World Literature

World Literature

38 World Literature frequent among adolescent mothers in an inner-city population. Abused substances included cigarettes, alcohol, and illicit drugs...

151KB Sizes 0 Downloads 131 Views


World Literature

frequent among adolescent mothers in an inner-city population. Abused substances included cigarettes, alcohol, and illicit drugs. Stress and depressive symptoms were commonly associated features. Cigarette smoking and peer group substance abuse were associated with postpartum substance abuse. These data suggest that questions regarding activities of friends should be included when interviewing adolescents.

Mune T, Rogerson FM, Nikkila H, et al: Human hypertension caused by mutations in the kidney isozyme of 11(3-hydroxysteroid dehydrogenase. Nature Genetics 1995; 10:394-399. Low renin hypertension and hypokalemic metabolic acidosis with low mineralocorticoid concentrations characterize the syndrome of apparent mineralocorticoid excess (AME). Affected individuals show decreased conversion of cortisol to cortisone. Their blood pressure can be further increased by the administration of cortisol or adrenocorticotrophic hormone (ACTH). These data suggested that AME was due to decreased activity of 11 phydroxysteroid dehydrogenase (1IP-HSD), the enzyme that converts cortisol to biologically inactive cortisone. Because cortisol and aldosterone bind with identical affinity to the type I mineralocorticoid receptor and circulating cortisol levels are higher than those of aldosterone, 11 p- HSD preserves mineralocorticoid specificity at the type I kidney receptor. Hypertension associated with excessive licorice ingestion is believed to be due to inhibition of this enzyme. The authors performed molecular genetic studies on the kidney 11 p- HSD isozyme in nine affected families. Through DNA sequence analysis, mutations on both alleles were recognized in eight. of these families. The majority of the mutations were missense mutations, changing amino acid codons or creating inframe deletions. Transient transfection studies confirmed the deleterious nature of the identified mutations. A single nucleotide substitution in intron 3 resulted in skipping of exon 4. Mutations were not detected in one family. The structure-function relationship of the protein was related to the positions of the mutations. The authors communicated that the kidney 11p- HSD isozyme is expressed at high levels in the placenta and that placental 11 p- HSD activity and birth weight correlate in human infants. Questions regarding the potential role of the kidney 11p- HSD isozyme in essential hypertension and intrauterine growth retardation were raised. Comment: The authors have ascertained the genetic basis for the AME syndrome. They identified mutations on both alleles and confirmed the deleterious nature of the mutations. In a separate publication (Agarwal et al., Genomics, in press), the authors describe isolation of the gene encoding the kidney 11P-HSD isozyme and its localization to chromosome 16q22. Importantly, detection

of a renal-specific isozyme may have implications in the pathogenesis of essential hypertension.

Chaisson RE, Keruly JC, Moore RD: Race, sex, drug use, and progression of human immunodeficiency virus disease. N Engl J Med 1995; 333:751-756. Apparent discrepancies in survival among demographic groups has led to speculation that the natural history of human immunodeficiency virus (HIV) disease differs in various groups. The authors postulate that another explanation is dissimilar utilization of medical intervention. To test their hypothesis, they analyzed the initial and follow-up clinical information for 1372 patients observed for almost 5 years at the Johns Hopkins University HIV Clinic. Demographic information showed that 70% were male and 30% were female. Most of the subjects were of African-American ethnic background (77%). Risk factors for HIV were homosexual contact (27%), heterosexual contact (14%), injection drug use (29%), and combined drug use and sexual contact (25%). No significant differences in survival were observed between men and women, injection drug users and nonusers whites and nonwhites, or among types of health ~ 3 care Insurance. A CD4 cell count <200 mm was associated with an increased risk of death. Progression of disease was associated with CD4 cell count of 201-3501 mm:', prior antiretroviral treatment, older age, and increased symptoms at the initial visit. The authors conclude that there are no significant biologic differences in disease progression. Rather, the apparent differences reported in previous studies may reflect different usage of health care. The authors interpret the association of prior antiretroviral therapy with disease progression as due to the time-limited benefit of zidovudine therapy. "Patients in our cohort who began receiving zidovudine before enrollment had already obtained a partial survival benefit from the drug, whereas those who started treatment after enrollment obtained all the benefit during the follow-up period of the study." Comment: This large study demonstrates that the natural history of HIV infection shows no favoritism to any specific demographic group. Instead, access to and uti1ization of health care appear to be important for prolonging survival.

Koebert DD, McGillivray B, Sybert VP: Prenatal diagnosis of 45,Xl46,XX mosaicism and 45,X: implications for postnatal outcome. Am J Hum Genet 1995; 57:661-666. The authors report their experience regarding patients with 45,X/46,XX mosaicism and patients with 45,X karyotypes. Patients were ascertained by prenatal amniocentesis for advanced maternal reasons or by postnatal phenotypic features. Prenatal studies identified 12 fetuses as carrying 45,X/46,XX mosaicism and 11 fetuses