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Biomedical subjects

M Holland

Publications and source records attributed to M Holland.

At least 91 records · Page 5Linked to original sources

Effects of BAY K 8644, nifedipine, and low Ca2+ on halothane and caffeine potentiation.

The purpose of this investigation was to examine the effects of the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine on halothane- and caffeine-induced twitch potentiation of mammalian skeletal muscle. Muscle fiber bundles were taken from normal Landrace pigs and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), and low Ca2+ media administered alone and in combination with halothane (3%) or with increasing concentrations of caffeine (0.5-8.0 mM). Both BAY K 8644 and halothane potentiated twitches by approximately 80%; when they were administered in combination, twitch potentiation was nearly double that caused by either drug alone. In the presence of nifedipine, halothane increased twitches by less than 30%. Low Ca2+ significantly depressed twitches by approximately 25% but also inhibited halothane's inotropic effect. BAY K 8644 augmented caffeine potentiation but only at low caffeine concentrations (0.5-2.0 mM). Nifedipine and low Ca2+ failed to inhibit caffeine's inotropic effects. These results suggest that halothane potentiates twitches via a mechanism that involves or is influenced by extracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Lack of sex differences with the Baldwin illusion.

Responses of college students (16 men and 16 women) to the Baldwin illusion showed a significant effect for size of square but not for sex. Findings are consistent with those reported previously by Porac, Coren, Girgus, and Verde for adults and for the oldest group of children tested by Pressey and Wilson.

Adult↗

Effects of the calcium antagonist, TMB-8 on halothane and on caffeine contractures of malignant hyperthermia susceptible skeletal muscle.

This investigation sought to determine if the Ca2+ antagonist, TMB-8, alters the contracture responses of malignant hyperthermia susceptible (MHS) skeletal muscle to halothane and to caffeine. Muscle fiber bundles were excised from both MHS and normal pigs and exposed to TMB-8 (100 microM), halothane (3%) and caffeine (0.5-8.0 mM), administered alone and in combination. TMB-8 depressed tension developed during isometric twitches in both MHS and normal muscle but had no effect on resting tension (RT). Halothane, however, increased RT in MHS but not in normal muscle. TMB-8 failed to reduce the halothane contracture of MHS muscle but hastened its onset. Caffeine concentrations of greater than or equal to 2 mM increased RT in MHS whereas only 8 mM evoked contracture of normal muscle. These effects were also unaltered by TMB-8. Results suggest that TMB-8 does not inhibit halothane nor caffeine contractures of MHS muscle.

Animals↗

Clinical use of the neuromuscular blocking agents atracurium and pancuronium for equine anesthesia.

Neuromuscular blocking agents (muscle relaxants) are useful and common adjuncts to general anesthesia for human beings, but have not been used extensively during anesthesia of large animal species. Over a 3-year period, atracurium or pancuronium were used as adjuncts to general anesthesia for 89 anesthetic procedures in 88 equids (of 18 breeds and age ranging in age from 5 weeks to 25 years) at the teaching hospital. Forty-one of the anesthetic procedures were for abdominal surgery, and orthopedic (n = 19), ophthalmologic (n = 17), thoracotomy (n = 1), and soft tissue (n = 14) procedures composed the rest. Most equids were given atracurium because it was less expensive than pancuronium. Initial dosage of either relaxant ranged from 0.12 to 0.2 mg/kg of body weight IV, and repeat doses ranged from 10 to 30 mg. Relaxants were used for as long as 205 minutes. Muscles of the face or hind limb digital extensor muscles were used to monitor relaxation. Muscles of the hind limb were more sensitive to the effects of relaxants than were muscles of the face. At the end of a surgical procedure, just prior to being taken to the recovery stall, a relaxant antagonist, edrophonium (0.5 to 1 mg/kg), was administered IV to each equid. Edrophonium caused blood pressure to increase in most of the equids. Heart rate change was variable, with approximately half the equids having no change or increased heart rate and the remainder having decreased heart rate. Recovery to standing after anesthesia was rated excellent or good for 72 equids, fair for 11, and poor for 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Enhancement of monoclonal antibody dependent cell mediated cytotoxicity by IL2 and GM-CSF.

Rodent monoclonal antibodies (MAb) directed against cells of the immune system may be used in vivo for applications including conditioning prior to marrow transplantation and treatment of lymphoid malignancies. Although some MAb may lyse targets by complement fixation, MAb dependent cell mediated cytotoxicity (MAb-DCC) appears to be an important additional effector mechanism. We have investigated the cellular basis of the phenomenon and the response of the effector cells to recombinant cytokines in an attempt to maximize the efficacy of MAb-DCC and thereby increase the therapeutic potency of MAbs. Blood mononuclear cells (PBM) coated with CAMPATH 1G (pan lymphocyte reactive rat IgG2b) MAb were used as targets (T) and autologous lymphocytes or granulocytes were used as effector (E) cells. We studied function in normal donors as well as patients 1 week before and 3-6 weeks after bone marrow transplantation (BMT). In the absence of CAMPATH 1G, specific 51Cr release from autologous PBM was less than 1% in all groups, even after pre-incubation of the effector cells with granulocyte-macrophage, colony stimulating factor (GM-CSF) or interleukin-2 (IL2). In the presence of 5 micrograms/ml of MAb, and at an E:T ratio of 50:1, lymphocytes from normal donors induced a low level (6.5%) of 51Cr release from auto PBM rising to 9% after pre-incubation of effector cells with IL2 (P = 0.02). Granulocytes had greater activity inducing 10% 51CR release (range 2-23%) which rose to 21.6% with GM-CSF (range 12-48%) (P less than 0.001). Pre-BMT, killing by lymphocytes and granulocytes was not significantly different from normal, and responded to IL2 and GM-CSF. In contrast, granulocyte killing after BMT was significantly impaired (51Cr release 3%) and showed no rise with GM-CSF. Killing by lymphocytes, however, remained normal, as did their IL2 response. Loss of granulocyte mediated MAb-DCC coincided with significant post-BMT impairment of oxidative metabolism; expression of Fc receptors II and III, however, was normal. Optimum therapeutic effect of MAb-DCC is likely to be achieved when MAb are given together with appropriate cytokines, the choice of which will depend upon the clinical circumstances.

Antibodies, Monoclonal↗

The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses.

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P less than 0.05), despite Day 7 cholinesterase activity that was 16% of pre-trichlorfon values. For atracurium Injections 1 and 2-5, 85 and 43 micrograms/kg of atracurium, respectively, were required to produce a 95-99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2-5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre-atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect on yeast LEU2 expression of upstream activation sequence from yeast ENO2 gene coding for enolase.

The upstream activation sequence from ENO2, one of two genes coding for yeast enolase, was inserted into the upstream 405 HpaI site of LEU2, which codes for beta-isopropylmalate dehydrogenase (E.C. 1.1.1.85), utilizing shuttle plasmid YEp13. The effect of the ENO2 upstream activation sequence on expression of yeast LEU2 was studied. Our results revealed a fourfold increase in expression for LEU2 in both orientations after activation by the ENO2 upstream activation sequence. Leucine repressed LEU2 expression. Glucose did not induce the ENO2 upstream activation sequence effect on LEU2 expression. It is possible to construct a high-level expression system in yeast by using the ENO2 upstream activation sequence.

3-Isopropylmalate Dehydrogenase↗

[Screening of the new analgesic, bromfenac].

A method is described for the screening of the new analgesic bromfenac via thin-layer chromatographic analysis of its acid hydrolysis product and subsequent Bratton-Marshall detection.

Analgesics↗

[Function and morphology of intraperitoneal segmental pancreas allotransplants with cyclosporin monotherapy in the dog--a comparison of 4 drainage procedures of exocrine secretions].

Dogs which had received cyclosporine A for immunosuppression were investigated to elucidate functionality and morphological alterations in pancreas allografts, with enteral, vesical, peritoneal or occluded exocrine drainage. None of the animals with enteral drainage survived the first four postoperative weeks, with lethal infections being responsible for allograft failure. Full functionality three months from transplantation was recorded from three of seven transplants with ductal occlusion and unobstructed drainage into the abdominal cavity. Ductal occlusion was repeatedly accompanied by pancreatitis and pseudo-cysts. Fibrotisation of the organ and loss of endocrine islets of pancreas were recordable from these cases just as from grafts with unobstructed drainage into the abdominal cavity. Drainage of exocrine secretion into the bladder yielded good success in one of seven animals and was morphologically and functionally characterised primarily by occlusive metaplastic ossification along the transition to the anastomosis.

Animals↗

Morphologic alterations observed during experimental ischemia of the equine large colon.

Morphologic changes that develop sequentially in the large colon during experimentally induced ischemia were documented in 14 halothane-anesthetized horses. Colonic ischemia was induced by 4 types of vascular occlusion, 24 cm proximal and distal to the pelvic flexure. The effect of transmural (colonic wall) vascular compression combined with either venous occlusion (3 horses, group A) or venous and arterial occlusion (3 horses, group B) of the colonic vessels was studied for 1, 2, and 6 hours of occlusion. Also observed was the effect of reperfusion for 0.5 hour after release of the clamps for the 1- and 2-hour occlusions and for 1 hour after release of the clamps for the 6-hour occlusion. Effects of occluding only the colonic veins (4 horses, group C), or the colonic veins and arteries (4 horses, group D) were studied for 0.5, 1, 1.5, and 2 hours of occlusion and during reperfusion for 0.5 hour. Full-thickness intestinal biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 0.75, 1, 1.5, and 2 hours during occlusion and at 0.5 hour after release of vascular occlusion. Biopsy specimens were obtained at hourly intervals from the 2 horses in which 6-hour occlusion was performed and at 1 hour after release of vascular occlusion. Macroscopic changes (serosal color, mucosal color, serum leakage) in the colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Role of immunoblotting in the diagnosis of culture negative and enterococcal endocarditis.

Serum samples from patients with endocarditis and septicaemia due to Enterococcus faecalis, Enterococcus faecium, Streptococcus bovis, and Streptococcus sanguis were immunoblotted against antigenic extracts from all four species. In E faecalis endocarditis there was a strong IgM response to E faecalis antigenic bands of 112, 88-90, and 45-47 Kd and a strong IgG response to 88-90 and 45-47 Kd bands. In E faecium endocarditis there was a pronounced IgG response to an E faecium band of 82-90 Kd. For S bovis endocarditis, there was a strong IgG response to several components of S bovis including bands of 66, 58, 52 and 4 Kd. For S sanguis, there was a strong IgG response to bands of 80-82, 76, 60 and 45 Kd. These patterns of antibody production were absent in patients with uncomplicated septicaemia and in controls. The delineation of these patterns enabled confirmation of the final diagnosis in seven patients initially suspected of having culture negative endocarditis.

Antibodies, Bacterial↗

Laryngotracheal injury associated with nasotracheal intubation in the horse.

Laryngotracheal damage following short-term nasotracheal intubation was studied in 7 healthy horses. A flexible fiberoptic endoscope was used to examine the upper respiratory tract of each horse before nasal intubation with a cuffed silicone endotracheal tube and again at 1 hour, 24 hours, and 48 hours after extubation. Any abnormalities still evident at 48 hours were evaluated at 7 days after extubation. Mucosal damage involved the nasal meatus (5 of 7 horses), the arytenoid cartilages (5 of 7 horses), the trachea (5 of 7 horses), the dorsal pharyngeal recess (4 of 7 horses), the vocal folds (3 of 7 horses), and the entrance to the guttural pouch (3 of 7 horses). Laryngeal injury was attributable to tube pressure on the arytenoid cartilages and vocal folds. Tracheal damage appeared to be a function of pressure exerted by the inflated cuff on the tracheal mucosa.

Animals↗

[immunosuppression following kidney transplantation using antilymphocyte globulin followed by treatment with cyclosporin. A prospective study].

In a prospective study three different immunosuppressive schemata after renal transplantation were compared. In group A (47 patients) conventional treatment with azathioprin and steroids was administered; in group B (47 patients) antilymphocyte globulin (ALG) was additionally given for three weeks. In group C (47 patients) ALG-azathioprin-steroid administration lasted for a mean of nine days after the transplantation, followed by ciclosporin. One-year transplant survival rate was 59.6% in group A, 70.2% in group B and 89.4% in group C; one-year patients survival rate 95.7%, 89.4% and 100%, respectively. Thus conventional immunosuppression with ALG followed by ciclosporin was statistically significantly superior to the other two treatment schedules, both with respect to patient and transplant survival. This was also true of postoperative dialysis rate, which was lowest in group C, at 17%, compared with group A (85.1%) and group B (42.6%). Under the chosen study conditions there was no evidence of a negative effect of ciclosporin on long-term renal function.

Adult↗

Gentamicin tissue concentrations in equine small intestine and large colon.

Gentamicin sulfate (2.2 mg/kg of body weight, IV) was given to anesthetized horses. Jejunal and large colon tissue samples (1 g), serum, and urine were collected over a 4-hour period. Maximum gentamicin concentrations in serum (10.06 +/- 2.85 micrograms/ml) occurred at 0.25 hours after injection. Maximum gentamicin concentrations in the large colon (4.13 +/- 1.80 micrograms/ml) and jejunum (2.26 +/- 1.35 micrograms/ml) occurred in horses at 0.5 and 0.33 hours, respectively. Tissue concentrations decreased in parallel with serum concentrations and were still detectable at the end of the 4-hour period. During the time that samples were collected, the total amount of gentamicin excreted in the urine ranged from 7.21 +/- 3.11 mg to 11.91 +/- 7.12 mg, with a mean urinary concentration of 57.01 +/- 5.37 micrograms/ml. Over the 4-hour collection period, the fraction of dose that was excreted unchanged in the urine was 4.8 +/- 1.9%. Pharmacokinetic analyses of the serum concentration-time data gave a serum half-life of 2.52 +/- 1.29 hours, volume of distribution of 227 +/- 83 ml/kg, and body clearance of 1.12 +/- 0.26 ml/min/kg. The half-lives of the antibiotic in the jejunum and large colon were 1.32 and 1.33 hours, respectively.

Animals↗

Surface oximetry of healthy and ischemic equine intestine.

Measurements of jejunal, ileal, and large colon (pelvic flexure) surface O2 tension (PSO2) were made in halothane-anesthetized horses with a nonheated miniature oxygen polarographic electrode. Assisted ventilation with 100% O2 was used to maintain PaCO2 tension at 50 +/- 8 mm of Hg while mean arterial blood pressure was maintained greater than or equal to 70 mm of Hg. Mean +/- SD PSO2 for the intestinal segments were: jejunum (horses 1 to 4), 71 +/- 20 mm of Hg; ileum (horses 1 to 4), 61 +/- 8 mm of Hg; and pelvic flexure of the large colon (horses 1 to 10), 55 +/- 13 mm of Hg. The response of the sensor to intestinal ischemia was studied in the large colon of an additional 12 halothane-anesthetized horses, using 4 types of vascular occlusion: venous (4 horses); arterial and venous (4 horses); venous and intramural vascular obstruction (2 horses); and arterial, venous, and intramural obstruction (2 horses). Venous and arterial occlusions were maintained for 30, 60, 90, and 120 minutes, whereas intramural obstruction combined with either type of vascular obstruction was studied for 60 to 120 minutes. After vascular occlusion, PSO2 decreased to 8 +/- 7 mm of Hg for venous obstruction, 4 +/- 3 mm of Hg for arterial and venous obstruction, 6 +/- 0 mm of Hg for intramural and venous obstruction, and 3 +/- 0 mm of Hg after intramural and arterial and venous obstruction. Thirty minutes after release of the clamps, the PSO2 increased to greater than or equal to 50% of the preoccluded large colon value.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antithrombin III activity in horses with large colon torsion.

A chromogenic peptide substrate assay was used to determine serially plasma antithrombin III (AT III) activity in 4 groups of horses. Group I consisted of healthy, mature horses in which AT III activity was determined twice daily for 7 consecutive days. Groups 2 and 3 contained healthy horses in which AT III activity was monitored for 7 days after controlled, but varying, conditions of general anesthesia and surgery (median celiotomy). Group 4 was made up of patients with a presurgical diagnosis of colonic torsion. In healthy awake horses (group I), there was no difference in AT III values over time. Postoperative AT III activity in the halothane-anesthetized horses (group 2) and in the sham-operated horses (group 3) was not significantly (P = 0.05) different from base-line values at any time. A significant decrease (P = 0.05) in AT III activity was observed on postoperative days 1 through 3 in the group of horses with large colon torsion, but returned to preoperative values by day 4 after surgery in the horses that survived. In those horses that did not survive, AT III activity remained below base-line values for the duration of observation. Seemingly, plasma AT III activity in horses was not significantly affected by halothane anesthesia or surgery. Serial evaluation of AT III activity may be useful for predicting survival in horses with large colon torsion.

Animals↗