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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 19 recordsLinked to original sources
PubMed1992

Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. METHODS: We determined the frequency with which host-specific interleukin-2-secreting donor T-cell precursors occurred in 16 consecutive pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after transplantation. RESULTS: High frequencies of host-specific T-cell precursors (> or = 1 per 100,000) were detectable before transplantation in eight donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to eight patients with mild (grade 0 or 1) acute GVHD, low frequencies (< 1 per 100,000) were found. CONCLUSIONS: Analysis of the frequency of such cells before transplantation may be a useful predictor of severe acute GVHD in allogeneic bone marrow transplantation between HLA-identical siblings. It is possible that the patients at risk for serious acute GVHD after marrow grafting may benefit from some alternative form of immunosuppressive therapy.

Acute Disease↗
PubMed1992

Low hepatic clearance of peptide YY (PYY) in the perfused rat liver.

The hepatic clearance rate and secretion rate mainly determine peripheral plasma concentrations of regulatory peptides released from the gastrointestinal tract. In the present study hepatic extraction of peptide YY (PYY) during a single passage was investigated in the in situ perfused rat liver excluding modulating actions of circulating hormones. During perfusion of low amounts of PYY (50, 100, 500 pmol l-1), peptide concentrations in the portal vein (5.1 +/- 4.6, 98.1 +/- 2.6, 558 +/- 13.6 pmol l-1) and in the hepatic vein (50.2 +/- 1.4, 88.6 +/- 2.2, 503 +/- 18.1 pmol l-1 was only 22.1%. PYY had no influence on hepatic glucose and lactate production, portal flow as well as bile flow and bile acid secretion at these concentrations. PYY seems to traverse the liver almost intact and reaches the target organs without any significant hepatic extraction. Concomitant studies on metabolic and excretory functions of the liver showed no effect of PYY.

Animals↗
PubMed1992

Balloon dilatation of the arterial duct in congenital heart disease.

The systemic circulation of newborn infants with congenital left-heart obstruction is supplied from the right ventricle via a patent arterial duct between the pulmonary artery and descending aorta. The duct closes during the first few days of life, but infusion of prostaglandin E2 can prevent closure in some cases. We report four newborn infants (aged 3-8 days) with intractable heart failure due to severe obstruction of the left heart in the presence of a closing arterial duct. Infusion of prostaglandin E2 did not improve their clinical condition. Cardiac catheterisation and balloon dilatation of their arterial ducts resulted in a dramatic improvement in the babies' clinical condition; during subsequent surgical repair of the infants' hearts, the arterial ducts were found to be widely patent. Balloon dilatation gives immediate and sustained wide patency of the arterial duct in infants who do not respond adequately to prostaglandin E2.

Catheterization↗
PubMed1992

Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin.

The aim of the present study was to assess the role of cholecystokinin and neurotensin in converting the cyclical interdigestive pattern of pancreatic secretion into the non-cyclical fed pattern. Six healthy male volunteers were studied on 4 separate days. During each experiment a mixed liquid meal or solutions of individual nutrients were perfused intraduodenally for 180 min at 2 ml/min. The mixed meal contained 4.3 g glucose, 2.0 g fractionated soya oil, and 1.7 g casein hydrolysate per 100 ml, which delivered a caloric load of 0.9 kcal/min into the duodenum. The isocaloric and isotonic solutions of individual nutrients contained 44.5 g glucose, 17.8 g fractionated soya oil, or 44.5 g hydrolysed serum bovine albumin per liter and delivered 0.36 kcal/min into the duodenum. Duodenal aspirates and blood samples were collected at regular intervals for determination of pancreatic enzyme outputs and plasma levels of cholecystokinin and neurotensin, respectively. The mixed meal converted the cyclical interdigestive secretory pattern into the noncyclical fed pattern whereas none of the three individual nutrients abolished the interdigestive pattern. Not only the mixed meal but also lipid and protein perfusion consistently stimulated cholecystokinin release. Integrated incremental cholecystokinin release amounted to 32.3 +/- 9.9 pg/ml x 180 min with the mixed meal, 23.2 +/- 6.5 with lipid perfusion (P < 0.05 versus mixed meal) and 13.4 +/- 3.8 with protein perfusion (P < 0.05 versus mixed meal). The carbohydrate solution did not significantly release cholecystokinin. None of the duodenal perfusates raised neurotensin plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Somatostatin in preoperative therapy and postoperative diagnosis of a patient with Verner Morrison syndrome].

We report the case of a patient with Verner-Morrison syndrome due to a malignant MEN I-associated vipoma. Marked tumor-associated hypercalcemia could be treated successfully with somatostatin analogues prior to surgical therapy of the pancreatic tumor. Sixteen months after extirpation of the primary tumor recurrent tumor growth was diagnosed; at this time the patient was clinically asymptomatic and had no abnormal laboratory test results. Liver metastases and local metastases were identified using somatostatin receptor scintigraphy. We report and discuss the use of somatostatin in the treatment of tumor-associated symptoms in endocrine tumors and the possibility of identifying endocrine tumors by means of somatostatin receptor scintigraphy.

Adult↗
PubMed1992

Parvovirus B19 infection and bone marrow transplantation.

Parvovirus B19 lytically infects erythroid progenitor cells and thereby causes cessation of erythropoiesis in infected individuals. Anemia develops only if red cell turnover is increased, as in patients with chronic hemolysis (transient aplastic crisis). In addition to transient marrow failure, B19 can cause chronic anemia and, rarely, pancytopenia in immunodeficient patients who are not able to mount an adequate immune response to clear the virus. Bone marrow transplantation, although causing significant immunosuppression, is rarely complicated by symptomatic B19 infection. This is probably due to effective passive immunotherapy by immunoglobulin infusions immediately after transplantation and early reconstitution of antibody responses after uncomplicated transplantation.

Adult↗
PubMed1992

Effect of gastrin receptor blockade on endocrine cells in rats during achlorhydria.

Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug-induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Gastroenteropancreatic endocrine tumors: effect of Sandostatin on tumor growth. The German Sandostatin Study Group.

One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 micrograms Sandostatin three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatin cannot prevent disease progress when it is far advanced. In the evaluation of 68 patients monitored for at least 3 months, partial regression was observed in 4.4%, stable disease in 50%, and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.

Endocrine Gland Neoplasms↗
PubMed1992

Absent left-sided atrioventricular connexion, with right atrium connected to left ventricle: prospective diagnosis in infancy, and outcome.

Prospective echocardiographic diagnosis of absence of the left atrioventricular connexion, with the right atrium connected to a morphologic left ventricle through a bileaflet morphologically mitral valve, was made in six infants. The rudimentary right ventricle was left-sided in all patients, and separated from the left atrium by sulcus tissue. The ventriculoarterial connexions were discordant. Associated defects included subpulmonary stenosis (2 patients), pulmonary atresia (1 patient), and a patent duct (4 patients). All patients developed early left atrial hypertension due to a restrictive interatrial septum, and required transcatheter septostomy (5 patients), or surgical septectomy (3 patients). One patient who had a severely restrictive ventricular septal defect died following cardiac catheterization. In three others the ventricular septal defect has become progressively restrictive on serial catheterization. Successful intermediate term palliation has been performed in two patients using a bidirectional Glenn anastomosis, together with enlargement of the ventricular septal defect and a Damus-Kay-Stansel procedure in one. It is possible to distinguish this malformation from "mitral atresia" using cross-sectional echocardiography. The long-term outlook is influenced by early relief of left atrial hypertension. Balloon atrial septostomy alone is usually inadequate, and either blade septostomy or surgical septectomy are required. Serial cardiac catheterization is mandatory for planning definitive palliation.

Cardiac Catheterization↗
PubMed1992

Thrombolysis with tissue-type plasminogen activator following cardiac surgery in children.

Three children with major intracardiac or vascular thrombosis following cardiac operations were treated with intravenous recombinant tissue-type plasminogen activator. The first patient, aged 10 yr, developed a left atrial thrombus following replacement of the mitral valve with a Björk-Shiley prosthesis. The second patient, aged 16 months, had a right atrial thrombus following a modified Fontan procedure for tricuspid atresia. Both were successfully treated with a short course of intravenous tissue plasminogen activator. The third patient, aged 19 months, developed the Budd-Chiari syndrome with occlusion of the inferior caval vein following a modified Fontan operation for double inlet left ventricle. Even though near-complete thrombolysis and recanalization of the inferior caval vein was achieved with three courses of tissue plasminogen activator on successive days, she died with failure of multiple organs. In all cases, the diagnosis was established by cross-sectional and Doppler echocardiography, and the response to therapy was monitored using the same technique. Thrombolytic therapy with systemic tissue-type plasminogen activator was safe and effective in the postoperative period, with no major haemorrhagic complications.

Cardiac Surgical Procedures↗
PubMed1992

Ethical conflicts in the prehospital setting.

STUDY OBJECTIVE: To assess the range of ethical conflicts that confront prehospital care providers. DESIGN: Convenience sample, from October 1989 to January 1990. SETTING: An urban advanced life support emergency medical service that transports approximately 3,000 patients per month. METHODS: Six hundred seven paramedic responses were analyzed by a single observer. An ethical conflict was identified when the paramedic faced a dilemma about what "ought to be done" and the paramedic's values conflicted or potentially conflicted with the patient's. Cases with potential ethical consequence were brought to experts in medical ethics and epidemiology for further analysis and classification. RESULTS: Ethical conflicts arose in 14.4% of paramedic responses (88 of 607 cases). Twenty-seven percent of the conflicts involved issues of informed consent, such as refusal of treatment or transport, conflicts of hospital destination, treatment of minors, and consent for research. Difficulties regarding the duty of the paramedics, usually under threatening circumstances, accounted for 19% of the dilemmas encountered. Requests for limitation of resuscitation accounted for 14%. Other circumstances that presented ethical conflicts involved questions of patient competence (17%), resource allocation (10%), confidentiality (8%), truth telling (3%), and training (1%). CONCLUSION: The data demonstrate a range of ethical conflicts in the prehospital setting and point to areas in which policy needs to be developed. The data also can be used in a prehospital ethics curriculum for paramedics and physicians. Because case sampling was not strictly random, absolute conclusions should not be drawn regarding the frequency of the dilemmas.

Beneficence↗
PubMed1992

Healing and relapse of duodenal ulcer during ranitidine therapy in the elderly. The RUDER Study Group.

A total of 2,109 outpatients with active duodenal ulcer (DU) entered an open, prospective study in order to investigate factors influencing healing and relapse during 2 years of ranitidine therapy (300 mg daily for healing, 150 mg as maintenance treatment). In a retrospective analysis, we evaluated the influence of age. Symptoms related to DU in 1,899 evaluable cases in patients over 65 years of age (n = 185) were identical to those of DU patients younger than 65 years old (n = 1,714). Rapid healing within 2 weeks of ranitidine therapy was less frequent in the elderly (32.5%) than in younger patients (40.7%) though identical healing rates (94.1%) in each group were achieved by continuation of ranitidine therapy for 8 weeks. Cumulative recurrence rates during the 2 years of long-term therapy were lower (17.3%) in old age than in patients under 65 years of age (23.3%). Adverse events were rare in both age groups. We conclude that DU healing during ranitidine is delayed in old age. Additional differences in relapse rates in favor of the elderly suggest that DU disease has a different course in the elderly.

Adult↗
PubMed1992

Stimulation of insulin release is uncoupled from insulin biosynthesis in tumoral RINm5F cells.

RINm5F cells, an insulin-secreting subclone of a rat insulinoma cell line, were incubated in serum-free medium up to 24 hours in the presence or absence of glucagonlike peptide-1(7-36)amide in various concentrations, 3-isobutyl-1 methylxanthine (1 mM), choleratoxin (10 nM), carbachol (1 mM), and potassium (40 mM). Insulin release and biosynthesis were measured by the immunoreactive insulin content of the cells and the medium. Steady-state levels of insulin-specific mRNA were determined by Northern and slot blot analysis. Short-term insulin release is significantly stimulated by all secretagogues tested. A significant increase of insulin biosynthesis by any of the various secretagogues was not detectable on the peptide and mRNA level. Sodium butyrate (1 mM), a differentiating agent, increased insulin-specific mRNA levels in RINm5F cells after 72 hours. In conclusion, substances known to stimulate short-term insulin release in RINm5F cells do not stimulate insulin biosynthesis, indicating an uncoupling of insulin secretion and biosynthesis in these transformed beta cells.

Animals↗
PubMed1992

Recurrent acute pancreatitis and intraluminal duodenal diverticulum.

An intraluminal duodenal diverticulum (IDD) and a partial pancreas divisum were diagnosed in a 22-year-old man who exhibited recurrent attacks of acute pancreatitis. Resection of the diverticulum resulted in a complete disappearance of symptoms. The possible etiological relationship between IDD and recurrent acute pancreatitis is discussed.

Acute Disease↗
PubMed1992

Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man.

A highly specific monoclonal antibody directed against the C-terminal part of glucagon-like peptide-1 (GLP-1) was raised to immunohistochemically evaluate the distribution of GLP-1 containing cells in the entire gastrointestinal tract including pancreas of rat, pig and man. In the pancreas GLP-1-immunoreactive cells were found variously shaped and predominantly located in the periphery of the islets. Ultrastructurally, GLP-1 was co-localized with glucagon in the alpha-granula of A-cells and was mainly restricted to the electrondense core. In the intestine open type cells reaching the lumen via a slender apical process were stained with the GLP-1 antibody. They occurred in all parts of the crypts but predominantly in the basal portion. The density of GLP-1 immunoreactive cells varied between species in a characteristic order: rat greater than pig greater than man. In pig and human gut a large number of cells occurred in the distal jejunum and ileum. A continuous increase of cell densities was found from the proximal to the distal colon resulting in highest numbers in the rectum. In rats the highest cell density occurred in the ileum. Again, a continuous increase of GLP-1-positive cell numbers was evident from the proximal to the distal portion of small and large bowel. GLP-1 was partly co-localized with PYY. The GLP-1 positive cells appeared electronmicroscopically as L-cells with the typical large granula. This morphological data indicates that GLP-1-releasing cells in the small intestine are appropriately positioned in the distal part to sense and respond to the presence of nutrients that have escaped the absorptive surface of the upper small intestine.

Animals↗