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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 379 records · Page 21Linked to original sources

[In vivo effects of high density lipoprotein rich serum fractions (HDLF) in the human. 1. Modification of circulating thrombocyte aggregates, cardiovascular parameters and lipid metabolism by HDLF].

By means of the modified Cohn-method 6 Cohn-IV-1-fractions were prepared in the small pool technique as sterile, pyrogen-free and HDL-rich serum fractions (HDLF), the HDL-concentrations of which were 15-20 g/l. In in-vitro investigations they inhibited the spontaneous aggregation of erythrocytes as well as the ADP-induced aggregation of thrombocytes and activated the molar and fractional initial cholesterol estirification rates as well as the prostacyclin synthesis. From HDLF intravenously applied in people as immediate effects result significant decreases of the cardiac pre- and afterload, an increase of the cardiac ejection fraction as well as a complete dissolution of circulating aggregates of thrombocytes. In 35 patients with hyperlipidaemias after infusion of 100 ml HDLF up to the 5th day increasing and for 14 days remaining increases of concentration of biliary bile acids, total phospholipids and of cholesterol were observed in lithogenic indices remaining in the normal region. The plasmatic lipo- and apolipoproteins reacted with increases, decreases or constancy of concentration which might be based on the different ethryopathogeneses of the hyperlipoproteinaemias.

Cholesterol, HDL↗

Modulation by somatostatin of nerve-mediated activation of glycogenolysis in the perfused rat liver.

Perivascular nerve stimulation of rat livers perfused in situ with erythrocyte-free Krebs-Henseleit buffer at constant pressure in a non-recirculating system resulted in an increase of glucose and lactate production and in a decrease of portal flow. Infusion of somatostatin in different concentrations (2 x 10(-7), 10(-8), 10(-9) mol.l-1) reduced the nerve-mediated activation of glucose release maximally to 66%. There was only a slight effect on the lactate output, the nerve-mediated reduction of portal flow was unaltered. In controls, somatostatin alone had no effect on the metabolic and hemodynamic parameters. In order to differentiate between a presynaptic and postsynaptic mechanism, the noradrenaline overflow was calculated. The unaltered release of the neurotransmitter in the presence or absence of somatostatin excluded a presynaptic mechanism. To mimic the nerve effects on the carbohydrate metabolism and on the hemodynamics, noradrenaline (2 x 10(-7) mol.l-1) was infused instead of the nerve stimulation over a period of 5 min. Somatostatin did not change the endocrine effects of the catecholamine under these conditions. The nerve-dependent effect of somatostatin suggests that other neurotransmitters (e.g. VIP) or mediators (e.g. prostanoids) may be influenced by somatostatin.

Animals↗

[Treatment of acute stomach ulcer with H2 receptor antagonists. A direct therapy comparison with 300 mg nizatidine nightly and 2 times 150 mg nizatidine with twice daily 150 mg ranitidine].

In this endoscopically controlled, double-blind study involving 242 patients with acute benign gastric ulcer, it was shown that the selective inhibition of nocturnal gastric acid secretion with 300 mg nizatidine administered on retiring represents an effective and reliable form of therapy. After four weeks of treatment, 90% of the patients receiving 300 mg nizatidine, no longer experienced nocturnal pain, in comparison with 83% receiving 2 X 150 mg nizatidine daily (n.s.). The total healing rates after four weeks were 60% in the patients receiving 300 mg nizatidine, 60% in those on 2 X 150 mg nizatidine daily, and 58% in those receiving 2 X 150 mg ranitidine daily. After eight weeks, the respective figures rose to 85%, 84% and 84%. Clinically relevant side effects were observed in none of the three groups. With a dose on retiring of 300 mg nizatidine, it is possible to accelerate the healing of a benign gastric ulcer, simply by the nocturnal suppression of gastric acid production, and, during the day, preserving physiological gastric function, thus avoiding the possible risks of protracted hypochlorhydria.

Adolescent↗

Physicians' attitudes toward using deception to resolve difficult ethical problems.

To assess physicians' attitudes toward the use of deception in medicine, we sent a questionnaire to 407 practicing physicians. The questionnaire asked for responses to difficult ethical problems potentially resolvable by deception and asked general questions about attitudes and practices. Two hundred eleven (52%) of the physicians responded. The majority indicated a willingness to misrepresent a screening test as a diagnostic test to secure an insurance payment and to allow the wife of a patient with gonorrhea to be misled about her husband's diagnosis if that were believed necessary to ensure her treatment and preserve a marriage. One third indicated they would offer incomplete or misleading information to a patient's family if a mistake led to a patient's death. Very few physicians would deceive a mother to avoid revealing an adolescent daughter's pregnancy. When forced to make difficult ethical choices, most physicians indicated some willingness to engage in forms of deception. They appear to justify their decisions in terms of the consequences and to place a higher value on their patients' welfare and keeping patients' confidences than truth telling for its own sake.

Adult↗

Characterization of phospholipase A2 activity in aspirates of human pancreatic pseudocysts after isolation by reversed-phase high performance liquid chromatography.

Phospholipase A (PLA) is able to attack membrane phospholipids and thereby plays a putative role in the pathogenesis of pancreatic pseudocysts. We looked for PLA2-like activity in aspirates from human pancreatic pseudocysts. In material originating from one cyst which occurred shortly after an acute pancreatitis attack, hydrolyzing enzymatic activity measured by a sensitive bioassay system for PLA2 activity was found without prior trypsin activation (67 x 10(3) U/min/100 microliters). A biochemical characterization of this hydrolyzing enzymatic activity was provided after resolution of the respective proteins contained in the cyst fluid by HPLC. High hydrolyzing activities were found in correspondence to one specific, early eluting peak. The purified enzyme had pH optima at 3.5 and 6. Addition of EDTA (5 mM) to the test system abolished the enzymatic activity which mirrored the requirement for calcium ions. The activity was optimal at calcium concentrations ranging from 1-2 mM. Higher calcium concentrations reduced the enzymatic activity. The enzyme showed high heat stability. SDS-gel analysis of the peak showed one single band with a molecular weight of about 20,000 Daltons. Our findings demonstrate the possibility of activated, PLA-like activity in human pancreatic pseudocyst fluid. We speculate that an inappropriate activation of this enzyme in peri- or intrapancreatic "fluid collections" could account for pseudocyst formation after an acute pancreatitis attack.

Calcium↗

Role of circulating catecholamines in the control of pancreatic polypeptide and gastrin release.

The influence of circulating catecholamines on the release of pancreatic polypeptide (PP) and gastrin was studied in volunteers. Physical exercise increased plasma epinephrine by 374 +/- 123% and plasma norepinephrine by 167 +/- 30%, but plasma PP concentrations remained unchanged during standardized bicycle ergometry. Immediately after cessation of exercise catecholamine levels decreased rapidly, whereas PP concentrations increased by 55%. In a second series, epinephrine infusion (5, 25, and 75 ng.kg-1.min-1) increased epinephrine levels by 38 +/- 12, 331 +/- 69, and 1229 +/- 131%, respectively, whilst norepinephrine was unaffected. Neither during nor after catecholamine infusion PP secretion was affected. Gastrin release increased by a maximum of 85 +/- 38% (at epinephrine 75 ng.kg-1.min-1). It is concluded, that (1) changes in circulating adrenaline do not significantly influence PP secretion in man; (2) the PP increase immediately following physical exercise cannot be attributed to a rapid fall of catecholamine levels; (3) endogenous catecholamines are of minor importance in the control of gastrin secretion.

Adult↗

Internalization of glucagon-like peptide-1(7-36)amide in rat insulinoma cells.

Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide] is supposed to be an important physiologic incretin. Recently, high affinity receptors for GLP-1(7-36)amide have been demonstrated on rat insulinoma-derived RINm5F cells. The present study examined the internalization and degradation of the GLP-1-receptor complex. Internalization of the peptide was time- and temperature-dependent. At 37 degrees C binding and internalization was rapid. At 60 min 35% of 125I-labeled GLP-1(7-36)amide was internalized. Incubation in the presence of increasing concentrations of non-labeled GLP-1(7-36)amide resulted in a decrease of internalization of 125I-labeled peptide indicating that this process is saturable. Incubation in the presence of 0.2 mM chloroquine, an inhibitor of intracellular hormone degradation, resulted in intracellular accumulation of 125I-GLP-1(7-36)amide. HPLC-supported analysis of cell content after internalization of 125I-GLP-1(7-36)amide during a 60-min incubation period at 37 degrees C revealed an elution profile showing two maxima of radioactivity: one represented intact labeled GLP-1(7-36)amide, the other an intracellular degradation product of the peptide. Chloroquine caused a 5-fold increase of the peak representing intact 125I-GLP-1(7-36)amide thus demonstrating inhibition of degradation of labelled peptide. Furthermore, a 4-fold increase of the other peak occurred possibly mirroring a delay of release of degradation products by chloroquine. It was excluded that chloroquine is able to interfere with GLP-1(7-36)amide-binding to its receptor.

Adenoma, Islet Cell↗

Release of tryptophan and serotonin into the portal vein of the isolated perfused rat small intestine.

To investigate the release of serotonin from intestinal enterochromaffin cells, we used an in vitro technique which allows studies excluding overlapping influences from outside the gut. The entire small intestine of rats fed a standard or tryptophan-enriched (3% of total) diet was totally isolated by ligatures with the exception of the superior mesenteric artery and portal vein that supply and drain the intestine. Simultaneously to the vascular perfusion (Krebs-Ringer bicarbonate buffer, 0.4% human albumin, 5 mM glucose, 0.6 mM glutamine) the gut lumen was infused (buffer or 0.1 N HCL). Acidification of the gut lumen resulted in an increment of venously released tryptophan and serotonin. After feeding tryptophan-enriched food the release of tryptophan was increased. However, the total amount of released serotonin after tryptophan diet did not differ as compared to that after standard diet. Addition of a monoamino-oxidase inhibitor (pargyline) to the arterial perfusate enhanced the released amount of serotonin 3-fold in the portal venous effluent (at a concentration of 1 mM but not 0.1 mM). Recovery studies done by arterial infusions of serotonin (1 microM, 10 microM) and evaluation of the amounts venously released revealed a high loss of infused serotonin (40%-70%). Our data suggest gut-born serotonin to more likely play a paracrine role than a role as a classical hormone.

Animals↗

Differential effects of atropine and a cholecystokinin receptor antagonist on pancreatic secretion.

The present study evaluates the effect of atropine and of the cholecystokinin receptor antagonist loxiglumide on feedback regulation of basal pancreatic secretion in 6 healthy volunteers. The intraduodenal instillation of the protease inhibitor camostate reduced enzymatic activities of trypsin and chymotrypsin by 80%. This was accompanied by a strong increase in amylase and lipase output. The intravenous infusion of atropine (5 micrograms/kg.h) completely abolished the stimulatory effect of camostate on enzyme output. The infusion of loxiglumide (10 mg/kg.h) caused no changes in camostate-induced stimulation of enzyme output. Plasma levels of cholecystokinin were not altered after intraduodenal instillation of camostate whether atropine, loxiglumide, or saline were infused. We suggest that the protease inhibitor camostate, by inhibition of the enzymatic activity of trypsin and chymotrypsin, interferes with feedback regulation of basal pancreatic secretion in humans, and this mechanism is predominantly mediated by the cholinergic system.

Adult↗

Percutaneous balloon aortoplasty of recoarctation: an alternative approach using the axillary artery.

A female infant, presenting with congestive cardiac failure at 6 weeks of age, was found to have severe juxtaductal coarctation of the aorta and multiple ventricular septal defects. She underwent resection of the coarctation with end-to-end anastomosis. Four months postoperatively, she developed severe recoarctation with impalpable femoral pulses. Successful balloon aortoplasty was carried out using a percutaneous approach via the right axillary artery.

Angioplasty, Balloon↗

The effect of the first dose of captopril on blood pressure in infants in heart failure.

In a double-blind controlled study, six infants with congestive heart failure were given captopril to observe the effect on blood pressure. There was a significant fall in systolic (P less than 0.02) and diastolic (P less than 0.01) blood pressure at 90 minutes after the first dose. There was no correlation with plasma renin activity or plasma sodium concentration. The need to monitor blood pressure after introduction of captopril therapy for the treatment of heart failure in infants is demonstrated.

Blood Pressure↗

Right-sided intrathoracic bypass graft for complex or recurrent coarctation of the aorta.

A simple technique is described for the interposition of a tube graft between the ascending and descending aorta in the right chest. Directing the graft posteriorly preserves the integrity of the pericardium and avoids potential damage to the prosthesis at a subsequent sternotomy for open heart surgery. This procedure was used successfully and without complication in an 18-month-old boy who had undergone two previous operations for coarctation of the aorta, and in a 20-year-old girl with William's syndrome and diffuse hypoplasia of the distal aortic arch.

Adult↗

Evolution of clinical ethics teaching at the University of Pittsburgh.

The authors explain that several years of effort, by many faculty from a variety of disciplines, were required to expand medical ethics teaching at the University of Pittsburgh School of Medicine beyond the preclinical years. Since 1986, faculty associated with the school's Center for Medical Ethics have begun a comprehensive ethics teaching program for all four years and the residency period; they also are attempting to develop an ethics consultation service. The authors describe the program, its promise and plans, and the significant difficulties involved in establishing and maintaining it, not only problems of long-term funding but of the uninformed and negative attitudes of some students and faculty toward ethics teaching, especially in the clinical setting. Also discussed are the pros and cons of using cases in ethics teaching and the program's approaches to evaluation and to training clinical faculty in clinical ethics issues.

Education, Medical↗

Irradiation-induced duodenal ulcer disease refractory to ranitidine: healing by omeprazole.

In two patients duodenal ulcer refractory to high dose H2-blocker treatment started several months after irradiation therapy following right nephrectomy because of renal adenocarcinoma. Established antiulcer drugs like ranitidine, famotidine, sucralfate, pirenzepine, and antacids alone or in combination were unable to control ulcer pain and failed to induce ulcer healing. Initiation of omeprazole treatment at dosages to produce complete achlorhydria were necessary for ulcer healing and maintenance therapy. We suggest that (a) irradiation may cause duodenal ulcer disease indistinguishable from idiopathic duodenal ulcer; (b) radiation-induced ulcers in the duodenal bulb are refractory to various antiulcer drugs but may heal after administration of omeprazole in dosages that completely suppress acid secretion.

Aged↗