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Biomedical subjects

M Deutsch

Publications and source records attributed to M Deutsch.

At least 127 records · Page 7Linked to original sources
PubMed1995

Polyamines in brain tumor therapy.

In the search for ways to augment current brain tumor therapies many have sought to exploit the fact that adult brain tissue is virtually lacking in cell division. This endorses a special appeal to therapeutic approaches which target the dependence on cell division for brain tumor growth. Polyamines play an essential role in the proliferation of mammalian cells and depletion results in inhibition of growth. As a result, there are investigations into the feasibility of controlling tumor growth by targeting the enzymes in polyamine metabolism with specific enzyme inhibitors. DFMO, an inhibitor of putrescine synthesis, is a cytostatic agent which in combination with tritiated radioemitters or cytotoxic agents such as, MGBG or BCNU is an effective antitumor agent, but the effectiveness of DFMO in vivo is reduced by tumor cell uptake of polyamines released into the circulation by normal cells and from gut flora or dietary sources. However, DFMO therapy combined with elimination of exogenous polyamines inhibits tumor growth but also results in body weight loss, reduced protein synthesis and evidence of toxicity. Furthermore, tumor growth recurs upon termination of treatment. In contrast, competitive polyamine analogs function in the homeostatic regulation of polyamine synthesis but fail to fulfill the requirements for growth and they continue to inhibit tumor growth for several weeks after cessation of treatment. Analogs are now in clinical trials. However, their action may be highly specific and differ from one cell type to another. We suggest that the effectiveness of polyamine based therapy would be enhanced by two approaches: local delivery by intracerebral microdialysis and tumor cell killing by internal radioemitters such as tritiated putrescine or tritiated thymidine which are taken up in increased amounts by polyamine depleted tumor cells. The growth inhibition by polyamine depletion prevents the dilution of the radioactive putrescine and thymidine. The overload of radioactivity kills the growth inhibited cells so that growth cannot recur when treatment terminates.

Adult↗
PubMed1995

On the development of an interstitial radiation protocol for a multicenter consortium. Experience with permanent low-dose rate and temporary high-dose rate 125I implants in 'failed' and 'newly diagnosed' glioblastoma patients: quality assurance methodology and a possible future adjuvant for therapeutic enhancement.

Three interstitial implant trial groups (one permanent low-dose rate 125I and two temporary high-dose rate 125I implants) in glioblastoma patients ('newly diagnosed' and 'failed') were compared to non-randomized similar control groups for efficacy. The results formed the basis for the BTCG 87-01 national implant trial. The 'pilot' trial demonstrated: 1) the effectiveness of a temporary high-dose rate 125I implant in 'failed' and 'newly diagnosed' patients; 2) the ability of a multicenter consortium to adhere to a standard protocol; 3) a methodology to insure quality assurance; and 4) the possibility of the future adjuvant application of hyperthermia using a single catheter system.

Brain Neoplasms↗
PubMed1995

Fluorescence polarisation changes in lymphocyte cytoplasm as a diagnostic test for breast carcinoma.

Lymphocytic cytoplasm from individuals with malignant disease, and from those without, differ in such a way as to be diagnostic both of malignancy generally and of specific types of cancer. Mitogenic stimulation of lymphocytes by phytohaemagglutinin (PHA) and antigenic stimulation by encephalitogenic factor (EF) and certain specific tumour-associated antigens, provokes changes in the structure of the cytoplasmic matrix (SCM) which are detectable upon fluorescence polarisation. The degree of change is quantifiable both by calculating the polarisation ration (PR, polarisation before and after stimulation) and the relative ratio (RRSCM, the ratio between the polarisation obtained after exposure to EF [PEF] and to the polarisation measured after exposure to PHA [PPHA]). A new tumour-associated antigen specific for breast cancer, CaBr, was tested for its diagnostic efficacy in comparison with that of EF, by prospectively testing blood samples from 138 consecutive women with suspicious breast masses. The previously known discriminatory power (sensitivity 60.7% and specificity 90.7%) of the polarisation-derived RRSCM was reconfirmed. However, the RR'SCM (the new ratio using CaBr instead of EF), was significantly more sensitive (77.4%; P < 0.01) and specific (94.4%) than the RRSCM in detecting breast cancers. The polarisation changes in the cytoplasmic matrix after stimulation by CaBr alone suggest the best discriminatory power (sensitivity 90.5% and specificity 94.4%) between cancerous and non-cancerous patients.

Adult↗
PubMed1995

Arterial grafts for coronary artery surgery.

Fifty specimens of left internal mammary artery, right gastroepiploic artery and right inferior epigastric artery were examined for length, diameter and frequency of atherosclerotic changes. Mean usable length was 132.4 mm for internal mammary arteries, 127.9 mm for gastroepiploic arteries and 128.4 mm for inferior epigastric arteries. One gastroepiploic artery was occluded. Histological examination revealed atherosclerotic plaques in seven internal mammary arteries (14%), 12 gastroepiploic arteries (24%) and 14 inferior epigastric arteries (28%). These findings emphasize the superiority of the inferior epigastric artery as the graft of choice for coronary artery bypass grafting. Gastroepiploic artery and inferior epigastric artery should only be used as additional grafts if 'all-arterial-grafting' is intended.

Aged↗
PubMed1995

Fatal fungal infection of an ascending aortic graft.

In a 57-year-old male with aortic valve stenosis and severe poststenotic dilation of the ascending aorta an aortic valve replacement and interposition of the dilated aortic segment with a Dacron prosthesis were carried out. Perioperative course was uneventful. Four months after dismission the patient presented with septic fever and recurrent arterial emboli. Histological evaluation of the thrombotic material found fungal masses of Aspergillus flavus. Although adequate antimycotic treatment was started immediately the patient died two days later. Postmortem examination revealed massive fungal infection of the Dacron prosthesis while the aortic allograft appeared free from infection. The symptoms of a fungal infection and possible diagnostic strategies are discussed.

Aortic Aneurysm↗
PubMed1995

Platelet size, fibrinogen and lipoprotein(a) in coronary heart disease.

BACKGROUND: An increase in mean platelet volume has been reported to be associated with arterial thrombosis and myocardial infarction. A larger mean platelet volume has been regarded as an independent risk factor for recurrent myocardial infarction. We therefore investigated whether it is also increased in patients with coronary heart disease examined a few days before cardiac surgery. METHODS: Four hundred and twenty-six patients with coronary heart disease who were waiting for cardiac surgery and 125 healthy individuals were included in the study. Mean platelet volume and other platelet parameters were obtained from a routine blood count procedure using a flow cytometric haematology analyser. RESULTS: Mean platelet volume did not differ significantly between patients and controls; however, as expected from the literature, patients had significantly elevated levels of fibrinogen, cholesterol, triglyceride, apolipoprotein B and apolipoprotein(a). Furthermore, we observed no significant difference in mean platelet volume between patients without myocardial infarction and those who had survived at least one myocardial infarction. CONCLUSION: Our findings suggest that, using a routine laboratory procedure, mean platelet volume cannot be used as a predictive marker for coronary heart disease or myocardial infarction.

Adult↗
PubMed1995

Intracranial ependymomas of childhood: long-term outcome and prognostic factors.

A detailed outcome analysis was performed on 40 children with intracranial ependymomas treated at our institution between 1975 and 1993 to identify those factors that were predictive of overall and progression-free survival. Three patients (7.5%) who were treated in the first 5 years of the study died within 3 months of surgery and were excluded from further outcome assessments. Eight (22%) of the 37 patients who survived the perioperative period had evidence of leptomeningeal dissemination at presentation, on the basis of either imaging (three children) and/or cytological (six children) results. The 5- and 10-year progression-free survival rates among these 37 patients were 45.1 and 36.1%, respectively; overall survival rates were 57.1 and 45.0%, respectively. The site of progression was local in 17 of 19 patients with progressive disease. Three factors were found to have a significant association (P < or = 0.05) with the outcome on both univariate and multivariate analyses: 1) the extent of the resection, 2) the age of the patient at diagnosis, and 3) the duration of the symptoms before diagnosis. The 5-year progression-free and overall survivals were 8.9 and 22%, respectively, among patients who had evidence of residual disease on postoperative imaging studies, compared with 68 and 80% rates among patients with no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients younger than 3 years fared significantly worse than older children (5-year progression-free and overall survival rates of 12 and 22%, respectively, in the younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01, respectively). In addition, patients with a duration of symptoms before diagnosis of < 1 month had a worse outcome than those with a more protracted course (5-year progression-free and overall survival rates of 33 and 33%, respectively, versus rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of evidence for dissemination at presentation nor the detection of anaplastic histological features (e.g., dense cellularity or high numbers of mitoses) were associated with a significantly worse outcome in this series. The combination of variables that had the strongest association with both favorable and unfavorable outcomes was the combination of the age of the patient and the resection extent. Only 2 of 17 patients older than 3 years with gross total resections have died, whereas 13 of 20 children who were either younger than 3 years or had radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases.

Low-grade gliomas constitute the largest group of cerebral hemispheric tumors in the pediatric population. Although complete tumor resection is generally the goal in the management of these lesions, this can prove difficult to achieve because tumor margins may blend into the surrounding brain. This raises several important questions on the long-term behavior of the residual tumor and the role of adjuvant therapy in the management of these lesions. To examine these issues, the authors reviewed their experience in 71 children with low-grade cerebral hemispheric gliomas who were treated at their institution between 1956 and 1991 and assessed the relationship between clinical, radiographic, pathological, and treatment-related factors and outcome. Only seven patients in the series died, one from perioperative complications, five from progressive disease, and one (a child with neurofibromatosis) from a second neoplasm. For the 70 patients who survived the perioperative period, overall actuarial survivals at 5, 10, and 20 years were 95%, 93%, and 85%, respectively; progression-free status was maintained in 88%, 79%, and 76%, respectively. On univariate analysis, the factor that was most strongly associated with both overall and progression-free survival was the extent of tumor resection (p = 0.013 and p = 0.015, respectively). A relationship between extent of resection and progression-free survival was present both in patients with pilocytic astrocytomas (p = 0.041) and those with nonpilocytic tumors (p = 0.037). Histopathological diagnosis was also associated with overall survival on univariate analysis; poorer results were seen in the patients with nonpilocytic astrocytoma compared to those with other low-grade gliomas, such as pilocytic astrocytoma, mixed glioma, and oligodendroglioma (p = 0.021). The use of radiotherapy was not associated with a significant improvement in overall survival (p = 0.6). All three patients who ultimately developed histologically confirmed anaplastic changes in the vicinity of the original tumor had received prior radiotherapy, 20, 46, and 137 months, respectively, before the detection of malignant progression. In addition, children who received radiotherapy had a significantly higher incidence of late cognitive and endocrine dysfunction than the nonirradiated patients (p < 0.01 and 0.05, respectively). The authors conclude that children with low-grade gliomas of the cerebral hemispheres have an excellent overall prognosis. Complete tumor resection provides the best opportunity for long-term progression-free survival. However, even with incomplete tumor excision, long-term progression-free survival is common.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1995

[Peripheral cranial nerve paralysis as a sequela of operations of the carotid artery].

265 carotid endarterectomies in 210 patients (all vein patch in the carotid bifurcation) were investigated postoperatively for the presence and reversibility of cranial nerve palsy especially for N. facialis, N. hypoglossus, and N. vagus paresis. Additionally, the anatomical relationship between the affected cranial nerve and the carotid artery and the influence of surgical case load on the incidence of cranial nerve paresis were investigated. Altogether 28 (10.5%) cranial nerve injuries were registered. In 6 (2.2%) cases the hypoglossus nerve was injured, in 13 (4.9%) the vagal nerve (N. laryngeus recurrens) and in 9 (3.4%) facial nerve paresis occurred. Cranial nerves VII and X, which are not directly connected with the area operated on, show significantly more injuries than the hypoglossal nerve (p < 0.01), which is located closer to the carotid artery. Significantly lower rates of cranial nerve injuries (p < 0.01) were recorded in cases operated on by surgeons with greater experience (> 30 cases) than by surgeons with a case load below this threshold. Although different reasons for cranial nerve injuries such as direct pressure, retraction or edema are known, all pareses show an excellent spontaneous recovery rate within the period of one year.

Aged↗
PubMed1994

Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer.

BACKGROUND: The purpose of this study was to assess the ability of administering to patients induction chemotherapy with carboplatin and etoposide (VP-16), followed by full-course radiation therapy and weekly carboplatin with tolerable toxicity as preoperative therapy to down-stage disease thus allowing the resection of clinically staged IIIA non-small cell lung cancer. METHODS: Twenty-eight eligible patients with good performance status and previously untreated, marginally resectable stage IIIA non-small cell lung cancer received induction chemotherapy with carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/m2) followed by 6000 cGy of chest radiotherapy over six weeks administered concurrently with weekly doses of 100 mg/m2 of carboplatin. Patients who had either responsive or stable disease underwent thoracotomy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pneumonectomy were used whenever feasible. RESULTS: Fifty-two cycles of induction chemotherapy were administered. The average initial dose of carboplatin was 407 mg/m2. Toxicity was tolerable with grade 3-4 neutropenia and/or thrombocytopenia in 48 and 27% of the patients. There were no septic deaths. Full-dose radiotherapy was administered to 82% of patients, with 73% receiving at least five weekly doses of carboplatin. The radiographically assessed response rate to the neoadjuvant treatment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negative pathologic margins. Six patients had pneumonectomy. There were three perioperative deaths (19%); two were secondary to respiratory failure after the patients underwent a pneumonectomy. The median survival for all 28 patients was 15 months, and for the 16 patients undergoing thoracotomy was 23 months. Eight patients were alive and in remission, with follow-up ranging from 8 to 31 months. CONCLUSIONS: The authors conclude that (1) carboplatin and VP-16, followed by full-dose radiotherapy with weekly carboplatin administration, is a well tolerated and effective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiotherapy can be administered before surgical resection without additional surgical morbidity or mortality.

Adult↗
PubMed1994

Apparatus for high-precision repetitive sequential optical measurement of living cells.

A system is described which permits the repetitive spectroscopic measurement of individual cells within a population of many cells, while the location of each cell is preserved during various manipulations of the cells and/or their surrounding medium. The central mechanical feature of the system is the cell carrier, a matrix of apertures in which the cells become trapped. The detector electronics operate in a preset photon counting mode, permitting the measurement of low and high light intensities with the same degree of precision. The present instrument configuration is specifically designed for the accurate and precise measurement of the polarization of fluorescence of probes within living cells for application to routine performance of the Cercek SCM test for cancer. With modifications, the apparatus can be applied to a wide range of other clinical and research tasks.

Cell Separation↗
PubMed1994

Clinical in vitro endothelialization of femoropopliteal bypass grafts: an actuarial follow-up over three years.

PURPOSE: The creation of an endothelial coverage on prosthetic vascular surfaces may improve the performance of synthetic small diameter vascular grafts. In vitro lining with cultured autologous endothelial cells offers a confluent endothelium at the time of implantation. METHODS: Between June 1989 and December 1991, 49 patients who had no saphenous vein available entered the study. Indication for operation was disabling claudication in 37 patients and critical ischemia in 12 patients. With a random 1:2 assignment, 33 patients were admitted to the endothelialized group and 16 control patients received an untreated polytetrafluoroethylene prosthesis. Cultured autologous endothelial cells from the external jugular vein were confluently lined onto polytetrafluoroethylene grafts precoated with fibrinolytically inhibited fibrin glue. The follow-up was based on angiography, platelet labeling studies with indium 111-labeled oxine, assessment of the ankle-brachial index, and duplex sonography. RESULTS: First-passage mass cultures of 16 million endothelial cells-required for the confluent lining of a 70 cm long 6 mm graft-were reached 25.1 +/- 11.2 days after vein excision. Growth failure occurred in 27.3%. After 32 months, the actuarial patency was 84.7% for endothelialized grafts and 55.4% for control grafts (p < 0.041 by Breslow test; p < 0.068 by Mantel-Cox test). The ankle-brachial index was continually diverging, reaching significantly lower values in the control group at 24 months (0.98 +/- 0.14 in the endothelialized group versus 0.70 +/- 0.12 in the control; p < 0.0023). The uptake of indium 111-labeled platelets--measured at 9 days, 3 months, 6 months, and 12 months--was significantly lower in the endothelialized group during the entire observation period.

Actuarial Analysis↗
PubMed1994

In vitro endothelialization of a mesosystemic shunt: a clinical case report.

The existence of a confluently covering endothelium that is free of any thrombotic appositions can be proved 30 days after clinical implantation of an in vitro endothelialized expanded polytetrafluoroethylene graft. The recipient of the mesosystemic H-graft was a 69-year-old man who had a thrombosed portal vein following pancreatitis. Autologous endothelial cells were obtained from the external jugular vein under local anesthesia, applying the in situ cannulation technique. After low-density plating, first-passage mass cultures of 1.22 x 10(6) endothelial cells were obtained 14 days after vein excision. After precoating was accomplished with fibrinolytically inhibited fibrin glue, a 10 mm expanded polytetrafluoroethylene graft was confluently lined with the autologous endothelial cells at a seeding density of 1.2 x 10(5) cells/cm2. After a maturation period of an additional 9 days and the microbiologic exclusion of a possible infection, an 11 cm graft segment was implanted between the superior mesenteric vein and the inferior vena cava. In spite of a patent shunt the patient had a repeat bleeding episode, needed parenteral nutrition, and died of sepsis on day 30. Immediately after the graft had been taken out, specimens were processed by scanning electron microscopy and light microscopy for the immunohistochemical proof of the endothelial nature of the surface-covering cell layer. The entire graft surface displayed a confluent cell lining that was free of any thrombotic appositions. A strongly positive stain result for both factor VIII-related antigen and the fixation-resistant CD34 molecule identified these cells as endothelial. No alpha-actin-positive cells could be detected. The underlying protein matrix was well preserved and unaltered in thickness and appearance, compared with preimplantation samples. None of the specimens showed any evidence of infection. This human demonstration of an intact endothelium on a patent venous prosthesis further establishes in vitro lining as a method that actually creates a persistent and functioning endothelium on a synthetic graft surface.

Aged↗
PubMed1994

Prevalence of factor XII (Hageman factor) deficiency among 426 patients with coronary heart disease awaiting cardiac surgery.

BACKGROUND: Several case reports of myocardial infarction in patients with factor XII deficiency have been published. In the present study we investigated the prevalence of this condition. METHODS: Factor XII activity (one-stage clotting assay), fibrinogen (derived method), and lipoprotein (a) (enzyme-linked immunosorbent assay) were measured in the plasma of 426 consecutive patients with coronary heart disease awaiting cardiac surgery. RESULTS: Among the 426 patients, 44 (10.3%) were found to be moderately deficient in factor XII (factor XII activity 17-50%, antigen 15-57%). The prevalence of factor XII deficiency was significantly higher (P < 0.0001) among patients with coronary heart disease than among 300 healthy blood donors (2.3%). Among coronary heart disease patients with this deficiency, elevated levels of fibrinogen, lipoprotein (a), and blood pressure were no more prevalent than in those without the deficiency; nor were cigarette smoking or a positive family history of thromboembolism more prevalent. CONCLUSIONS: Coronary heart disease patients showed a 10% prevalence of factor XII deficiency. However, the pattern of atherosclerotic risk factors did not differ between patients with or without the deficiency.

Blood Coagulation Tests↗