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Biomedical subjects

D Fraser

Publications and source records attributed to D Fraser.

At least 19 recordsLinked to original sources

Intensive surveillance for infections in a three-year study of nursing home patients.

The authors report the results of a 3-year (August 1984-May 1987) prospective study of intensive surveillance for nursing home-associated infections in 666 patients in a 300-bed nursing home in San Diego, California. Ninety-three percent (666 of 714) of the eligible subjects enrolled; 75% were women. The mean age of the subjects was 81.6 years. Lengths of stay ranged from 1 day to 1,025 days, with a mean of 166 days; the cumulative length of stay for all subjects was 110,746 days (303 years). Operational definitions that were heavily dependent on evaluation of clinical signs and symptoms were used by nurse practitioners in weekly or biweekly assessments of all patients to identify infections. The overall incidence of nursing home-associated infection was 7.1 infections/1,000 patient-days. Many of the infections would not have been recognized by persons less skilled than nurse practitioners. Among the 788 nursing home-associated infections identified, 362 (47%) were in the respiratory tract (286 lower respiratory and 76 upper respiratory); 200 (25%) were associated with skin and subcutaneous and mucous membranes; 140 (18%) were symptomatic urinary tract infections; 13 (2%) were bacteremia; and 73 (9%) were other infections.

Adult

[Screening for colorectal cancer and polyps].

Screening programs for the early detection of colorectal neoplasms may prevent cancer or improve its prognosis. We screened 1101 individuals (89% of whom were asymptomatic) using 3 methods. The fecal occult blood test, done in 96% of those screened, was positive in only 1.9% and was low in both sensitivity (2.1%) and positive predictive value (6.7%). However, flexible sigmoidoscopy, performed in 48%, gave positive results in 7.8% of those screened, revealing 41 cases of polyps and 1 of cancer. Colonoscopy was performed in 8% and 37 cases of polyps and 1 of cancer were detected. Of the 3 screening methods tested, sigmoidoscopy appeared to be the best because of its high diagnostic yield. The risk of colorectal neoplasm was shown for the first time to be equal in Jews of oriental and occidental origin.

Colonoscopy

Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases.

We have determined the sequence of cDNA for the human histidyl-tRNA synthetase (HRS) in a hepatoma cell line and confirmed it in fetal myoblast and fibroblast cell lines. The newly determined sequence differs in 48 places, including insertions and deletions, from a previously published sequence. By sequence specific probing and by direct sequencing, we have established that only the newly determined sequence is present in genomic DNA and we have sequenced 500 hundred bases upstream of the translation start site. The predicted amino acid sequence now clearly demonstrates all three motifs recognized in class 2 aminoacyl-tRNA synthetases. Alignment of E. coli, yeast, and when available, mammalian predicted amino acid sequences for three of the four members of the class 2a subgroup (his, pro, ser, and thr) shows strong preservation of amino acid specific signature regions proximal to motif 2 and proximal to motif 3. These probably represent the active site binding regions for the proximal acceptor stem and for the amino acid. The first two exons of human HRS contain a 32 amino acid helical motif, first described in human QRS, a class 1 synthetase, which is found also in a yeast RNA polymerase, a rabbit termination factor, and both bovine and human WRS, suggesting that it may be an RNA binding motif.

Amino Acid Sequence

[Resistance in uterine arcuate arteries of pregnant hypertensive patients].

Hypertensive pregnant women were examined by continuous Doppler-ultrasound to measure resistance to blood flow in the uterine arcuate arteries. 20/26 had increased resistance. Those with bilateral increased resistance delivered after a mean of 33.2 weeks of pregnancy, 46.1% of them by cesarean section, and the mean birthweight was 1743 g. Those with unilateral increased resistance delivered after a mean of 38.0 weeks, 28.5% by cesarean section, and the mean birthweight was 2813 g. Measurement of blood flow by the Doppler method seems to be useful in the management of hypertensive disorders in pregnancy, as it helps to assess deficiency of the uterine circulation.

Arteries

Transfection of wild-type and 'Fanconi anemia-like' mouse lymphoma mutant cells by electroporation.

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.

Animals

Factors associated with neonatal problems in twin gestations.

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.

Adult

Ethnicity and sex ratio 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.

Adult

Presence of an oestradiol receptor-related protein in the skin: changes during the normal menstrual cycle.

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.

Adult

Inflammatory bowel disease in the Bedouin Arabs of southern Israel: rarity of diagnosis and clinical features.

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.

Adolescent

Reduced frequency of hypertensive disorders in placenta previa.

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.

Adult

Prolonged endometrial stimulation associated with oestradiol implants.

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.

Adult

Transdermal administration of oestrogen/progestagen hormone replacement therapy.

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.

Administration, Cutaneous

The prevalence of cardiovascular risk factors among male Bedouins: a population in transition.

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.

Adult

Factors influencing birth weight in newborns of diabetic and non-diabetic women. A population based study.

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.

Adult

Endometrial, physical and psychological effects of postmenopausal oestrogen therapy with added dydrogesterone.

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.

Affective Symptoms