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Biomedical subjects

R Arnold

Publications and source records attributed to R Arnold.

At least 181 records · Page 10Linked to original sources
PubMed1996

Intestinal phase of human antro-pyloro-duodenal motility: cholinergic and CCK-mediated regulation.

In this study the muscarinic receptor antagonist atropine and the cholecystokinin (CCK)-A receptor antagonist loxiglumide were used to investigate the relative importance of cholinergic and CCK-mediated regulation of intestinal phase antro-pyloro-duodenal motility. Plasma levels of gastrointestinal hormones [pancreatic polypeptide (PP), gastrin, CCK] were concomitantly determined to estimate biological potency of the doses of the receptor antagonists. In eight healthy male volunteers, a 30-min basal interdigestive period was followed by duodenal perfusion of a mixed liquid meal for 150 min at 1.6 kcal min-1 against a background of saline or atropine (5 micrograms kg-1 h-1) or loxiglumide (10 mg kg-1 h-1). Antropyloro-duodenal motility was continuously monitored with a sleeve straddling the pylorus. Against a background of saline, duodenal nutrients persistently stimulated isolated pyloric pressure waves. After 60 min, the initially low antral and duodenal contraction rates increased. In the fed state, atropine reduced total number of antral contractions and integrated motility index by 73% (P < 0.01) and 76% (P < 0.005), total number of pyloric contractions and integrated motility index by 43% and 50% (P < 0.05) with inhibition increasing over time. It did not alter duodenal contraction frequency but diminished duodenal motility index by 39% (P < 0.05) owing to a reduction in amplitude and duration of contractions. Loxiglumide decreased total numbers of antral, pyloric and duodenal contractions by 44% (P < 0.05), 74% (P < 0.005) and 41% (P < 0.005) respectively. It reduced cumulative antral, pyloric and duodenal motility indexes by 60% (P < 0.01), 80% (P < 0.01) and 61% (P < 0.05) respectively. Atropine fully abolished PP release to duodenal nutrients whereas loxiglumide reduced it by 60% (P < 0.05). Both atropine and loxiglumide enhanced gastrin release whereas only loxiglumide markedly stimulated CCK release. We conclude that both cholinergic input and endogenous CCK are major stimulatory regulators of antro-pyloroduodenal motility in the intestinal phase. There appears to be a regional heterogeneity of cholinergic and CCK control. Cholinergic input predominates in the antrum. Both systems are equipotent at the pylorus. CCK predominates in the duodenum. We suggest that CCK primarily interacts with receptors on cholinergic neurons in the antropyloric region and primarily affects smooth muscle receptors in the duodenum.

Acetylcholine↗
PubMed1996

Patient refusal of care in the out-of-hospital setting.

A case vignette of out-of-hospital refusal of emergency care is reported with accompanying discussion. This case illustrates the challenges faced by out-of-hospital emergency care personnel in these scenarios and provides guidance to the emergency physician and emergency medical technician. Recommendations are provided for preparing the emergency medical services system to handle these cases.

Aged↗
PubMed1996

Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours.

Antiproliferative treatment of patients with metastatic endocrine gastroenteropancreatic tumours (GEP) is based mainly on chemotherapeutic protocols whereby drug toxicity is a major handicap. Octreotide is the first choice in the control of hormone mediated symptoms. From retrospective and a few prospective studies it has been suggested that octreotide exhibits antiproliferative properties. The prospective German Sandostatin multicentre phase II trial investigated the effects of 200 micrograms octreotide thrice daily for one year on tumour growth and endocrine abnormalities in 103 patients. Octreotide treatment was continued in those patients responding to the drug until tumour progression occurred. In 28 of those with tumour progression during 200 micrograms thrice daily octreotide dose was increased to 500 micrograms thrice daily. The study sample consisted of 52 patients with computed tomography confirmed tumour progression and 13 patients with stable disease before octreotide treatment, whereas no preobservation period was available in 38 patients. Nineteen patients (36.5%) with computed tomography confirmed tumour progression experienced stabilisation of tumour growth lasting for at least three months. Median duration of stable disease was 18 months. At month 12, stable disease continued in 12 patients, declined after 24 months to nine patients, and after 36 months to five patients. Tumour regression has not been seen in this or other subgroups. In the subgroup with stable disease before octreotide, stable disease continued in 53.8% of patients over 12 months. Increase of octreotide dose to 500 micrograms thrice daily did not influence progression seen during the lower dose with the exception of one patient in whom tumour progression changed to stable disease. No association of tumour size response and patients' characteristics could be detected. The results suggest that octreotide inhibits tumour growth in patients with metastasised endocrine GEP tumours. The antiproliferative effect is, at least in some patients, longlasting. Currently, octreotide can only be recommended as an antiproliferative drug if patients with clearly progressive disease show stabilisation after treatment for three to six months.

Adenoma, Islet Cell↗
PubMed1996

Prognosis of supravalve aortic stenosis in 81 patients in Liverpool (1960-1993).

OBJECTIVE: To determine the prognosis of supravalve aortic stenosis into early adult life and the factors affecting this prognosis. DESIGN: 81 patients with supravalve aortic stenosis were followed for a median duration of 8.3 (range 1 to 29) years. PATIENTS: 40 patients (49.4%) had Williams' syndrome, 18 (22.2%) familial supravalve aortic stenosis, 18 (22.2%) sporadic supravalve aortic stenosis, and five (6.2%) other syndromes. Nineteen patients had additional levels of left ventricular outflow tract obstruction. RESULTS: 47 patients (58%) underwent operation; 20% within a year of presentation. Multivariable analysis predicted that 88% of patients would undergo intervention within 30 years of follow up. The chance of intervention was increased by more severe aortic stenosis at presentation and the presence of multilevel obstruction in patients with sporadic supravalve aortic stenosis. Three deaths occurred before operation and 13 within a month of operation. Ten (62.5%) of the postoperative deaths were in patients with multilevel obstruction. Predicted survival 30 years after presentation was 66%. Risk factors for survival were age and severity of aortic stenosis at presentation. Multilevel obstruction did not emerge as a significant risk factor for death because of the high association with the severity of stenosis at presentation. 74% of survivors had mild or insignificant stenosis at follow up. CONCLUSIONS: Long-term survival is related to age and the severity of aortic stenosis at presentation. Most patients will require intervention, and most survivors will have mild stenosis.

Aortic Valve Stenosis↗
PubMed1996

Transcatheter occlusion of the patent ductus arteriosus with Cook detachable coils.

OBJECTIVE: To report initial experience with a new occlusion device for native and residual patent ductus arteriosus. DESIGN: Descriptive study of consecutive non-randomised patients undergoing a new method of patent ductus arteriosus closure with detachable coils. SETTING: Tertiary centres for paediatric cardiology. PATIENTS: 71 consecutive patients, aged 1.2-22 years, with a patent ductus arteriosus (PDA) underwent elective transcatheter closure. 45 had native PDAs (group A) with a minimum diameter of 1.0 mm-5.0 mm (median 2.0 mm). A further 26 had undergone one or more previous occlusion attempts (group B). INTERVENTIONS: A total of 133 detachable (Cook) spring coils were successfully implanted in 70 patients. The procedure was performed transvenously in 51 patients, retrograde arterially in 13, and by both routes in a further 6 patients. One 5 mm coil migrated but was successfully retrieved. MAIN OUTCOME MEASURES: In group A colour flow Doppler echocardiography showed that complete occlusion was achieved in 40/45 (89%) at 24 hours, 41/45 (91%) at 1 month, and 44/45 (98%) by 6 months post procedure. Occlusion rates in residual PDAs were 22/25 (88%) occluded at 24 hours, 23/25 (92%) at 1 month, and 24/25 (96%) at 6 months follow up. CONCLUSIONS: Transcatheter occlusion using detachable (Cook) spring coils is a safe and effective alternative to presently available devices. The delivery system allows full retrieval of the coil until a satisfactory position is obtained.

Adolescent↗
PubMed1996

Studies on the viability of the isolated vascularly perfused rat colon.

The colon contains large numbers of endocrine cells. Insight into their physiological function is limited. This is due to the fact that no sufficient model of isolated endocrine colon cells is available. In the present study we introduce an isolated vascularly perfused colon model for in vitro studies. This model offers the advantage that it keeps the endocrine cells in their physiological orientation and environment. The gut mucosa is highly sensitive to ischemia. Therefore, a careful validation of its viability is crucial in gut organ preparations. This study demonstrates that, by utilizing an oxygenated vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of the colon is achieved for at least 1 h without obvious tissue injuries. During this time parameters such as perfusion pressure, venous lactate dehydrogenase release, glucose consumption, lactate output, oxygen consumption, perfusate loss by the preparation and morphology were analyzed. Dependent on stimulation, the endocrine L cells of the colon released glucagon-like peptide-I upon arterial perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model for the isolated perfusion of the colon is introduced which is suitable for studies of endocrine colon cells.

Animals↗
PubMed1996

Control of growth in neuroendocrine gastro-enteropancreatic tumours.

This paper reviews data on the effect of pharmacological anti-tumour agents on tumour growth in patients with malignant gastro-enteropancreatic (GEP) tumours. Agents include long-acting somatostatin analogues, interferon-alpha, a combination of both, chemotherapy, and chemo-embolisation. Characteristics of tumours are considered which should be taken into account in the management of patients with metastatic endocrine GEP tumours, including growth rate. Tumour type should be matched to the anti-proliferative strategy.

Animals↗
PubMed1996

Expression of extracellular matrix macromolecules around demineralized freeze-dried bone allografts.

In the present study histochemical techniques were used to identify specific macromolecular components of the extracellular matrix associated with the tissue reaction to demineralized freeze-dried bone allografts (DFDBA) placed under barrier membranes for ridge augmentation. Small biopsies were obtained from tissues underneath the membranes at various times after placement of the DFDBA and processed for routine immunohistochemistry. Sections were stained with antibodies to osteocalcin, collagen type I, collagen type III, decorin, and biglycan. Non-immune serum, irrelevant antibodies, and omission of the primary antibodies served as negative controls. Histologic examination of the biopsies revealed allograft particles surrounded by well-formed fibrous connective tissue with little or no evidence of new bone formation. Vital autogenous bone fragments were present in the peripheral portions of the biopsies and served as positive controls for comparative purposes with the DFDBA particles. Only 7 out of the 20 biopsies studied were found to have any signs of bone formation around the DFDBA particles and in these such bone formation was irregular and inconsistent around the DFDBA particles. Around the periphery of the allograft particles, osteocalcin, collagen type I, collagen type III, decorin, and biglycan all showed relatively strong staining. Osteocalcin staining was also noted within the vital bone matrix but not in the surrounding fibrous connective tissue. Decorin, biglycan, collagen type I, and collagen type III were also found within the vital bone matrix. None of these antibodies stained the DFDBA particles. The unremarkable osteogenic response of the tissues to the DFDBA particles after healing periods of up to 12 months raises questions as to the predictability of these agents in inducing new bone.

Adult↗
PubMed1996

Antibodies to interferon-alpha: a novel type of autoantibody occurring after allogeneic bone marrow transplantation.

Antibodies to IFN-alpha have been recognized as a novel type of autoantibody developing after allogeneic BMT. Ninety-six patients undergoing BMT for various hematologic disorders were followed for the presence of spontaneous IFN-alpha antibodies until 12 years after transplantation. Seven of them (7.3%) developed IFN-alpha antibodies occurred late after BMT (> or = 15 months), rose to very high titers in some patients, and persisted for years despite combined immunosuppressive treatment. They were oligo- or polyclonal in nature, predominantly IgG with a broad IgG subclass distribution, and neutralized the antiviral and antiproliferative activity of various natural and recombinant IFN-alpha types including the patients' endogenous IFN-alpha in vitro. All antibody-positive recipients suffered from chronic GVHD (n = 5) or chronic viral hepatitis (n = 2), but the only significant association was with prior severe aplastic anemia (3/9, 33%; P = 0.022). There was no discernible HLA association of IFN antibody development. Although the clinical relevance of the IFN-alpha antibodies is uncertain they may interfere with cellular defence mechanisms and immune regulation after BMT.

Adolescent↗
PubMed1996

Rapid KABP survey for evaluation of NGO HIV/AIDS prevention projects.

The Johns Hopkins University HAPA Support Program (HSP) provided technical assistance to Save the Children (SC), a U.S.-based nongovernmental organization, to conduct a survey of knowledge, attitudes, beliefs, and practices (KABP) related to AIDS among rural Zimbabweans. The objectives of the HSP technical assistance were to field test a rapid KABP survey methodology and to assist SC to provide data that would contribute to their final project evaluation. The entire process of planning, implementation, preliminary data analysis, and preparation of a draft report of survey results was completed in a four-week period. A total of 660 respondents, aged 18-45 years, selected by a modified 30-cluster sampling method, were interviewed in two SC project areas. Although knowledge about HIV/AIDS was high, a number of misconceptions about HIV transmission and unfavorable attitudes to people with AIDS were noted. Of five knowledge and attitude variables that could be compared with the baseline survey results, 4 showed favorable changes and 1 showed an unfavorable trend. Comparing responses from those who were educated by SC with those who had other sources of information about HIV/AIDS, higher levels of knowledge were seen in the SC-educated group and, in one area, somewhat greater willingness to care for family members with AIDS. However, there were no differences seen in other attitudes, beliefs, or in practices regarding condom use. The rapid KABP survey approach was successful in providing, with a relatively modest investment of resources, quantitative data useful for project evaluation, and for developing HIV/AIDS-intervention strategies.

Acquired Immunodeficiency Syndrome↗
PubMed1996

[Ulcer--an infection?].

In the past gastric acid was considered to be the major factor in the pathogenesis of peptic ulcers. For the first time bacteria were found in the stomach at the end of the last century. However, Helicobacter pylori could be detected and characterized not before 1983. Specific factors of virulence enable H. pylori to colonize the gastric mucosa. Infection occurs during childhood and due to a cohort-phenomenon the prevalence increases continuously with age. H. pylori infection can be diagnosed in about 95% of patients with duodenal ulcer and 70% of gastric ulcers. The important pathogenetic role of H. pylori infection could be demonstrated in eradication trials. According to our present knowledge gastric acid and H. pylori are independent prerequisits in peptic ulcer pathogenesis. H. pylori negative ulcer derive from NSAIDs or from the rare Zollinger-Ellison syndrome.

Adolescent↗
PubMed1996

Intragastric pH and serum gastrin during administration of different doses of pantoprazole in healthy subjects.

OBJECTIVE AND DESIGN: The effect of increasing doses of pantoprazole, a newly developed proton pump inhibitor, given at once daily doses of 40, 80 and 120 mg, on intragastric pH and serum gastrin profiles was studied in 15 healthy subjects in a randomized, double-blind, crossover study and compared to recordings without therapy. Measurements of intragastric pH and serum gastrin were performed on the 7th day of treatment by continuous pH recording and radioimmunoassay in blood samples obtained in 1-h intervals, respectively. RESULTS: Pantoprazole significantly increased gastric pH above basal at all pantoprazole doses studied: median 24-h pH rose from 1.2 without therapy to 3.4, 3.3 and 3.6 at 40, 80 and 120 mg daily, respectively. The corresponding integrated 24-h gastrin output was 1632, 2338 and 2248 pg/ml x 24 h compared to 575 pg/ml x 24 h without pantoprazole. There was no interindividual correlation between values of 24-h median pH and 24-h gastrin output at any pantoprazole dose studied. However, fasting gastrin levels closely correlated with 24-h gastrin output (r = 0.789; P < 0.0001). The acid inhibitory effect was significantly (P < 0.01) augmented in Helicobacter pylori positive subjects. CONCLUSION: It is concluded that pantoprazole is an effective inhibitor of gastric acid secretion. Increasing a single pantoprazole dose above 40 mg does not lead to increased median pH elevation. The individual extent of acid inhibition does not predict the magnitude of gastrin elevation. Acid inhibition appears more efficient in Helicobacter pylori positive subjects.

2-Pyridinylmethylsulfinylbenzimidazoles↗