertained and offered genetic counselling. Linkage studies have been performed in these families using polymorphic DNA markers identifying loci linked to Duchenne and Becker muscular dystrophy. The clinical features of the probands are discussed: there was marked intrafamilial resemblance in the severity of the disease. We estimate that a complete study of potential carriers in these families would require analysis of samples from approximately 1400 subjects. The results of linkage studies tended to move women's carrier risk estimates (based on CK and pedigree data) towards the extremes of the risk categories, providing a more definitive risk estimate for 81% of the women who were previously in the middle range of carrier risk probabilities. About 70% of the families had only one affected member. Linkage analysis altered carrier risk estimates in 95% of sisters and aunts of index cases, but only affected estimates of the mother's carrier risks in about 11% of isolated cases. Even where linkage studies were not helpful in elucidating carrier risks, information could usually be obtained for use in prenatal diagnosis if required. We have assessed the attitudes to pregnancy and prenatal diagnosis of women at risk of being carriers of Duchenne or Becker muscular dystrophy and report 17 pregnancies in these women.

Amniocentesis

Thromboxane synthetase inhibition in primary pulmonary hypertension.

Thromboxane synthetase inhibitors have been shown to reduce thromboxane, a potent vasoconstrictor, and increase prostacyclin, a potent vasodilator, in normal subjects. We evaluated the acute and chronic (three months) effects of the thromboxane synthetase inhibitor CGS13080 administered 200 mg every six hours on the resting hemodynamics in ten patients with primary pulmonary hypertension (PPH), and on their response to 20 mg of nifedipine given sublingually before and after the thromboxane synthetase inhibitor treatment. It was concluded that one can modulate the levels of endogenous thromboxane and prostacyclin in patients with primary pulmonary hypertension using a thromboxane synthetase inhibitor. Although the thromboxane synthetase inhibitor alone produced only modest hemodynamic changes over time, the addition of nifedipine was able to produce a further lowering of pulmonary artery pressure and pulmonary vascular resistance.

Adult

Antinuclear antibodies in primary pulmonary hypertension.

The association of positive antinuclear antibodies with the clinical and hemodynamic features of 43 patients with primary pulmonary hypertension and 16 patients with secondary pulmonary hypertension was investigated. Each patient had determinations of antinuclear antibodies using a KB cell substrate immunofluorescent test. Of the patients with primary pulmonary hypertension, 40% had positive antinuclear antibodies at titers of 1:80 dilutions or greater. There were no differences between patients with primary pulmonary hypertension and positive antinuclear antibodies compared with those with negative antinuclear antibodies in relation to clinical or hemodynamic status. A 6% incidence rate of antinuclear antibodies was found in patients with secondary pulmonary hypertension, similar to that in the normal population. The clinical, hemodynamic, serologic and histologic similarity between patients with primary pulmonary hypertension and those with unexplained pulmonary hypertension associated with collagen vascular disorders suggests that primary pulmonary hypertension in some patients may represent a collagen vascular disease confined to the lungs. The frequency of positive antinuclear antibody tests would place primary pulmonary hypertension between rheumatoid arthritis and scleroderma in the spectrum of collagen vascular diseases. Further studies are necessary, however, before one might expect that immunosuppressive therapy would be beneficial to these patients.

Adult

Control of expression of an integrated Rous sarcoma provirus in rat cells: role of 5' genomic duplications reveals unexpected patterns of gene transcription and its regulation.

Rat cells transformed by Rous sarcoma virus frequently contain duplications of viral (and sometimes cellular) DNA 5' to the integrated provirus, suggesting that such rearrangements favor provirus expression. In one cell line, A11, the duplication includes the viral src gene and proviral sequences that flank it. We examined three possible roles for this structure. Since the proviral v-src gene transformed recipient cells upon DNA transfer and was the major template for v-src transcription in A11 cells, the presence of v-src in the duplication is presumably not necessary for transformation. Since the size and structure of transcripts from the proviral v-src gene in A11 cells were conventional, the duplication does not facilitate transformation by providing a novel transcriptional strategy. Thus, we favor the concept that the duplication either attenuates a negative effect of flanking elements at the host chromosome integration site or augments the positive regulation of conventional provirus expression or both. Gene transfer and transcription analyses with both genomic and cloned DNA showed that the mechanisms of such regulatory phenomena are complex. Identical sequences in the provirus and the 5' duplication displayed different patterns of expression in A11 cells that could be disrupted in segments of cloned DNA. Among the elements that influenced such expression were sequences from the gag-pol region of the provirus.

Animals