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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 289 records · Page 16Linked to original sources
PubMed1988

Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake.

Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism.

Animals↗
PubMed1988

[Intensive chemotherapy and bone marrow grafting during the consolidation phase of stage IV neuroblastoma].

Sixty-five patients more than one year of age at diagnosis with stage IV neuroblastoma were prospectively treated since january 1983. Seventeen per cent were not consolidated with massive therapy and ABMT (progression: 3 cases; died at induction: 4 cases; died at surgery: 1 case; parental refusal: 2 cases) and all died. Among 49 evaluable cases, 31 were grafted in PR and 18 in CR or VGPR. Actuarial progression free survival at 35 months is 33% for the grafted group and 24% for the whole group. These results are better than previous experience of this group (8% at 30 months).

Actuarial Analysis↗
PubMed1988

[Contribution of immunohistochemical technics to the study of malignant infiltration of bone marrow].

Immunohistochemistry using monoclonal antibodies has been proved of diagnostic value in bone marrow pathology. Several monoclonal antibodies identifying antigens not denatured by fixation are now available. In anaplastic tumors infiltrating bone marrow these antibodies allow the distinction of large cell lymphomas which express the leucocyte common antigen (Dako-LC+) from undifferentiated carcinomas which are reactive with anti-cytokeratin antibodies (KL-1+, Dako-EMA+), neuroblastoma (NSE+) and rhabdomyosarcoma (desmin+). KL-1 and Dako-EMA antibodies are also considered to be powerful tools to disclose micrometastases from carcinoma, particularly breast carcinoma, which otherwise may be undiagnosed. The detection of residual or minimal bone marrow involvement in malignant lymphomas (particularly Burkitt type) remains difficult. However, in some cases, Dako-LC and MB2 (anti-B) antibodies are useful to detect bone marrow involvement in some lymphoproliferative disorders composed of small or medium-sized cells scattered among hematopoietic cells, and in some large cell lymphomas (i.e. centroblastic or immunoblastic types). These antibodies allow the detection of minimal or residual involvement by malignant cells, which can be confused with immature hematopoietic cells, on routine stainings. No anti-T antibody was found to react satisfactorily with T cell on decalcified biopsy specimens. In anaplastic large cell lymphomas (so-called malignant histiocytosis), malignant cells coexpress Ki-1 and EMA antigens. Antibodies recognizing these two antigens were found to be of value to demonstrate scarce neoplastic cell in bone marrow.

Antibodies, Monoclonal↗
PubMed1988

Biosynthesis of glycosaminoglycans in the human colonic tumor cell line Caco-2: structural changes occurring with the morphological differentiation of the cells.

The human colon cancer cell line Caco-2 cultured in vitro displayed morphological differentiation which was shown to be a growth-related event. We have investigated this phenomenon further in relation to the cell surface glycosaminoglycans produced by growing (5-day, i.e., prior to differentiation) and confluent (9-day, i.e., after morphological and functional differentiation) cultures. Neosynthesized [35S]glycosaminoglycans were purified on DEAE-cellulose; at confluency, they were bound more strongly to the column than the corresponding fractions from the growing cells. Analysis of Kav values of heparan sulfate and chondroitin sulfates from growing and confluent cells indicated an increase in chain length of both glycosaminoglycans in morphologically differentiated cells. Heparan sulfate was the main 35S-labeled glycosaminoglycan of the cell surface of both 5-day and 9-day cultures. Paper chromatography of the unsaturated disaccharides obtained by chondroitinase digestion showed that chondroitin sulfate chains were primarily 6-sulfated in the 2 studied extracts. Heparan sulfate chains were isolated as chondroitinase-resistant material and treated with nitrous acid. Analysis of N- and O-sulfate group-related radioactivity showed an increase in the amount of 35S-label in the form of N-sulfate groups and an increase in the O-35S-sulfation pattern in heparan sulfate from morphologically differentiated cells. Thus, the structural features of both chondroitin sulfates and heparan sulfate were significantly different when the growing cells became morphologically differentiated.

Cell Differentiation↗
PubMed1987

Gastric antisecretory activity of cycloheximide due to inhibition of protein synthesis.

Treatment of rats with cycloheximide 1 h before carbachol dose-dependently reduced the secretagogue-stimulated gastric acid secretion in pylorus ligated rats, and partially blocked carbachol- or histamine-induced activation of rat gastric (H+ + K+)-ATPase which includes translocation of reserve intracellular (H+ + K+)-ATPase into the apical membrane of the parietal cells and induction of a KCl pathway. Time-course studies showed that the drug was effective only when administered at least 30 min before the secretagogues. Puromycin showed the same effect as cycloheximide. Pulse labelling studies with [35S]methionine led to identification of two most actively synthesized polypeptides in rat gastric mucosa; the proteins of 38,000 and 14,000 molecular weight. The larger polypeptide was identified as rat pepsinogen. The identity of the smaller protein is not known yet. We suggest that synthesis of nascent polypeptide(s) is required for certain steps of the acid secretory process leading to the activation of the acid pump.

Adenosine Triphosphatases↗
PubMed1987

Prostaglandin deficiency by itself is not the cause of mepirizole-induced duodenal ulcers in rats.

The purpose of these studies was to determine the role played by endogenous prostaglandins in the development of gastric ulcers produced by indomethacin, and of duodenal ulcers produced by mepirizole in rats. Indomethacin (10 mg/kg subcutaneously) produced gastric ulcers, whereas mepirizole (100 mg/kg subcutaneously) produced exclusively duodenal ulcers. Both drugs, given at ulcerogenic doses, reduced the gastric and duodenal generation of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2. In this regard, the extent of reduction was more pronounced after indomethacin than after mepirizole. Despite this greater inhibition of prostaglandin synthesis by indomethacin, this drug did not produce duodenal ulcers, whereas mepirizole was duodenoulcerogenic. In addition, mepirizole increased gastric acid secretion by 74%, whereas indomethacin had no effect on acid secretion. Oral administration of 16,16-dimethyl PGE2, given at nonantisecretory doses (0.5-5 micrograms/kg), prevented formation of indomethacin-induced gastric ulcers, whereas antisecretory doses were required to prevent formation of mepirizole-induced duodenal ulcers. We conclude that a reduction of prostaglandin formation in the duodenal mucosa is not by itself sufficient to induce duodenal ulcers. We hypothesize that three changes, produced by mepirizole, must be present for duodenal ulcers to develop: increased gastric acid secretion, decreased duodenal bicarbonate secretion (as demonstrated earlier), and decreased duodenal content of prostaglandins. The decreased prostaglandin formation, although not causing duodenal ulcers, may lower the resistance of duodenal mucosa to the hyperacidity induced by mepirizole. On the other hand, in the case of gastric ulcers following administration of indomethacin, a decrease in gastric mucosal levels of prostaglandins may play a more important role than changes in gastric acidity.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Ejection fraction response to upright exercise in hypertension: relation to loading conditions and to contractility.

The respective roles of peripheral and myocardial determinants of exercise ventricular performance were studied in 10 normal volunteers and in 9 mildly hypertensive patients without evidence of coronary disease. Hemodynamic measurements and equilibrium blood pool scintigraphy were simultaneously performed at rest and during maximal upright exercise. In hypertensive patients, mean systolic and diastolic blood pressure were, respectively, 199 +/- 23 and 102 +/- 12 mm Hg at rest, and 271 +/- 28 and 113 +/- 8 mm Hg at peak exercise. Ejection fraction response to exercise was normal (increase by more than 5%) in 4 hypertensive patients (normal hypertensive group: 63 +/- 4 to 77 +/- 6%) and in volunteers (65 +/- 3 to 78 +/- 4%) and abnormal in 5 hypertensive patients (abnormal hypertensive group: 66 +/- 6 to 58 +/- 10% at peak exercise). The abnormal response in the abnormal hypertensive group was not due to an inadequate decrease in systemic vascular resistance during exercise. By contrast, the ratio systolic blood pressure/end-systolic volume, an index of contractility, decreased by 2.3 +/- 4.9 in the abnormal hypertensive group, whereas it increased by 9.8 +/- 9.1 in the normal hypertensive group and by 7.3 +/- 2 in volunteers. Thus, abnormal exercise ejection fraction response in mild hypertension was not related to increased afterload but rather to intrinsic myocardial factors.

Adult↗
PubMed1987

Clinical correlation between hypercoagulability and thrombo-embolic phenomena.

A study of the coagulolytic balance as well as platelet aggregation was carried out in 64 nephrotic patients. The data were correlated, in a prospective attempt, with the clinical demonstration of thrombo-embolic events. Activating factors (factors I, VIIIc, VIIIr:Ag) were increased as well as certain clotting inhibitors, alpha-1-antitrypsin and alpha-2-macroglobulin. There was a platelet hyperaggregability in 31.5% of our patients. Thrombo-embolic complications occurred in six subjects (9%). The data of these six patients were compared with that of the other patients; no significant correlation were found between clotting abnormalities and thrombosis. Low level of ATm (less than 0.8 U.Fr) and severe hypoalbuminemia (less than 20 g/liter) were of no predictive value for the occurrence of thrombo-embolic events.

Adult↗
PubMed1987

"Sensitive tests" are poor predictors of the decline in forced expiratory volume in one second in middle-aged smokers.

In 1978, we studied 3 groups of steelworkers 45 to 55 yr of age who were all smokers: "obstructive" smokers (OS) with a FEV1/VC less than 66.6% (59.8% in average) (n = 37), smokers with "small airways disease" (SAD) and an abnormal closing capacity and/or slope of phase III (delta N2) but normal FEV1/VC (n = 32), and "resistant" smokers (RS) with normal functional indices (n = 36). Smokers with SAD had a lower (p less than 0.05) FEV1/VC (71.7%) than did RS (74.9%). We studied again 6 yr later about 85% of survivors in each group. Analysis of variance showed that FEV1 decreased significantly (p less than 0.001) only in OS (from 2.67 to 2.46 L). In RS and smokers with SAD, FEV1 declined from 3.34 to 3.26 L and from 2.95 to 2.85 L, respectively (p greater than 0.05). In all 3 groups, delta N2 increased (p less than 0.001) from 0.77 to 1.30% N2/L in RS, 1.41 to 2.43% N2/L in smokers with SAD, and 2.22 to 4.20% N2/L in OS. A multivariate analysis showed that the initial N2 explained about 30% (p less than 0.001) of the decline in FEV1 in OS, but only 10% (p less than 0.001) in the 3 groups together. In fact, the link between delta N2 and fall in FEV1 was restricted to OS. Closing volume and maximal expiratory flow rates were not related to decline in FEV1. The link between uneveness of ventilation and subsequent loss of FEV1 is of physiopathologic interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Forced Expiratory Volume↗
PubMed1987

Sequential cisplatin/VM-26 and vincristine/cyclophosphamide/doxorubicin in metastatic neuroblastoma: an effective alternating non-cross-resistant regimen?

We report the results of a French multicentric pilot study of remission induction therapy in metastatic neuroblastoma. Thirty-five successive unselected patients entered the study over 1 year and were treated by alternating sequences of cisplatin/VM-26 (PE) and vincristine/cyclophosphamide/doxorubicin (CADO). Three courses of each sequence were delivered. Disease reevaluation was extensive, with special focus on bone marrow status. Using strict criteria, 24 patients (68%) achieved a good partial response (GPR), which comprised normalization of bone marrow, and ten (28%) achieved a partial response (PR), and one progressed. The overall response rate was 96%. Thirty-two patients underwent surgery, and complete macroscopic removal of the primary was achieved in 21 (65%). After completion of induction and surgery, six patients (17%) were in complete remission (CRm), without evidence of any residual disease; nine (26%) were in very good partial remission (VGPRm; same as CRm except persistence of nonpathologically evaluable improved bone scan), and 19 (51%) were in partial remission (PRm). Toxicity was acceptable, and no treatment-related deaths occurred. These results show no substantial improvement compared with those previously reported with similar but nonalternating regimens. We advocate a two-category concept (response, remission) to describe initial therapy results in metastatic neuroblastoma and emphasize the need to assess bone marrow by an extensive evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

High-dose chemoradiotherapy with bone marrow transplantation as consolidation treatment in neuroblastoma: an unselected group of stage IV patients over 1 year of age.

Since January 1983, 56 consecutive children over 1 year of age with stage IV neuroblastoma entered an aggressive protocol, including chemotherapy, radiation therapy, and bone marrow transplantation. The induction protocol included platinum and epipodophyllotoxin (VM-26), alternating with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH), and vincristine (PE/CADO). Surgery was performed after 2 to 4 months, and consolidation with intensive chemoradiotherapy and bone marrow transplantation (BMT) was performed within 12 months of diagnosis. The combination of vincristine, melphalan and total body irradiation (TBI) was used before BMT, and no further treatment was administered before progression. With the exception of two allografts, autologous BMT (ABMT) was given in all cases and was purged using an immunomagnetic procedure (Kemshead technique) in 32 of 35 cases, and a chemical procedure in three of 35. Of the 56 patients, 45 were evaluable. Of those, 23 were grafted in partial remission (PR), and 14 were grafted in either complete remission (CR) or very good partial remission (VGPR). The acute toxic death rate was 19%, the relapse rate was 32%, and the progressive disease rate was 19%. The progression-free survival in the CR/VGPR group (ie, 44% at 32 months post-diagnosis) and in the PR group (13% at 32 months) was not significantly different (P greater than .05). At 24 months, the overall survival of the 56 unselected patients was 39% compared with 12% for comparable patients previously treated by our group (P less than .005).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Preoperative left ventricular dysfunction and operative risks in coronary bypass surgery.

Preoperative left ventricular function variables were evaluated as potential risk factors for peroperative and postoperative complications in 183 consecutive patients undergoing coronary bypass surgery. Fifty-six patients had no abnormal criteria and 127 had at least one criterion (AN). The incidence of history of infarction was significantly greater in the AN (71.6 percent) than in the N (39.6 percent) group (p less than 0.04). During the early postoperative course, N and AN differentiated significantly in (1) the need for inotropic therapy (II vs 30 percent, p less than 0.05); (2) intra-aortic balloon pump (0 vs 13 percent); (3) arrhythmias (20 and 40 percent, p less than 0.002); and (4) stay in the Intensive Care Unit (2.3 +/- 0.8 and 3.9 +/- 2 days, p less than 0.01). Perioperative necrosis and mortality were not different. During a follow-up period of two years, N and AN did not show any difference in mortality and recurrence of angina.

Arrhythmias, Cardiac↗
PubMed1987

The grafting of burns with cultured epidermis as autografts in man. Two case reports.

In two patients full-thickness burns were grafted with cultured autologous epidermis obtained using the technique described by H. Green. The grafts only took partially but produced satisfactory covering. Better efficiency and more information about the long-term characteristics of the resulting skin are necessary before routine use can be recommended.

Adult↗
PubMed1987

[Are there risk factors for pure systolic hypertension?].

Pure systolic hypertension (PSH) is mainly observed in subjects over 60 years of age, and it is always due to a loss of compliance of the greater arteries. Blood pressure itself is partly responsible for loss of compliance, but other factors have been suggested. We have investigated this matter in a study of 3,388 subjects aged from 20 to 69 years. In a first stage, PSH patients (systolic BP greater than or equal to 160; diastolic BP less than 95 mmHg), aged from 50 to 59 years, were compared with normotensive subjects (systolic BP less than 140; diastolic BP less than 95 mmHg) and with other types of hypertensive patients with regard to cigarette smoking, alcohol consumption, obesity and plasma cholesterol, triglycerides, gamma-GT, glucose and uric acid levels. Several of these variables were significantly higher in all hypertensive patients than in normotensive subjects, but cigarette smoking and gamma-GT levels were predominantly or exclusively higher in PSH patients. In a second stage, correlations between differential BP and the variables listed above were studied in subjects with two levels of diastolic BP: 70-79 and 80-89 mmHg, thus taking into account all degrees between normal BP and PSH proper. Weakly positive correlations were found with alcohol consumption, plasma gamma-GT and glucose levels, and with percentages of smokers or ex-smokers. It is therefore conceivable that in addition to BP itself other factors, such as alcohol consumption, cigarette smoking and hyperglycaemia, contribute to the loss of arterial compliance progressively leading to pure systolic hypertension.

Adult↗