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Biomedical subjects

H Cohen

Publications and source records attributed to H Cohen.

At least 289 records · Page 16Linked to original sources

Prenatal diagnosis of congenital dysgranulopoietic neutropenia.

Congenital dysgranulopoietic neutropenia is a severe life-threatening disease characterized by specific dysmorphic granulocytes. Prenatal diagnosis of congenital neutropenia was reported first in 1983. In 1989 we reported a family with congenital dysgranulopoietic neutropenia in two siblings (one male and one female); in 1992 the mother became pregnant and prenatal diagnosis was performed by cordocentesis. The results we obtained from the fetus at risk enabled us to suggest that it was not affected, and we advised the parents that the pregnancy could continue: a healthy female was born. The neutrophil count at 2 and 4 months was normal.

Consanguinity↗

Transcriptional regulation of the phosphoenolpyruvate carboxykinase gene by cooperation between hepatic nuclear factors.

To study the transcriptional regulation of the liver gluconeogenic phenotype, the underdifferentiated mouse Hepa-1c1c7 (Hepa) hepatoma cell line was used. These cells mimicked the fetal liver by appreciably expressing the alpha-fetoprotein and albumin genes but not the phosphoenolpyruvate carboxykinase (PEPCK) gene. Unlike the fetal liver, however, Hepa cells failed to express the early-expressed factors hepatocyte nuclear factor 1 alpha (HNF-1 alpha) and HNF-4 and the late-expressed factor C/EBP alpha, thereby providing a suitable system for examining possible cooperation between these factors in the transcriptional regulation of the PEPCK gene. Transient transfection assays of a chimeric PEPCK-chloramphenicol acetyltransferase construct showed a residual PEPCK promoter activity in the Hepa cell line, which was slightly stimulated by cotransfection with a single transcription factor from either the C/EBP family or HNF-1 alpha but not at all affected by cotransfection of HNF-4. In contrast, cotransfection of the PEPCK construct with members from the C/EBP family plus HNF-1 alpha resulted in a synergistic stimulation of the PEPCK promoter activity. This synergistic effect depended on the presence in the PEPCK promoter region of the HNF-1 recognition sequence and on the presence of two C/EBP recognition sequences. The results demonstrate a requirement for coexistence and cooperation between early and late liver-enriched transcription factors in the transcriptional regulation of the PEPCK gene. In addition, the results suggest redundancy between members of the C/EBP family of transcription factors in the regulation of PEPCK gene expression.

Animals↗

Evaluation of patients' knowledge about anticoagulant treatment.

OBJECTIVE: To develop a questionnaire to evaluate patients' knowledge of anticoagulation. DESIGN: Anonymous self completed questionnaire study based on hospital anticoagulant guidelines. SETTING: Anticoagulant clinic in a 580 bed district general hospital in London. SUBJECTS: 70 consecutive patients newly referred to the anticoagulant clinic over six months. MAIN MEASURES: Information received by patients on six items of anticoagulation counselling (mode of action of warfarin, adverse effects of over or under anticoagulation, drugs to avoid, action if bleeding or bruising occurs, and alcohol consumption), the source of such information, and patients' knowledge about anticoagulation. RESULTS: Of the recruits, 36 (51%) were male; 38(54%) were aged below 46 years, 22(31%) 46-60, and 10(14%) over 75. 50 (71%) questionnaires were returned. In all, 40 respondents spoke English at home and six another language. Most patients reported being clearly advised on five of the six items, but knowledge about anticoagulation was poor. Few patients could correctly identify adverse conditions associated with poor control of anticoagulation: bleeding was identified by only 30(60%), bruising by 23(56%), and thrombosis by 18(36%). Only 26(52%) patients could identify an excessive level of alcohol consumption, and only seven (14%) could identify three or more self prescribed agents which may interfere with warfarin. CONCLUSION: The questionnaire provided a simple method of determining patients' knowledge of anticoagulation, and its results indicated that this requires improvement. IMPLICATIONS: Patients' responses suggested that advice was not always given by medical staff, and use of counselling checklists is recommended. Reinforcement of advice by non-medical counsellors and with educational guides such as posters or leaflets should be considered. Such initiatives are currently being evaluated in a repeat survey.

Aged↗

Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction.

The prognostic value of pretreatment pulse pressure as a predictor of myocardial infarction and the relation of pulse pressure and in-treatment diastolic blood pressure reduction to myocardial infarction were investigated in a union-sponsored systematic hypertension control program. In a prospective study, 2207 hypertensive patients with a pretreatment systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 95 mm Hg grouped according to tertile of pulse pressure (PP1, < or = 46; PP2, 47 to 62; PP3, > or = 63 mm Hg) were further stratified by the degree of diastolic fall: large (L), > or = 18; moderate (M), 7 to 17; small (S), < or = 6 mm Hg. During an average follow-up of 5 years, 132 cardiovascular events (50 myocardial infarctions, 23 strokes) were observed. Myocardial infarction rates per 1000 person-years were positively related to pulse pressure (PP1, 3.5; PP2, 2.9; PP3, 7.5; PP3 versus PP1, P = .02). Wide pulse pressure was identified as a predictor of myocardial infarction (PP3 versus [PP1 + PP2]: relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.2-4.1), controlling for other known risk factors by Cox regression. A curvilinear relation (resembling a J shape) between diastolic fall and myocardial infarction was observed in patients with the widest pulse pressure, PP3 (L, 9.5; M, 3.9; S, 11.2; L versus M: RR = 2.5, 95% CI = 1.0-6.2; S versus M: RR = 2.9, 95% CI = 1.1-8.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome.

Pathological and clinical data from 56 patients operated on for craniopharyngioma since 1981 were analyzed to determine the utility of dividing patients with this tumor into distinct clinical groups based on recognized pathological type and to determine the prognostic import of brain invasion. Of the tumors in the 30 adult patients, 66% were adamantinomatous, 28% were squamous papillary, and the remainder were mixed. However, of the tumors in the 26 children, 96% were adamantinomatous and none were pure squamous papillary (P < 0.01). Forty-six percent of the children compared with 17% of the adults had brain invasion (P < 0.01). Brain invasion was present in 37% of the adamantinomatous but in only 13% of the squamous papillary tumors. Seventy-seven percent of the children underwent gross total resection (GTR) compared with 27% of the adults (P < 0.01). Sixty-three percent of the squamous papillary tumors underwent GTR compared with 54% of the adamantinomatous and mixed tumors. Follow-up ranged from 7 to 187 months (mean, 49 mo). After subtotal resection, with or without radiation therapy, 58% of the tumors recurred compared with 17% recurrence after GTR (P < 0.01), with a mean time to recurrence of 34 months. In both tumor histological types, subtotal resection was associated with a higher rate of tumor recurrence compared with gross total resection. Among the subtotally resected craniopharyngiomas, 2 of the 3 (67%) squamous papillary and 11 of the 21 (52%) adamantinomatous and mixed tumors recurred. In contrast, among the totally resected tumors, none of the 5 squamous papillary and only 5 of the 25 (20%) adamantinomatous and mixed tumors recurred. There were no significant differences in Karnofsky performance status score, mortality rate, or visual and endocrine outcomes when comparing patients based on histological tumor type. When controlling for age and extent of resection, we found that brain invasion had no significant effect on recurrence rate in totally resected tumors. Based on the limited number of patients in this series, we conclude as follows. 1) Contrary to previous reports, squamous papillary craniopharyngiomas, like adamantinomatous tumors, may recur when subtotally resected. 2) For both tumor variants, the most significant factor associated with craniopharyngioma recurrence is the extent of surgical resection rather than histopathological subtype. 3) Contrary to prior hypotheses, brain invasion in totally resected tumors does not predict higher recurrence. 4) GTR is associated with a significantly lower recurrence rate and can be achieved without sacrificing functional outcome.

Adolescent↗

Heterogeneity of the prolactin receptor in the rat mammary gland and liver during various physiological states.

This work was undertaken to determine variations in the 125I-labelled ovine prolactin (oPRL) binding in rat liver and mammary gland membranes, and to study the molecular forms of prolactin receptor in different physiological situations. Prolactin binding was determined using 125I-labelled oPRL in the 100,000 g pellet. 125I-Labelled oPRL was cross-linked to receptors in membranes from rat liver and mammary gland and subjected to SDS-PAGE under reducing conditions, followed by autoradiography of dried gels. In the mammary gland, the specific binding of oPRL to membranes, expressed as mean +/- S.E.M. fmol/mg protein increased from 1.36 +/- 0.24 on the day of dioestrus to 3.26 +/- 0.60 on the day of oestrus. It remained very low during pregnancy but increased during lactation to reach 4.78 +/- 0.99. In the liver, the specific binding of oPRL to membranes was higher than in the mammary gland on the days of dioestrus 1, dioestrus 2 and oestrus, but not on the day of pro-oestrus. It increased until day 14 of pregnancy when the specific binding of 125I-labelled oPRL was 17.01 +/- 0.30. Cross-linking revealed different molecular forms in the mammary glands and the liver. In the mammary gland we observed four prolactin-binding forms of 80, 50, 40 and 16 kDa, all of which were specific for prolactin. The 80, 50 and 40 kDa forms were also able to bind to a Concanavalin A-Sepharose column, indicating that these binding forms were glycosylated while the smaller one (16 kDa) appeared to be unglycosylated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The determinants of hypertension awareness, treatment, and control in an insured population.

OBJECTIVES: The purpose of the study was to identify the determinants of awareness, treatment, and control of hypertension in a population with full access to medical care. METHODS: Unionized New York City health care workers (n = 1394) with comprehensive medical insurance were screened for hypertension. Union records documenting all physician visits and prescription medications for the year before screening provided the opportunity to relate patterns of treatment to blood pressure outcomes. RESULTS: Of the 409 employees found to have hypertension, 289 (71%) were aware of their condition and 201 (49%) had been treated, but only 51 (12%) had their blood pressure controlled at the recommended level (< 140/90 mm Hg). In a logistic regression model, the only variable of treatment associated with control was days of antihypertensive medication. The total number of physician visits was not associated with control. CONCLUSIONS: These findings demonstrate that in conventional community settings, even in the absence of financial barriers, treatment for hypertension continues to be characterized by poor outcomes. Improving access to primary care, without changes in the nature of that care, may not substantially improve blood pressure control.

Aged↗

The role of cordocentesis in assessment of mosaicism found in amniotic fluid cell culture.

Chromosomal mosaicism presents one of the most difficult problems in prenatal cytogenetic diagnosis, requiring the differentiation of true mosaicism from pseudomosaicism. To overcome associated problems and to prevent termination of normal pregnancies, we investigated 23 pregnancies in which true mosaicism has been found in amniotic fluid cell culture. A fetal blood sample was obtained by cordocentesis for rapid karyotyping, and meticulous sonographic examinations were carried out for detecting fetal abnormalities. The 23 cases in which mosaicisms were found in amniocytes involved five cases with sex chromosomal abnormalities, twelve with autosomal trisomy, four with autosomal structural defects, one with a supernumerary marker and one with tetraploidy. The karyotype from fetal leukocytes confirmed the diagnosis of mosaicism in only three out of 23 cases. These three included: two autosomal trisomies (47,XY + 13/47,XY + 21 and 46,XY/47,XY + 21) and one sex chromosome mosaicism (45,X/46,XY). These were all selected for elective termination of pregnancies by the parents' request. Post abortion karyotype re-confirmed previous karyotype. The other twenty lymphocyte karyotypes were normal, and of these, 19 patients gave birth at term, and one delivered prematurely due to premature rupture of membranes. All 20 born infants were found normal by both neonatal examination and re-karyotypes. We conclude that finding of mosaicism in amniotic fluid culture requires further investigation. Furthermore, in the presence of amniotic fluid cell true mosaicism and normal karyotype in fetal blood, continuation of the pregnancy is safe and to be recommended.

Abortion, Therapeutic↗

Vestibular rehabilitation improves daily life function.

This article reviews recent research that addresses the functional outcomes of intervention for vestibular disorders. Vestibular impairments cause disequilibrium, blurred vision, disorientation, and vertigo. These sensory disturbances and motor impairments in turn cause dysfunction in many activities of daily living and in social interactions that traditional medical treatments do not address. The motor sequelae of some vestibular disorders can be treated successfully with programs of graded exercises and activities, the functional implications of which are described herein. The functional impairments caused by other vestibular disorders, which cannot be treated with graded activities, are also described. These disorders include bilateral vestibular loss caused by connective tissue disorders or by the use of ototoxic medications, tumors of the labyrinth or vestibular nerve, and Meniere's disease. Occupational therapy intervention for these conditions may involve providing adaptive equipment, teaching alternative strategies for performing activities of daily living, and psychological intervention for depression and anxiety.

Activities of Daily Living↗

Secondary Prevention of Breast Cancer in the Older Woman: Issues Related to Screening.

With advancing age, the prevalence of breast cancer and consequently the positive predictive value of screening tests increase. However, limited life expectancy may reduce the benefit of cancer screening. The integration of serial mammography, yearly or every two years, with yearly physical examination of the breast, reduces the breast cancer related mortality among women aged 50 to 70 years and may be beneficial for older women. Of all age-related barriers to screening, the lack of physician support has been the most significant. A reversal in this trend was witnessed by a recent increase in mammography use by women aged 69 to 75 years. On the basis of existing data, it is reasonable to recommend screening for women up to age 75 years and for older women whose life-expectancy is estimated at three years or longer.

Journal Article↗

Serum prolactin-binding protein (PRL-BP) of human and rat are identified as IgG.

Heterogeneity of circulating prolactin in various species including rat and man is well known. We have recently shown that PRL was able to bind to a protein of high molecular weight in plasma obtained from estradiol treated ovariectomized females rats. This study was undertaken to look for a possible PRL-binding in woman serum and to identify the PRL-BP in both rat and human sera. Pooled sera from normal women taking oral contraception and from women on the 3rd trimester of pregnancy were purified on affinity chromatography column, prepared with sepharose 4B-CNBr coupled to oPRL (ovine PRL). Elution resulted in a protein of 160 kD mol wt when subjected to SDS PAGE in non reducing conditions. Under reducing conditions 2 forms of 50 and 27 kD were found. The 160 kD and the 50 kD forms were able to bind to hPRL. The 3 forms (160, 50 and 27 kD) were recognized by monoclonal antibodies against PRL receptors. Both the 50 and 27 kD forms obtained from rat and human sera were sequenced and revealed to be the heavy and light chain of IgG1. This result was confirmed by specific immunoprecipitation of the PRL-BP by antibodies against human and rat IgG. This study showed, that autoantibodies to PRL were present in rat and human sera, even in physiological conditions such as pregnancy.

Amino Acid Sequence↗

Prenatal testing for Down syndrome in the Jewish and non-Jewish populations in Israel.

The present work evaluated the efficacy of a prenatal diagnosis program in which amniocentesis and chorionic villus sampling were offered free of charge to all pregnant women in Israel aged > or = 37 years. The number of Down syndrome (DS) live births that occurred during the period of the program (1978-92) was correlated to the prevalence of old maternal age (> 35 years) and the utilization of prenatal test in the Jewish and non-Jewish populations in 1990 and 1992. It was noted that in the Jewish population, there was a slight increase in the DS live birth rate, from 1.05 in 1978, to 1.37 DS cases/1,000 live births in 1987, which corresponded to an increase in the prevalence of older pregnant women, from 8.0% in 1978 to 14.8% in 1987. Thereafter, however, there was a continuous decline, to 0.71 DS cases/1,000 live births in 1992, as a result of increased acceptance of prenatal testing by women > or = 37 years (67%) and, recently, also by younger women (from 5.6% in 1990 to 14% in 1992). In the non-Jewish population, there has been a very low acceptance rate of prenatal testing (23.3-16.1% in women > or = 37 years and 0.36-0.63% in women < 37 years). As a result, a very low prenatal detection rate (8-16% of all DS cases) and a high prevalence of DS live births (1.4 cases/1,000 live births) were observed. We suggest that a unique genetic counseling approach is required in the non-Jewish population to improve prenatal DS prevention in Israel.

Adult↗

Measurement of ultrasound biomicroscopy images: intraobserver and interobserver reliability.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurement of images obtained during ultrasound biomicroscopy. METHODS: Four anterior segment images of four normal patients were obtained by a single examiner. The measurements of three independent observers were compared to assess interobserver reproducibility in quantifying the images. Thirteen different anterior segment parameters were measured by each observer on each image. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. RESULTS: Intraobserver reproducibility was high. Interobserver reproducibility for the measured parameters varied considerably and was affected by subjective interpretation of visualized anatomic landmarks. CONCLUSIONS: The optimal parameters for quantitative ultrasound biomicroscopy require refinement. Measurements of alterable parameters are best measured presently by a single observer. Ultrasound biomicroscopy has the potential to elucidate anatomic relationships underlying much anterior segment disease, but caution in interpreting quantitative differences is warranted.

Anterior Eye Segment↗

What may be gained from neuropsychological investigations of tardive dyskinesia?

As an iatrogenic movement disorder, tardive dyskinesia (TD) offers a unique opportunity to study brain-behavior relationships. The authors provide a brief overview of TD and discuss its association to cognitive dysfunction. It is argued that, given the complexity of the variables involved in the study of TD, there is pressing need for greater applications of neuropsychological research paradigms to help elucidate this disorder.

Antipsychotic Agents↗