New directions for radiologic research.
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Biomedical subjects
Publications and source records attributed to D Fraser.
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An electroporation protocol for the successful transfection of mouse lymphoblastoid cells has been developed. Two cell lines, a normal and a mutant sensitive to DNA cross-linking agents, were used. The optimum conditions of electroporation in terms of uptake of the fluorescent dye lucifer yellow coupled with low toxicity were established. Subsequently, these conditions were used to achieve stable transfection by a plasmid expression vector. The plasmid integration patterns were determined by Southern blot analysis.
We examined the neonatal outcome of 644 twins weighing 500 g or more and 656 singletons, born in the years 1984-1986 in the Soroka Medical Center, Beer-Sheva, Israel. There was nearly a four-fold risk of antepartum death in twins vs singletons, which disappeared when birth weight was controlled for. The risks for intrapartum and early neonatal mortality were not raised in this population. A statistically significant relative risk for congenital heart malformations in twins vs singletons remained (RR = 5.0, 95% CI = 1.5-16.3), after controlling for maternal age. Significantly higher rates of hyalin membrane disease, hypoglycemia, hyperbilirubinemia, anemia and septicemia were found in twins. Controlling for the confounding of the association between twinning and mortality or morbidity caused by differences in distributions of mode of delivery or gestational age between twins and singletons, was not as efficient as the controlling for birth weight. Thus, adjustment for birth weight removed all the excess risks detected except in hypoglycemia. Our findings suggest that the lower birth weight of twins, which is so intimately associated with multiple gestations, is probably the single most important factor associated with neonatal problems found in twin births.
The patterns of sex ratio in Israeli twins by maternal age and parity are described in two ethnic subpopulation. Jews and Bedouins differ one from the other in genetic, environmental, lifestyle, and reproductive factors. In the Jewish subpopulation, the proportion of males was significantly lower in twin than in singleton births; parity increased the odds of male twin births while maternal age had the inverse effect. In the Bedouin subpopulation, the sex ratio did not differ significantly from that of singletons, and no consistent patterns were found by maternal age and parity. The data suggest that several factors may influence the sex ratio in twin births. In Jewish twin births, the findings are consistent with the literature and can be largely explained in terms of high level of maternal gonadotropins. In the Bedouin subpopulation, paternal influence which could be related to lifestyle may be present, and as yet undefined genetic factors may also be involved. It would be of great interest, therefore, to continue monitoring of the effects of changes in lifestyle on the Bedouin population in order to tease out the relative importance of the varying factors on the sex ratio of twin births.
OBJECTIVE: To investigate the presence of an oestradiol receptor-related protein (P29) in skin and skin organelles, and to assess changes in its content during the normal menstrual cycle. DESIGN: An observational study. SETTING: King's College School of Medicine and Dentistry, London. SUBJECTS: Twenty-one premenopausal women with regular menstrual cycles undergoing gynaecological surgery. They were allocated to proliferative or secretory phases of the menstrual cycle on the basis of menstrual dating and histological examination of an endometrial sample. INTERVENTIONS: Small full thickness sections of skin (about 5 mm in depth) taken from the anterior abdominal wall at hysterectomy or laparoscopic sterilization. MAIN OUTCOME MEASURES: The concentration of the oestradiol receptor-related protein in skin and its organelles was assessed semi-quantitatively, using a monoclonal antibody technique. The intensity of staining was compared between the proliferative and secretory phases of the cycle. RESULTS: The receptor-related protein was consistently observed in epidermis, sebaceous glands, hair follicles and sweat ducts; there was no significant difference in its concentration between the proliferative and secretory phases of the menstrual cycle. The protein was not present in dermis and sweat ducts. CONCLUSIONS: Epidermis and some skin organelles contain an oestradiol receptor-related protein and must be considered as oestrogen target tissues. However, the content of this protein does not appear to change significantly during the normal menstrual cycle.
A prospective epidemiological and clinical study of ulcerative colitis and Crohn's disease was undertaken in the Bedouin Arabs of southern Israel between 1981 and 1990. There were six patients with ulcerative colitis and the prevalence rate in 1990 was calculated to be 9.8/10(5) (95% confidence intervals 3.6-17.4) in the total population, or 6.2/10(5) (0.8-22.5) in men and 13.7/10(5) (3.7-35.0) in women. Two cases of Crohn's disease occurred, both in women; the prevalence rate was 3.2/10(5) (0.4-11.8) in the entire population, and 6.8/10(5) (0.8-17.5) in women. The prevalence rates (age adjusted) in Arabs were significantly lower (p less than 0.01) than the corresponding rates in the local Jewish populations. The Bedouin patients were aged mean (SD) 34.0 (16.4) years at time of diagnosis. The clinical features of both diseases resembled those in the Jewish and other reported populations. It is suggested that the exposure of the Bedouin Arabs to the environmental causative factors of ulcerative colitis and Crohn's disease has hitherto been limited and thereby accounts for the rarity of these diseases in this population.
The isthmic segment of the uterine artery's ascending branch has a freer course and wider diameter than distal parts of the vessel. Therefore, we assumed that this arterial segment would provide better blood flow and prevent hypoxia of the trophoblast. As a result, placenta previa pregnancies would be complicated by hypertensive disorders less often than are pregnancies with normally implanted placentas. To test this hypothesis, 491 placenta previa pregnancies, among a population of 106,866 pregnant women, were compared with pregnancies with normally implanted placentas. Clinically meaningful and statistically significant reductions in the rates and risks of hypertensive disorders were found in placenta previa pregnancies (P = .002, relative risk = 0.44, 95% confidence interval 0.25-0.78). The differences persisted when primiparous and multiparous women were examined separately and when preterm and term deliveries were separated. In a multivariate logistic regression analysis, patients with placenta previa had a third of the risk for hypertensive disorders compared with pregnant women with normally implanted placentas (relative risk = 0.36, 95% confidence interval 0.20-0.64), even after controlling for parity and preterm or term delivery. In the same model, primiparity and preterm delivery were each associated with a doubling of risk for hypertensive disorders, regardless of the placental implantation site. Thus, regardless of parity and preterm or term delivery, placenta previa and hypertensive disorders are inversely related.
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OBJECTIVE: To provide information on endometrial stimulation after discontinuation of treatment with oestradiol implants. DESIGN: Long term follow up of withdrawal bleeding patterns in women taking progestogens cyclically every month after oestradiol implant treatment was ended. SETTING: Specialist menopause clinic. SUBJECTS: 10 Postmenopausal patients (at least 12 months' amenorrhoea after the last spontaneous period) who were treated with oestradiol implants for typical symptoms of oestrogen deficiency. The oestradiol dose was 50 mg, reimplantation occurring roughly every six months. Patients subsequently either needed to discontinue the hormone treatment for medical reasons or expressed a desire to stop treatment. MAIN OUTCOME MEASURE: Duration of endometrial stimulation--defined as the presence of withdrawal bleeding in response to progestogen given cyclically--after insertion of the last oestradiol implant. RESULTS: Four patients eventually stopped bleeding, their mean duration of bleeding being 35 months (range 27-43 months). One patient required hysterectomy 26 months after the last implantation because of persistent irregular bleeding despite treatment with high doses of progestogen. Three patients bled for 22, 30, and 36 months and then restarted oestrogen treatment because symptoms returned. The last two patients subsequently continued to bleed 12 and 21 months after the last implantation. CONCLUSIONS: The duration of endometrial stimulation after implantation can be prolonged, up to 43 months. Insertion of oestradiol implants can carry a long term commitment to the cyclical administration of progestogen and regular withdrawal bleeding if endometrial hyperplasia and carcinoma are to be avoided.
The effects of an oestrogen/progestagen transdermal therapeutic system (TTS) were evaluated in sixteen oestrogen-deficient women. The patients applied conventional oestradiol-TTS for 14 days, then two combined norethisterone acetate/oestradiol patches for a further 14 days. The treatment was repeated for five cycles. Ten patients then underwent metabolic studies. One patient had amenorrhoea, but the rest experienced regular withdrawal bleeding which was seldom heavy. Fourteen endometrial biopsy samples were taken during the fifth treatment cycle; none showed proliferative or hyperplastic features. The effects of transdermal norethisterone acetate on symptoms, lipid metabolism, and psychological status were determined by comparing features in the oestrogen-only phase and in the combined phase; the effects were very mild. These preliminary findings show that transdermal progestagen can be successfully administered in hormone replacement therapy to prevent endometrial proliferation while minimising the adverse effects that may be seen with oral administration.
Accumulating evidence suggests that cardiovascular disease which was very rare among Negev Bedouins until the 1970's is now on the increase. The Bedouin nomads are being settled in townships and are changing habits and lifestyles as a result. The aim of this study was to determine the prevalence of known cardiovascular risk factors in Bedouins at different levels of lifestyle changes. To do so, the prevalence of the risk factors was examined in a traditional tribal group and in a settled Bedouin group. Among settled Bedouins, 15% were obese (BMI greater than 30) and a further 35% were overweight (BMI 25-29.9), as compared with no obesity and only 23% of overweight in the tribal group. The differences were most marked in the younger age group. Mean LDL-cholesterol levels also differed between the two study groups, being significantly higher in settled than in tribal Bedouins (113.9 mg% +/- SD 28.6 vs 96.9 mg% +/- SD 27.1 respectively, p less than 0.05). High BMI and LDL-cholesterol were both significantly and independently associated with being settled. No differences between the groups were found in relation to blood pressure, smoking and fasting blood glucose. It appears therefore that settlement of nomadic Bedouins and the changes associated with it, alter the pattern of cardiovascular risk factors in this population.
Maternal diabetes is known to be related to an increase in birth weight of the offspring. However, the mechanism of the association is not entirely clear. In addition, the contribution of the demographic, obstetric and metabolic factors to birth weight in diabetic mothers is not well defined. All the diabetic women (68 requiring insulin-treatment and 403 on diet alone) and a random sample of 1 in 12 of all non-diabetic women (893 women) who delivered in one regional hospital between March 1987 and June 1988 inclusive, were included in the study. Tests for gestational diabetes are routinely performed in our pregnant women population, thus, the study is a population based one. The mean birth weight of infants of diabetic mothers adjusted for gestational age was higher than in those of non-diabetic mothers. However, no relationship was found between maternal glycosylated hemoglobin measured at delivery and the infants birth weight. Furthermore, at each week of gestation, infants born to diabetic mothers were heavier than the infants of non-diabetic mothers (for weeks 37 to 40, p less than 0.05), while no differences were found in glycosylated hemoglobin levels between the two groups at any time. In a multivariate model we showed that after controlling for gestational age, the only factors which independently and significantly affected birth weight in our population were diabetes, ethnic origin, and the parity of the mother. Our findings support the possibility that substances which induce hyperinsulinemia, other than glucose, may be related to the higher birth weight of infants of diabetic mothers.
Sixteen postmenopausal women receiving conjugated equine oestrogens 1.25 mg/day, continuously, were randomly allocated to add dydrogesterone 20 mg/day for 12 days each calendar month for 3 months and then 10 mg/day in an identical fashion for a further 3 months, or to receive the dydrogesterone doses in reverse sequence. The effects of the two dydrogesterone doses on endometrial histology, vaginal bleeding, and the symptomatic and psychological status were compared. Endometrial samples were obtained around day 10 of progestogen addition. Dydrogesterone, 20 mg, induced uniform, late secretory transformation in all samples; with 10 mg one sample showed mixed early and late secretory features and another demonstrated late secretory changes associated with atypical hyperplasia. Both dydrogesterone doses induced an acceptable withdrawal bleed; most bleeding episodes were 'spotting' or normal in amount, and heavy bleeding was reported infrequently. There was one episode of breakthrough bleeding. There were no differences in bleeding patterns between the two dose regimens. Anxiety, and the physical and psychological status were significantly improved after 3 months of therapy. Significant benefits on depression were observed less clearly. There were no differences between the two dydrogesterone doses on anxiety, depression and the physical and psychological status, and, overall, the addition of the progestogen did not antagonize oestrogen benefits.
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Several features of Fanconi's anemia (FA) are reported: relative inefficiency in the processing of DNA cross-links and monoadducts, hypomutability at the two loci analysed, complementation of the cytogenetic defect by cocultivation with mouse cells and homology of the FA group A with the mouse cellular mutant MCS attempts to clone and characterise a DNA fragment which complements the defect. The relation between observed features and predisposition to leukemia are discussed.
Litters of domestic piglets show strong sibling competition, large differences among litter-mates in birth weight and rate of growth, and, in the absence of human intervention, a high mortality rate. This combination of traits suggests that pigs are using a reproductive strategy similar to that of certain bird species which produce one or more small 'spare' young whose death or survival is determined by sibling competition. Death through competition is natural in such species. Prevention of death requires the early identification and separate rearing of unsuccessful competitors. The major behavioural pathways leading to piglet deaths are considered to be malnutrition through unsuccessful suckling behaviour, and crushing of piglets by the sow. Crushing involves two distinct behavioural sequences: posterior crushing (beneath the sow's hind quarters) and ventral crushing (beneath the udder and rib cage). Farrowing crates are designed to prevent posterior but not ventral crushing. Malnourished piglets appear to be more vulnerable to crushing, perhaps because persistent suckling attempts cause them to spend more time near the sow. Prevention of crushing thus requires a reduction in malnutrition, not merely restriction of the sow's movements. Under certain conditions, dehydration may be an important but neglected aspect of malnutrition. Some litters of piglets have much higher death losses than others, presumably because of risk factors that apply to the litter as a whole. Early malnutrition, resulting from hypogalactia in the sow in the first days after farrowing, appears to be an important risk factor. Farrowing difficulties leading to piglet hypoxia during the birth process may be another. Risk factors that affect whole litters deserve greater emphasis in future research.
Breast cancer is the leading cause of cancer mortality among women is Israel. On average, 1 in every 12 women develops the disease. While breast self-examination has not proved effective, and routine mass mammography is at present unavailable to the population at large, regular routine breast examination by primary care physicians can effectively screen a large fraction of this country's population. In order to do so, full acceptance of the procedure by women and their physicians is required. This study examines the attitudes and practice of primary care physicians with regard to routine breast examination, and compares them with routine detection of hypertension and diabetes mellitus. A structured questionnaire was distributed to all 97 Kupat Holim (workers' federation sick fund) primary care physicians in the Negev. They included 40 family physicians (FP), board-certified or completing specialization, and 57 general practitioners (GP), not board-certified. There was no difference in response rate between the 2 groups (47%). Nearly all physicians perform routine examinations for detection of hypertension (100% of the FP and 96% of the GP) and diabetes mellitus (91% and 74%, respectively). Of the FP, 96% consider routine breast examination as the task of the primary care physician, versus only 68% of the GP. Accordingly, 92% of the FP stated that they routinely perform the procedure, but only 52% of the GP. Being an FP was positively related with the performance of breast examination, while seeing a large number of patients per clinic session and low job satisfaction were negatively associated with it.
Seasonality of births in southern Israel was examined in two populations, Jews and Bedouins, with distinctly different life-styles. The study included 1,444 twin births that occurred between the years 1970 and 1986. The peak month for the birth of monozygotic twins was September in both populations, while the maximum number of deliveries occurred in January for the Bedouins and August for the Jews. Of Jewish dizygotic twin births, higher rates were found from July to December. In addition, the peak months of singleton births in women aged 35 years and older and in women of high parity did not coincide with the peak months of multiple births. Maternal age and parity have been shown to greatly influence twin birth rates. The autumnal peak we found, which was independent of ethnic origin and its associated cultural and sociologic differences, was also independent of maternal age and parity and was consistent with findings in other populations in the northern hemisphere. That finding suggests that a seasonal factor, as yet undefined, affects the rates of multiple births.