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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 19 recordsLinked to original sources

Gastric ulceration in horses: 91 cases (1987-1990).

Gastroendoscopy was performed on 111 horses (1 to 22 years old) that had signs of abdominal discomfort of variable duration and severity. At least 1 episode of colic had been observed within 48 hours of examination in 31 horses. Recurrent episodes of colic were observed in 28 horses within 2 to 10 days of examination, 31 horses within 11 to 30 days, 12 horses within 31 to 60 days, and in 9 horses at more than 60 days after the initial examination. Gastric ulceration was found in 91 of 111 horses examined. Other abnormalities involving the gastrointestinal tract or other abdominal viscera were not found on examination in 57 of 91 horses with gastric ulcers. The most frequent concurrent abnormalities found in the remaining 34 horses with gastric ulcers were impaction of the large colon (n = 6), colonic tympany (n = 6), peritonitis (n = 6), gastric impaction (n = 4), ileocecal intussusception (n = 3), small-colon impaction (n = 4), and proximal enteritis (n = 2). Thirteen horses with gastric ulceration underwent abdominal surgery, and in 5 horses, lesions were not found at surgery. Gastric ulceration was determined to be the primary cause of colic in 31 horses on the basis of the lack of other abnormalities, clinical response to treatment with histamine type-2 receptor (H2) antagonists, and confirmation of improvement or resolution of gastric ulceration via endoscopy. Gastric ulceration was the suspected cause of colic in 26 other horses on the basis of the lack of other abnormalities, severity of lesions, and clinical response to treatment with H2 antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

A national survey on the practice patterns of anesthesiologist intensivists in the use of muscle relaxants.

OBJECTIVE: To determine the practice patterns of anesthesiologist intensivists (with the special certificate of competence in critical care medicine from the American Board of Anesthesiology) in the use of neuromuscular blocking drugs, in the ICU setting. DESIGN: A survey. PARTICIPANTS: All anesthesiologists with the special certificate of competence in critical care (n = 374) were selected for this study. Of the 339 who could be contacted and who were still actively practicing, 185 (55%) completed the survey. RESULTS: In the ICU setting, anesthesiologist intensivists most commonly used vecuronium (52%) administered by bolus injection, bolus injection followed by infusion, or by continuous infusion. The most frequent indication for muscle relaxation was facilitation of mechanical ventilation (89%). Neuromuscular blockade was most commonly monitored clinically (55%), with only 34% of respondents using a peripheral nerve stimulator. All respondents indicated the concomitant use of sedatives or narcotics with muscle relaxants. CONCLUSIONS: This study was created to address the dearth of information regarding actual usage of muscle relaxants in the ICU setting. The survey population was chosen as one with great familiarity in the use of muscle relaxants. The 55% response rate was significantly greater than the expected response rate for a single mailing survey. In the ICU setting, neuromuscular blocking drugs are most frequently used to facilitate mechanical ventilation. The prevalence of vecuronium use is of interest in light of recent case reports of prolonged neuromuscular blockade after long-term vecuronium administration. The low frequency of peripheral nerve stimulator monitoring during muscle relaxation may contribute, in part, to the problem of prolonged blockade after drug withdrawal. Muscle relaxants are not used in the absence of sedation and/or analgesia by this practitioner population.

Anesthesiology

The effects of stress on gastric ulceration, T3, T4, reverse T3 and cortisol in neonatal foals.

Sixteen neonatal foals stressed by disease underwent endoscopic examination of their stomachs and blood was assayed for triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4) and cortisol, to determine the effects of severe physiological stress and the occurrence of gastric ulcers. compared with eight age-matched controls, six foals had abnormal cortisol, seven had abnormal T3 and 12 had abnormal T4. Eleven of 13 foals had rT3 outside the 95 per cent confidence interval for clinically normal foals of comparable ages. Gastric lesions were seen more frequently in stressed foals, and gastric glandular mucosal lesions were noted in 40 per cent of the stressed foals. Previous studies report low (3 per cent) occurrence of gastric mucosal lesions. The frequency of squamous mucosal lesions was not different from that reported previously, indicating that stress has little effect on the development of lesions at this site.

Animals

Epidermal growth factor-like activity in mares' milk.

Epidermal growth factor (EGF)-like activity was measured in mares' colostrum and milk by radioreceptor assay. Milk samples were collected from 22 mares 1 or more times during early lactation. Samples of colostrum were taken after parturition and before the foal first suckled (presuckle), within 6 hours after the foal first suckled (postsuckle), and on days 1, 2, 4, and 8 of lactation. In the 5 mares from which milk samples were obtained at each sampling time, presuckle colostral mean EGF-like activity (17.8 ng/ml) was greatest (P less than 0.05). The mean values for EGF-like activity at all other sampling times were not significantly different from each other (postsuckle colostrum, 9.7 ng/ml; day 1, 9.6 ng/ml; day 2, 8.5 ng/ml; day 4, 8.0 ng/ml; day 8, 7.8 ng/ml).

Animals

Spinal cord injury in experimental thoracic aortic occlusion: investigation of combined methods of protection.

The efficacy of combined methods of spinal cord protection during thoracoabdominal aortic reconstruction was evaluated because a recent clinical study failed to substantiate the value of cerebrospinal fluid drainage when used alone in the prevention of paraplegia. The effect of cerebrospinal fluid drainage and aortofemoral shunting were analyzed with regard to neurologic outcome and spinal cord blood flow in a model of thoracic aortic occlusion. In addition, we studied the use of motor-evoked potentials as compared with somatosensory-evoked potentials in monitoring cord perfusion. Thirty-two dogs underwent proximal and distal thoracic aortic occlusion for 60 minutes. The control group (n = 8) underwent thoracic aortic cross-clamping only. Spinal cord protection was used in three groups: cerebrospinal fluid drainage alone (n = 8), aortofemoral shunting alone (n = 8), and cerebrospinal fluid drainage and aortofemoral shunting (n = 8). Neurologic outcome improved in all treatment groups as compared with controls (p less than 0.001). The addition of cerebrospinal fluid drainage to aortofemoral shunting did not further improve neurologic outcome. Spinal cord blood flow measured with microspheres in the lumbar gray matter was significantly higher in the dogs with aortofemoral shunting (+/- cerebrospinal fluid drainage) as compared with those with cerebrospinal fluid drainage alone (p less than 0.05) or the controls (p less than 0.001). Aortofemoral shunting also prevented the development of acidosis and hyperglycemia. Loss or changes in amplitude and latency of motor-evoked potentials did not distinguish between the groups. Loss of somatosensory-evoked potentials had a high sensitivity (92%) but lower specificity (68%) in predicting neurologic injury, whereas loss of motor-evoked potentials had a high specificity (100%) but a very low sensitivity (16%). We conclude that cerebrospinal fluid drainage or aortofemoral shunting significantly improve spinal cord blood flow and neurologic outcome. The greatest increase in spinal cord blood flow was seen with aortofemoral shunting, which also prevented metabolic disturbances of reperfusion. Although the addition of cerebrospinal fluid drainage to aortofemoral shunting was the only group in which no neurologic injury occurred, this group did not have a significant improvement in outcome when compared with aortofemoral shunting alone. Spinal cord ischemia was more accurately detected with somatosensory-evoked potentials when aortofemoral shunting was used, whereas motor-evoked potentials recorded from the spinal cord were not sensitive enough to predict neurologic injury.

Analysis of Variance

Intestinal myxosarcoma in a thoroughbred mare.

A large fibrotic mass originating from the cecal base was discovered upon surgical exploration of the abdomen in a Thoroughbred mare with a history of chronic colic and weight loss. The mass protruded intraluminally resulting in partial obstruction. Surgical excision was not feasible due to the location of the mass and the inability to exteriorize it adequately from the abdominal cavity. The mass was fibrous with a shiny, gelatinous material present throughout the neoplasm. Histologically, large confluent spaces filled with mucopolysaccharides were identified by staining with Alcian blue. The diagnosis of myxosarcoma was based upon finding of atypical fibroblastic cells, mucinous stroma, local invasiveness, and metastasis to the regional lymph nodes. Myxomatous tumors have not previously been documented to occur in the equine intestinal tract.

Animals

Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation.

High affinity binding of platelet-derived growth factor (PDGF) has been proposed to involve the interaction of the dimeric PDGF ligand with two receptor subunits, designated alpha and beta. We have cloned and expressed a human PDGF receptor cDNA which differs in sequence from the beta-subunit and which has the PDGF binding properties and monoclonal antibody recognition, predicted for the alpha-subunit. Scatchard analysis indicated that PDGF-AA and PDGF-AB bound to transfected alpha-subunits with affinities of Kd = 0.06 and 0.05 nM, respectively. PDGF-BB bound with a significantly lower affinity (Kd = 0.4 nM). Nevertheless, this affinity is still great enough to mediate substantial PDGF-BB binding at physiological concentrations and would be considered to be "high affinity." We have used wild-type and kinase-inactive human beta-subunits to show that PDGF binding promotes receptor subunit dimerization in intact cells. In addition, we found that PDGF stimulates tyrosine phosphorylation of the kinase-inactive beta-subunit when it is expressed with alpha-subunits. The kinase-inactive beta-subunits were phosphorylated at tyrosine 857 and 751, the major phosphorylation sites of the wild-type beta-subunit, indicating either that intra- and intermolecular phosphorylation occurs on the same sites, or that a significant fraction of receptor tyrosine phosphorylation is intermolecular.

Animals

Failure of motor evoked potentials to predict neurologic outcome in experimental thoracic aortic occlusion.

Motor evoked potential monitoring was tested as an alternative to somatosensory evoked potential monitoring in evaluating spinal cord function during thoracic aortic occlusion in dogs. Twenty-seven animals underwent 60 minutes of cross-clamping of the proximal descending thoracic aorta with (n = 18) or without (n = 9) cerebrospinal fluid drainage. Spinal cord blood flow was measured with microspheres, and neurologic outcome was evaluated at 24 hours with Tarlov's scoring system. Cerebrospinal fluid drainage improved neurologic outcome (p less than 0.05). Motor evoked potentials recorded over the lumbar spinal cord were lost in 9 of 20 dogs with ischemic cord injury and were not lost in any of the 7 dogs that were neurologically normal. Somatosensory evoked potential were lost in 19 of 20 paraplegic/paraparetic dogs and lost in 3 of 7 normal dogs (p less than 0.01). After reperfusion, motor evoked potentials returned in all nine neurologically injured dogs that lost the potentials and were still present at 24 hours. Changes in amplitude, latency, or time until loss or return of motor evoked potentials or somatosensory evoked potentials did not predict neurologic injury. Loss of somatosensory evoked potentials had a high sensitivity (95%) but had low specificity (67%) because of peripheral nerve ischemia. Loss of motor evoked potentials recorded from the spinal cord had high specificity (100%) but a low sensitivity (46%) and was therefore not a reliable predictor of neurologic injury. Return of motor evoked potentials during reperfusion did not correlate with functional recovery. Motor evoked potentials stimulated in the cortex and recorded from the spinal cord had low overall accuracy (59%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sepsis and septic shock. Deadly complications that are on the rise.

Most patients are already hospitalized when sepsis and septic shock develop, and in spite of therapy, at least 50% die. Although newer therapeutic agents are being evaluated, current management consists of antibiotics, fluids for volume resuscitation, inotropic agents, and surgery for septic foci. Greater emphasis on preventive measures is recommended.

Anti-Bacterial Agents

Differences in the biological activities of transforming growth factor-beta and platelet-derived growth factor in vivo.

Transforming growth factor-beta 1 (TGF-beta 1 and recombinant platelet-derived growth factor-BB (rPDGF-BB) promoted an extensive, dose-dependent development of fibrous connective tissue when continuously delivered for 8 days by mini-osmotic pumps implanted subcutaneously in adult guinea pigs. Biochemical analyses demonstrated that TGF-beta 1 and rPDGF-BB stimulated dose-dependent increases in the dry weight, and protein, DNA, collagen, and glycosaminoglycan (GAG) contents of the fibrous connective tissue capsule that enveloped the pumps. The GAG/DNA mass ratio was markedly elevated by TGF-beta 1, but the collagen/DNA, protein/DNA, and collagen/protein ratios were not significantly increased. In contrast, rPDGF-BB generally decreased these mass ratios. Histological analyses suggested that this was due to the fact that rPDGF-BB induced a very cellular response with a marked influx of neutrophils and fibroblasts. TGF-beta 1 induced significantly less cellular response, which consisted primarily fibroblasts and macrophages. These results indicated that rPDGF-BB and TGF-beta 1 induced connective tissue deposition in vivo in a dose-dependent fashion, although the cellular nature of the responses as well as the structural composition of the extracellular matrices were clearly distinguishable between the two growth factors.

Animals

Protamine-heparin-induced pulmonary hypertension in pigs: effects of treatment with a thromboxane receptor antagonist on hemodynamics and coagulation.

Adverse hemodynamic reactions after protamine neutralization of heparin are an infrequent but important clinical problem. Pre-treatment of swine with a thromboxane A2 receptor antagonist has been reported to prevent the pulmonary hypertensive response occasionally seen after protamine reversal of heparin anticoagulation. In the current study, a control group of pigs (n = 9) received intravenous heparin (300 IU/kg), followed after 10 min by a neutralizing dose of protamine (3 mg/kg). A treatment group of pigs (n = 11) was treated identically, except that the thromboxane A2 receptor antagonist L-670596 (2 mg/kg) was infused intravenously 2 min after the protamine infusion. Hemodynamic and coagulation profiles were monitored during these procedures. Pulmonary hypertension developed and reached a peak within 2 min of protamine administration, often at the same time that L-670596 was administered in the treatment group. There was no statistical difference between control and treatment groups' peak pulmonary arterial pressure and peak pulmonary vascular resistance. However, the interval for return of mean pulmonary artery pressure from peak to baseline values was 11.6 +/- 3.1 versus 5.5 +/- 1.9 min (mean +/- SD) for control and treatment groups, respectively (P less than 0.01). Thromboxane B2 plasma concentrations increased in both groups and were correlated with the pulmonary hypertensive response (r = 0.86, P less than 0.01). Platelet aggregation to collagen was inhibited by the thromboxane A2 receptor antagonist (P less than 0.05). Bleeding time was prolonged beyond normal range in 50% of L-670596-treated pigs. All other coagulation tests in both groups returned to baseline after reversal of heparin with protamine and were unaffected by L-670596.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hypothyroidism and respiratory insufficiency in a neonatal foal.

Hypothyroidism was diagnosed in a neonatal Thoroughbred foal that was weak, hypothermic, and septicemic. Administration of thyroid-releasing hormone elicited attenuated increases in concentrations of free and total triiodothyronine and thyroxine, as compared with a clinically normal, age-matched foal. The foal died of apparent respiratory insufficiency, pre- and postmortem findings compatible with hypothyroidism included hypothermia, large thyroid glands with distended, colloid-filled follicles, and severe, diffuse atelectasis, with thickened alveolar septae and degenerating alveolar squamous epithelial cells.

Animals

Endoscopic evaluation of changes in gastric lesions of Thoroughbred foals.

Gastroendoscopic examinations were conducted on thirty-two 2- to 60-day-old Thoroughbred foals on 5 breeding farms. Repeat gastroendoscopic examinations were performed 35 to 135 days after the initial examination, with the age of foals ranging from 39 to 190 days. On initial endoscopic examination, lesions consisting of ulcers and/or erosions were most prevalent in the stratified squamous epithelial mucosa adjacent to the margo plicatus along the greater curvature of the stomach (15 of 32 foals), and were observed much less frequently at other sites within the stomach. In addition to ulcers and erosions, squamous epithelial desquamation at the margo plicatus was observed in 16 of 19 foals less than 30 days old and in 3 of 13 foals 30 to 60 days old, and was not seen in any foal on repeat endoscopy. At the time of repeat endoscopic examination, the frequency of ulcers and erosions at the margo plicatus was significantly (P less than 0.01) less than at initial examination (4 of 32 foals vs 15 of 32 foals). Lesions had healed in 14 of the 15 foals with lesions at the margo plicatus on the initial examination. Lesions were observed in the glandular mucosa of the fundus in 3 of 32 foals on initial examination and in 6 of 32 foals reexamined. Lesions in the glandular fundus observed on initial examination had healed in 2 of 3 foals, and of the 6 foals with glandular mucosal lesions on reexamination, 5 had developed lesions since the initial examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Examination of immune parameters and host resistance mechanisms in B6C3F1 mice following adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Adult female B6C3F1 mice were given a single ip dose of 0, 01, 1.0, or 10.0 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and examined for immune function and host resistance 7-10 d later. Exposure to TCDD resulted in a significant dose-related decrease in induction of both IgM and IgG antibody-forming cells. This suppression was noted for both T-dependent and T-independent antigens. TCDD at a dosage of 10 micrograms/kg was shown to suppress production of antibody to viral hemagglutinin. In contrast, TCDD exposure had no significant effect on natural killer cell function, production of interferon, or various parameters of macrophage function. Assessment of host resistance revealed a significant increase in susceptibility to fatal infection with influenza virus, but no significant alteration in susceptibility to infection with the bacterium Listeria monocytogenes.

Animals

Endotoxin does not directly alter norepinephrine release or vasoactivity in dog pulmonary artery and portal vein.

The direct effect of Escherichia coli endotoxin on the release of norepinephrine (NE) and the contractile response consequent to the release of NE were studied in isolated, superfused segments of dog pulmonary artery and portal vein during resting conditions and during electrical stimulation (ES). High-pressure liquid chromatography with electrochemical detection was used to quantify the endogenous NE released and that remaining in the tissue after stimulation. Endotoxin (1 micrograms/ml and 10 micrograms/ml in superfusate) had no effect on the release of NE from either pulmonary artery or portal vein. Endotoxin also had no effect on vasoactivity in response to ES. Thus, in isolated pulmonary artery and portal vein, endotoxin, in the doses employed, does not directly affect release of NE from adrenergic nerve endings, nor does it affect the sequence of events that starts with transmitter-receptor interaction and ends with contraction of smooth muscle cells.

Adrenergic Fibers