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Biomedical subjects

M C Cohen

Publications and source records attributed to M C Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Aneuploid nucleomegaly of bronchial cells in ataxia-telangiectasia: cytologic recognition in bronchial brushings.

Ataxia-telangiectasia (AT) is an autosomal recessive disorder of childhood onset characterized by cerebellar ataxia and cutaneous and conjunctival telangiectasias, which affects many systems and organs. One histologic feature of AT is the presence of enlarged dystrophic nuclei, predominantly in satellite cells of sympathetic ganglia and dorsal roots. This paper describes the recognition of nucleomegaly of respiratory cells in bronchial brushings of a 9-year-old patient with AT. The enlarged nuclei displayed smooth nuclear contour, coarse and clumped chromatin granules, and one or two conspicuous nucleoli. The average size was 0.1015 mm in the AT case and 0.0573 mm in control cells. Ploidy analysis demonstrated an aneuploid population of cells with a DNA index of 1.31 and a S-G2M fase of 4.48% in the AT, while the control nuclei showed normal diploid values. To our knowledge, this is the first report of a description of aneuploid nucleomegaly of bronchial cells detected in bronchial smears from a patient with AT. Given that malignant transformations are usually preceded by ploidy alterations, it seems likely that the presence of an aneuploid cell population probably correlates with the increased cancer risk observed in AT patients. Cytopathologists must bear in mind these morphologic features of aneuploid nucleomegaly exhibited by certain cell populations when examining a smear from AT patients. Moreover, this finding may even represent a clue for diagnosis of AT in cases in which the disease has gone unrecognized.

Aneuploidy↗
PubMed1997

Expert opinion regarding indications for coronary angiography before noncardiac surgery.

Whether to perform coronary angiography on the basis of preoperative noninvasive cardiac testing remains a difficult decision. We hypothesized that there are noninvasive test results for which experts have general agreement about the indication for preoperative coronary angiography. We asked 30 experts (24 in specific diagnostic tests and six in clinical cardiology) to comment on statements regarding hypothetical noninvasive test results. There was agreement that catheterization should be performed for (1) exercise electrocardiographic ischemia with a blood pressure drop > 10 mm Hg, (2) stress perfusion scan reversibility in one half or more of single-photon emission computed tomographic slices, and (3) stress echo ischemia in more than five segments, two or more coronary artery zones, or four left anterior descending coronary artery segments. Therefore coronary angiography should be performed for results of noninvasive tests that indicate large zones of myocardial ischemia and not for limited ischemia or test abnormalities without other significant findings.

Cardiac Catheterization↗
PubMed1997

Safety of MR imaging in patients who have retained metallic materials after cardiac surgery.

OBJECTIVE: Epicardial pacing wires retained in patients who undergo cardiac surgery are thought to be a relative contraindication to MR imaging. However, to our knowledge no published evidence supports this belief. Because other metallic materials retained after cardiac surgery might represent a hazard to patients who undergo MR imaging, we sought to determine the safety of such imaging. SUBJECTS AND METHODS: We examined 200 patients who underwent MR imaging at 1 or 1.5 T after cardiac surgery. Eighty-one were examined with ECG monitoring. The presence of temporary epicardial pacing wires, prosthetic valves, and other metal materials was confirmed by chest radiography. RESULTS: Of the 200 patients reviewed, all had postoperative metallic material visible on chest radiographs. Temporary epicardial pacing wire, cut short at the skin, was seen in 51 patients. Of the 81 patients examined with ECG monitoring, we found that MR imaging produced no changes from baseline ECG rhythms. None of the 200 patients reported symptoms suggesting arrhythmia or other cardiac dysfunction during MR imaging. CONCLUSION: MR imaging can be performed safely in patients who have undergone cardiac surgery and have retained metallic material, including valve replacements and temporary epicardial pacing wires cut short at the skin. MR imaging of patients with pacemakers was not evaluated, and we recommend that pacemakers remain a contraindication to MR imaging.

Cardiac Surgical Procedures↗
PubMed1996

Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1,081 vascular surgical candidates.

OBJECTIVES: This study sought to develop and validate a Bayesian risk prediction model for vascular surgery candidates. BACKGROUND: Patients who require surgical treatment of peripheral vascular disease are at increased risk of perioperative cardiac morbidity and mortality. Existing prediction models tend to underestimate risk in vascular surgery candidates. METHODS: The cohort comprised 1,081 consecutive vascular surgery candidates at five medical centers. Of these, 567 patients from two centers ("training" set) were used to develop the model, and 514 patients from three centers were used to validate it ("validation" set). Risk scores were developed using logistic regression for clinical variables: advanced age (>70 years), angina, history of myocardial infarction, diabetes mellitus, history of congestive heart failure and prior coronary revascularization. A second model was developed from dipyridamole-thallium predictors of myocardial infarction (i.e., fixed and reversible myocardial defects and ST changes). Model performance was assessed by comparing observed event rates with risk estimates and by performing receiver-operating characteristic curve (ROC) analysis. RESULTS: The postoperative cardiac event rate was 8% for both sets. Prognostic accuracy (i.e., ROC area) was 74 +/- 3% (mean +/- SD) for the clinical and 81 +/- 3% for the clinical and dipyridamole-thallium models. Among the validation sets, areas were 74 +/- 9%, 72 +/- 7% and 76 +/- 5% for each center. Observed and estimated rates were comparable for both sets. By the clinical model, the observed rates were 3%, 8% and 18% for patients classified as low, moderate and high risk by clinical factors (p<0.0001). The addition of dipyridamole-thallium data reclassified >80% of the moderate risk patients into low (3%) and high (19%) risk categories (p<0.0001) but provided no stratification for patients classified as low or high risk according to the clinical model. CONCLUSIONS: Simple clinical markers, weighted according to prognostic impact, will reliably stratify risk in vascular surgery candidates referred for dipyridamole-thallium testing, thus obviating the need for the more expensive testing. Our prediction model retains its prognostic accuracy when applied to the validation sets and can reliably estimate risk in this group.

Aged↗
PubMed1996

A new method for isolation of cardiac myocytes by percutaneous endomyocardial biopsy.

The objective of this study was to demonstrate the feasibility of isolating viable canine cardiac myocytes from percutaneous right ventricular endomyocardial biopsy specimens. Although histologic data can be obtained from percutaneous endomyocardial biopsies, this approach has not been used as a source of viable cells for evaluating pathological conditions. Study of isolated viable myocytes may provide insight into the electrical, biochemical, and physiologic functions of the heart. Using a standard 8F sheath, a 5F bioptome was introduced via the right femoral vein and advanced to the right ventricle, where 85 biopsies were obtained from 8 mongrel dogs. An average of six biopsy specimens were pooled for processing to provide adequate tissue substrate. This resulted in 14 groups of specimens which were then processed to isolate individual myocytes. Viable myocytes were striated, rod-shaped, and excluded trypan blue dye. Nonviable myocytes were rounded, had no cross-striations, and did stain with trypan blue. Partially-injured myocytes contracted spontaneously and had a region of loss of cross-striations. The average number of viable cells recovered per group of pooled specimens was 1.8 x 10(4) (1.8 x 10(3) cells/mg of tissue). The greatest yield of viable myocytes recovered was 8.0 x 10(4), which represented a viability of 90% by trypan blue dye exclusion and morphological criteria. Percutaneous right ventricular endomyocardial biopsy is a novel method for obtaining viable cardiac myocytes. Its feasibility and utility in humans warrant further investigation.

Animals↗
PubMed1996

Magnetic resonance angiography demonstration of congenital heart disease in adults.

OBJECTIVE: There are limitations when using spin-echo MR imaging to evaluate congenital heart disease (CHD). These include limited ability to detect small shunts, long acquisition times, in-plane or slow flow signal and limited ability to represent complicated three-dimensional (3D) anatomy. However, MR angiography can image flow direction and disturbances, assess function and easily represents 3D anatomy. This may be valuable when evaluating adults with CHD. PATIENTS AND METHODS: Fifty consecutive adult patients were referred for MR evaluation of possible or known CHD using time-of-flight MR angiography. Cine, breathhold and presaturation cine MR angiography were acquired as appropriate, with 3D (MIP) reconstruction of all extracardiac anomalies. RESULTS: Forty-nine patients had a diagnostic examination (one was unsatisfactory because of arrhythmia). Correlation with alternative imaging (TTE = 36, TOE = 13, cardiac catheter = 16) or surgery was available in 39 patients (MR angiography correct in 36 patients). MRA demonstrated or excluded all confirmed congenital valve (12/12), aortic (9/9), and venous (7/7) anomalies. Thirty-five patients were evaluated for shunts. MR angiography detected 31/33 confirmed shunts (shunts present in 26 patients, sensitivity 94%, specificity 95%). Although not used in all cases, spin-echo was unreliable in demonstrating shunts as signal loss in the region of the secundum septum frequently mimicked atrial septal defects (reducing accuracy for excluding intracardiac shunts, specificity 58%). CONCLUSION: MR angiography accurately defines intra- and extra-cardiac anatomy and is superior to spin-echo in detecting or excluding shunts. MR angiography safely and accurately demonstrates many aspects of CHD in adults.

Adult↗
PubMed1996

Magnetic resonance imaging of pericardial constriction: comparison of cine MR angiography and spin-echo techniques.

AIM: Spin-echo (SE) MRI detects pericardial thickening in pericardial constriction but the validity of extrapolating SE criteria to cine MRA imaging has not been tested. Pericardial thickness measured by SE and cine MRA was compared in patients with and without pericardial thickening to determine if the range of pericardial thickness measured by the two techniques is the same. PATIENT AND METHODS: Fourteen patients, investigated for possible pericardial constriction (PC), were compared with 24 subjects without evidence of pericardial disease (controls). Images were acquired using SE and cine MRA. Pericardial thickness was compared with final diagnosis. RESULTS: Pericardial thickening ( > 3.5 mm) by SE detected pericardial constriction: sensitivity = 100% specificity = 96%, kappa = 0.91. Cine MRA had a sensitivity = 86%, specificity = 63%, kappa = 0.33. Maximum differences between SE and cine MRA pericardial thickness ranged from +2.5 mm to -2/7 mm. CONCLUSIONS: Spin-echo identifies pericardial thickening with little overlap between measurements in patients with and without pericardial constriction. Pericardial thickness on cine MRA usually exceeds SE thickness, but with considerable overlap of thickness measurements in patients with and without pericardial constriction. Cine MRA cannot be used alone to diagnose pericardial thickening.

Diagnosis, Differential↗
PubMed1996

Cytokine function: a study in biologic diversity.

Cytokines are a group of hormone-like polypeptide mediators that play a variety of regulatory roles in both host defense and normal and abnormal homeostatic mechanisms. They may he produced by diverse cell types and exert their function on a variety of cells. Their effects (which may be suppressive or enhancing) are on cellular proliferation, differentiation, activation, and motility. In addition, cytokines can exert cytodestructive effects on infectious agents or tumor cells, either directly or by activating cells with cytodestructive potential. Any given cytokine may have many different biologic effects. However, two different cytokines may have similar or identical activities. Cytokines may be classified on the basis of their cell of origin, their spectrum of activity, the category of activity they influence, the cells that are their targets, or on specific features of their ligand-receptor interaction. The mode of action of many of the cytokines involves typical signal transduction events such as protein phosphorylation, and to date there is only limited understanding of the mechanisms that lead to one activity over another when a specific cytokine is involved in a specific biologic reaction. Nevertheless, elucidation of their role in other pathologic processes has provided insight into autoimmune and allergic diseases, as well as a variety of systemic disorders. Because of their broad spectrum of activity, cytokines have been used in a variety of therapeutic settings involving both infectious diseases and neoplasia. As the number of known cytokines continues to grow, it will be increasingly difficult for the non-"cytokinologist" to follow the exponentially expanding literature. Hopefully, this brief review will provide an overview that can serve as a framework for the understanding of this important area of biology and pathology.

Chemokines↗
PubMed1996

Routine perioperative dipyridamole 201Tl imaging in diabetic patients undergoing vascular surgery.

OBJECTIVE: To assess the utility of dipyridamole thallium testing in symptomatic and asymptomatic patients with diabetes undergoing vascular surgery. RESEARCH DESIGN AND METHODS: Dipyridamole 201Tl myocardial scintigraphy was performed preoperatively in 93 consecutive patients with diabetes undergoing peripheral vascular procedures. The utility of clinical and thallium variables in predicting cardiovascular complications was assessed. RESULTS: Two groups of patients were identified: group A (36 patients) without clinical evidence of cardiac disease and group B (57 patients) with clinical evidence of cardiac disease. Dipyridamole thallium scans were abnormal in 21 of 36 (58%) of group A patients compared with 53 of 57 (93%) of group B patients (P < 0.0001). Compared with group B patients with perfusion defects, group A patients with perfusion abnormalities tended to have fewer defects per scan (2.7 +/- 1.5 vs. 3.6 +/- 1.9, P = 0.05). No perioperative cardiac complications occurred in group A patients while perioperative cardiac complications occurred in 9 of 57 (16%, 95% CI 7-28%) group B patients (P = 0.01). For the entire study population, the complication rate was 10%. CONCLUSIONS: Diabetic individuals without clinical markers for coronary artery disease appear to be at low risk for adverse postoperative cardiac events after vascular surgery. Preoperative myocardial perfusion imaging may add little to cardiovascular risk assessment in this subgroup of patients with diabetes.

Aged↗
PubMed1995

Stimulatory effect of ouabain on VCAM-1 and iNOS expression in murine endothelial cells: involvement of NF-kappa B.

Endothelial cells play a pivotal role in the development of atherosclerosis. An 'activated' phenotype of these cells is manifested by signal transduction-dependent expression of genes encoding cytokines, pro- and anticoagulant factors, and cell adhesion molecules. In the current study we examined the effect of ouabain, an inhibitor of Na+/K(+)-ATPase, on the process of endothelial cell activation. We demonstrated that ouabain was able to stimulate VCAM-1 expression and potentiate the effect of IFN-gamma on this process. Moreover, ouabain provided a complementary signal for either TNF or IFN-gamma in inducing iNOS expression. Our data also show, for the first time, that inhibition of Na+/K(+)-ATPase led to activation of the transcription factor, NF-kappa B, which may provide an explanation for the effects of ouabain on endothelial cells.

Animals↗
PubMed1995

Requirements for controlled clinical trials of preoperative cardiovascular risk reduction.

Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed.

Cardiovascular Diseases↗
PubMed1994

Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.

In response to exposure to the inflammatory cytokines tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma), murine brain microvascular endothelial cells (MME) synthesize the cell surface molecule, vascular cell adhesion molecule-1 (VCAM-1), and the intracellular enzyme, inducible nitric oxide synthase (iNOS). However, iNOS synthesis requires the presence of both TNF and IFN-gamma, while VCAM-1 can be induced by either cytokine alone. We examined the induction of VCAM-1 and iNOS under a variety of conditions to better define the regulation of TNF and IFN-gamma signal transduction pathways in MME. We utilized the analysis of steady-state levels of iNOS mRNA as well as the measurement of MME-released NO-EDRF (nitric oxide as an endothelium-derived relaxing factor) activity and accumulation of nitrite in the culture medium to define iNOS expression and activity. VCAM-1 expression was determined by flow cytometric analysis. Our data indicate that low density lipoproteins inhibited cytokine-induced iNOS activity by affecting the steady-state levels of iNOS mRNA. Methylxanthines (caffeine and theophylline) as well as several calcium-mobilizing agents inhibited the expression/activity of both iNOS and VCAM-1 in MME. The effectiveness of these agents was dependent upon the degree of disruption in cell calcium homeostasis during cytokine treatment. Cells which had been pretreated with calcium-modulating drugs and then washed and allowed to return to normal calcium homeostasis showed little to no effect from these agents. In addition, our results suggest that NO produced by iNOS acts as a metabolic switch during inflammation by inhibiting oxidative phosphorylation and forcing vascular endothelial cells to temporarily utilize anaerobic energy metabolism.

Amino Acid Oxidoreductases↗
PubMed1994

Syphilitic placentitis: an immunopathy.

The placentas of eight infants with congenital syphilis were examined by both immunohistochemical and immunofluorescent techniques. Significant IgM, C3 and rheumatoid factor reactivity were observed in all the syphilitic placentas. We postulate that their presence plays an important role in the evolution of the pathological changes.

Antigen-Antibody Complex↗
PubMed1994

Discordance of dual-isotope (hybrid) myocardial perfusion imaging results in patients who have undergone revascularization procedures.

Three hundred twenty-one separate acquisition dual-isotope myocardial perfusion scans were reviewed retrospectively. Studies performed in six patients demonstrated a relative improvement in Tc-99m sestamibi uptake during stress in segments that appeared abnormal on rest injected Tl-201 images. All patients who demonstrated this pattern had a prior history of myocardial infarction and interventional revascularization. While many factors may contribute to this appearance, the authors favor the presence of a patent infarct-related artery as being the most significant.

Angioplasty, Balloon, Coronary↗
PubMed1994

MR imaging of the thoracic aorta: comparison of spin-echo, angiographic, and breath-hold techniques.

PURPOSE: To compare magnetic resonance (MR) angiography and fast MR imaging with spin-echo (SE) and non-MR imaging techniques in examination of the thoracic aorta. MATERIALS AND METHODS: Eighty-nine patients underwent breath-hold or cine MR angiography; SE was used in 67 patients and fast MR imaging in 28. A comparison was made with non-MR imaging (transthoracic echocardiography in 49 patients, transesophageal echocardiography in 18, and arteriography in 33) findings and those from surgery or autopsy (16 patients). RESULTS: MR angiography enabled differentiation of slow flow from thrombus, demonstrated aortic valve anatomy and aortic regurgitation, and accurately showed anatomy with only one error. It demonstrated two communications, flaps, and three branch stenoses better than SE, which produced some artifacts that mimicked thrombus or flaps. Fast MR imaging often produced artifacts or poor image quality (10 of 28 patients). CONCLUSION: Compared with SE MR imaging, MR angiography provides additional useful anatomic and functional information concerning diseases of the thoracic aorta, usually gained only with echocardiography or arteriography.

Aorta, Thoracic↗