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Biomedical subjects
Publications and source records attributed to J Brown.
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The treatment of end-stage cardiac disease is the focus of extensive investigation. Both cardiac transplantation and mechanically powered assist devices are currently in use. However, transplant recipients are at constant risk of infection and rejection, and patients with mechanical assists are tethered to external driving devices. These limitations have led to the investigation of methods of cardiac support that rely on autogenous tissue. The current study tests the ability of skeletal muscle to produce cardiac-type work. The cephalic half of one rectus abdominis muscle was mobilized (taking care to preserve the attachment to the superior epigastric vessels) in 12 canines. The muscle was formed into a cylindric pouch around a bladder device. This allowed the determination of the pressure and flow produced by the muscle. The muscle was stimulated to contract at a rate of 60 contractions per minute using twin stimuli of 80 ms duration. The muscle pouch yielded a maximal isovolumetric pressure of 282 mm Hg, which equalled 245 per cent of the dog's systolic blood pressure. In addition, the pouch produced a flow of 1.88 L per minute (73% of the dog's cardiac output) and a power output of 0.22 watts (39% of the dog's left ventricular power), while pumping against an afterload of approximately 2/3 the systemic resistance. Also, the muscle demonstrated an ejection fraction of 62.7 per cent. These data indicate that a hydraulic pouch formed from rectus abdominis muscle is capable of pumping function that may be able to assist the compromised ventricle. However, total replacement of cardiac function does not seem feasible.(ABSTRACT TRUNCATED AT 250 WORDS)
Supernatants from Epstein-Barr virus (EBV)--stimulated B lymphocytes obtained from two adult Gambians who were partially immune to malaria markedly inhibited the growth of Plasmodium falciparum in vitro (55-95% inhibition). When 22 separate colonies were derived by micromanipulation from one of these primary cultures and their supernatants assayed, the degree of inhibition correlated with levels of IgG fluorescent antibody and total IgG. The inhibitory anti-P. falciparum IgG immunoprecipitated an antigen of mol. wt 195,000, identified as the major schizont surface glycoprotein by dual biosynthetic labelling with 3H-glucosamine or 35S-methionine. Other studies on the analogous schizont surface protein of rodent malarias have shown that this antigen stimulates protective immunity. Production of this inhibitory antibody by adult Gambians may therefore contribute to their immunity to malaria. Human antibodies produced by EBV-stimulated B lymphocytes may be used to identify other important P. falciparum antigens and have potential applications for immunotherapy.
Groups of fentanyl-droperidol-pentobarbital-anesthetized dogs (n = 6 dogs/group) were given IV saline solution (control group), graded doses of naloxone (0.01, 0.1, 1.0, 10.0 mg/kg) or fixed doses of 4-aminopyridine (0.5 mg/kg), yohimbine (0.4 mg/kg), or doxapram (5.0 mg/kg) alone or in combination with a fixed dose of naloxone (1.0 mg/kg). The purpose was to determine which drug or drug combination would produce arousal most quickly without producing obvious undesirable side effects. Control group mean arousal time, mean walk time and mean duration of postarousal sedation were 66.1 minutes, 112.4 minutes and 5.6 hours, respectively. Naloxone (1.0 mg/kg) decreased mean arousal time to 10.8 minutes without significantly decreasing mean walk time or mean duration of postarousal sedation. The combination of naloxone + doxapram decreased mean arousal time and mean walk time to 1.0 minute and 57.1 minutes, respectively, without decreasing mean duration of postarousal sedation. In all groups, emergence from anesthesia was smooth. Relapses or undesirable side effects were not observed. Naloxone + doxapram is superior to naloxone alone for arousal of fentanyl-droperidol-pentobarbital-anesthetized dogs.
Chronic Escherichia coli prostatitis was induced in 6 dogs, with 5 sham-operated dogs serving as controls. Semen volume and sperm motility, concentration, and appearance were measured 3 times (every other day) before surgery and 3 times during the 3rd and 5th week after surgery. When values for these collections were compared, using a 2-factor analysis of variance, no significant differences (P greater than 0.05) were found. However, the percentage of normal sperm decreased markedly (from 92% to 61% to 64%) in 2 infected dogs because of an increase in primary (from 6% to 32%) or secondary (from 2% to 28%) sperm abnormalities. Testes from both of these dogs were histologically normal.
It is unknown if parenteral antibiotics commonly used for prophylaxis reach adequate therapeutic levels in the intestinal tissue to inhibit the growth of bacteria, such as Escherichia coli and Bacteroids fragilis, commonly associated with injury to the gastrointestinal tract. We have designed an experiment using dogs to study this problem. We considered an antibiotic to be effective if a single dose reached increased levels in the intestinal tissue to inhibit the growth of the majority of Escherichia coli and Bacteroides fragilis strains isolated from the gastrointestinal tract. Of 14 different antibiotics studied, we conclude that carbenicillin, mezlocillin, piperacillin, cefbuperazone and cefoxitin as single drugs and Timentin (ticarcillin with clavulanic acid) and clindamycin with gentamicin and co-trimoxazole (trimethoprium and sulfamethoxazole) achieved therapeutic levels. Azlocillin, cefoperazone, cefmenoxime and minocycline failed to achieve significant concentrations. This experiment using dogs was extremely useful to determine the pharmacokinetics of antibiotics in the small intestine and to predict the efficacy of antibiotics considered for prophylaxis.
A field evaluation of an enzyme-linked immunosorbent assay (ELISA) for swine trichinosis was done with sera obtained from 5 herds experiencing ongoing transmission of Trichinella spiralis. Epizootiologic studies conducted on these herds offered an opportunity to evaluate the accuracy of an ELISA, using larval T spiralis excretory-secretory antigens. Sera from 162 infected pigs and 143 serum samples from noninfected pigs originating from the same farms were tested. The infection status of the pigs was determined by digestion of diaphragm or tongue muscle samples. Two criteria were established to classify the ELISA optical density (OD) readings: Criterion I stated that an OD greater than or equal to 5 times the mean OD of several normal swine sera pools was positive; criterion II stated that a OD greater than or equal to 4 times the normal sera values was positive. The results obtained did not reveal obvious serologic variations among infected herds located in the 4 states involved. Overall, the test detected 93% (criterion I) and 96% (criterion II) of infected pigs. The majority of false-negative sera was from hogs that had less than 5 larvae/g of muscle; 1 hog had 73.8 larvae/g of diaphragm muscle. The false-positive rates were 8% for criterion I and 9% for criterion II. The actual rate for these false-positive samples may have been overestimated, because generally, only small tissue samples (0.4 to 10 g) were digested; larger sample sizes might have altered the results. The relevance of this qualification is that these pigs originated from herds with prevalence rates greater than 50%. Other factors that may account for occasional false-positive sera or false-negative sera in the swine trichinosis ELISA are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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A universal concern of those in nursing care is the occurrence of decubitus ulcers. To minimize this problem foam overlays are routinely used on hospital beds throughout the country. This study was undertaken to develop laboratory testing procedures which will reliably predict the support characteristics of mattress overlays in clinical service. Initially, test methods based on constant load and constant deformation boundary conditions were developed. These methods were applied to measure the pressure-distributing properties of 10 polyurethane foams fabricated in a wide range of pliancies and densities. Based on these laboratory data, a single index was developed to express the effectiveness of each overlay in distributing interface pressures. This index was found to be influenced by the stiffness (ILD), density, and thickness of each device. These data were then compared with measurements of interface pressure obtained from volunteer subjects who were supported on mattress overlays fabricated from each of the original foams. Correlation of these data with the laboratory results demonstrated that the effectiveness index was an accurate predictor of mattress overlay performance under end-use conditions.
Little is known about the adverse consequences of anemia during infancy or maternal anemia during pregnancy on the behavioral development of the infant. The present research investigates one aspect of these relationships.
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Specimens obtained from pyogenic skin lesions of 210 dogs were culturally examined for staphylococci. A total of 215 isolates of staphylococci were biotyped, using the biochemical tests contained in a commercial staphylococcal identification system. Of 201 coagulase-positive isolates, 197 were identified as Staphylococcus intermedius, 3 as S aureus, and 1 as S hyicus. Of 14 coagulase-negative isolates, 5 were identified as S epidermidis, 5 as S xylosus, 3 as S simulans, and 1 as S hominis. Antimicrobial susceptibility tests were done on all staphylococcal isolates, using the standard disk-diffusion method. Staphylococcus intermedius isolates were susceptible to cephalothin, methicillin, and gentamicin. Resistance to ampicillin, penicillin G, and tetracycline was frequent. Antibiotic resistance was not associated with the depth of skin infection. Resistance to ampicillin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole was not associated with previous antibiotic use. Increased resistance to chloramphenicol, clindamycin, and erythromycin was associated with previous antibiotic therapy. Antimicrobial susceptibilities of the other Staphylococcus species isolated are reported, but the small numbers of these species precluded making meaningful comparison with S intermedius.
Investigations of the oesophagus were undertaken in 50 consecutive patients who presented with recurrent chest pain thought to be non-cardiac in origin after cardiological assessment. An oesophageal disorder was demonstrated in 60%, gastro-oesophageal reflux and diffuse oesophageal spasm being the two commonest entities. However, routine contrast radiology and upper gastrointestinal endoscopy revealed abnormalities in only a minority of patients. Patients with non-cardiac chest pain of uncertain origin should initially undergo endoscopy. If no major abnormalities are detected radionuclide oesophageal transit studies, oesophageal manometry, and ambulatory monitoring of oesophageal pH should be carried out.
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The exercise response to a single oral dose (25 mg) of a new beta-blocking agent that also has potent vasodilating properties, carvedilol (BM 14,190), was assessed in 15 patients with stable exertional angina, positive exercise test responses (greater than or equal to 1 mm of ST depression) and coronary artery disease. A single-blind, placebo-controlled, randomized, crossover design was used. Compared with placebo, 25 mg of carvedilol significantly reduced both heart rate (HR) and blood pressure (BP) at rest (p less than 0.01). After administration of carvedilol, 10 of 15 patients did not have angina at peak exercise (p less than 0.01) and 5 had ST shifts of less than 1 mm (p less than 0.05). Total exercise time and time to 1 mm of ST depression were prolonged and ST-segment depression at peak exercise was significantly reduced (p less than 0.01). Systolic BP was reduced both at peak exercise and at 1 mm of ST depression (p less than 0.05), whereas mean HR at peak exercise did not change significantly compared with placebo. Overall, mean HR-BP product at peak exercise was significantly reduced by carvedilol compared with placebo (p less than 0.05). However, 4 patients actually achieved a higher HR-BP product but did not have angina and had less ST depression (or no ST-segment shifts) at peak exercise. This indicates an increase in their coronary flow reserve. These results suggest that carvedilol is effective therapy for effort-induced angina, and this may be related to its combined beta-blocking and potent vasodilatory properties.
Using a canine model, leukocyte populations enriched for monocytes and lymphocytes were isolated from blood during three week periods after kidney allotransplantation corresponding to episodes of acute rejection. Relative to controls, these cells incubated in vitro for five hours were found to generate increased amounts of PCA (procoagulant activity) characterized as tissue factor, the extrinsic clotting pathway activator. Controls included comparable blood leukocyte populations isolated from kidney autograft recipients and healthy animals. Differences in results for these two control groups were insignificant. These contrasts observed between allografted animals and controls demonstrate that leukocyte PCA generation is stimulated by the allogeneicity of histoincompatible kidneys rather than by direct effects of organ transplantation or non-specific postoperative effects. Results of in vitro transfer experiments provide evidence that cellular stimulation or induction in vivo accounted for the PCA increases observed. Stimulation of leukocyte tissue factor generation as a consequence of allogeneic kidney transplantation may in part account for coagulopathies and fibrin deposition during kidney rejection.
In vitro and animal experimental data suggest the combination of edetate sodium (EDTA) by aerosol plus oral antimicrobials might be effective in the treatment of chronic Pseudomonas infection in patients with cystic fibrosis (CF). For six months we studied the effects of edetate sodium administered by ultrasonic nebulizer to ten children with CF and chronic Pseudomonas aeruginosa infection in a double-blind, placebo-controlled, crossover study. The children had evidence of mild to moderate disease at entry in the study, with a mean (+/- SD) forced expiratory volume in the first second of 85% (+/- 18%) of the predicted value and a mean (+/- SD) Shwachman-Kulczycki score of 83 (+/- 7)/100. Each child was on a three-month regimen of aerosolized edetate sodium plus oral tetracycline twice daily followed by three months of placebo aerosol plus tetracycline or vice versa. Progress was assessed by measurement of pulmonary function, physical examination, and sputum cultures at four weekly intervals, plus chest roentgenograms on entry and after each of the three-month treatment periods. Daily symptoms were assessed using a diary card system. Two patients could not complete the study, one because of severe respiratory relapse, the other because of antibiotic side effects. Of the remaining eight patients, none showed any improvement in pulmonary function, weight gain, or growth acceleration, and none was rendered free of Pseudomonas lung infection. Daily symptom scores and chest roentgenograms were unaltered by edetate sodium. We conclude that the combination of aerosol edetate sodium plus oral tetracycline over a three-month period does not modify the clinical course nor the pulmonary flora in patients with CF with chronic Pseudomonas lung infection.