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Biomedical subjects

H Cohen

Publications and source records attributed to H Cohen.

At least 181 records · Page 10Linked to original sources

Cerebral hemispheric control of speech during the intracarotid sodium amytal procedure: An acoustic exploration.

In this study we investigated lateralized control of speech during the intracarotid amobarbital procedure. Vowel segments were extracted from recordings made during two separate amobarbital procedures and involving two patients. Subjects were right-handed, presented with focal left mesial temporal epileptogenic foci. Age of onset of seizure disorders was 1.5 years for one subject and 16 years for the other. Recorded pre- and postinjection speech samples were digitized. Analyses were conducted on formants 1 and 2 (F1, F2) measures to determine the extent of formant fluctuation in the time course of the IAP. Preliminary results showed, for these two cases, that the left hemisphere is involved in the control of both F1 and F2 and the right in the control of F2 only. The data reveal the potential of coupling the IAP procedure and the acoustical analysis of speech in the study of cerebral control of speech.

Adult↗

Role of the isoforms of CCAAT/enhancer-binding protein in the initiation of phosphoenolpyruvate carboxykinase (GTP) gene transcription at birth.

The gene for phosphoenolpyruvate carboxykinase (PEPCK), a target of CCAAT/enhancer-binding protein-alpha (C/EBPalpha) and -beta (C/EBPbeta), begins to be expressed in the liver at birth. Mice homozygous for a deletion in the gene for CEBPalpha (C/EBPalpha-/- mice) die shortly after birth of hypoglycemia, with no detectable hepatic PEPCK mRNA and negligible hepatic glycogen stores. Half of the mice homozygous for a deletion in the gene for CEBPbeta (C/EBPbeta-/- mice) have normal glucose homeostasis (phenotype A), and the other half die at birth of hypoglycemia due to a failure to express the gene for PEPCK and to mobilize hepatic glycogen (phenotype B). Insulin deficiency induces C/EBPalpha and PEPCK gene transcription in the livers of 19-day fetal rats, whereas dibutyryl cyclic AMP (Bt2cAMP) increases the expression of the gene for C/EBPbeta and causes a transient burst of PEPCK mRNA. Bt2cAMP induces PEPCK mRNA in the livers of fetal C/EBPalpha-/- mice, but at only 20% of the level of control animals; however, there is no induction of PEPCK mRNA if the cyclic nucleotide is injected into C/EBPalpha-/- mice immediately after delivery. The expression of the gene for C/EBPbeta is markedly induced in the livers of C/EBPalpha-/- mice within 2 h after the administration of Bt2cAMP. C/EBPbeta-/- mice injected at 20 days of fetal life with Bt2cAMP have a normal pattern of induction of hepatic PEPCK mRNA. In C/EBPbeta-/- mice with phenotype B, the administration of Bt2cAMP immediately after delivery induces PEPCK mRNA, causes the mobilization of hepatic glycogen, and maintains normal glucose homeostasis for up to 4 h (duration of the experiment). We conclude that C/EBPalpha is required for the cAMP induction of PEPCK gene expression in the liver and that C/EBPbeta can compensate for the loss of C/EBPalpha if its concentration is induced to appropriate levels.

Animals↗

Compliance to naltrexone treatment after ultra-rapid opiate detoxification: an open label naturalistic study.

Studies have found that naltrexone, a long-acting opiate antagonist, owing to poor patient compliance, is of limited value in preventing relapse. The current study investigates compliance with a 9-month course of naltrexone (25-50 mg daily) given with counseling after ultra-rapid opiate detoxification which uses clonidine and naltrexone under general anesthesia. Eighty-three of 113 randomly selected patients (out of 640), who were detoxified more than 1 year prior (average 1.5 years), responded to phone interviews. Phone questionnaire asked about patients' compliance with naltrexone, counseling and drug use since detoxification. Similar interviews were also conducted with patients' significant other. Non-relapse patients (n = 47, 57%) took naltrexone an average of 2 months longer than did relapse patients (n = 36, 43%). About half of the non-relapse patients completed at least 5 months of naltrexone, 30% completed at least 7 months and about 20% completed 9 months. Fifty-five percent of the relapse patients stopped using naltrexone by the end of the 3rd month, and by the end of 7th month 10% continued to take it. After the first 2 months the decline in naltrexone compliance was about the same for relapse and non-relapse patients. These results are more encouraging about the use of naltrexone for relapse prevention than previous studies. This method of using naltrexone should be further tested in prospective random assignment controlled studies.

Anesthesia, General↗

Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients.

BACKGROUND: Short-acting calcium antagonists may increase coronary artery morbidity, mortality, and non-cardiovascular complications in hypertensive patients. We assessed whether this association was also true for long-acting calcium antagonists. METHODS: We did a case-control study, which was nested within a systematic hypertension control programme for a prospective cohort of 4350 people (first seen 1981-94). Cases (n = 189) were hypertensive patients who had had a first cardiovascular event, including all cardiovascular deaths and hospitalisations, between 1989 and 1995. Controls (n = 189) were individually matched to cases for sex, ethnic origin, age, type of previous antihypertensive treatment, year of entry into the study, and length of follow-up. We collected data on any prescribed drug regimen that was being taken on the event data for cases and on the same date for matched controls. Calcium antagonists were classified by duration of action. FINDINGS: Compared with those on beta-blocker monotherapy, patients on long-acting calcium antagonists (n = 136) had no increased risk of a cardiovascular event (adjusted odds ratio 0.76 [95% CI 0.41-1.43]), whereas patients on short-acting calcium antagonists (n = 27) were at significantly greater risk (adjusted odds ratio 3.88 [1.15-13.11], p = 0.029). Among 38 matched pairs who were both on calcium antagonists, the adjusted risk ratio for short-acting versus long-acting was 8.56 (1.88-38.97), p < 0.01. INTERPRETATION: Long-acting and short-acting calcium antagonists differ in cardiovascular outcomes. Consistent with earlier findings, the use of short-acting calcium antagonists was associated with increased risk of a cardiovascular event. This finding highlights the need to complete on-going clinical trials so that the relative cardiovascular impact of various antihypertensive agents can be assessed.

Antihypertensive Agents↗

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.

Abortion, Habitual↗

Anorectal malignant melanoma. A clinicopathologic study, including immunohistochemistry and DNA flow cytometry.

BACKGROUND: Anorectal malignant melanoma is a rare tumor with an extremely poor prognosis. DNA flow cytometric study as well as detailed immunohistochemical study have not been reported previously. METHODS: Eighteen cases of anorectal melanoma were studied, including immunohistology for melanoma markers and epithelial markers and DNA flow cytometric study of paraffin blocks. RESULTS: Most patients were Ashkenazi Jews, compared with Sephardi Jews and Arabs. Of the 17 patients followed, 14 died of disease at 4-39 months from presentation. Three patients were alive with disease at 12, 53, and 72 months of follow-up. Tumor thickness ranged from 3-35 mm (mean, 12.8 mm). The 2 long term survivors had tumor thickness < or = 7 mm. No correlation was found between the mode of primary surgical treatment (8 patients: abdominoperineal resection; 10 patients: local excision) and outcome. Vimentin, HMB-45, and S-100 protein stainings were positive in 18, 17, and 15 tumors, respectively. Polyclonal carcinoembryonic antigen (CEA), broad-spectrum cytokeratin, epithelial membrane antigen, monoclonal CEA, and TAG-72 (B72.3) stainings were positive in 13, 3 (only focal and rare staining), 2, 0, and 0 tumors, respectively. Thirteen tumors had adequate material for DNA analysis, and all were DNA aneuploid. S-phase fraction could be assessed in 11 tumors and ranged from 7.7-24% (mean, 14%). An S-phase fraction of < 10% was observed in the 2 long term survivors. CONCLUSIONS: Anorectal melanoma in this study carried a grave prognosis. The frequent staining for polyclonal CEA (with negative monoclonal CEA staining) was probably due to nonspecific cross-reacting antigens. The occasional staining for epithelial markers warrants a comprehensive immunohistochemical study to ensure a correct diagnosis, especially in small biopsies of amelanotic undifferentiated tumors that lack junctional changes. The aneuploidy of all tested tumors reflected their highly malignant behavior. A trend toward longer survival was observed in patients with thin tumors and an S-phase fraction of < 10%. However, due to the small number of survivors, the latter observation should be further tested in a larger scale series.

Adult↗

Myoblastomatoid carcinoma of the breast: an unusual variant of apocrine carcinoma: report of a case with fine-needle aspiration cytology and immunohistochemical study.

Fine-needle aspiration cytology, immunohistochemistry, and histopathologic findings are described in a case of myoblastomatoid carcinoma of the breast. The aspirate contained many small and large clusters of cohesive atypical cells with abundant foamy-to-granular cytoplasm and nuclei that show moderate pleomorphism. These tumors can be easily misinterpreted as either fibrohistiocytic or myoblastomatoid (granular cell) tumors, and by using immunohistochemical stains, the epithelial origin can be elucidated. This case report provides the first description of the fine-needle aspiration cytomorphology of this distinctive variant of apocrine carcinoma.

Aged↗

High affinity presentation of an autoantigenic peptide in type I diabetes by an HLA class II protein encoded in a haplotype protecting from disease.

Polymorphism of the genes coding for the human histocompatibility leukocyte antigen class II DR and DQ molecules makes the single largest genetic contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM) and can be associated with highly elevated as well as decreased disease frequency. The mechanism of IDDM risk modification by HLA polymorphism is likely to involve differential presentation of autoantigenic peptides by HLA class II proteins. We have generated T cell lines (TCL) with specificity for the IDDM autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two patients carrying HLA class II alleles associated with distinct risk of IDDM (DRB1*0101/0401 and 1302/1501). For both patients, TCL generated at various time points all recognized single epitopes mapped as GAD 88-99 and 248-257, respectively. These epitopes are presented by the DRB1*0101 and DRB5*0101, HLA class II molecules associated with a moderately elevated risk of IDDM, or carried in a strongly protective haplotype, respectively. In an HLA/peptide binding assay, epitope GAD 248-257 was shown to possess high affinity for DRB5*0101. This epitope overlaps with a central GAD peptide binding to the high risk allele DQB1*0302 and containing a Coxsackie P2C-identical mimicry sequence, raising the possibility of competition of DRB5*0101 and DQB1*0302 for binding of a central GAD65 fragment.

Adult↗

Inositol has behavioral effects with adaptation after chronic administration.

Inositol is a simple dietary polyol that serves as a precursor in important second messenger systems. Inositol in pharmacological doses has been reported recently to be therapeutic in depression, panic disorder and obsessive compulsive disorder. We hereby report effects of inositol on the elevated plus maze model of anxiety. These results should allow development of new inositol analogs that could expand psychoactive drug development possibilities via second messenger manipulation.

Adaptation, Psychological↗

bcl-2 protein expression in astrocytomas in relation to patient survival and p53 gene status.

bcl-2 protein expression was characterized in a series of 58 astrocytomas from 21 pediatric and 37 adult patients. As part of a continuing attempt to define relevant prognostic factors which may predict clinical outcome, we have determined the impact of bcl-2 accumulation in malignant astrocytes on the length of patient survival. Aberrant overexpression of bcl-2 protein in tumor cells was detected in 57% (12 of 21) of pediatric and 73% (27 of 37) of the adult cases. Among pediatric patients, the median survival in months showed no relationship with the incidence of bcl-2-positive tumors. Among the adult patients, a favorable prognostic indicator was low-tumor grade (P = 0.05). bcl-2-positive tumors occurred with similar frequencies in WHO grades III and IV of malignancy. When bcl-2 expression in tumor cells was tested as a variable to predict for patient survival, the 6 patients without bcl-2 expression among 23 adult patients with grade IV tumors had a shorter median survival. The same 58 tumors had been previously analyzed for alterations of p53:4 pediatric and 16 adult tumors had p53 gene mutations. There was no significant difference in median survival related to p53 gene status. There was no relationship between bcl-2 expression and p53 gene status: approximately equal numbers of tumors with either wild-type or mutant p53 were bcl-2 negative or bcl-2 positive. bcl-2 expression is high (40-100%) among other tumors of the central nervous system which also show low malignant potential. Up-regulation of bcl-2 in malignant astrocytes or constitutive expression in some tumor types may be a factor leading to a more favorable clinical outcome.

Adolescent↗

Prospective comparison of H&E, Giemsa, and Genta stains for the diagnosis of Helicobacter pylori.

BACKGROUND: H. pylori is more easily visualized with special stains than with H&E, but this adds time and expense to the diagnostic workup. We sought to determine if the diagnostic accuracy was improved with special stains. METHODS: One hundred-one patients had two "jumbo" biopsies taken from the gastric antrum and two from the body for examination with H&E, Genta, and Giemsa stains. Four separate biopsy specimens were also taken from the antrum and the body for culture and for three types of rapid urease test, and 13C-urea breath tests were also performed. Mixed, coded biopsies were assessed for H. pylori, and density was scored from 0 to 4. A case was considered positive for H. pylori if culture was positive, two rapid urease tests and a urea breath test were positive, or two different stains were positive. Biopsy specimens were excluded from analysis if the slides were missing or there was inadequate tissue for review, or if the specimen showed a lack of staining. RESULTS: Fifty-two (13%) of 404 specimens were excluded because of a poor Genta stain. Sensitivities were comparable for the three stains (H&E, 92%; Giemsa, 88%; Genta, 91%), while H&E specificity (89%) was significantly lower than that of the special stains (98%). Sensitivity for all three stains was significantly lower at low (grade 0 to 1) H. pylori density than at high (grade 2 to 4) density (H&E, 70% vs 98%; Giemsa, 64% vs 96%; Genta, 66% vs 97%), and 20 of 22 false positives were grade 1. CONCLUSIONS: The sensitivities of H&E and special stains are comparable at around 90%, but the specificity of H&E is significantly lower. The Giemsa stain appears to be the preferred stain for H. pylori diagnosis on the basis of its good sensitivity, excellent specificity, and lack of technical difficulty in preparation. However, H&E provides excellent accuracy when more than minimal (grade 1) H. pylori density is present.

Adult↗

Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients.

To determine whether pretreatment plasma renin activity (PRA), without accompanying 24-h urine sodium, can predict myocardial infarction (MI), the PRA levels of 2,902 hypertensive patients [white (38%), male (65%), median age 55 years], with mean entry blood pressure (BP) of 150/97 mm Hg were examined. During an average 3.6 years follow-up (87% > or = 9 months), there were 55 MIs, 21 strokes, and 16 other cardiovascular disease (CVD) deaths. Classification of PRA levels into 3 renin strata [high (H) PRA > or = 4.5 (n = 354), normal (N) 0.75 to 4.49 (n = 1,622), and low (L) < 0.75 (n = 926) ng/mL/h] yielded subgroups that did not differ in LVH (9% v 11%) or smoking prevalence (26% v 25%) but high versus low PRA subjects included more aged < 55 years (64% v 53%); white (49% v 25%); men (79% v 52%); cholesterol > or = 6.3 mmol/L (33% v 25%); all P values < .01. MI rates per 1,000/year were H: 9.3, N: 5.5, L: 2.5 (H v L, RR = 3.8, 95% CI: 1.7 to 8.4). A similar relationship was seen with total CVD (H: 12.5, N: 9.3, L: 5.2; RR = 2.4, 95% CI: 1.3 to 4.5) and all-cause mortality (H: 7.0, N: 6.2, L: 2.5; RR = 2.8, 95% CI: 1.2 to 6.8) but not CVA (H: 1.6, N: 2.0, L: 1.9). In a Cox survival analysis only renin, age, sex, smoking, LVH, and cholesterol were significantly (P < .02) related to MI occurrence. There was, for every 2 unit increase in PRA, an overall 25% increase in MI incidence. Among hypertensive subjects, PRA level (without urine sodium), is independently and directly associated with the incidence of MI.

Black People↗

Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects.

Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction.

Adult↗

Endoscopic methods for the diagnosis of Helicobacter pylori.

This article reviews endoscopic methods for the diagnosis of Helicobacter pylori. At the time of endoscopy certain findings (gastroduodenal ulceration and/or antral nodularity) may be highly suggestive of H. pylori infection. Endoscopic acquisition of gastric biopsies, however, leads to a definitive diagnosis of infection on the basis of both direct and indirect tests. Direct tests include culture and histological detection (considered the gold standard). There are a variety of stains available for the detection of H. pylori; their choice is influenced by local expertise and the clinical situation. If at least three biopsies are obtained from non-adjacent gastric sites, incorrect assessment of H. pylori status should be rare. Indirect methods utilize the detection of urease. The three biopsy rapid urease tests commercially available in the USA have similar performance characteristics, except that two are gel tests requiring up to 24 h to read, while one is a strip test which is read up to 1 h. Specificity is excellent for these tests, while sensitivity is more variable. Rapid urease tests are the endoscopic tests of choice for initial evaluation due to their low cost.

Anti-Ulcer Agents↗

Evaluation of a nurse specialist anticoagulant service.

Safe levels of anticoagulation are normally considered to be achieved if patients are maintained within their therapeutic international normalized ratio (INR) range for 70% or more time, but evidence in the United Kingdom suggests that this is often not attained. Recently, alternative models in the management of out-patient anticoagulation have been investigated with favourable results. We report on a study which compared a consultant anticoagulant service (CAS) with a nurse specialist service (NSAS). A sequential design was used with data collected on the consultant run service (CAS), followed by similar data on a NSAS over two 6 month periods. Two patient groups were recruited: those newly referred (group A) and those on long-term treatment (group B). Outcomes were the proportion of time patients spent within INR range, documentation of relevant clinical details, number of drugs taken which may adversely interact with and/or inhibit haemostatic function and patient knowledge. The results indicate that the NSAS was as good as the CAS in maintaining therapeutic control and better at documenting relevant clinical details in reducing the number of drugs taken which may adversely interact with and/or inhibit haemostatic function and in improving some aspects of patient knowledge.

Adult↗

Urinary sodium excretion and myocardial infarction in hypertensive patients: a prospective cohort study.

Reduced-sodium diets are frequently recommended for hypertensive patients. To determine the relation of sodium intake to subsequent cardiovascular disease, 24-h urinary excretion of sodium, potassium, and creatinine and plasma renin activity (PRA) were measured in 2937 mildly and moderately hypertensive patients unmedicated for > or = 3-4 wk. Morbidity and mortality in these treated subjects were ascertained. Subjects were stratified by sex-specific quartiles of urinary sodium excretion; race, cardiovascular status, and blood pressure before and during treatment were similar for each stratum. Patients with lower urinary sodium excretion were thinner, excreted less potassium, and had higher PRA. During an average 3.8-y follow-up, 55 myocardial infarctions (MIs) occurred. Incidence of MIs and urinary sodium excretion were inversely associated in the total population and in males but not in females. In males, age- and race-adjusted MI incidence in the lowest compared with the highest quartile of urinary sodium excretion was 11.5 compared with 2.5 (RR: 4.3; 95% CI: 1.7, 10.6). No association was observed between mortality from causes other than cardiovascular disease (n = 11) and urinary sodium excretion. There was a significant linear trend in proportions of MI by quartile of urinary sodium excretion, with a breakpoint after the lowest quartile. In Cox multivariate analysis, the logarithm of PRA, age, systolic blood pressure, and cholesterol as continuous variables, as well as left ventricular hypertrophy and smoking, had a direct association and urinary sodium excretion an inverse, independent association (P = 0.036) with incidence of MI.

Cardiovascular Diseases↗