Search PubMed⌕ Search

Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 379 records · Page 21Linked to original sources
PubMed1995

Radioisotopic pacemaker: long-term clinical results.

In order to prolong the service life of the generator, the isotopic pacemakers, powered by Pu238, have been developed and implanted since 1970. We report the follow-up of 325 patients (mean age 39 +/- 18 years) implanted with an isotopic pulse generator (Medtronic 9000/9090) between April 1970 and July 1982. The mean follow-up was 12 years (range 6 days to 18.5 years). The generator was highly reliable; the mean value of pacing rate between implantation and last follow-up decreased significantly but no more than 1 beat/min (72.7 vs 71.8 beats/min; P < 0.001) and the pulse width did not change significantly. The actuarial survival of the device was 97% at 18.5 years. During the follow-up period, 122 reoperations were performed in 85 patients: 88 explanations of the entire pacing system and 34 modifications of the lead system. Lead dysfunction accounted for 68% of the 122 reoperations, generator failure for 6%, and miscellaneous reasons for 26%. However, 72% of patients remain free of intervention during the follow-up period and 61 patients (20%) died during this period. Most deaths (52%) were of nonsudden cardiovascular origin, 17% were related to cancer, and 13% to sudden death. After 5, 10, and 18.5 years, 94%, 89%, and 73% of the patients were alive, respectively. No side effect could be attributed to the radioisotope. We conclude that this isotopic pacemaker demonstrated its reliability for long-term cardiac pacing.

Actuarial Analysis↗
PubMed1995

Final height of girls with Turner's syndrome: correlation with karyotype and parental height.

Final height of 75 adults with Turner's syndrome (45 Israeli, 30 Italian), never treated with GH, was examined to see if a relationship with karyotype patterns and parental height existed. Patients were divided into five groups according to their chromosome pattern, as follows: group A = 45, X karyotype (34 patients); group B = mosaicism (11 with karyotype 45,X/46,XX and 7 with karyotype 45,X/46,XY); group C = deletion of all or part of Xp (19 patients); subgroup C1 = 6 with complete deletion of Xp; subgroup C2 = 9 with mosaicism 45,X/46,X,i(Xq); subgroup C3 = 4 with 45,X/46,X,ring(X); group D = deletion of Xq (4 patients); pure gonadal dysgenesis (PGD) group = 9 patients with pure 46,XX gonadal dysgenesis. No statistical difference was noted between the mean height of the two national populations studied (Italian 142.2 +/- 5.7 and Israeli 143.0 +/- 7.2 cm). The mean heights of group D (148.9 cm; range 147-166.2) and the PGD group (156.0 cm; 141-171.5) were found to be significantly higher than those observed in groups A, B and C (p < 0.03, p < 0.02 and p < 0.02, respectively), even though gonadal distinction existed in all five groups. Subgroup C1, where a deletion of the entire Xp segment [46,X,i(Xq)] was present, was found to be the shortest group (median height 134.5; range 131.9-138 cm).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Primary products of break-induced recombination by Escherichia coli RecE pathway.

Alternative models for break-induced recombination predict different distributions of primary products. The double-stranded break-repair model predicts a noncrossover product and equimolar amounts of two crossover products. The one-end pairing model predicts two crossover products, but not necessarily in equimolar amounts, and the single-stranded annealing model predicts deletion of the fragment between the pairing sequences. Depending on the structure of the recombining substrate(s) and the nature of the resectioning step that precedes strand annealing, the single-stranded annealing mechanism would yield only one or both crossover products. We tested these predictions for the RecE recombination pathway of Escherichia coli. Nonreplicating intramolecular recombination substrates with a double-stranded break (DSB) within one copy of a direct repeat were released from chimera lambda phage by in vivo restriction, and the distribution of primary circular recombination products was determined. Noncrossover products were barely detectable, and the molar ratio of the two crossover products was proportional to the length ratio of the homologous ends flanking the DSB. These results suggest an independent pairing of each end with the intact homolog and argue against the double-stranded break-repair model. However, the results do not distinguish alternative pairing mechanisms (strand invasion and strand annealing). The kinetics of heteroduplex formation and heteroduplex strand polarity were investigated. Immediately following the DSB induction, heteroduplex formation was done by pairing the strands ending 3' at the break. A slow accumulation of the complementary heteroduplex made by the pairing of the strands ending 5' at the break (5' heteroduplexes) was observed at a larger stage. The observed bias in heteroduplex strand polarity depended on DSB induction at a specific site. The 5' heteroduplexes may have been generated by reciprocal strand exchange, pairing that is not strand specific, or strand-specific pairing induced at random breaks.

Crossing Over, Genetic↗
PubMed1995

Comparative evaluation of microagglutination test and serum agglutination test as supplementary diagnostic methods for brucellosis.

The diagnosis of brucellosis in cattle and small ruminants requires the use of more than one serological test. The complement fixation test (CFT), the rose bengal test (RBT), and the serum agglutination test (SAT) are among the most useful tests for routine diagnosis. The microagglutination test (MAT) was developed as a simpler and more efficient test than the SAT. The relative efficacy of this test compared with that of the SAT was evaluated by using brucella-free sheep and goats prior to and after vaccination treatment. The specificities of the MAT and the SAT were 100%. Of the ewes and goats with a vaccination history, one ewe, expectedly a negative responder, had reactions in the MAT, the complement fixation test, and the rose bengal test but not in the SAT, suggesting a lower sensitivity of the SAT in this case. The calculated sensitivities of the MAT and the SAT were 93.9%. The agreement between MAT and SAT results from nonresponders was examined by using sera from unvaccinated lambs and kids (95.2% agreement), unvaccinated ewes and goats (84.4%), and ewes and goats with a vaccination history (43.9%). For the latter group higher levels of agglutination units were observed by the MAT than by the SAT in 51.5% of the samples. In testing sera from positive reactors after vaccination neither method was superior (MAT values were greater than SAT values for 23.5% of the samples, and MAT values were less than SAT values for 21.9% of the samples). Comparison of the methods on the individual sample level revealed a significant correlation between the MAT and the SAT (r = 0.96 +/- 0.005; P < 0.001). Since the MAT is simpler to perform than the SAT and can potentially be automated, the inclusion of the MAT as a supplementary test in brucellosis control programs is recommended.

Agglutination Tests↗
PubMed1995

A skeletal muscle-specific enhancer regulated by factors binding to E and CArG boxes is present in the promoter of the mouse myosin light-chain 1A gene.

The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult heart, is one of the first muscle genes to be activated when skeletal as well as cardiac muscles form in the embryo. It is also transcribed in skeletal muscle cell lines at the onset of differentiation. Transient transfection assays of mouse skeletal muscle cell lines with DNA constructs containing MLC1A promoter fragments fused to the chloramphenicol acetyltransferase (CAT) gene show that the first 630 bp of the promoter is sufficient to direct expression of the reporter gene during myotube formation. Two E boxes located at bp -76 and -519 are necessary for this regulation. MyoD and myogenin proteins bind to them as heterodimers with E12 protein and, moreover, transactivate them in cotransfection experiments with the MLC1A promoter in nonmuscle cells. Interestingly, the effect of mutating each E box is less striking in primary cultures than in the C2 or Sol8 muscle cell line. A DNA fragment from bp -36 to -597 confers tissue- and stage-specific activity to the herpes simplex virus thymidine kinase promoter in both orientations, showing that the skeletal muscle-specific regulation of the MLC1A gene is under the control of a muscle-specific enhancer which extends into the proximal promoter region. At bp -89 is a diverged CArG box, CC(A/T)6AG, which binds the serum response factor (SRF) in myotube nuclear extracts, as does the wild-type sequence, CC(A/T)6GG. Both types of CArG box also bind a novel myotube-enriched complex which has contact points with the AT-rich part of the CArG box and adjacent 3' nucleotides. Mutations within the CArG box distinguish between the binding of this complex and binding of SRF; only SRF binding is directly involved in the specific regulation of the MLC1A gene in skeletal muscle cell lines.

Animals↗
PubMed1995

[Morphological study by transesophageal echocardiography and clinical aspects of ruptured chordae tendineae in the elderly].

Ruptured mitral chordae tendinae is a classical complication of myxomatous mitral valves or Barlow's syndrome. This complication is controversial in non-myxomatous mitral valve. Of 91 consecutive patients with mitral valve prolapse examined over an 18 months period by transthoracic and transesophageal echocardiography, 42 (18 women and 24 men) with an average age of 76 +/- 8 years (60-93 years) had ruptured mitral chordae tendinae. The thickness of the anterior mitral leaflet measured at the distal third of the valve by transesophageal echocardiography enabled the identification of two groups of patients; group I: > 3 mm (24 patients), average 4.8 +/- 0.8 mm and group II: < or = 3 mm (18 patients), average 2.6 +/- 0.3 mm. The diameter of the mitral ring and left atrium, the length of the anterior mitral leaflet, the left ventricular end diastolic dimensions and fractional shortening, were measured by transthoracic 2D echocardiography (mitral ring) and M mode (other parameters). Ruptured chordae were detected in only 13 cases (31%) by transthoracic echocardiography; 38% were asymptomatic and a chance finding at transesophageal echocardiography. No significant difference was observed between the two groups with respect to age, gender presence of hypertension, dimensions of the cardiac chambers, fractional shortening or localisation of the prolapse related to the ruptured chordae. Fifty-eight per cent of patients in group I were in NYHA functional classes 3-4 as compared to 16% in group II (p < 0.02). The size of the left atrium was significantly greater in group I, 51 +/- 8 mm vs 38 +/- 7 mm (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Growth in patients after allogeneic bone marrow transplant for hematological diseases in childhood.

The growth of 66 long-term survivors, transplanted in two centres (Genoa S. Martino and Monza) is reported. Patients were all under age 15 at the time of bone marrow transplantation (mean 9.8 +/- 3.4 years; range 1.07-15 years) with a minimum follow-up of at least 12 months. They were divided into four groups. Group 1: eight patients with severe aplastic anemia (SAA): conditioning included cyclophosphamide (CY) 200 mg/kg only. Group 2: 32 patients with acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML): conditioning included CY 120 mg/kg and 10-12 Gy fractionated total body irradiation (fTBI). Group 3: 20 patients with ALL, who had previously received cranial irradiation; conditioning included CY 120 mg/kg and fTBI with an additional testicular irradiation (4 Gy). Group 4: six patients with chronic myeloid leukemia (CML) and AML; conditioning included CY 200 mg/kg and busulfan (BU) 16 mg/kg. Group was impaired in all four groups, including the unirradiated groups (-0.2 +/- 0.7 and -0.5 +/- 0.6 delta-SDS in groups I and 4, respectively). Growth impairment-SDS was statistically significant in the two irradiated groups (-0.7 +/- 1.0 and -0.9 +/- 1.0 delta-SDS in groups 2 and 3, respectively), more marked in patients who had had previous cranial irradiation. Chronic graft-versus-host disease and its treatment were not found to have a major effect on growth.

Acute Disease↗
PubMed1995

[Diabetic cardiomyopathy].

Type I and type II diabetes is associated with increased cardiovascular complications, the most common of which are ischaemic cardiomyopathy and left ventricular dysfunction. The existence of an independent disease, diabetic cardiomyopathy, was suggested by initial anatomic studies, experimental models, and, more recently, by epidemiological studies. The exact cause of this ventricular dysfunction is not known: several mechanisms have been proposed, such as metabolic abnormalities of glucose transport, cellular overload in fatty acid metabolites, alteration of calcium uptake by the sarcoplasmic reticulum leading to cellular calcium overload, coronary microangiopathy, structural collagen abnormalities, interstitial and perivascular fibrosis or the presence of an autonomic neuropathy. The condition is characterised by abnormal left ventricular filling suggesting poor compliance or prolongation of left ventricular relaxation. Left ventricular systolic function is usually normal at rest but abnormally decreased on effort. The value of strict metabolic control and the place of drug therapy, especially calcium antagonists which oppose cellular calcium overload, has yet to be established. The natural history of diabetic cardiomyopathy should be defined by clinical studies taking care to differentiate it from the cardiovascular consequences of hypertension or obesity which aggravate or stimulate this condition.

Cardiomyopathies↗
PubMed1995

B-lineage lymphoid blast crisis in juvenile chronic myelogenous leukemia: II. Interleukin-1-mediated autocrine growth regulation of the lymphoblasts.

A pre-B acute lymphoblastic leukemia (ALL) cell line with monosomy 7 was established from a child with juvenile chronic myelogenous leukemia (JCML) in lymphoid blast crisis. Analysis of the growth properties of the cell line, termed 'W1' showed an interleukin-1 (IL-1) mediated autocrine pattern of cell proliferation with the following features: W1 colony growth without added growth factor was density-dependent and colony growth was augmented with serum-free autologous cell culture supernatant; exogenous IL-1 beta had a growth-promoting effect on W1 colony numbers when cells were seeded at low density; W1 cells constitutively expressed mRNA for IL-1 beta, and high levels of IL-1 beta were measured in W1 cell lysates; anti-IL-1 beta antibodies as well as IL-1 receptor antagonist markedly suppressed W1 colony growth when either was added to cultures of cells seeded without growth factors at low density; anti-GM-CSF antibodies and anti-IL-3 antibodies had no inhibitory effect on W1 colony growth. Whereas W1 colony growth was also augmented by adding IL-3, IL-4, IL-6, IL-7, GM-CSF, Steel factor and erythropoietin individually to the cultures, W1 cells did not constitutively express mRNA for any of these cytokines. W1 colony growth was markedly suppressed by exogenous TNF-alpha which contrasts sharply with the autocrine growth promoting effect of TNF-alpha on myelomonocytic elements of JCML in 'chronic' phase. The inhibitory effect of TNF-alpha on W1 cells was not due to downregulation of IL-1 production. The IL-1-dependent growth of W1 cells appeared to be unique because none of five other pre-B lineage ALL cell lines established as controls showed an autocrine growth loop via IL-1. W1 cells provide a valuable opportunity to examine the relationship of monosomy 7, B-lineage acute lymphoblastic leukemia, aberrant genetic expression of cytokines and their receptors, and IL-1 mediated autocrine cell growth in cancer.

B-Lymphocytes↗
PubMed1995

[Transesophageal echocardiography in cardiac and paracardiac tumors. A multicenter study].

A multicentre study was undertaken to determine the diagnostic value of transoesophageal echocardiography (TOE) in tumours of the heart and pericardium. Forty-five cases were recensed: 24 myxomas, 1 fibroma, 1 hydatid cyst, 2 lymphomas, 3 sarcomas, 1 pleuropericardial cyst, 1 branchogenic cyst and 12 cardiac metastases. The diagnosis was made in all 45 cases by TOE but only in 35 cases by conventional transthoracic echocardiography which failed to recognise 2 myxomas, 1 hydatid cyst, 1 sarcoma, 2 paracardiac cysts and 4 cardiac metastases. The site of the tumour was identified 45 times by TOE compared with only 12 times by transthoracic echocardiography. However, the anatomical investigation of mediastinal tumours requires complementary computerised tomography. Moreover, TOE, like all other imaging techniques, is unable to predict the benign or malignant nature of the tumour, 1 leiomyosarcoma having been confused with a myxoma.

Adult↗
PubMed1995

Comparison of rectal to intranasal administration of midazolam for premedication of children.

Sixty children aged 3 to 9, undergoing minor surgical procedures, were studied to compare 0.5 mg/kg intranasal with 0.5 mg/kg rectal midazolam as a premedication. The children were evaluated for their ability to tolerate the medication, preanesthetic sedation, and alertness after anesthesia. Both premedication routes were equally effective in sedating the children. In both groups, a significant loss of effectiveness was noted if induction of the anesthesia began more than 30 minutes after administration of the medication (p < 0.0003). Rectal midazolam was much better tolerated by the children than the intranasal route (30 versus 3, p < 0.0001). We advocate the rectal over the intranasal route for premedication with midazolam in children, and anesthetic induction should occur no more than 30 minutes after administration of premedication.

Administration, Intranasal↗
PubMed1994

In vitro effects of brain derived neurotrophic factor released from microspheres.

The principal objective of these studies was to microencapsulate brain derived neurotrophic factor (BDNF) and to test its biological effects in vitro. Two types of microspheres with BDNF were prepared using biodegradable polymers: chitosan and poly-(L-lactic acid):poly-(L-glycolic acid). Depending on the procedure, sizes ranged from 1 micron to 1 mm as determined by an image analysis system. The biological assays confirmed that the released BDNF remains biologically active in vitro. Microencapsulation of BDNF and other trophic factors may represent a viable alternative to currently employed delivery systems in vivo and holds potential for eventual therapy of neurodegenerative disorders, in particular for peripheral neuropathies and CNS disorders where supplementation of neurotrophins retards or even prevents neural degeneration.

Animals↗
PubMed1994

Atherosclerotic disease of the aortic arch and the risk of ischemic stroke.

BACKGROUND: Atherosclerotic disease of the aortic arch has been suspected to be a potential source of cerebral emboli. We conducted a study to quantify the risk of ischemic stroke associated with atherosclerotic disease of the aortic arch. METHODS: Using transesophageal echocardiography, we performed a prospective case-control study of the frequency and thickness of atherosclerotic plaques in the ascending aorta and proximal arch in 250 consecutive patients admitted to the hospital with ischemic stroke and 250 consecutive controls, all over the age of 60 years. RESULTS: Atherosclerotic plaques > or = mm in thickness were found in 14.4 percent of the patients but in only 2 percent of the controls. After adjustment for atherosclerotic risk factors, the odds ratio for ischemic stroke among patients with such plaques was 9.1 (95 percent confidence interval, 3.3 to 25.2; P < 0.001). Among the 78 patients who had brain infarcts with no obvious cause, 28.2 percent had plaques > or = 4 mm in thickness, as compared with 8.1 percent of the 172 patients who had infarcts whose possible or likely causes were known (odds ratio, 4.7; 95 percent confidence interval, 2.2 to 10.1; P < 0.001). Plaques of > or = 4 mm in the aortic arch were not associated with the presence of atrial fibrillation or stenosis of the extracranial internal carotid artery. In contrast, plaques that were 1 to 3.9 mm thick were frequently associated with carotid stenosis of > or = 70 percent. CONCLUSIONS: These results indicate a strong, independent association between atherosclerotic disease of the aortic arch and the risk of ischemic stroke. The association was particularly strong with thick plaques. Atherosclerotic disease of the aortic arch should be regarded as a risk factor for ischemic stroke and as a possible source of cerebral emboli.

Aged↗
PubMed1994

Platelet serotonin transporter in drug-naive migrainous children and adolescents.

Platelet [3H]imipramine binding was measured in 17 children and adolescents suffering from common (n = 10) and classical (n = 7) migraine and 10 healthy control subjects. All patients had more than a 1-year history of the disease and suffered at least one attack per month. All subjects had been drug-free for at least 4 weeks prior to the study and had never been treated with drugs active at the serotonergic system. An increased density in [3H]imipramine binding sites was detected in the migraine patients (+51%; p < 0.05). The increase in maximal binding was more prominent in the classical migraine group (+63%) than in the common migraine group (+43%). These results disagree with previous studies that reported decreased platelet imipramine binding in adult migraine patients. The discrepancy may be related to chronicity of drug treatment, long-term duration of disease and comorbidity of depression and anxiety disorders in adult migrainous patients.

Adolescent↗
PubMed1994

Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase.

We have previously described a type of selective T cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency. We show here that STD patients carry a mutation of zap-70, resulting in loss of the activity of this kinase. The thymi of zap-70-/- patients show the presence of CD4+CD8+ cells in the cortex; however, only CD4, not CD8, single-positive cells are present in the medulla. Peripheral CD4+ T cells from the zap-70-/- patients exhibit markedly reduced tyrosine phosphorylation, fail to produce interleukin-2, and do not proliferate in response to T cell receptor stimulation by mitogens or antigens. Thus, Zap-70 kinase appears to be indispensable for the development of CD8 single-positive T cells as well as for signal transduction and function of single-positive CD4 T cells.

Amino Acid Sequence↗
PubMed1994

Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update.

BACKGROUND: We studied three new dose schedules of hepatic arterial infusion of floxuridine (FUDR) and leucovorin and update survival analysis of a previously reported trial using these drugs by hepatic arterial infusion for patients with hepatic metastases from colorectal carcinoma. METHODS: Untreated patients with hepatic metastases from colorectal cancer were treated with three dose schedules: Group D, FUDR (0.3 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day continuous infusion through an implantable hepatic arterial pump alternating with a 4-week rest period; Group E, a lower dose of FUDR (0.25 mg/kg/day) and leucovorin (30 mg/m2/day) as a 14-day infusion alternating with 2 weeks of saline; and Group F, FUDR (0.3 mg/kg/day) with a lower leucovorin dose (15 mg/m2/day) for 2 weeks followed by a 2-week rest. RESULTS: In 42 patients with unresectable hepatic metastases, the complete-plus-partial response rate was 56%, with a median survival of 24.2 months. Complete-plus-partial response rates for groups D, E, and F were 30%, 54%, and 75%, respectively. Twelve percent of the 42 patients developed biliary sclerosis; the percentages of patients per group were 17%, 15%, and 6%, respectively. Updated median survival of the original 24 patients treated with FUDR and leucovorin by hepatic arterial infusion and these 42 new patients (66 total) was 28.8 months. One-, two-, three-, four-, and five-year survival rates were 86%, 62%, 31%, 15%, and 7%, respectively. CONCLUSIONS: Hepatic arterial chemotherapy with FUDR and leucovorin for patients with hepatic metastases from colorectal carcinoma yields a high response rate and 1- and 2-year survivals of 86% and 62%, respectively. Although a lower dose of leucovorin (15 mg/m2) with FUDR produces a high response rate with less toxicity, before larger scale trials are initiated, further investigation is needed to reduce toxicity. A study of hepatic arterial dexamethasone with FUDR and leucovorin has been initiated for this purpose.

Adult↗
PubMed1994

Preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer.

BACKGROUND: A Phase I trial was performed to determine the maximum tolerated dose of concurrent preoperative radiation therapy (5040 cGy) and 2 cycles (bolus daily times 5) of 5-fluorouracil (5-FU) and low-dose leucovorin (LV) (20 mg/m2), followed by surgery and 10 cycles of postoperative 5-FU/LV in patients with primary or recurrent rectal cancer. METHODS: Twenty-four patients were entered into the study. Preoperatively, the initial dose of 5-FU was 325 mg/m2. 5-FU was escalated 50 mg/m2, while the dose of LV and radiation therapy remained constant. Chemotherapy and radiation began concurrently on day 1. The postoperative chemotherapy was not dose escalated; 5-FU, 425 mg/m2, and LV, 20 mg/m2. The median follow-up was 10 months (range, 4-19 months). RESULTS: The resectability rate with negative margins in the 23 patients who underwent surgery was 100%. One patient refused surgery. The pathologic complete response rate was 13% (3 of 23). An additional four patients had negative nodes and a microscopic foci of tumor in the bowel wall. Therefore, the total clinical complete response rate was 30% (7 of 23). The maximum tolerated dose of 5-FU for the preoperative combined modality segment was 375 mg/m2; therefore, the recommended Phase II dose level is 325 mg/m2. The incidence of Grade 3+ toxicity for the 22 patients treated at the recommended 5-FU dose level (325 mg/m2) during the preoperative combined modality segment was as follows: diarrhea, 14%; erythema, 5%; hematologic, 10%; and total, 18%. The median nadir counts were leukocyte count, 3.7 (range, 1.5-5.9); hemoglobin count, 12.2 (range, 10.2-14.3); and platelet count (times 1000), 165 (range, 92-237). CONCLUSIONS: With this regimen, the recommended doses of chemotherapy in the combined modality segment are slightly higher than those recommended in arm 2 of the Intergroup postoperative adjuvant rectal trial 0114. This regimen will serve both as the preoperative arm of the Intergroup randomized trial of preoperative versus postoperative combined modality therapy for resectable rectal cancer (INT R9401) as well as the basis for the combined modality segment of NSABP RO-3.

Adenocarcinoma↗