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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 397 records · Page 22Linked to original sources
PubMed1989

Signal transmission after GLP-1(7-36)amide binding in RINm5F cells.

Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], probably representing an important incretin, binds to receptors on RINm5F cells resulting in an adenosine 3',5'-cyclic monophosphate increase. Guanine nucleotides (GTP, GTP-gamma-S, GDP-beta-S) decreased the binding of GLP-1(7-36)amide to receptors on RINm5F cell membranes. Further analysis revealed that GTP (10(-4) M) decreased the receptor affinity with an increase of the Kd from 2.5 +/- 0.99 x 10(-10) M to 9.43 +/- 2.16 x 10(-10) M. In cross-linking experiments the amount of labeled peptide linked to receptors was reduced in the presence of GTP (10(-4) M). Further studies investigated the involvement of membrane depolarization or changes in the cytosolic free calcium level in the intracellular signaling of GLP-1(7-36)amide-induced insulin secretion. In contrast to fuel and nonfuel secretagogues, GLP-1(7-36)amide did not cause a depolarization of the membrane potential. This was unaffected by various glucose concentrations (0-20 mM) or by previous cell depolarization by D-glyceraldehyde. Similarly, the cytosolic calcium concentration remained unchanged after addition of GLP-1(7-36)amide (10(-12)-10(-8) M). The effect of guanine nucleotides on binding of GLP-1(7-36)amide indicates that the action of the peptide is mediated by the adenylate cyclase system. GLP-1(7-36)amide binding neither changed the membrane potential nor altered the intracellular calcium concentration, making an involvement of the inositol 1,4,5-trisphosphate pathway or an activation of protein kinase C in the postreceptor signaling after GLP-1(7-36)amide binding unlikely.

Adenoma, Islet Cell↗
PubMed1989

Omeprazole: long-term safety.

Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H2-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H2 blockers if administered in doses recommended for treatment of peptic diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1989

Influence of chronic rioprostil treatment on gastric endocrine function.

The influence of 4 weeks of treatment with the prostaglandin E1 analogue, rioprostil, 300 micrograms b.i.d., or placebo, on gastric endocrine function is tested in healthy male volunteers. Basal serum gastrin levels and postprandial gastrin output are unchanged after treatment with rioprostil. Similarly, plasma pancreatic polypeptide levels are unaffected. Antral gastrin tissue concentrations as well as antral somatostatin concentration and volume densities of antral G-cells and D-cells are unchanged. Neither basal nor pentagastrin-stimulated gastric acid secretion after rioprostil therapy differ from pretreatment values. Rioprostil, given in a dose of 100 micrograms b.i.d. to rats for 1 week significantly increases antral mucosal height but has no influence on the mucosal concentrations and cell densities of the gastric peptides, gastrin and somatostatin. It is concluded that rioprostil in the dose used does not affect the endocrine stomach after 4-weeks' administration at a dose of 300 micrograms b.i.d.

Adult↗
PubMed1989

Do bile acids exert a negative feedback control of cholecystokinin release?

The influence of intraduodenal bile deficiency due to chronic bile duct obstruction and acute exogenous administration of bile acids on plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) was investigated. Fourteen patients with tumor-induced bile duct stenosis and five healthy volunteers were given a liquid test meal. Four of the patients had a simultaneous pancreatic duct stenosis. On another day 4 g chenodeoxycholic acid were administered concomitantly with the liquid test meal in six of the patients and all controls. Basal and meal-stimulated plasma CCK did not differ between patients and controls. A pancreatic duct stenosis, which was associated with diminished plasma PP concentrations, had no influence on plasma CCK release. Exogenous bile acids significantly reduced the postprandial CCK response in both groups. Bile-induced inhibition was significantly greater in patients than in controls (75 +/- 7% and 44 +/- 11%, respectively; p less than 0.05). It is concluded that intraduodenal bile is an important modulator of the postprandial secretory activity of the CCK cell. Although chronic intraduodenal bile acid reduction in tumor-induced biliary duct stenosis did not influence plasma CCK levels, a negative feedback control of plasma CCK by acute bile acid administration could be demonstrated.

Adult↗
PubMed1989

Evaluation of remission state in chronic myeloid leukemia patients after bone marrow transplantation using cytogenetic and molecular genetic approaches.

The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.

Adolescent↗
PubMed1989

Anomalous origin of the left coronary artery from the pulmonary trunk. Anatomic findings in relation to pathophysiology and surgical repair.

Anomalous origin of the left coronary artery from the pulmonary trunk, though a discrete anatomic malformation, manifests a spectrum of clinical and pathologic consequences. The objectives of this study were to characterize the primary anatomic findings in a group of specimens with anomalous left coronary artery and the extent of secondary morphologic and pathologic changes. Although the cases studied probably represent the least favorable end of the spectrum, the observed pathogenesis and evolution of secondary changes suggest that reconstruction of a two-coronary arterial system supplied through two coronary arteries would be advantageous to most patients. A high origin of the right coronary artery or location of the left coronary artery adjacent to a pulmonary cusp or branch may complicate the tunnel-type repair. In these cases, transfer of the left coronary artery to the aorta may be preferable.

Abnormalities, Multiple↗
PubMed1989

[Validity of immunohistology and in situ hybridization in the differential diagnosis of cytomegalovirus pneumonia and idiopathic interstitial pneumonia after allogenic bone marrow transplantation].

Interstitial pneumonia (IP) is currently the most frequent and severe complication of allogeneic bone marrow transplantation (BMT). Post-BMT-IP is due partially to infection by cytomegalovirus (CMV-IP) and partially to idiopathic induction (IIP). Because of the different therapeutic consequences it is important to distinguish between these two kinds of pneumonia. Therefore, the validity of immunohistochemistry (IHC) and in situ hybridization (ISH) for the differential diagnosis of CMV-IP and IIP was studied. The investigations were performed using postmortem tissue samples (lung) of 23 patients decreased after allogeneic BMT. In 22 of the 23 patients the primary cause of death was IP (CMV 13x, idiopathic 7x, pneumocystis 1x, toxoplasmosis 1x). One patient died from thrombopenic cerebral bleeding. All 3 CMV-detecting systems tested disclosed certain advantages and disadvantages. The sensitivity of routine histology was 12/13 (92.3%), of IHC 13/13 (100%), and of ISH 12/13 (92.3%). The specificity corresponded to the order: ISH greater than IHC greater than histology. The application of ISH and IHC did not change significantly the routine histologic classification of pneumonias into CMV-IP and IIP. The validity of the three procedures used for detecting CMV in patients after allogeneic BMT is discussed in detail.

Bone Marrow Transplantation↗
PubMed1989

Allogeneic bone marrow transplantation for myelodysplastic syndromes (MDS).

In the literature 63 patients with myelodysplastic syndromes (MDS) are reported who were treated with syngeneic or allogeneic bone marrow transplantation. 62 patients were prepared for BMT with TBI containing regimens or Busulfan/Cyclophosphamide. GvHD prophylaxis was heterogenous. 33/63 patients are alive and well between 4 and 132 months after BMT. 23/63 patients died due to GvHD (n = 6), interstitial pneumonitis (n = 6), other infections (n = 4), toxicity of the preparative regimen (n = 5) or graft failure (n = 2). 9/63 patients relapsed between 2 and 98 (in median 6) months after BMT. There seems to be a correlation between the subtype of the MDS and the relapse rate: only 1/18 patients with RA/RARS relapsed compared to 7/42 patients with RAEB/RAEB-T. These results indicate that marrow transplantation can induce long term survival and may result in cure of patients with MDS.

Adolescent↗
PubMed1989

Homograft replacement of the pulmonary artery bifurcation.

Severe deformity or nonconfluence of the pulmonary arteries was repaired during correction of congenital heart defects by implantation of a complete, fresh, antibiotic-sterilized homograft pulmonary artery bifurcation in 17 patients, aged 15 months to 17 years. Six patients had Fallot's tetralogy; five, pulmonary atresia and ventricular septal defect; three, truncus arteriosus; two, ventricular septal defect; and one, pulmonary atresia with intact ventricular septum. All but one had previously undergone one or more palliative or corrective operations. Thirteen patients survived the operation (76%; 70% confidence interval = 61% to 88%) and were followed up from 2 to 56 months postoperatively (mean = 16 months). All had symmetrical pulmonary perfusion on chest x-ray films and satisfactory homograft function on Doppler echocardiograms. There were no late deaths or reoperations. Four patients (24%; 70% confidence interval = 12% to 39%) died in the hospital of pulmonary or cardiac dysfunction despite a technically satisfactory reconstruction. Comparison of predicted and observed ventricular pressure ratios in nine patients showed that the factor contributed by a right pulmonary artery branch stenois was cancelled in most. The use of a complete, adult-size homograft has thus facilitated reconstruction of the pulmonary artery bifurcation and given encouraging early results.

Adolescent↗
PubMed1988

[Segmental colonic stenosis in intestinal metastasis of breast carcinoma. A contribution to the differential diagnosis of colitis].

Four years after mastectomy for a scirrhous carcinoma a 71-year-old woman developed diarrhoea. Crohn's disease was suspected. At endoscopy a stenosis of the sigmoid colon was found which could not be passed: the mucosa was normal looking. Gastrointestinal radiography revealed segmental subtotal stenoses of the colon with linitis plastica, typical for tumour-caused infiltration, as well as indentations in the small intestine by mesenteric metastases. The diagnosis was confirmed by computed tomography and, finally, operation. Chemotherapy failed to produce any regression of the colon stenoses, and the patient died from mechanical ileus. In case of a similar history and colon stenoses of uncertain aetiology the possibility of intestinal metastases should be considered in the differential diagnosis.

Adenocarcinoma, Scirrhous↗
PubMed1988

[Bone marrow transplantation as therapy in chronic myeloid leukemia].

Between April 1982 and December 1986, HLA-identical bone marrow transplantations were performed on 25 patients with Philadelphia chromosome-positive chronic myelocytic leukaemia (CML), 18 in the chronic phase, 7 in acceleration or blast crisis. Twelve of the 18 patients (67%) in the chronic phase are still alive a median period of 570 days after transplantation, but only two of the seven (29%) in acceleration or blast crisis a median period of 227 days after transplantation (P less than 0.025). The duration of the chronic phase was of great importance for survival after transplantation: 86% of patients in the chronic phase for less than two years survived, but all patients in the chronic phase for over two years died (P less than 0.001). CML relapses occurred in one patient in a late chronic phase and in two in an advanced stage of the disease. These results confirm the unfavorable outcome of bone marrow transplantation in the accelerated phase or blast crisis, as well as in the late chronic phase. Since at present there are no reliable risk factors for the occurrence of acceleration or blast crisis, bone marrow transplantation should be undertaken as early as possible in the chronic phase of CML.

Adolescent↗
PubMed1988

Plasma CCK levels in patients with pancreatic insufficiency.

After stimulation with a Lundh test meal, plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and output of pancreatic enzymes were measured in 33 patients with exocrine pancreatic insufficiency and 26 healthy subjects. Patients with impairment of pancreatic function were subdivided into those with moderate and severe insufficiency. Plasma CCK and PP were measured by radioimmunoassay. Fasting plasma CCK in patients with pancreatic insufficiency (5.8 +/- 1.1 pmol/liter) did not differ significantly from controls (4.2 +/- 0.6 pmol/liter). After endogenous stimulation with a Lundh meal, plasma CCK increased in both groups without significant differences over 2 hr. Basal and stimulated plasma levels of pancreatic polypeptide (PP) were markedly decreased only in patients with severe pancreatic insufficiency. Our results demonstrate that basal and meal-stimulated CCK levels in patients with pancreatic insufficiency do not differ from controls. Furthermore the extent of functional impairment of the exocrine pancreas did not influence basal and postprandial CCK release.

Adult↗
PubMed1988

Antimicrobial prophylaxis in neutropenic patients after bone marrow transplantation.

Fourty-one patients with haematological malignancies or severe aplastic anaemia underwent allogeneic or syngeneic bone marrow transplantation and received one of two forms of infection prophylaxis while granulocytopenic: total decontamination in strict reverse isolation (ITD, 26 patients) or selective decontamination of the digestive tract with barrier nursing (SD, 15 patients). The patients were evaluated for infection acquisition, fever days, days on systemic antibiotics and granulocyte transfusions from 48 hours after the beginning of the decontamination procedure until 1,000 granulocytes/microliter have been reached. Ten of 26 patients of the ITD group remained free of febrile episodes and infections, whereas all patients of the SD group acquired infections (p less than 0.001). During granulocytopenia patients of the ITD group had fewer fever days, were less frequently on systemic antibiotics and received fewer granulocyte transfusions as compared with the SD group. Both methods were obviously very effective in preventing gram-negative infections, infections caused by Staphylococcus aureus and infections due to yeasts or fungi. No death due to infection occurred in either group. However, the data of this study provide evidence that ITD is a more effective antimicrobial prophylaxis in bone marrow transplant recipients than SD.

Adolescent↗