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Biomedical subjects

A Lahad

Publications and source records attributed to A Lahad.

16 recordsLinked to original sources
PubMed1998

Echocardiographic assessment of pulmonary hypertension in Gaucher's disease.

BACKGROUND: Enzyme therapy has been shown to decrease the signs and symptoms of Gaucher's disease. A few patients, however, develop pulmonary hypertension on such treatment. We investigated the frequency of pulmonary hypertension in Gaucher's disease. METHODS: We studied 134 adults with type 1 Gaucher's disease, including 73 patients on enzyme replacement, with echocardiography. We measured tricuspid incompetence (TI) with continuous-wave doppler. Pulmonary hypertension was indicated by a TI gradient of more than 30 mm Hg. FINDINGS: Nine (7%) patients had pulmonary hypertension: all were treated and six had undergone splenectomy. Chest radiographs confirmed the presence of pulmonary hypertension in these patients as well as in most patients with TI gradients of 25-29 mm Hg. INTERPRETATION: The confounding effects of disease severity and splenectomy in many treated patients precluded definitive conclusion of cause and effect. Nonetheless, we found an unexpectedly high rate of pulmonary hypertension and recommended routine echocardiographic monitoring of all treated and untreated patients with type 1 Gaucher's disease. We also suggest consideration of treatment withdrawal if the TI gradient progresses to more than 30 mm Hg.

Adult↗
PubMed1997

Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.

Severe jaundice leading to kernicterus or death in the newborn is the most devastating consequence of glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G-6-PD) deficiency. We asked whether the TA repeat promoter polymorphism in the gene for uridinediphosphoglucuronate glucuronosyltransferase 1 (EC 2.4.1.17; UDPGT1), associated with benign jaundice in adults (Gilbert syndrome), increases the incidence of neonatal hyperbilirubinemia in G-6-PD deficiency. DNA from term neonates was analyzed for UDPGT1 polymorphism (normal homozygotes, heterozygotes, variant homozygotes), and for G-6-PD Mediterranean deficiency. The variant UDPGT1 promoter allele frequency was similar in G-6-PD-deficient and normal neonates. Thirty (22.9%) G-6-PD deficient neonates developed serum total bilirubin >/= 257 micromol/liter, vs. 22 (9.2%) normals (P = 0.0005). Of those with the normal homozygous UDPGT1 genotype, the incidence of hyperbilirubinemia was similar in G-6-PD-deficients and controls (9.7% and 9.9%). In contrast, in the G-6-PD-deficient neonates, those with the heterozygous or homozygous variant UDPGT1 genotype had a higher incidence of hyperbilirubinemia than corresponding controls (heterozygotes: 31.6% vs. 6.7%, P < 0.0001; variant homozygotes: 50% vs. 14.7%, P = 0.02). Among G-6-PD-deficient infants the incidence of hyperbilirubinemia was greater in those with the heterozygous (31.6%, P = 0.006) or variant homozygous (50%, P = 0.003) UDPGT1 genotype than in normal homozygotes. In contrast, among those normal for G-6-PD, the UDPGT1 polymorphism had no significant effect (heterozygotes: 6.7%; variant homozygotes: 14.7%). Thus, neither G-6-PD deficiency nor the variant UDPGT1 promoter, alone, increased the incidence of hyperbilirubinemia, but both in combination did. This gene interaction may serve as a paradigm of the interaction of benign genetic polymorphisms in the causation of disease.

Cohort Studies↗
PubMed1997

Hostility, aggression and the risk of nonfatal myocardial infarction in postmenopausal women.

Hostility can predict coronary heart disease (CHD) and total mortality in men. However, in women this association has not been as thoroughly explored. This study examines whether hostile and aggressive attitudes are associated with myocardial infarction (MI) in postmenopausal women. Cases included 277 women who presented with an incident MI. Controls included a random sample of 988 female health maintenance organization enrollees. Women were asked the Hostile-Affect and the Aggressive-Responding factors of the Cook-Medley Hostility Scale. The Hostile-Affect score was linearly associated with increased risk for MI (odds ratio [OR] per point = 1.22; 95% confidence interval [CI95%] = 1.07-1.38), whereas the Aggressive-Responding score had a modest protective effect (OR = 0.92 per point; CI95% = 0.84-1.02); p = 0.009. Adjustment for sociodemographic and MI risk factors altered these results only slightly. These hostility measures are easily administered, and could help to identify women who are at high risk for CHD and who may benefit from preventive measures.

Adult↗
PubMed1997

Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families.

Germ-line BRCA1 and BRCA2 mutations account for most of familial breast-ovarian cancer. In Ashkenazi Jews, there is a high population frequency (approximately 2%) of three founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. This study examined the frequency of these mutations in a series of Ashkenazi women with ovarian cancer unselected for family history, compared with the frequency of these mutations in families ascertained on the basis of family history of at least two affected women. Penetrance was compared, both according to the method of family ascertainment (i.e., on the basis of an unselected ovarian cancer proband vs. on the basis of family history) and for the BRCA1 founder mutations compared with the BRCA2 6174delT mutation. There was a high frequency (10/22; [45%]) of germ-line mutations in Ashkenazi women with ovarian cancer, even in those with minimal or no family history (7/18 [39%]). In high-risk Ashkenazi families, a founder mutation was found in 59% (25/42). Families with any case of ovarian cancer were significantly more likely to segregate a founder mutation than were families with site-specific breast cancer. Penetrance was higher in families ascertained on the basis of family history than in families ascertained on the basis of an unselected proband, but this difference was not significant. Penetrance of BRCA1 185delAG and BRCA1 5382insC was significantly higher than penetrance of BRCA2 6174delT (hazard ratio 2.1 [95% CI 1.2-3.8]; two-tailed P = .01). Thus, the high rate of germ-line BRCA1/BRCA2 mutations in Ashkenazi women and families with ovarian cancer is coupled with penetrance that is lower than previously estimated. This has been shown specifically for the BRCA2 6174delT mutation, but, because of ascertainment bias, it also may be true for BRCA1 mutations.

Adult↗
PubMed1996

Wide range in age of onset for chromosome 1--related familial Alzheimer's disease.

Mutations in three different genes on chromosomes 1, 14, and 21 cause autosomal dominant forms of familial Alzheimer's disease (FAD). Most result in an early-onset phenotype. However, several kindreds of Volga German ancestry have the same chromosome 1 gene mutation and demonstrate a relatively older mean age of onset and include individuals with late age of onset. In these families, the mean age of onset is 54.9 +/- 8.4 years (range, 40-75 years), mean age at death is 65.9 +/- 10.2 years (range, 43-88 years), and mean disease duration is 11.3 +/- 4.6 years (range, 5-23 years). This contrasts with a group of 7 families with chromosome 14 mutations in which the mean age of onset is 44.8 +/- 4.8 years (range, 30-55 years), mean age at death is 52.6 +/- 5.7 years (range, 39-65 years), and mean disease duration is 7.6 +/- 3.2 years (range, 2-17 years). (All means are significantly different in the 2 groups of families, p < 0.005.) In the chromosome 1 families, 7 persons (16%) had an age of onset at or older than 65 years and 22 (54%) survived to age 65 or older versus none in the chromosome 14 families. An example of probable nonpenetrance of disease at age 89 was also found in a chromosome 1 kindred. It is concluded that, unlike the chromosome 14 gene, mutations in the chromosome 1 FAD gene may result in individuals with a late age of onset overlapping with the more common sporadic form of the disease occurring in the general population. In light of the great variability in age of onset in persons with identical mutations, study of the genetic and environmental factors contributing to delayed onset of disease in chromosomal 1 FAD kindreds will be an important area for further investigation. Apolipoprotein E genotype may be one such factor that plays a partial role in this variability.

Adult↗
PubMed1996

Effect of low-dose enzyme replacement therapy on bones in Gaucher disease patients with severe skeletal involvement.

Gaucher disease, the most common glycolipid storage disorder, is characterized by hepatosplenomegaly and skeletal involvement. Enzyme replacement therapy in both the high- and low-dose regimens has been shown to be effective in reducing the organomegaly and improving the hematological parameters of symptomatic patients with type I disease. Herein we report subjective and objective responses of bone-related complications after 2 to 4 years of low-dose enzyme replacement therapy in 14 adult type I patients with severe skeletal involvement pre-treatment. We discuss our results relative to those reported in patients on the high-dose regimen, as well as with reference to a single patient who developed new avascular necrosis despite objective improvement in radiological studies.

Adolescent↗
PubMed1996

Hostility, aggression and the association with hypertension in post-menopausal women.

In order to determine whether a hostile attitude is associated with hypertension in post-menopausal women, we conducted a cross-sectional study of a sample of post-menopausal women enrollees from the Group Health Cooperative (Seattle, Washington). Out-patient medical records were reviewed for all subjects. Hypertension was defined as a recorded diagnosis of hypertension and treatment with an anti-hypertensive drug. Borderline hypertensives were excluded. Women were interviewed by telephone and asked the 14 questions comprising the Hostile-Affect (HOS) and Aggressive-Responding (AGGR) factors of the Cook-Medley hostility scale. Scores were grouped into high vs low HOS and AGGR. The AGGR score was available for 430 hypertensives and 628 normotensives. The HOS score was available for 436 hypertensives and 616 normotensives. High AGGR scores had a borderline association with hypertension (Odds Ratio (OR) = 1.26; 95% Confidence interval (CI) = 0.97-1.62). HOS was not associated with hypertension. Adjusting for age, physical activity, diabetes mellitus, cholesterol level, tobacco and alcohol use, weight and race, changed the association of AGGR with hypertension only slightly (OR = 1.22; CI = 0.92-1.63). We found a weak association between the prevalence of treated hypertension and AGGR in post-menopausal women. There was no association between the HOS component and hypertension. The results of this study support the need for prospective studies of the role of psychological factors in the development of hypertension in post-menopausal women. If this association is confirmed, AGGR measures may help identify women at high-risk who are most likely to benefit from hypertension screening and primary prevention.

Aged↗
PubMed1995

Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease.

The effect of the apolipoprotein E (APOE) epsilon 4 allele on age of onset was analyzed in two groups of families with early-onset Alzheimer's disease (AD), (1) Volga German (VG) kindreds, in which AD is caused by an unknown locus and (2) early-onset non-VG families showing evidence of linkage to chromosome 14. The epsilon 4 allele did not have a detectable effect on age of onset in either group. This finding suggests some forms of early-onset familial AD are not modifiable by APOE status, or that AD can be caused by APOE-independent pathways.

Age of Onset↗
PubMed1994

The effectiveness of four interventions for the prevention of low back pain.

OBJECTIVE: Low back pain affects 60% to 80% of US adults at some time during their lives. This review evaluates the effectiveness of four strategies to prevent low back pain for asymptomatic individuals: back and aerobic exercises, education, mechanical supports (corsets), and risk factor modification. DATA SOURCES: The MEDLINE database was searched for all relevant articles published in English between 1966 and 1993. Bibliographies of identified articles were searched to ensure that all pertinent articles had been gathered and back pain specialists reviewed our final bibliography for completeness. STUDY SELECTION AND DATA EXTRACTION: A total of 190 articles were identified, and the 64 that contained original data about preventing low back pain were reviewed. Studies were graded according to strength of study design. DATA SYNTHESIS: There is limited evidence based on randomized trials and epidemiological studies that exercises to strengthen back or abdominal muscles and to improve overall fitness can decrease the incidence and duration of low back pain episodes. There is minimal evidence to support the use of educational strategies to prevent low back pain and insufficient evidence to recommend about the use of mechanical supports. Although there is no evidence supporting risk factor modification for preventing low back pain (smoking cessation and weight loss), there are other reasons to recommend the interventions. CONCLUSION: There is limited evidence to recommend exercise to prevent low back pain in asymptomatic individuals, but there is insufficient evidence to recommend other prevention strategies. These conclusions should be viewed cautiously since they are primarily based on studies conducted in the workplace rather than in clinical settings.

Behavior Therapy↗
PubMed1993

Impact of comorbidity on well-being in hypertension: case control study.

The impact of hypertension and comorbidity on reporting of well-being was compared in hypertensives (n = 45) and normotensives (n = 45) matched for age, sex and ethnic origin. Self-reported health, measured by the Duke profile, was worse for most measures for the hypertensive group. The mean DUSIO (Duke Severity of Illness Scale) severity of illness score, the physicians' assessment of the subject's health, was significantly higher in hypertensives than in normotensives (40.8 vs. 29.1, P = 0.04). Approximately 20% of the variance in well-being scores could be explained by comorbidity. Hypertension per se explained only 2% of the variance and its correlation with well-being was not statistically significant. Perception of health (a subscale of the DUKE) was somewhat more dependent on existence of hypertension. In this study, self-assessment of health and well-being are explained to a large extent by differences in comorbid conditions. Well-being is independent of hypertension. These findings underscore the importance of defining and ameliorating co-existing disease in patients with hypertension.

Adolescent↗
PubMed1991

Drug induced suicidal ideation.

The authors present a case study of a mentally healthy man who repeatedly experienced short-lived, obsessional-like suicidal ideas and images after ingestion of the anti-fungal drug ketoconazole. Ego-alien, suicidal ideas are an extremely rare form of adverse drug reaction. This is probably the first report of drug-induced ego-dystonic, mood incongruent suicidal ideas appearing in a fully conscious, healthy individual.

Hallucinations↗