Genomewide linkage study in the Irish affected sib pair study of alcohol dependence: evidence for a susceptibility region for symptoms of alcohol dependence on chromosome 4.

Alcoholism is a relatively common, chronic, disabling and often treatment-resistant disorder. Evidence from twin and adoption studies indicates a substantial genetic influence, with heritability estimates of 50-60%. We conducted a genome scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Most probands were ascertained through alcoholism treatment settings and were severely affected. Probands, affected siblings and parents were evaluated by structured interview. A 4 cM genome scan was conducted using 474 families of which most (96%) were comprised by affected sib pairs. Nonparametric and quantitative linkage analyses were conducted using DSM-IV alcohol dependence (AD) and number of DSM-IV AD symptoms (ADSX). Quantitative results indicate strong linkage for number of AD criteria to a broad region of chromosome 4, ranging from 4q22 to 4q32 (peak multipoint LOD=4.59, P=2.1 x 10(-6), at D4S1611). Follow-up analyses suggest that the linkage may be due to variation in the symptoms of tolerance and out of control drinking. There was evidence of weak linkage (LODs of 1.0-2.0) to several other regions, including 1q44, 13q31, and 22q11 for AD along with 2q37, 9q21, 9q34 and 18p11 for ADSX. The location of the chromosome 4 peak is consistent with results from prior linkage studies and includes the alcohol dehydrogenase gene cluster. The results of this study suggest the importance of genetic variation in chromosome 4 in the etiology and severity of alcoholism in Caucasian populations.

Pregnancy following a single lung transplant.

Successful pregnancy in a single lung transplant recipient has not been reported previously. The long term effect of pregnancy on graft function and management of deteriorating pulmonary function is not defined. This case describes the management, outcome, and problems encountered when a single lung transplant recipient developed a progressive deterioration in pulmonary function during pregnancy, attributed to accelerated obliterative bronchiolitis.

Routine radiographer screening for fetal abnormalities by ultrasound in an unselected low risk population.

A screening programme for fetal abnormalities began at The Hillingdon Hospital in July 1986. Second trimester ultrasound scans are performed by radiographers. A combined prospective and retrospective study of the ultrasound findings and outcome in all pregnancies delivered in 1989-1990 was undertaken. 6412 babies were born during this period, of whom 6183 (96%) were examined by ultrasound in the second trimester; 29 pregnancies were terminated for fetal abnormality. Of the 89 fetuses who were abnormal at birth or at induced termination of the pregnancy (1.4%), 84 were scanned in the second trimester. In 51 cases the abnormality was detected before 22 weeks gestation (sensitivity, 60.7%). 56 of these 84 abnormal fetuses scanned had potentially lethal or major handicapping abnormalities of which 41 were detected by ultrasound before 22 weeks gestation (sensitivity, 73%). There was one false positive diagnosis of abnormality which did not affect outcome. 6352 babies were normal at delivery or on discharge from hospital (specificity, 99.98%).

Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth.

In a double-blind trial of vitamin D supplements in pregnant Asian women calciferol (ergocalciferol, 1000 IU/day) was administered to 59 women and placebo to 67 controls during the last trimester. The two groups had similar distributions of maternal age, height, parity, number of vegetarians, countries of origin, and sex and gestation of the infants. At entry to the trial maternal serum 25-hydroxy vitamin D (25-OHD) concentrations were low in both treatment and control groups and significantly lower in vegetarians than non-vegetarians. Mothers in the treatment group gained weight faster in the last trimester than those in the control group, and at term they and their infants all had adequate plasma 25-OHD concentrations, Mothers and infants in the control group, however, had low plasma concentrations of 25-OHD and calcium and raised plasma alkaline phosphatase (bone isoenzyme) activity. Five of these infants developed symptomatic hypocalcaemia. Almost twice as many infants in the control group were small for gestational age (29% v 15%), but there were no significant differences between the two groups of infants in antropometric measurements. Infants in the control group, however, had larger fontanelles, suggesting impaired ossification of the skull. Because of the benefits to mothers and infants in the treatment group and the absence of side effects, vitamin D supplements should be given to all pregnant Asian women in the United Kingdom.