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Biomedical subjects

A Allen

Publications and source records attributed to A Allen.

At least 37 records · Page 2Linked to original sources
PubMed1998

High-affinity benzodiazepine antagonists reduce responding maintained by ethanol presentation in ethanol-preferring rats.

In the present study, we examined two high-affinity and selective benzodiazepine (BDZ) receptor antagonists (ZK 93426, CGS 8216) in ethanol (EtOH)-preferring rats whose responding (i.e., lever pressing) was maintained by the presentation of EtOH. The in vivo actions of CGS 8216 (1-30 mg/kg) and ZK 93426 (5-75 mg/kg) were examined after intraperitoneal or oral administration. Flumazenil (10-40 mg/kg) was used as a reference BDZ antagonist. EtOH (10% v/v) and saccharin (0.05 g/v) solutions were concurrently available for 30 min each day under a two-lever fixed-ratio schedule in which four responses on one lever produced the EtOH solution and four responses on the other lever produced the saccharin solution. A 40 mg/kg intraperitoneal injection of flumazenil given on the first injection day (day 1) nonsignificantly reduced control levels of responding maintained by EtOH by 36%. No effects were observed 24 hr after drug administration (day 2). Oral administration of flumazenil was without effect. On day 1, intraperitoneal administration of CGS 8216 (1-20 mg/kg) and ZK 93426 (1-50 mg/kg) reduced control levels of responding maintained by EtOH by 44% to 73%; on day 2, EtOH maintained responding continued to be suppressed with the highest doses (> or = 20 mg/kg) suppressing control levels of responding by as much as 62%. Oral administration of higher doses of CGS 8216 (5-30 mg/kg) and ZK 93426 (10-75 mg/kg) reduced responding maintained by EtOH by as much as 54% to 84% of controls; however, no effects were seen on day 2. Only the highest intraperitoneal dose of ZK 93426 (50 mg/kg) suppressed responding maintained by saccharin. These findings demonstrate that some BDZ antagonists decrease responding maintained by EtOH. The findings suggest that certain BDZ antagonists may have potential as pharmacotherapies to prevent or decrease EtOH abuse in humans.

Animals↗
PubMed1998

A novel method for the visualization of the in situ mucus layer in rat and man.

1. The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa. 2. In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 degreesC) and the use of a water-soluble mountant. 3. A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) micrometer; B, 179 (48) micrometer; C, 184 (50) micrometer; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) micrometer. 4. This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.

Aged↗
PubMed1997

A polydisperse linear random coil model for the quaternary structure of pig colonic mucin.

The distribution of molecular weights for polymeric colonic mucus glycoprotein or "mucin" isolated and solubilised in the presence of protease inhibitors from pig colons is shown to be considerably greater than its "subunit" (thiol reduction product) and papain digested forms using the technique of size-exclusion chromatography coupled to multi-angle laser light scattering, and confirmed by sedimentation equilibrium measurements. The conformation of this mucin is probed by examining the molecular weight-intrinsic viscosity relationship in terms of the Mark-Houwink-Kuhn-Sakurada analysis for its polymeric (or "whole"), reduced and papain-digested forms: an exponent "a" of (1.1 +/- 0.1) is obtained indicating a linear random coil conformation consistent with other mucins. Size-exclusion chromatography coupled to multi-angle laser light scattering is shown to provide a relatively simple complementary technique to sedimentation equilibrium for the molecular weight distribution analysis of polydisperse materials.

Animals↗
PubMed1997

Prospective, randomized, double-blind study of high-dose aprotinin in pediatric cardiac operations.

BACKGROUND: Perioperative aprotinin decreases postoperative blood loss in adults undergoing cardiac operations, but its role is less clear in children. Therefore, a trial of aprotinin in pediatric cardiac operations was conducted to study the efficacy of its use in children. METHODS: Forty-two patients were randomly assigned to receive either high-dose aprotinin or placebo. Aprotinin efficacy was assessed using time from protamine administration to skin closure, postoperative blood loss and hemoglobin loss, and postoperative transfusion requirements. Measures of fibrinolysis (fibrin degradation product titers) and platelet preservation (beta-thromboglobulin levels) were also assessed. RESULTS: There were no statistically significant differences between groups in any of the blood loss or transfusion parameters. Fibrin degradation product levels, measured 4 hours postoperatively, had increased significantly for control patients, but remained unchanged for the aprotinin group (p < 0.02). beta-Thromboglobulin levels increased more rapidly during cardiopulmonary bypass in the control group (p = 0.03). CONCLUSIONS: Aprotinin appears to provide no clinical benefit in routine pediatric cardiac operations. A reduction in fibrinolysis, with perhaps an early preservation of platelet structure, is seen in the aprotinin group.

Aprotinin↗
PubMed1997

Effect of nicotine on large bowel mucus thickness, eicosanoids and faecal proteinase in ferrets.

BACKGROUND: Following observations on the effect of subcutaneous nicotine on rectal mucosal eicosanoids and mucus in the rabbit we have repeated the work in ferrets which may be a more suitable animal model. AIMS AND METHODS: The effect of nicotine on mucosal eicosanoids, the adherent mucus layer, and faecal proteinases in the large bowel of ferrets was examined in forty animals randomly allocated to five groups, a control and four treatment groups. They were given subcutaneous saline or nicotine via an Alzet pump in doses of 0.3, 0.6, 1.2 and 2.0 mg/kg/day for 10 days and then sacrificed; measurements were made of serum nicotine and cotinine levels, rectal mucosal eicosanoids, adherent rectal and colonic mucus thickness, and faecal proteinases. RESULTS: No significant differences were observed for any measurements, except for serum nicotine and cotinine levels, which were raised consistent with the dose given. CONCLUSION: Nicotine had no effect on measurements, which may possibly be important in the relationship between smoking and ulcerative colitis.

Animals↗
PubMed1997

Relationship between gastric mucus synthesis, secretion and surface gel erosion measured in amphibian stomach in vitro.

1. The layer of adherent mucus that protects the surface of the stomach reflects a dynamic balance between biosynthesis of glycoprotein, secretion of preformed mucus and erosion of the adherent gel layer. The present study is the first in which all these processes have been measured concomitantly and was undertaken to define interrelationships between the three parameters. 2. A chambered sac preparation of amphibian gastric mucosa is described. Biosynthesis was determined by specific incorporation of radiolabelled sugars into purified glycoprotein. Mucus secretion was determined by measuring the thickness of the adherent gel and erosion of the surface layer was assessed from the appearance of soluble mucin in the luminal solution. 3. 16,16-Dimethyl-prostaglandin (PG) E2 stimulated glucosamine incorporation by 10-fold, but did not alter the rate of incorporation of galactose. There was a rapid two-fold increase in the thickness of the adherent mucus layer but no change in the rate of erosion. Dibutyryl-cAMP also stimulated mucus release but, unlike PG, increased glycoprotein labelling by galactose. 4. Both distention or the application of a cholinergic agonist increased adherent mucus thickness. Stimulation of mucus release in response to carbachol was accompanied by a decrease in glycoprotein labelling by galactose. In contrast, the adrenergic agent noradrenaline decreased secretion but did not influence labelling. 5. These results indicate that biosynthesis and secretion of gastric mucus are subject to differential regulation. Moreover, the profile of incorporation of sugars in response to secretagogues also differs, indicating the need for caution when interpreting effects on glycoprotein biosynthesis.

16,16-Dimethylprostaglandin E2↗
PubMed1997

A cost analysis of a tele-oncology practice.

Costs were monitored for three different types of oncology practice: a telemedicine clinic and a fly-in outreach clinic, both held in rural areas, and a traditional clinic held in a city hospital. Total expenses were calculated over the year May 1995 to April 1996. The average cost per telemedicine visit was $812. The average cost per outreach clinic visit was $897. Flying in oncology support for this practice was therefore about 10% more costly than telemedicine. While the outreach cost may have been inappropriately high due to a slow start-up phase, it was still less expensive during this period to be seen via telemedicine. For comparison, the average cost per traditional oncology clinic visit was $149. However, this figure does not take into account the costs of access to a city-based service by rural patients.

Cost-Benefit Analysis↗
PubMed1997

Practising oncology via telemedicine.

Although there are increasing numbers of telemedicine programmes in the USA, few have offered teleoncology services, so that the role of telemedicine in the practice of clinical oncology has yet to be fully defined. Telemedicine has been used successfully for direct patient care in Kansas. It is also a method of providing supportive care for the cancer patient, including assessments of pain and nutrition. In addition, televised tumour conferences and nursing education courses can help smaller communities develop a level of expertise that allows patients to be treated locally. Telemedicine may well be used in future for access to national and international cancer experts, and for participation in new cancer treatment protocols through cooperative group trials. When practising oncology via telemedicine, there are unique problems, including issues regarding technology (interactive video and radiograph review) and practice (patient/oncologist preferences and doctor-patient communication). Very little has been published in the area of tele-oncology so far, and studies concerning its efficacy, cost-effectiveness and the best organizational structure are still in progress. However, telemedicine appears to be a useful technique in the practice of oncology.

Efficiency↗