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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 469 records · Page 26Linked to original sources

Control of rat gastric somatostatin release by gamma-aminobutyric acid (GABA).

The influence of gamma-aminobutyric acid (GABA) on gastric somatostatin and gastrin release was studied using an isolated perfused rat stomach preparation. GABA dose-dependently inhibited somatostatin release (maximal inhibition of 44% at 10(-5)M GABA), whereas gastrin secretion was not affected. The GABA agonist muscimol led to a decrease in somatostatin release of similar magnitude. The GABA-induced changes were partially reversed by 10(-5)M atropine. Gastrin secretion was not influenced by either protocol. It is concluded that GABA as a putative neurotransmitter in the enteric nervous system is inhibitory to rat gastric somatostatin release in vitro via cholinergic pathways.

Animals↗

A kwashiorkor-like syndrome in a Caucasian with enteropathy.

A Caucasian child with congenital heart disease (CHD) presented at the age of 19 months with a kwashiorkor-like syndrome. Jejunal biopsy showed sub-total villus atrophy. The clinical picture of repeated infection causing growth faltering followed by oedema, hair and skin changes, resembled the response to infection of many nutritionally stressed children in the tropical world. The exact aetiology of kwashiorkor and the diagnostic specificity of its clinical features remain in doubt, as does precise definition. This case highlights the problems of diagnosing a condition which is essentially the end point of a combination of nutritional and environmental stresses.

Celiac Disease↗

Assessment of the Datex Relaxograph during anaesthesia and atracurium-induced neuromuscular blockade.

The Datex Relaxograph is a recently introduced electromyographic monitor of neuromuscular transmission. It has been assessed in patients requiring neuromuscular blockade and the results compared with those obtained simultaneously with a force transducer. There was a good correlation between the two methods of measurement for both twitch height and train-of-four ratio (correlation coefficients 0.93 and 0.97, respectively). The Datex Relaxograph proved easy to use in the clinical setting.

Anesthesia, General↗

Exocrine pancreatic function in oleic acid-induced pancreatic insufficiency in rats.

Pancreatic insufficiency was induced in rats by a single injection of 50 microliter oleic acid into the pancreatic duct over a period of 3 min. Exocrine tissue was destroyed within 3-6 days, and after 6 weeks the remaining pancreas equaled 2.7% of the original organ. The rats showed retardation of body weight in spite of normal food intake. After 7 weeks the fecal weight increased by 23%, and the fecal chymotrypsin activity decreased by 90% compared to controls. At this time plasma cholecystokinin (CCK) concentrations were significantly elevated. The amylase content in the remaining pancreas was reduced by 99%, and trypsin content was reduced by 93%. Unstimulated protein discharge from the remnant pancreas in vitro was threefold higher compared to secretion from control tissue. Thus a simple, reproducible model for inducing persistent pancreatic insufficiency was developed. To compensate for the loss of exocrine tissue, the remaining acinar cells adapt by a CCK-mediated increase in protein secretion.

Adaptation, Physiological↗

Endogenous CCK release and pancreatic growth in rats after feeding a proteinase inhibitor (camostate).

The serine proteinase inhibitor camostate was fed to rats in single, daily doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg for 5, 10, or 15 days. Within 5 days, pancreatic size and protein, DNA, and enzyme content increased significantly. After prolonged administration, this trophic effect was more pronounced, and anticoordinate regulation of the synthetic rate of individual secretory proteins was observed. While enzyme content and protein synthesis of trypsinogen and chymotrypsinogen were increased, respective values for amylase were drastically reduced. Plasma levels of cholecystokinin (CCK) did not differ from controls when measured 24 h after administration of camostate. Immediately after oral feeding of camostate, CCK levels increased 10-fold above controls, reached a maximum after 90 min, and remained elevated for more than 6 h. Proglumide, a CCK-receptor antagonist, only slightly reduced the trophic action of the proteinase inhibitor. The data indicate that endogenous CCK release by a proteinase inhibitor is as potent in the modulation of pancreatic growth and individual enzyme synthesis as exogenous hormone application.

Animals↗

Cyclosporine as an alternative to cyclophosphamide in the treatment of chronic graft-versus-host disease.

Four patients with progressive extensive chronic graft-versus-host disease or dose-limiting toxicity on conventional therapy (cyclophosphamide + prednisolone) were treated with a regimen of cyclosporine + prednisolone as induction therapy and cyclosporine as maintenance therapy. All 4 showed clinical improvement and 3 of 4 are alive at 9 months. The incidence of infections was not affected by this regimen, but steroid requirements were reduced.

Acute Disease↗

Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation.

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).

Adolescent↗

Morphology and morphometry of the rabbit uterus during pseudopregnancy.

Morphometry was carried out on the luminal epithelium of the rabbit uterus from oestrus to day 21 of pseudopregnancy. This indicated that syncytia increased in size until day 18, after which a rapid reduction occurred with approximate oestrous dimensions being restored on day 21. Involution of syncytia took place in two overlapping stages with reduction in nuclear numbers occurring from day 12 onwards, followed by loss of cytoplasm mainly after day 18. Ciliated cells predominated at oestrus and day 21 but were sparse at other times. When ciliated cells were plentiful, they were concentrated on the tops of the mucosal folds.

Animals↗

Trophic effect of truncal vagotomy on the rat pancreas.

The trophic effect of truncal vagotomy was studied in rats. Three months after vagotomy and pyloroplasty pancreatic weight was significantly increased by 40% (p less than 0.001). Gastric stasis and consecutive distension of the stomach was observed in the majority of vagotomized animals despite pyloroplasty; the trophic effect of vagotomy on the pancreas was most pronounced in animals with severe stomach distension. Basal gastrin levels were increased after truncal vagotomy but did not correlate to gastric stasis and to the hypertrophy and hyperplasia of the exocrine pancreas. Basal pancreatic polypeptide hexapeptide levels were not altered after vagotomy. Morphometric studies on the endocrine pancreatic tissue showed that the relative volume density decreased due to the increase in exocrine tissue. However, the total islet cell mass remained constant. It is concluded that chronic truncal vagotomy has a trophic effect on the exocrine but not on the endocrine pancreas; additional factors besides gastrin seem to be responsible for this.

Animals↗

Effect of the prokinetic drug cisapride on gastrointestinal hormone release.

The influence of the prokinetic drug cisapride on the release of gastrointestinal hormones was studied in volunteers. First, acute effects of single doses of cisapride compared with saline were investigated. Cisapride at doses of 8 mg and 20 mg intravenously significantly increased plasma concentrations of pancreatic polypeptide (hPP) by 145% and 146%, respectively. Cholecystokinin (CCK) levels were increased by 176% at 8 mg cisapride, whereas gastrin and insulin levels remained unchanged. Enhancement of PP and CCK secretion was almost completely abolished by pretreatment with 1 mg atropine. Carbachol (250 micrograms subcutaneously) increased PP release by 62% but did not affect the other hormones. Second, the influence of a 1-week treatment (10 mg three times daily, given orally) on plasma hormone levels was studied. After 1 week the postprandial CCK release was diminished by 58%. Basal levels and postprandial responses of gastrin, PP, and insulin were not altered by prolonged cisapride administration. It is concluded that acute application of cisapride stimulates secretion of PP and CCK via atropine-sensitive mechanisms and that chronic treatment with cisapride diminishes CCK release by an unknown mechanism.

Adult↗

Effect of acid inhibition on gastric endocrine cells.

There is increasing evidence that the numbers of antral G cells and of fundic argyrophil (ECL) cells are influenced by agents that inhibit gastric acid secretion. Antral G cells increase in states of achlorhydria in man and animals provided atrophic antral gastritis is absent. In rats, treatment with substituted benzimidazoles like omeprazole and BY 308 increase G-cell densities dose-dependently. Even high doses of histamine H-2 antagonists and antacids increase antral G-cell densities. In contrast to G cells, antral D cells decrease in these instances. Fundic ECL cells increase in all experimental conditions of complete achlorhydria provided intact antral mucosa is present, i.e. there is elevated serum gastrin. Antacid treatment is not followed by an increase of fundic ECL cells, which could be explained by the less sustained increase of serum gastrin.

Animals↗

Hemopoietic reconstitution after bone marrow transplantation.

Forty-one patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anemia or hematologic malignancies. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, and clonal assays for hemopoietic progenitors (CFUc, CFUe, and BFUe), along with bone marrow morphology. The number of transplanted nucleated cells and the number of transplanted progenitors (CFUc, CFUe, and BFUe) correlated significantly with the time of reticulocyte recovery. The number of transplanted CFUc correlated significantly with the time of granulocyte recovery. Platelet recovery occurred late and showed large variations. No correlation between the transplanted cells and the recovery of nucleated cells or hemopoietic progenitors (CFUc, CFUe, and BFUe) in the bone marrow was found. Bone marrow cellularity and hemopoietic progenitors showed a rapid, but incomplete, recovery during the first 56 days after BMT. Hematologic studies on seven long-term survivors with an uncomplicated posttransplantation course revealed subnormal bone marrow cellularity and hemopoietic progenitor incidence up to three years after BMT, despite normal peripheral blood counts. The low progenitor incidence could be explained by a proliferative defect of the stem cells, compensated for by an amplification in the more differentiated compartment of hemopoiesis.

Anemia, Aplastic↗

Hematopoietic colony formation after allogeneic bone marrow transplantation: enhancement by cyclosporin A and anti-gamma-(immune) interferon antiserum in vitro.

Bone marrow hematopoietic progenitors (CFU-GM, CFU-E, and BFU-E) were found to be markedly decreased in 21 bone marrow transplant recipients studied from one to 51 months after transplantation. In these patients, bone marrow colony formation could be significantly enhanced by in vitro incubation of the bone marrow target with cyclosporin A (CyA; 0.5 microgram/ml) or with a monoclonal anti-gamma-(immune) interferon (IFN-gamma) antibody. Both effects were highly correlated. The data indicate that (a) endogenous elaboration of IFN-gamma may contribute to decreased colony formation in allogeneic bone marrow transplant recipients, and (b) CyA may induce a gradual release of the progenitor cell pool from IFN-gamma-mediated suppression.

Antibodies, Monoclonal↗

Architecture of the ventricular mass and atrioventricular valves in complete transposition with intact septum compared with the normal: I. The left ventricle, mitral valve, and interventricular septum.

Venous correction for complete transposition with intact ventricular septum remains the preferred surgical option in most centers (Mustard or Senning procedures). The long-term function of the morphologically right ventricle and tricuspid valve, which continue to sustain the systemic circulation thereafter, remains a matter of concern. Some centers have been performing arterial redirection ("arterial switch") as the surgical treatment of transposition. Consequently, the status of the left ventricle and mitral valve is of equal interest. Yet, detailed morphological studies of the ventricles, atrioventricular valves, and their tension apparatus in "simple" complete transposition are lacking. We have examined the morphology of the left ventricle and the spatial relationships of the component parts of the interventricular septum (part I) as well as the morphology of the right ventricle and the tricuspid valve (part II). A total of 77 specimens with complete transposition and intact ventricular septum were examined and compared with 50 normal hearts. Consistent deformities were noted in relation to the orientation of the ventricular septum. The ratios of ventricular outlet to the inlet lengths were increased in both ventricles and the posterior arterial valve was abnormally related to the atrioventricular valves. These anomalies are similar in some respects to those found in atrioventricular septal defects. Their significance in relation to long-term function remains unclear.

Child, Preschool↗

Architecture of the ventricular mass and atrioventricular valves in complete transposition with intact septum compared with the normal: II. The right ventricle and tricuspid valve.

After the Mustard or Senning procedure for surgical correction of complete transposition of the great arteries, the right ventricle and tricuspid valve have to support the systemic circulation for life. Consequently their function is of prime importance. In this (second) part, the detailed anatomy of the right ventricles and tricuspid valves is described in the same series of 50 normal hearts and a series of 77 with complete transposition and intact septum. 21% of the transposition specimens showed significant abnormalities of the tricuspid valve. Consistent deformities were observed in the structure of the trabecula septomarginalis and the membranous septum. The ratios of ventricular outlet to inlet lengths were increased.

Aorta↗

The psychological characteristics of infantile hypercalcaemia: a preliminary investigation.

A sample of 23 children aged seven to 12 years with diagnoses of infantile hypercalcaemia was assessed on a battery of psychological tests and rating scales in an attempt to describe the psychological characteristics of this disorder. All children were found to have a mild or moderate degree of mental handicap. As a group, their expressive language skills were superior to their verbal comprehension. They displayed a high degree of behaviour and emotional disorders, most notably in terms of high levels of activity. Most children were reported as being highly sensitive to noise. This study clarifies some of the psychological correlates of infantile hypercalcaemia and some implications for management are suggested.

Adolescent↗