A Cross-cultural Study of Alcohol Dependence in Singapore

This is a comparative study of alcohol dependence in Chinese and Indian patients admitted to a hospital in Singapore. There were 46 patients-21 Chinese and 35 Indians. In both ethnic groups there was a preponderance of male over female patients. There was no significant difference in the mean ages of the two groups but Indian patients started drinking at an earlier age and more of them had a family history of alcohol problems. Comparing the severity of alcohol dependence, Indian patients scored higher on the SADQ but no patients scored above 30 points.     

Histopathologic studies of the liver following intravenous colloidal 198Au therapy

Histologic studies of liver tissue from 27 patients given up to 395 mCi (cumulative) of intravenous colloidal 198Au showed no definite radiation injury and no correlation between hepatic abnormalities and dose. Demonstration of aggregates of colloidal gold in the Kupffer cells was inconsistent, suggesting slow removal or dispersion. Although the liver ordinarily receives the highest radiation dose, the critical organ is the marrow. Results support the recent introduction of 198Au to supplement teletherapy for certain neoplasms diffusely infiltrating the liver. Apparently the beta distribution minimizes endothelial injury in large vessels, which has been shown to be the cause of radiation hepatitis.     

The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy

In 192 oocyte donation cycles performed between January 1993 and July 1996, we examined the width of 'the window for embryo transfer' using standard hormonal replacement methods. All transfers were performed within 48 h of insemination. We varied the day of embryo transfer with regard to the initiation of progesterone therapy and, thus, the duration of endometrial exposure to progesterone and analysed the resulting pregnancy rates. Patients were divided into five groups (I-V) and embryo transfers were performed 2, 3, 4, 5 or 6 days following initiation of progesterone therapy. The number of pregnancies per transfer cycle achieved in groups I-V were 0 (0%), 3 (12%), 16 (40%), 29 (48.3%), and 10 (20.4%) respectively. The increased pregnancy rate in group III in comparison to group II is statistically significant (P < 0.03). Furthermore, the pregnancy rate in group IV (5 days of progesterone administration before embryo transfer) was significantly higher than in group V (6 days of progesterone administration before embryo transfer; P < 0.005). We also noted that, when embryos were transferred 4 or 5 days after initiation of progesterone therapy, the pregnancy rates were not significantly different between menopausal and cycling recipients (50% vs 43.7%). Our results indicate that the window for embryo transfer is dependent on duration of treatment with progesterone; it begins approximately 48 h after starting progesterone administration and lasts for approximately 4 days. The optimum period for transferring embryos at the 4- to 8-cell stage corresponds to cycle days 18 and 19. Transfers performed on the 17th and 20th days of the cycle can result in successful implantation, although the rates of implantation are highest when transfers are done on days 18 and 19.      

Decreased in vitro sensitivity to dexamethasone in corticotropes from middle-age rats

A disregulation of the hypothalamic-pituitary-adrenal (HPA) axis due to a decline of negative feedback regulation is a consistent feature of the aging process. Hippocampus has been proposed to be a primary site responsible for this alteration in the HPA axis in aging in rat. In this study an alternative hypothesis that the decreased sensitivity of the HPA axis to glucocorticoids in aging occurs directly in pituitary corticotropes has been tested. The sensitivity of corticotropes isolated from 2- and 13-month old male Sprague-Dawley rats to dexamethasone (DEX) in vitro was examined using a modification of the combined DEX/CRH challenge test that was originally designed for investigation of relative glucocorticoid resistance in vivo. No significant difference in basal ACTH production by corticotropes from the two age groups was detected. Corticotropes from middle-aged rats showed a diminished response of ACTH to CRH stimulation. DEX treatment did not cause a significant inhibition of either basal or CRH-stimulated ACTH release in corticotropes from middle-aged rats. These findings demonstrate an age-related decrease in the sensitivity of corticotropes to glucocorticoids in vitro suggesting that there is a direct, pituitary-mediated dysregulation of the HPA axis in rat starting as early as middle age.     

Patient-Related and Angiographic Predictors of Restenosis After Excimer Laser Coronary Angioplasty

Excimer laser coronary angioplasty (ELCA) is a useful technique for the treatment of selected complex coronary lesions. However, this technology has been limited by significant restenosis and, to date, predictors of restenosis after use of this device are not clearly defined. In order to determine predictors of restenosis after ELCA, 43 lesions presenting with restenosis (> 50% diameter stenosis) at angiographic follow-up were compared to 46 lesions without restenosis, based on patient-related, qualitative and quantitative angiographic parameters. Univariate analysis revealed 9 variables with at least a borderline (p < 0.15) significant relation to restenosis: (1) age (p = 0.0759), (2) proximal left anterior descending site (p = 0.074), (3) presence of a restenotic lesion (p = 0.104), (4) lesion length (p = 0.0034), (5) reference diameter of the treated vessel (p = 0.0076), (6) post laser minimal luminal diameter (MLD) (p = 0.1160), (7) post-procedural MLD (p = 0.0001), (8) post-procedural stenosis (p = 0.0250) and (9) total procedural gain (p = 0.0051). After entering stepwise logistic regression analysis, only 3 variables emerged as independent predictors of restenosis: treatment of a restenotic lesion (p = 0.0255), lesion length (p = 0.0291) and post-procedural MLD (p = 0.0007). Based on these data, we conclude that post-procedural MLD is the most important predictor of restenosis after ELCA. Lesion length and the treatment of restenotic lesions are also independently associated with an increased risk of restenosis after ELCA. Therefore, achieving the best possible luminal result at the time of the first intervention should be the goal of the procedure, especially when treating high restenosis risk lesions.     

The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-&bgr;-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% for the top 5, 10 and 20% of individuals repectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole establishing that the mutation is a major determinant of homocystein levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.