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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 415 records · Page 23Linked to original sources
PubMed1994

Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts.

PURPOSE: To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas. PATIENTS AND METHODS: 131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy. Seven to 8 days before surgery, patients received 131I-mAbF19 at three dose levels, with at least four patients entered at each level. RESULTS: No toxicity associated with intravenous 131I-mAbF19 administration was observed. Tumor images were obtained on planar and single-photon emission tomography (SPECT) scans in 15 of 17 patients with hepatic metastases, tumor-infiltrated portal lymph nodes, and/or recurrent pelvic disease. The smallest lesion visualized was 1 cm in diameter. The optimal time for tumor imaging was 3 to 5 days after 131I-mAbF19 administration. The use of image registration techniques allowed precise anatomic localization of 131I-mAbF19 accumulation. Immunohistochemical analysis of biopsy tissues showed expression of FAP in the tumor stroma (but not in normal liver) in all patients studied and confirmed that the FAP-positive tumor stromal fibroblasts were interposed between the tumor capillaries and the malignant colon epithelial cells. At the time of surgery, tumor-to-liver ratios up to 21:1 and tumor-to-serum ratios up to 9:1 were obtained. The fraction of the injected 131I-mAbF19 dose per gram tumor (%ID/g tumor) localized to hepatic metastases at the time of surgery ranged from 0.001% to 0.016%. CONCLUSION: The FAP tumor fibroblast antigen is highly expressed in primary and metastatic colorectal carcinomas and shows limited expression in normal adult tissues. This highly selective expression pattern allows imaging of colorectal carcinoma lesions as small as 1 cm in diameter on 131I-mAbF19 scans. Because of the consistent presence of FAP in the stroma of epithelial cancers and the accessibility of FAP-positive tumor stromal fibroblasts to circulating monoclonal antibodies (mAbs), this study suggests possible diagnostic and therapeutic applications of humanized mAbF19 and mAbF19 constructs with novel immune and nonimmune effector functions.

Aged↗
PubMed1994

Transbronchial biopsy in patients with pulmonary eosinophilic granuloma. Comparison with findings on open lung biopsy.

We evaluated the findings on transbronchial biopsy specimens in reference to open lung biopsy specimens from 12 patients with pulmonary eosinophilic granuloma. Features in transbronchial biopsy specimens were further contrasted to those of patients with interstitial fibrosis and nondiagnostic biopsy specimens for localized lesions. Transbronchial biopsy specimens were randomized and graded for histologic features and cellularity. Patients with eosinophilic granuloma had more macrophages (P < .05) but equivalent numbers of eosinophils, neutrophils, and Langerhans' cells compared with those of the other two groups. Only two endoscopic biopsy specimens were histologically diagnostic or highly consistent with eosinophilic granuloma. We conclude that the diagnosis of eosinophilic granuloma is possible on transbronchial biopsy but requires a high index of suspicion. The demonstration of Langerhans' cells by immunohistochemical staining for S100 protein is a useful adjunct. The low diagnostic yield for eosinophilic granuloma on transbronchial biopsy results from inadequate sampling and from the nonspecific appearance of discrete lesions in small tissue samples.

Adult↗
PubMed1994

[Guidelines of the French Society of Cardiology on the training of echocardiographers and the performing of echocardiography].

The considerable advances achieved in the field of echocardiography have made this investigation an essential diagnostic tool. Under the auspices of the French Society of Cardiology, the Working group on Echocardiography publishes its practical recommendations for optimising the training of echocardiographers (theoretical instruction and practical courses) and for performing echocardiography (understanding the clinical problem, referral to previous examinations, necessary recordings and measurements, and appropriate equipment). In the future, these recommendations should be updated to take into account continuing technical improvements and changes in methods of studying cardiac disease by echocardiography.

Cardiology↗
PubMed1994

A randomized trial of early hospital discharge and home follow-up of women having cesarean birth.

OBJECTIVE: To determine the safety, efficacy, and cost savings of early hospital discharge of women delivered by unplanned cesarean delivery. METHODS: Using randomized assignment, 61 postpartum women were discharged from the hospital at the usual time, and 61 were discharged early and had nurse specialist home follow-up care. The latter group received comprehensive discharge planning, instruction, counseling, home visits, and daily on-call availability from the nurse specialists. Both groups were followed from delivery to 8 weeks postpartum. RESULTS: Women who were discharged early and received transitional home care services by clinical nurse specialists were sent home a mean of 30.3 hours earlier than the control group (P < .001). They had significantly greater satisfaction with care, more of their infants had timely immunizations at the end of follow-up, and they had a 29% reduction in health care charges compared to the control group receiving routine care. Although there were no statistically significant differences in maternal and infant rehospitalizations and acute-care visits, there were more maternal rehospitalizations in the control group than in the nurse specialist-followed group (three versus zero). No statistically significant differences were found between the groups in the outcomes of maternal affect and overall functional status. CONCLUSION: Early hospital discharge of women after unplanned cesarean birth, using the model of nurse specialist transitional home care, is safe, feasible, and cost-effective.

Adult↗
PubMed1994

Disorders of the central nervous system.

In this article, we have reviewed the most common CNS abnormalities seen in perinatal medicine. The prognosis in ventriculomegaly is most closely related to the presence or absence of associated anomalies. The current treatment for DWM consists of shunting of either the posterior fossa cyst or lateral ventricles. Facial abnormalities can frequently aid in distinguishing holoprosencephaly from other CNS lesions. Anencephaly is one of the most severe fetal anomalies and is incompatible with life. Spina bifida represents a spectrum of NTDs with a variable outcome depending on the size and location of the defect, as well as the presence of other anomalies.

Central Nervous System Diseases↗
PubMed1994

Hemimegalencephaly: a longitudinal MR study.

An infant with hemimegalencephaly was studied with MR at 5 days and again at 10 months of age. The initial scan showed an abnormally large left cerebral hemisphere. At the age of 10 months, the left cerebral hemisphere was smaller than the right--an apparent left-sided micrencephaly caused by normal growth of the right hemisphere and arrested growth of the left. The age of imaging of a patient with hemimegalencephaly can be important if the correct diagnosis is to be made.

Brain↗
PubMed1994

[Relationship between plasma antioxidants and coronary artery disease].

Plasma concentrations of the antioxidants, vitamin E, beta-carotene and vitamin A were studied. 29 patients in whom at least 70% obstruction of 1 coronary artery was found, and 73 who were normal according to noninvasive tests were compared using multivariable, logistic, regression analysis. The group with coronary disease had significantly lower plasma vitamin E and beta-carotene concentrations as compared with the normal group (means +/- SD: 44.2 +/- 18.3 micrograms/ml vs 50.6 +/- 22.4 and 1.0 +/- 0.5 micrograms/ml vs 1.1, respectively) but plasma vitamin A concentration was not reduced. Decrease in plasma antioxidant vitamin concentrations may be linked to atherogenesis by LDL oxidative modification, which explains the inverse relationship found between the risk of coronary artery disease and plasma antioxidant vitamins.

Antioxidants↗
PubMed1994

[Atherosclerosis of the aortic arch: a possible new source of cerebral embolism].

Atherosclerosis of the aortic arch is common in individuals aged over 60. Plaques are very often ulcerated. The normal healing process results in the regular formation of thrombi on these ulcerations. A mural thrombus can thus be the source of systemic or cerebral emboli. Since the advent of transesophageal echocardiography, it has become possible to detect atherosclerotic plaques of the aortic arch. However, a causal relationship has never been demonstrated and it is possible that they may merely be a marker of atherosclerotic disease. Certain arguments suggest that the aortic arch may be a source of cerebral emboli: the high incidence of aortic mural thrombi and atheroma emboli during aortography or coronary arteriography, or cardiac surgery with extracorporeal circulation requiring cannulation of the aorta. Recent studies have also shown that plaques of the aortic arch are commoner in cases of cerebral infarction of unknown origin than when another potential cause is detected. The natural history of this type of lesion must be studied before any management attitude can be defined. In the present state of knowledge, the only possible advice is antiplatelet treatment and case-by-case consideration of anti-coagulant treatment, in particular in the presence of a mobile thrombus of the aortic arch.

Adult↗
PubMed1994

[Value of transesophageal echocardiography in the cardiovascular assessment of an ischemic cerebral accident of suspected embolic origin].

Transoesophageal echocardiography (TOE) is a new modality of cardiac investigation allowing examination of cardiac structures and anomalies previously inaccessible to ultrasound. TOE is performed under local anaesthesia after fasting the subject for more than 4 hours and after premedication when the patient is admitted to hospital. In the assessment of an ischaemic cerebral vascular accident, TOE may reveal potential sources of emboli such as intracavitary thrombi and tumours (left atrium and left atrial appendage), atherosclerosis of the aortic arch, vegetations. Certain indirect causes may also be more clearly identified: aneurysm of the interatrial septum, patent foramen ovale for which the causal relationship is more difficult to establish. Intra-atrial blood stasis ("spontaneous echo contrast") is perfectly analysed in the form of intra-atrial "smoke" observed in the presence of atrial dilatation, particularly in the presence of atrial fibrillation and mitral valve obstruction (mitral stenosis, valve prosthesis). The indication for TOE in this context is currently under evaluation, particularly in young patients. It is routinely indicated in patients with known heart disease when peripheral embolism is suspected, looking for intracavitary thrombosis, generally not seen on transthoracic echocardiography.

Adult↗
PubMed1993

Accuracy and reproducibility of left ventricular mass measurement by subcostal M-mode echocardiography in hypertensive patients and professional bicyclists.

In some patients, left ventricular (LV) mass cannot be evaluated by M-mode echocardiography because the parasternal long-axis view is not available. The aim of this study was to determine whether the subcostal view obtained by M-mode echocardiography under 2-dimensional guidance allows accurate and reproducible LV mass determination. Using the cube formula, LV mass was calculated, from parasternal and subcostal views in 96 subjects: 73 hypertensives and 23 professional bicyclists, covering a wide range of LV dimensions. M-mode tracings were read by 2 experienced echocardiographers and the interobserver variability was evaluated. With use of the subcostal view, the interobserver reproducibility, expressed as observer 1-observer 2, was excellent: -0.3 +/- 1.3 mm for LV diastolic diameter, -0.1 +/- 1.0 mm for ventricular diastolic septal thickness, 0.2 +/- 0.6 mm for diastolic free wall thickness and 0.03 +/- 16.7 g for LV mass. In 96% of cases, the difference in LV mass between the 2 observers did not exceed 30 g. With use of the parasternal and subcostal approaches, LV mass was not statistically different (202.6 +/- 2.2 g and 206.5 +/- 2.0 g, respectively) and the difference was < 52 g (clinically significant threshold) in 91 of 96 cases. It is concluded that, using the cube formula, LV mass calculation based on the subcostal view was accurate and not statistically different from that provided by the usual parasternal approach.

Adult↗
PubMed1993

Autocrine and paracrine growth control by granulocyte-monocyte colony-stimulating factor of acute lymphoblastic leukemia cells.

Blast colony assays were performed on freshly obtained bone marrow samples from 19 newly diagnosed or relapsed children with acute lymphoblastic leukemia (ALL) of B lineage to determine the effect of added granulocyte-monocyte colony-stimulating factor (GM-CSF). Of the 19 marrow samples tested, 7 responded to GM-CSF with a mean increase in ALL blast colonies of 346%. Blast cells from one of the responders chosen for flow cytometric study showed expression of GM-CSF receptors on 38% of cells. These findings prompted us to establish five ALL cell lines of diverse phenotypes to examine the expression of GM-CSF and GM-CSF receptor genes in human leukemia, and to determine the role of GM-CSF in autocrine and paracrine growth control of ALL cells. One line, termed G2, manifested a GM-CSF-mediated autocrine pattern of cell growth with the following features: G2 blast colony growth in a serum-free system without added growth factor was density dependent; exogenous GM-CSF augmented G2 colony formation when the cells were seeded at low density; G2 cells constitutively expressed mRNA for GM-CSF and GM-CSF receptor; G2 cells also produced and secreted measurable amounts of GM-CSF into cell culture supernatant; and, monoclonal anti-GM-CSF antibodies abolished G2 colony growth when added to cultures with cells seeded at low density without growth factors. Of the other four ALL cell lines, three expressed mRNA for GM-CSF receptor and responded in vitro to added GM-CSF with increased blast colony growth; however, none of these four cell lines expressed mRNA for constitutive production of GM-CSF. A fifth ALL cell line lacked receptors for GM-CSF and did not respond in clonogenic assays to added GM-CSF. Thus, a bioregulator of normal hematopoiesis plays a central role in autocrine growth control of G2 ALL cells, and an important paracrine growth-promoting role in three of four other ALL cell lines.

Cell Division↗
PubMed1993

A pilot study of hepatic artery floxuridine combined with systemic 5-fluorouracil and leucovorin. A potential adjuvant program after resection of colorectal hepatic metastases.

BACKGROUND: Most patients with colorectal carcinoma metastatic to the liver have relapses after surgical resection of hepatic metastases with failures divided equally between hepatic and extrahepatic sites. A pilot study was begun using a regimen combining intrahepatic floxuridine (FUDR) and systemic 5-fluorouracil (5-FU) and leucovorin (LV) to determine its safety and efficacy. METHODS: Because this was a pilot study, 21 patients with unresectable hepatic metastases from colorectal carcinoma were treated to assess the regimen's toxicity. Eight patients had liver metastases that were resected completely; then they received treatment. FUDR was given by hepatic arterial pump through a 14-day continuous infusion at 0.25 mg/kg/day. Systemic therapy consisted of LV 200 mg/m2 and 5-FU 280 mg/m2 using a bolus dose of 5-FU for 5 days with escalation of the 5-FU dose in separate patient cohorts. The maximally tolerated 5-FU dose was 325 mg/m2. RESULTS: The median survival in the 21 unresectable patients was 16 months with a partial response rate of 56% (10 of 18 evaluable patients; 95% confidence interval, 38-79%). The major systemic toxicity was diarrhea, Grade 3 or 4, in 54% of patients being treated in the 4-week regimen and 19%, in the 5-week regimen. The level of hepatic toxicity was similar to that in previous studies using intrahepatic chemotherapy alone, i.e., 48% of patients had a 200% increase in alkaline phosphatase levels and 10% had bilirubin elevations of more than 3.0 mg/dl (one patient had documented biliary sclerosis). All eight patients treated with adjuvant therapy were alive without disease after a median follow-up of 23 months. CONCLUSIONS: Systemic 5-FU and LV can be combined safely with intraarterial FUDR without loss of efficacy or increased biliary toxicity. Eight patients treated with this regimen as adjuvant therapy after liver metastasis resection were alive and disease-free after a median follow-up of 23 months.

Adult↗