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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 217 records · Page 12Linked to original sources
PubMed1988

A randomized controlled trial of parenteral methotrexate compared with sodium aurothiomalate (Myochrysine) in the treatment of rheumatoid arthritis.

Forty patients with rheumatoid arthritis (RA) were enrolled in a double blind study of 26 weeks duration designed to compare the efficacy and safety of parenteral methotrexate and sodium aurothiomalate (GSTM) in the treatment of RA. All the patients had active RA and none had previously received gold, D-penicillamine or immunosuppressive therapy. Patients were randomized to receive weekly intramuscular (IM) injections of either methotrexate 10 mg or GSTM 50 mg. Two patients taking methotrexate and 7 taking GSTM were withdrawn before 26 weeks. Methotrexate was as effective as GSTM as measured by numbers of swollen or tender joints, morning stiffness, grip strength, pain scale and erythrocyte sedimentation rate. Five patients taking methotrexate and 11 taking GSTM presented side effects (p = 0.05). Total number of adverse reactions was 5 for the methotrexate group and 15 for the GSTM group (p less than 0.01). Our data suggest that low dose IM methotrexate is less toxic and as effective as GSTM for the treatment of RA during the first 6 months of therapy.

Adult↗
PubMed1987

Effects of beta-chlornaltrexamine on food intake, body weight and opioid-induced feeding.

beta-Chlornaltrexamine (beta-CNA) is a non-equilibrium opioid receptor antagonist which alkylates and inactivates opioid receptors. Because opioid peptides are thought to contribute to the regulation of food intake, we examined the effects of intracerebroventricular (icv) injections of beta-CNA on the food intake and body weight of male rats. We also tested the ability of beta-CNA to block food intake stimulated by selective agonists of kappa, mu and delta opioid receptors: dynorphin A2 (DYN), Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO), and [(D-Ser2,Leu5]-enkephalin-Thr6 (DSLET). Treatment with beta-CNA caused a long-term (2-4 days) reduction in daily food intake and a concomitant reduction in body weight. An additional experiment indicated that the weight loss after beta-CNA treatment could be completely accounted for by the reduction in intake. beta-CNA treatment also abolished or greatly attenuated the feeding effects of DAGO, DSLET and DYN, even when these peptides were tested 26 hours after beta-CNA administration. The long duration of the effects of beta-CNA suggests that this compound will be a useful pharmacological tool in further study of the opioid feeding system.

Animals↗
PubMed1987

The effects of dialysis on brain water and EEG in stable chronic uremia.

Cerebral edema in uremic animals and humans, as well as an EEG deterioration in humans, has been reported after dialysis. Both are manifestations of the dialysis disequilibrium syndrome (DDS). This study was designed to analyze the changes induced by dialysis in the EEG pattern (spectral analysis), in the cerebral hydration, and ventricular size (computed tomography [CT] of the brain) in a group of 11 stable uremic patients. They volunteered for a randomized crossover study of 4 months each of standard hemodialysis (HD) and hypertonic hemodiafiltration (H HDF). H HDF is a dialysis technique that is shorter and more efficient than HD. An EEG recording, a CT scan of the brain, and blood biochemistry were performed before and after a HD (four hours, blood flow rate 250 mL/min) and a H HDF run (three hours, blood flow rate 400 mL/min). Approximately 6 weeks of stabilization on each treatment were allowed before these studies. No difference was found in the density of seven specific brain structures (base and apical cuts), when comparing pre- v post-HD, pre- v post-H HDF, pre- HD v pre-H HDF, and post-HD v post-H HDF. Furthermore, no difference was evident either in the bicaudate diameter of the lateral ventricles or in the transverse diameter of the third ventricle. In addition, no significant in-between- and within-treatment difference was observed when analyzing the EEG% power (3-7/7-13 Hz) data. In conclusion, this study shows neither a postdialysis change in brain density and ventricular size nor a postdialysis EEG deterioration in a group of stable uremic patients undergoing both a rapid and a standard dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Twenty-four hour energy expenditure in critically ill patients.

Resting energy expenditure (EE) is often used as the basis of nutritional support for critically ill patients but whether resting EE is representative of total daily EE is not known. EE was measured for 24 h in ten mechanically ventilated, critically ill patients (average Acute Physiology and Chronic Health Evaluation II score 23) to determine EE, resting EE, and the energy expended during various ICU activities. Although activities, such as weighing the patient on a sling-type bed scale, repositioning, and chest physiotherapy resulted in dramatic EE increases above resting levels (36%, 31%, and 20%, respectively), the actual contribution of these activities to total EE was small (1.1%, 2.1%, and 3.6%, respectively). The mean measured resting EE was 47.3 +/- 22.3% above mean predicted EE based on the Harris and Benedict equation, and the mean total 24-h EE was 6.9 +/- 2.6(SD)% above the mean measured resting EE. In this group of mechanically ventilated, critically ill patients, an activity factor of no greater than 10% above resting EE is appropriate.

Adult↗
PubMed1987

A randomized clinical trial comparing ranitidine and antacids in critically ill patients.

In a randomized trial of gastric pH control for stress ulcer prophylaxis, 200 mg/day ranitidine iv was compared to antacids in 86 patients admitted to an ICU. Six (15%) patients receiving ranitidine and six (13%) given antacids failed to maintain greater than 50% of the hourly gastric pH measurements at or above 4. Increasing the ranitidine dosage to 300 mg/day did not provide additional control. One patient in the antacid group developed an overt upper GI bleed secondary to endoscopically proven erosive disease. We conclude that iv ranitidine in a dosage of 200 mg/day is as effective as antacids in reducing gastric acidity and preventing stress ulcer disease in critically ill patients.

Administration, Oral↗
PubMed1987

Effect of neuropeptide Y on ingestive behaviors in the rat.

Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.

Adrenalectomy↗
PubMed1987

Oral acyclovir and herpes labialis: a randomized, double-blind, placebo-controlled study.

A study of the effects of oral acyclovir (200 mg), administered five times per day for 5 days in 210 patients who cultured positive for herpes labialis, is made. A total of 149 patients were followed through three episodes each of herpes labialis while taking a placebo or acyclovir. Patients were evaluated for several clinical parameters, including the loss of lesion crust and reduction of the size of the area of the lesion between day 1 and day 5. Acyclovir showed a significant antiviral effect. Results show that oral acyclovir can favorably affect some parameters, but that higher doses or a "loading dose" could improve its efficacy.

Acyclovir↗
PubMed1987

Suppression of superoxide generation by normal polymorphonuclear leukocytes preincubated in plasma from patients with Felty's syndrome.

Polymorphonuclear leukocytes (PMN) isolated from patients with Felty's syndrome (FS) generate fewer superoxide anions (O-2) upon stimulation with fmet-leu-phe than PMN from normal controls or patients with rheumatoid arthritis (RA). In this study, plasma samples were obtained from 12 patients with RA and 12 patients with FS. Incubation of normal PMN in plasma from Felty patients resulted in a significant reduction in both the rate and total quantity of O-2 generation when activated with fmet-leu-phe. This was not observed with plasma from RA patients. The capacity of a plasma sample to suppress O-2 generation correlated with plasma IgG-PMN-binding activity (IgG-PBA) and, to a lesser extent, with the content of circulating immune complexes (CIC). These data suggest that IgG-PBA and possibly CIC have a pathogenetic role in both qualitative and quantitative defects in PMN in Felty patients.

Aged↗
PubMed1987

Effect of clot removal at 24 hours on chronic vasospasm after SAH in the primate model.

The efficacy of complete clot removal 24 hours after subarachnoid hemorrhage (SAH) in the prevention of chronic cerebral vasospasm was evaluated in monkeys in a blind randomized controlled trial. Twenty-four monkeys were randomized to one of three groups to undergo sham-operation (sham-operated group), clot placement only (clot group), or clot placement and removal (clot-removal group). By means of standard microsurgical techniques, the major cerebral vessels bilaterally were dissected free of arachnoid. An autologous hematoma averaging 5 gm was placed around the vessels in the subarachnoid spaces in the clot and clot-removal groups. Saline solution was instilled in the subarachnoid spaces of the sham-operated group. All animals underwent reoperation 24 hours after the first procedure. In the clot-removal group, the hematoma was evacuated. In the sham-operated and clot groups, the incision was simply closed again after 3 hours of anesthesia. Indices monitored before and 7 days after SAH induction included neurological status, angiographic cerebral vessel caliber, and arterial blood pressure. All animals were evaluated with magnetic resonance imaging (MRI); representative animals were evaluated with computerized tomography (CT) brain scans. There were no neurological deficits in either the sham-operated or the clot-removal groups. One animal in the clot group developed a progressive delayed ischemic deficit on Day 5 after SAH. A second animal in this group died suddenly on Day 4 post-SAH. An autopsy revealed a recent infarct in the territory of the superior cerebellar artery. Clinical findings correlated with MRI and CT images. Significant vasospasm (25% to 100% reduction in vessel caliber) was present on Day 7 in 100% of the clot animals (p less than 0.01). There was no significant vasospasm (p greater than 0.05) on Day 7 in either the sham-operated or the clot-removal groups. A large volume of clot placed bilaterally resulted in a 25% incidence of delayed ischemic deficit. Evacuation of subarachnoid hematoma within 24 hours of SAH prevented the development of chronic vasospasm and delayed ischemic deficit in the primate model.

Animals↗
PubMed1987

The effect of timing of clot removal on chronic vasospasm in a primate model.

The effect of complete clot removal at times from 48 to 96 hours after subarachnoid hemorrhage (SAH) on the development of chronic cerebral vasospasm was evaluated to determine whether there is a critical point after which clot removal is ineffective in preventing vasospasm. Thirty cynomolgus monkeys were randomized to one of five groups: sham-operated group, clot removal at 48 hours after SAH (48-hour group), clot removal at 72 hours after SAH (72-hour group), clot removal at 96 hours after SAH (96-hour group), and clot placement only (clot group). Standard microsurgical techniques were used to dissect bilaterally the major cerebral arteries free of arachnoid. An autologous blood clot averaging 4.2 gm was placed around the vessels in the subarachnoid space of the monkeys in the 48-hour, 72-hour, 96-hour, and clot groups. Physiological saline was instilled into the subarachnoid space of the sham-operated animals. Animals in the clot-removal groups underwent surgical clot removal at the determined times for each group. Two animals in each of the sham-operated and clot groups were subjected to reoperation at each of 48, 72, and 96 hours after SAH. The incisions were reopened and then simply reclosed. Neurological status, angiographic cerebral vessel caliber, and physiological status were evaluated before and 7 days after SAH induction. There were no significant neurological deficits in the sham-operated, 48-hour, or 72-hour groups. Two animals in each of the 96-hour and clot groups showed deterioration in level of consciousness developing on Day 4 or 5 after SAH induction. All the major cerebral arteries of the animals in the clot and 96-hour groups showed significant vasospasm (p less than 0.01) on Day 7. Animals in the 72-hour group had significant vasospasm (p less than 0.05) of the internal carotid and middle cerebral arteries but not the anterior cerebral arteries. There was no significant vasospasm (p greater than 0.05) in any of the cerebral arteries in the 48-hour group. Severity of vasospasm paralleled the duration of contact between the blood clot and the cerebral vessels. Evacuation of the subarachnoid hematoma later than 48 hours after SAH resulted in no significant reduction in the degree of chronic cerebral vasospasm. It is suggested that clot removal at early operation is likely to be useful only if it is performed within 48 hours of SAH.

Animals↗
PubMed1986

CRF antagonist partially reverses CRF- and stress-induced effects on feeding.

Exogenous corticotropin releasing factor (CRF) causes centrally mediated behavioral changes including decreased feeding and increased grooming. These behavioral changes are also seen in response to some stressors. However, the role of endogenous CRF in the behavioral response to stressors has not been investigated fully. We report below our findings on the behavioral effects of alpha-helical CRF (9-41), a recently discovered competitive antagonist of CRF-induced ACTH release. Alpha-helical CRF (9-41) partially reversed the decrement in feeding induced by CRF. Furthermore, the reduction in food intake due to restraint stress was partially reversed by alpha-helical CRF (9-41). These results indicate that changes in endogenous CRF release induced by the restraint stressor may play a role in stress-induced anorexia.

Animals↗
PubMed1986

Thermodilution cardiac output--an in vitro model of low flow states.

The accuracy and reproducibility of thermodilution cardiac output measurements were examined in vitro at low flows, using the Edwards cardiac output computer. For each of 18 different volumetrically measured flows between 130 and 1035 ml/min, three cardiac outputs were determined for each of four different injectate volumes (1,2,3, and 5 ml) at two different temperatures (0 degrees C and room temperature). There was a significant (p less than .001) correlation between measured flow and cardiac output for all injectate volumes at both temperatures. The slopes of the regression lines ranged between 0.97 and 1.25, and the y-intercepts were all greater than 0. Although this thermodilution technique overestimated cardiac output, it was a reproducible means of measuring cardiac output in this low-flow in vitro model.

Cardiac Output↗
PubMed1986

Acute cardiopulmonary effects of subarachnoid hemorrhage in monkeys.

Twenty-eight cynomolgus monkeys had an autologous subarachnoid blood clot placed in the basal cisternae via craniectomy. Twenty-three monkeys survived clot placement and five animals died within 24 h. An additional eight monkeys underwent sham procedures and six acted as anesthetic controls. Cardiopulmonary indices were measured before clot placement and 30 to 60 min thereafter, to determine if certain changes had prognostic value for immediate outcome. In the 24-h survivors, heart rate and arteriovenous oxygen content difference increased significantly (p less than .05 and .01, respectively), while stroke index (SI) (p less than .01), mean pulmonary artery pressure (p less than .001), pulmonary artery wedge pressure (p less than .001), and central venous pressure (p less than .05) fell. In the 24-h nonsurvivors, cardiac index (CI) (p less than .05) and SI (p less than .01) fell to an even greater extent than in the survivors. There was a significant (p less than .05) difference between the two groups for CI and SI. There were no significant differences in the sham-operated animals. In six control monkeys, neither heart rate nor CI significantly increased throughout 5 h of anesthesia.

Animals↗
PubMed1986

Nimodipine and chronic vasospasm in monkeys: Part 3. Cardiopulmonary effects.

A subarachnoid hemorrhage was induced in 30 cynomolgus monkeys by the placement of a 6- to 7-ml blood clot through a frontotemporal craniectomy (Day 0). The monkeys underwent a 1-week-long, randomized, blind trial comparing various doses of nimodipine to placebo, sham, and no treatment. The treatment groups were: nimodipine, 3 mg/kg every 8 hours (n = 6), 6 mg/kg every 8 hours (n = 6), and 12 mg/kg every 8 hours (n = 6); placebo (polyethylene glycol 400), 0.33 ml/kg every 8 hours (n = 6); and no treatment (n = 6). An additional sham group underwent craniectomy without clot placement (n = 6) so that 36 animals in total were operated upon. Differences in cardiopulmonary indices between Day 0 and Day 7 were compared within and between groups. No significant differences were obtained in the sham and no treatment groups. The nimodipine 6- and 12-mg/kg groups showed significant decreases in blood pressure (P less than 0.04 and P less than 0.015). Systemic vascular resistance was increased in the placebo and 3-mg/kg groups (P less than 0.02) and decreased in the 12-mg/kg group (P less than 0.015). Stroke index was increased in the 12-mg/kg group (P less than 0.05). Cardiac index and stroke index correlated positively with nimodipine dosage (r = 0.99, P less than 0.05). There were no pronounced changes in pulmonary artery wedge pressure, central venous pressure, alveolar-arterial oxygen pressure difference, arteriovenous oxygen content difference, and percentage of shunting.

Animals↗
PubMed1985

Peptide YY (PYY), a potent orexigenic agent.

Peptide YY (PYY) enhances feeding and drinking more potently than does neuropeptide Y after central administration. Chronic administration of PYY every 6 h for 48 h causes massive food ingestion. Tolerance to this effect of PYY does not appear to develop. This data suggests that PYY is one of the most potent orexigenic substances yet to be identified. PYY may play a role in the pathogenesis of bulimic syndromes.

Animals↗
PubMed1985

The kappa opioid receptor and food intake.

Many studies have suggested a role of opioid receptors in the modulation of food intake. Several distinct classes of opioid receptors have been postulated. In an attempt to establish which opioid receptor(s) modulate feeding we studied the effect of the kappa agonist, bremazocine, on feeding and compared its effects to the preferential mu agonist, morphine, and the mixed kappa-sigma agonist, butorphanol and the kappa agonist, ethylketocyclazocine. Bremazocine increased feeding to the same extent as morphine and was less potent than the mixed agonist/antagonists. The bremazocine effect demonstrated a bell-shaped dose response curve. Daily administration of bremazocine or morphine enhances the effect on increasing food intake. However, this effect of daily injections on enhancing food intake is not present when animals receiving morphine are crossed over to bremazocine and vice versa. The bremazocine effect is enhanced by diprenorphine and not inhibited by naloxone. Low doses of the dopamine antagonist, haloperidol, enhance the bremazocine effect and higher doses inhibit it. Finally, using another kappa agonist, tifluadom, we showed that the effect on food intake is stereospecific. Our studies provided further evidence for a role for the kappa opioid receptor in feeding. However, they also suggest that more than one subpopulation of opioid receptors is involved in feeding modulation.

Animals↗