Search PubMed⌕ Search

Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 235 records · Page 13Linked to original sources
PubMed1992

[Extracellular matrix and vascular pathologies. Role of proteases and oxygenated free radicals].

Vessel walls contain several types of mesenchymatous cells and many representatives of the 4 groups of macromolecules of the extracellular matrix secreted by those cells. Under normal conditions, a proportion of the macromolecules of the vascular wall is broken down by the neosynthesis of an equivalent amount of the same macromolecules which are then integrated into functional structures. Under pathological conditions, an excessive amount of macromolecules is broken down by proteases and free radicals, without any compensatory increase in biosynthesis and without the integration of biosynthesised compounds into functional structures. Thus, for example, a varicose saphenous vein may lose as much as 60 per cent of the collagen of its wall. Attempts at symptomatic treatment designed to combat this loss of substance, a notable cause of weakening of he vessel wall, are based upon three principles: inhibition of catabolic enzymes, chiefly proteases (e.g. leucocyte elastase), responsible for excessive breakdown; uptake of oxygenated free radicals; "substrate protection" designed to preserve undamaged fibrous proteins and to help the integration of neosynthesized compounds into functional structures. Only medications which act as "substrate protectors" are capable of coping at one and the same time with the effects of proteases and those of oxygenated free radicals.

Aging↗
PubMed1991

A homologue of dystrophin is expressed at the neuromuscular junctions of normal individuals and DMD patients, and of normal and mdx mice. Immunological evidence.

Polyclonal and monoclonal antibodies, which recognize different regions and epitopes of the dystrophin molecule, bind to a protein of Mr 400,000 which is present in extracts of mdx muscle from regions which contain neuromuscular junctions (NMJ) and is absent from those which do not. This NMJ-associated homologue of dystrophin has at least 2 epitopes which are different to usual Xp21 form of dystrophin expressed along the sarcolemma of muscle fibres in normal muscles. This protein is also expressed at the NMJ of a DMD patient who lacks the first 52 exons of the Xp21 dystrophin gene and it must therefore be translated from a different gene transcript.

Animals↗
PubMed1991

Gastric cytoprotection by intracisternal interleukin-1 beta in the rat.

The effects of intracisternal (ic) injection of recombinant interleukin-1 beta (IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The cytoprotective effect was dose dependent (ED175 ng/rat), long lasting with a maximal action when given 1-3 h prior to ethanol, blocked by ic injection of a IL-1 receptor antagonist protein (IRAP), and by intraperitoneal injection of indomethacin. IL-1, injected ic, was detected in the peripheral blood. However, IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose giving equal gastric protection. These data show that ic IL-1 induces long lasting gastric protection mediated by interaction with IL-1 receptors and prostaglandin pathways at central and/or peripheral sites that remain to be localized.

Animals↗
PubMed1991

Nonmetastatic thoracic neuroblastomas: a review of 40 cases.

From 1982 to 1987, 40 children with non-metastatic thoracic neuroblastoma were treated with the same therapeutic regimen. According to TNM staging, there were 11 CS I, 19 CS II, and 10 CS III. All patients underwent surgery; 30 had primary surgical excision; in 10 whose tumors were deemed unresectable, surgery was delayed until after a trial of chemotherapy. Operation was completed by several courses of chemotherapy in case of microscopic residual disease or regional lymph node involvement; radiotherapy was delivered in case of gross residual disease. Using this therapeutic approach, EFS is 92% with a median follow-up of 40 months. Severe complications were rare and sequellae appear to be related to the disease, i.e., neurologic consequences of cord compression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Interleukin-1 is cytoprotective, antisecretory, stimulates PGE2 synthesis by the stomach, and retards gastric emptying.

Human recombinant interleukin 1 beta (IL-1) administered intraperitoneally to rats produced the following gastric effects: 1. It was cytoprotective, preventing gastric mucosal necrosis produced by oral administration of one ml of absolute ethanol to fasted animals. The ED50 was 1200 units/kg (110 ng per animal). IL-1 was 125 times more potent than prostaglandin E2 (on a weight basis), and 6,000 times more potent (on a molar basis). 2. The cytoprotective effect of IL-1 was blocked by indomethacin (inhibitor of prostaglandin synthesis) and by IRAP (a specific interleukin-1 receptor antagonist protein). IRAP did not inhibit cytoprotection induced by PGE2. 3. IL-1 prevented the formation of gastric erosions induced by aspirin. 4. IL-1 inhibited gastric secretion (volume, acid concentration and output), in the pylorus-ligated rat, with an ED50 of 300 units/kg (3.2 ng per animal). 5. Indomethacin and IRAP blocked the antisecretory effect of IL-1. 6. IL-1 retarded gastric emptying, an effect blocked by IRAP, but not by indomethacin. 7. IL-1 increased synthesis of prostaglandin E2 by the gastric mucosa by 111%. IL-1 is the most potent of known agents that are gastric cytoprotective, antiulcer, antisecretory, and delay gastric emptying. It appears to act mostly by stimulating the synthesis of prostaglandins by the stomach. These studies suggest that the stomach possesses IL-1 receptors. These are probably located on parietal cells (that produce acid), on prostaglandin-producing cells, on smooth muscle cells (responsible for gastric emptying), and on as yet unidentified cells involved in gastric cytoprotection. Both IL-1 and IRAP, being natural substances, may play a physiological role in the maintenance of gastric mucosal integrity, and in the regulation of acid secretion and gastric motility.

Animals↗
PubMed1991

Studies on (H(+)-K+)-ATPase inhibitors of gastric acid secretion. Prodrugs of 2-[(2-pyridinylmethyl)sulfinyl]benzimidazole proton-pump inhibitors.

The synthesis of N-substituted benzimidazole (H(+)-K+)-ATPase or proton-pump inhibitors is described. These compounds were prepared to function as prodrugs of the parent N-H compound and evaluated for their ability to inhibit gastric (H(+)-K+)-ATPase and gastric acid secretion. The prodrugs reported rely on either in vivo esterase hydrolysis for liberation of the parent compound (type I and type II) or require an acid environment for release of the active drug (type III and type IV). The N-(acyloxy)alkyl-substituted benzimidazoles 9, 11, and 24 showed improved chemical stability in the solid state and in aqueous solutions when compared to their parent N-H compounds. When given orally, 24 was found to be twice as potent as omeprazole in both the Shay rat and inactivation of gastric (H(+)-K+)-ATPase in the rat. The N-ethoxy-1-ethyl-substituted benzimidazoles 48-50 were found equally as effective as the N-H compound for inhibition of rat (H(+)-K+)-ATPase activity. In the Shay rat 48 at 10 mg/kg was approximately twice as active as parent timoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

Antibody BNH9 detects red blood cell-related antigens on anaplastic large cell (CD30+) lymphomas.

Two new monoclonal antibodies--BNH9 and BNF13--were generated by using a human lung adenocarcinoma cell line and standard hybridoma techniques. Both were found to react with epithelial and endothelial cells in routinely fixed and embedded tissues. Unexpected membrane labelling of some large cell lymphomas while non-reacting with normal lymphoid cells, prompted further characterisation. The antibodies were found to recognise red blood cell-related oligosaccharide antigens. The specificities were directed towards H and Y determinants. A distinctive pattern of reactivity was found for BNH9 in studying 480 cases of various lymphoid neoplasms. Strong expression of H and/or Y antigens was observed in 65/127 (51%) cases of anaplastic large cell(ALC) (CD30+) lymphomas, which are also known to co-express epithelial membrane antigen (EMA) frequently. Only a minority (less than 6%) of other non-Hodgkin's lymphomas (NHL) (CD30-,EMA-; 208 cases) and Hodgkin's disease (HD) (CD30+, EMA-; 126 cases) were positive. Expression of H and Y antigens was inducible on normal lymphocytes by mitogenic stimulation and by Epstein-Barr virus infection. The data suggest remarkable biological differences of ALC lymphomas within NHL and from HD.

Antibodies, Monoclonal↗
PubMed1991

MR imaging in hemophilic arthropathy.

20 children with hemophilia were examined with Magnetic Resonance Imaging (MRI) to determine if MRI could be used to assess hemophilic arthropathy, especially in the early stages. 28 joints of the appendicular skeleton were imaged, including 17 knees, 10 ankles and 1 elbow. The results were compared to clinical and plain radiographic assessments and to the surgical findings when synovectomy was performed. MRI is able to evaluate the components of hemophilic arthropathy such as fluid effussion, synovial hypertrophy, the status of the articular cartilage, and bony lesions. These lesions can be discovered at an early stage when plain radiographs are still normal. MRI seems to be useful for the selection of patients needing early treatment of hemophilic arthropathy and in monitoring response to therapy.

Adolescent↗
PubMed1991

Clinical and economic evaluation of health care technologies: a joint and sequential approach.

Promising new technologies have to be carefully analyzed before their integration into clinical practice. Moreover, the existing technologies need to be confronted with the new ones in terms of effectiveness and efficiency. Logical guidelines for both clinical and economic evaluation are described in the present review paper which mainly deals with diagnostic technology. All the proposed steps are not instrumental for each technology assessment but they provide a more rational approach to the acceptance and diffusion of technology.

Cost-Benefit Analysis↗
PubMed1991

Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations in conscious dogs.

BACKGROUND: Increased plasma concentrations of endothelin-1, a potent vasoconstrictor produced by the endothelium, have been reported in various pathological conditions. This study was conducted to evaluate effects of endothelin-1 at pathophysiological and pharmacological plasma concentrations. METHODS AND RESULTS: Endothelin-1 was infused at increasing doses (2.5, 5, 10, and 20 ng/kg.min for 1 hour each) in nine conscious dogs. During endothelin-1 infusion, plasma endothelin-1 rose from a basal value of 1.8 +/- 0.4 pmol/l to 5.8 +/- 1.1 (pathophysiological), 20.8 +/- 3.9 (pathophysiological), 85.4 +/- 18.9 (pharmacological), and 311.4 +/- 55.7 (pharmacological) pmol/l at each dose, respectively. Heart rate increased at 2.5 ng/kg.min (from 129 +/- 7 to 146 +/- 12 beats/min) but decreased at 20 ng/kg.min (97 +/- 7 beats/min) (p less than 0.001). Such a biphasic response was also observed for peak (+)dP/dt and (dP/dt)/DP40 (p less than 0.005). Left ventricular systolic pressures, mean aortic pressure, and left atrial pressure increased over time (p less than 0.05, p less than 0.005, and p less than 0.001, respectively). The time constant of early isovolumic relaxation rose progressively (p less than 0.001). The percent systolic shortening decreased at 10 and 20 ng/kg.min (p less than 0.005). Pressure-segment length loops showed a reduction in systolic shortening associated with an increase in left ventricular systolic pressure at 20 ng/kg.min. Atrial natriuretic factor rose after 5 ng/kg.min from 28.5 +/- 6.5 to 92.0 +/- 18.2 pmol/l (p less than 0.005). Angiotensin II and catecholamines did not change significantly. Serum urea and creatinine rose progressively (p less than 0.05), whereas glucose decreased (p less than 0.05). The above results differed significantly from measurements obtained in a time-control group of six dogs. CONCLUSIONS: A fourfold increase of plasma endothelin-1 obtained after doubling the infusion rate suggests a reduction in endothelin-1 clearance or endothelin-1 endogenous production. The biphasic response of heart rate is consistent with baroreflex-mediated effects resulting from vasodilation at the pathophysiological level and vasoconstriction at the pharmacological level. Hemodynamic data suggest an increase followed by a decrease in contractility at both levels, respectively. Finally, endothelin-1 is a stimulator of atrial natriuretic factor.

Animals↗
PubMed1991

Improved survival at 2 and 5 years in the LMCE1 unselected group of 72 children with stage IV neuroblastoma older than 1 year of age at diagnosis: is cure possible in a small subgroup?

The objectives of this study were to determine (1) the role of selection before bone marrow transplantation (BMT), (2) the role of vincristine, melphalan, and total body irradiation (TBI) as consolidation of induction therapy for stage IV over 12 months at diagnosis, and (3) the role of immunomagnetic purging in metastatic neuroblastoma. Among 72 consecutive unselected patients, 10 were not grafted (four died at induction: two in complete remission [CR], two in partial remission [PR]); three had bone marrow progression before harvest; one had uncontrolled progression; and two had parental refusal). Sixty-two patients were grafted (23 in CR/very good PR [VGPR] and 39 in PR). Among the 62, 33 were consolidated with at least 90% excision of their initial tumor excised (53.2%), 15 with catecholamine secretions (24.2%), 22 with minor bone marrow involvement (35.5%), and 31 with positive bone scan (50%). Median observation time is 59 months. Progression-free survival (PFS) for the 10 excluded patients was 20% at 2 years and 0% at 4 years. PFS for the grafted population (n = 62) is 40% at 2 years, 20% at 4 years, and 13% at 7 years. No difference was observed between patients grafted in CR/VGPR or in PR. However, a group of 19 children was grafted resulting in complete normalization of metastasis (regardless of primary-site tumor status). In this group, PFS at 59 months was 38% with no relapses up to 7 years post-BMT. A group of 31 patients with no bone involvement at BMT was also identified. PFS at 5 years is 30% compared with 12% for bone-positive patients at BMT. Moreover, the 11 children presenting at diagnosis with no bone involvement (Evans stage IVS or stage C Memphis) and consolidated with BMT had PFS at 5 years of 50% with no late relapses. A subgroup of stage IV neuroblastoma patients older than 1 year of age at diagnosis may be curable with this therapeutic approach, and the use of multivariate analyses to search for prognostic factors is warranted in currently existing international registries.

Age Factors↗
PubMed1991

[Prenatal diagnosis of neuroblastoma].

One of the prognostic factors for neuroblastoma is age at the time of diagnosis: neuroblastoma detected prenatally or in the first year of live have a more favorable outcome. Antenatal diagnosis is essential early management. Knowledge of local tumor extent is invaluable in determining the appropriate treatment, and MR imaging has proved to be the most useful procedure in this regard.

Female↗
PubMed1991

Bacteriologic quality of intraoperative autotransfusion.

Controversies remain about the bacteriologic aspects of intraoperative blood salvage despite the widespread use of this technique. In this prospective study, intraoperative salvaged blood was cultured in 401 patients, according to a direct plating technique. Bacterial growth was detected in 12.7% of cases. These results were compared with those obtained in control studies with sterile water and blood bank units under the same culture conditions. Most microorganisms were coagulase-negative staphylococci, followed by other skin and environmental contaminants. Quantitative estimates of contaminations showed low counts of colony-forming units (CFU/ml): 82% of positive cultures yielded 1 or 2 CFU/ml and 6% had 5 to 20 CFU/ml. Patients were followed up for a minimum of 3 months to detect septic complications. No statistically significant correlation could be found between bacteriologic results of autotransfused blood and infectious complications. This study suggests that bacteriologic monitoring of patients who have undergone autotransfusion may help in detecting surgical field contamination. It also confirms that intraoperative autotransfusion adds little septic risk to cardiac surgery.

Bacteria↗