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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 235 records · Page 13Linked to original sources
PubMed1985

Environment modulates naloxone's suppressive effect on feeding in diabetic and non-diabetic rats.

We evaluated the effect of environment on naloxone-induced suppression of feeding in streptozotocin rats and sham injected controls. Naloxone was administered to animals fasted for 24 hours and food intake was measured at 30, 60 and 120 minutes. Diabetic rats, in their home cages, were insensitive to naloxone's suppressive effect for the first 30 minutes and the 5 mg/kg dose suppressed feeding only at 120 minutes. In control rats, feeding was suppressed at 1 and 5 mg/kg naloxone during the first 30 minutes. In contrast, when animals were placed in novel plastic cages, control animals were insensitive to naloxone at all time points at doses as high as 5 mg/kg. In novel cages, diabetic rats responded to doses of 1 and 5 mg/kg during the first 30 minute period by lowering food intake. It should also be noted that basal food intake was suppressed (40-53%) when animals were placed in novel cages. These data suggest that stress of a novel environment alters the neuroregulatory system involved in inducing feeding. Lack of response of normal rats to naloxone's suppressive effect in a novel environment suggests that (1) a non-opioid feeding system operates under these conditions, or (2) opioid receptors are occupied as a result of the release of endogenous opioids due to stress. The opposite result observed in the diabetics indicates that glucose has a modulating effect on opioid effects.

Animals↗
PubMed1985

Esophagogastrectomy without thoracotomy for carcinoma of the cardia and lower part of the esophagus.

Between 1 October 1979 and 1 September 1983, 34 patients with 25 adenocarcinomas and nine squamous cell carcinomas of the cardia and lower part of the esophagus have been treated with resection of the celiac lymph nodes (metastasis in 83 per cent of the patients), the lesser curvature of the stomach, cardia and total esophagus without thoracotomy. There was transmural spread of the cancer in 88 per cent of the patients. The esophagus was replaced by a tube made from the greater curvature of the stomach, which was brought through the mediastinum and anastomosed to the cervical esophagus. There was a hospital mortality of 2.9 per cent and the median hospital stay was 15 days. Morbidity included seven anastomotic leaks which closed spontaneously, intrathoracic bleeding (one), secretion retention (six), transient hoarseness (12), persistent dysphagia (one) and transient dumping syndrome (four). No patient has complained of aspiration or reflux of gastric juices. Satisfactory long term relief of dysphagia was achieved in 94 per cent of the patients. There have been no recurrences of tumor at the site of the anastomosis. The one year survival rate is 70 per cent and the median survival time is 19 months.

Abdomen↗
PubMed1984

The effect of ovariectomy, estradiol and progesterone on opioid modulation of feeding.

A number of lines of evidence have suggested that alterations in gonadal steroids may modulate opioid function. We report here the effects of manipulation of female gonadal steroids on the opioid feeding system. Naloxone produced a depression of feeding in all groups. Although the group X dosage interaction was not significant, an internally consistent tendency effect of naloxone among the different treatment groups was observed. Estradiol treated rats were 20 times less sensitive to naloxone's suppressive effects of feeding than ovariectomized animals. Sham operated controls and animals treated with estradiol and progesterone had sensitivities to naloxone which were intermediate to those seen in estradiol treated and ovariectomized animals. A significant drug X dosage interaction was present for the ketocyclazocine effects at 4 hours. Overall, ovariectomized animals were resistant to feeding induced by ketocyclazocine compared to the other groups. Ovariectomy significantly decreased ir-dynorphin levels in the cortex and these values were restored towards normal by a combination of estrogen and progesterone treatment. These studies add to the growing literature suggesting a role for the peripheral endocrine system in the modulation of opioid feeding system.

Animals↗
PubMed1984

Protein synthesis in rabbit reticulocytes: a study of the mechanism of action of the protein factor RF that reverses protein synthesis inhibition in heme-deficient reticulocyte lysates.

A eukaryotic initiation factor 2 (eIF-2)-ancillary protein factor Co-eIF-2 promotes displacement of GDP from eIF-2 X GDP and facilitates ternary complex (Met-tRNAf X eIF-2 X GTP) formation in the presence of Mg2+. Heme-regulated protein synthesis inhibitor, HRI, phosphorylates the alpha-subunit of eIF-2 and thus inhibits ternary complex formation as Co-eIF-2 does not displace GDP from eIF-2 alpha (P) X GDP. RF, a high molecular weight cell supernatant factor, reverses protein synthesis inhibition in heme-deficient reticulocyte lysates and also reverses HRI inhibition of ternary complex formation. RF contains Co-eIF-2 activity. In addition, an active RF preparation contains excess alpha-subunit of eIF-2 in the free and unphosphorylated form and this alpha-subunit of eIF-2 is not phosphorylated by HRI and ATP. In this paper we report (i) an active RF preparation contains excess alpha-subunit of eIF-2 and this alpha-subunit can be phosphorylated by HRI and ATP in the presence of GDP; (ii) RF promotes ternary complex formation by eIF-2 X [3H]GDP with accompanying GDP displacement; (iii) in the presence of HRI and ATP, RF promotes ternary complex formation by eIF-2 X [3H]GDP without accompanying GDP displacement; (iv) in the presence of HRI and ATP, the ternary complex formed using RF is active in Met-tRNAf X 40S initiation complex formation; (v) both the ternary complex and the Met-tRNAf X 40S complex formation in the presence of HRI and ATP are completely inhibited by prior incubation of RF with GDP; (vi) upon further fractionation of an active RF fraction, a preparation can be obtained that contains HRI-sensitive Co-eIF-2 activity. However, this preparation does not efficiently reverse protein synthesis inhibition in heme-deficient reticulocyte lysates and does not contain excess alpha-subunit of eIF-2. Based on these observations, we have suggested (a) RF provides the unphosphorylated alpha-subunit to eIF-2 alpha (P) X GDP and restores eIF-2 activity. This RF activity is inhibited as the alpha-subunit in the RF preparation becomes phosphorylated by HRI and ATP in the presence of GDP; (b) RF contains Co-eIF-2 activity, which has dual functions: (i) stimulation of ternary complex formation by eIF-2 and (ii) GDP displacement from eIF-2 X GDP during ternary complex formation. In the presence of HRI and ATP, Co-eIF-2 but does not displace GDP from eIF-2 alpha(P) X GDP.

Adenosine Triphosphate↗
PubMed1984

A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys. Part 1: Clinical and radiological findings.

The authors have developed a method to induce chronic cerebral vasospasm after subarachnoid hemorrhage (SAH) in monkeys. With microsurgical techniques, 33 monkeys had a frontotemporal craniectomy and unilateral opening of the subarachnoid cisterns. Cerebrospinal fluid was drained and a fresh hematoma, obtained from an average of 7 ml of autologous blood, was carefully placed against the major arteries of the anterior circulation on one side. The 30 monkeys studied for 7 to 14 days after the SAH were allocated randomly to two treatment groups of 15: one group received placebo and the other nimodipine, 1 mg/kg every 8 hours. Indices monitored before and after SAH included neurological status, cerebral blood flow, computerized tomography, and angiographic vessel caliber. In the placebo group, delayed ischemic neurological deficit developed in one monkey 4 days after clot placement and was present at sacrifice on Day 14. No such deficit occurred in the nimodipine group. The effect of nimodipine on vessel caliber at this dosage was equivocal. Significant vasospasm (31% to 100% reduction in vessel caliber) developed in 87% (26 of 30) of the animals. Overall, vasospasm was slightly more common in the placebo group: in this group, on Days 7 and 14, the incidence of vasospasm was significantly higher (p less than 0.05) than in the nimodipine group. However, the average percentage reduction in vessel caliber of the maximally constricted vessel in each monkey was not significantly different between the two groups.

Animals↗
PubMed1984

Combined modality approach in the management of locally advanced head and neck cancer.

Twenty-five patients with stage III or IV locally advanced head and neck cancer were treated from February 1981 to November 1982 with a combined modality approach utilizing chemotherapy followed by irradiation and surgery. Induction therapy with cisplatin and bleomycin was followed by a sequence integrating weekly cisplatin into a program of locoregional irradiation. After the administration of 4800 cGy, patients received either "boost" irradiation or surgery. At the completion of all therapy, 20 of 23 patients evaluable for response had achieved complete remission. Toxicity was tolerable and all patients are being followed closely to assess durability of remission and overall survival.

Adult↗
PubMed1984

Ranitidine in the treatment of symptomatic gastroesophageal reflux disease.

We undertook a multicenter double-blind study comparing ranitidine to placebo in 73 patients with symptomatic gastroesophageal reflux ranging in age from 22 to 80 years (mean 49). Initially, all patients had moderate to severe symptoms associated with abnormal endoscopic and/or microscopic appearance of the mucosa. After six weeks, 46% of ranitidine-treated patients had a one-grade improvement in their symptom of regurgitation, as compared with 19% treated with placebo (p less than 0.01); ranitidine was no better than placebo in the improvement of pain or dysphagia. Endoscopic improvement occurred in 61% of ranitidine- and 48% of placebo-treated patients (p less than 0.05). Histological improvement occurred in a similar and small portion of patients treated with ranitidine and placebo; there was no correlation between clinical, endoscopic, and histological improvement. Antacid consumption was only half as great in the ranitidine as in the placebo group. Therapy with ranitidine was maintained for up to 12 months. The patients remained free of regurgitation or pain and there was a trend towards further improvement in the endoscopic or histopathologic appearance of the esophagus. Ranitidine 150 mg b.i.d. is recommended for the relief of symptoms and improvement in the endoscopic appearance of the esophagus. Treatment should be for a minimum of 6 weeks, but may be continued for up to a year if the patient's symptoms persist or return.

Adult↗
PubMed1984

Effects of two "lipid-lowering" diets on plasma lipid levels of patients with peripheral vascular disease.

Fifty subjects with peripheral vascular disease were randomly assigned to either the American Heart Association Hyperlipidemia Diet C (AHA, N = 23) or a higher fiber, low fat diet based on the Pritikin maintenance diet (HFD, N = 27) and studied for a 12-month period. Diet counseling was provided, and the subjects were encouraged to exercise regularly, to decrease their consumption of salt, alcohol, and caffeine, and to restrict cigarettes as much as possible. Dietary intake data showed that energy distribution was approximately 49% and 64% carbohydrate, 20% and 22% protein, and 31% and 14% fat for the AHA and HFD groups, respectively. Cholesterol and dietary fiber intakes averaged 201 mg and 23 gm per day, respectively, for the AHA group and 108 mg and 43 gm per day, respectively, for the HFD group. Generally, both groups showed tendencies toward decreased serum triglycerides, cholesterol, and LDL cholesterol and increased HDL cholesterol. The HFD group achieved a significant decrease in serum cholesterol (at month 12) (p less than .01). The only significant between-group difference was in serum cholesterol at 4 months (p less than .01), with the lower value in the HFD group. There was a consistent negative correlation between dietary fiber and serum cholesterol levels (p less than .01). Average weight loss was 4.1 kg for the AHA group and 6 kg for the HFD group. We concluded that both dietary regimens, combined with exercise, can be of benefit to patients with peripheral vascular disease.

Aged↗
PubMed1984

Protein-energy intake and malnutrition in Crohn's disease.

A detailed nutrient assessment was made of 23 male and 24 female patients with Crohn's disease who entered sequentially into an outpatient clinic. Assessment included 48-hour dietary recall, anthropometric measurements, and biochemical and hematological tests appropriate to characterize protein-energy malnutrition. Approximately 40% of patients had energy intakes equal to only two-thirds of the Recommended Dietary Allowance (RDA). Three men and five women had relative body weights less than 85% of standard, but body weight was not correlated with energy intake. Relative body weight was correlated with arm muscle circumference in both male and female patients and with triceps skinfold and total lymphocyte count in women. Although the mean protein intake was greater than 150% of the RDA, evidence of protein malnutrition included low arm muscle circumference in 14% of the men and 15% of the women, low serum albumin concentration in 13% of the women, and low total lymphocyte count in one-half of the patients. The Crohn's disease activity index was correlated significantly with serum albumin, energy intake, and duration of disease in men and with serum ferritin and hemoglobin concentration in women. Thus, a reduced relative body weight or reduced serum albumin was not uncommon in patients with Crohn's disease but did not necessarily occur in those with reduced intakes of protein and energy. However, a low relative body weight may indicate need for further nutritional assessment.

Adolescent↗
PubMed1984

Vitamin and iron intake in patients with Crohn's disease.

A descriptive study was conducted in 23 male and 24 female adult patients with Crohn's disease to assess nutritional status. The mean daily intake of vitamin B6 and folate by the men and the women and of iron by the women was less than the Recommended Dietary Allowances. However, the range of individual intakes varied widely. According to Nutrition Canada Interpretive Standards, 50% of the female patients had inadequate intakes of iron; 13%, of riboflavin; 21%, of thiamin; and 21%, of vitamin A. The men consumed significantly less vitamin A and folate per 1,000 kcal than the women. Serum folate was the only laboratory parameter that correlated with nutrient intake; it was correlated with dietary folate, vitamin C, vitamin B12, and vitamin B6 intakes in the women only. Serum folate was low in 21% of the men and 26% of the women. Thus, a low serum folate was predictive of a potential risk of nutritional deficiency of folate and of vitamins B6, B12, and C. This study demonstrated that nutrient intake was reduced in some patients and therefore could be a factor contributing to observed nutritional deficiency in Crohn's disease.

Adolescent↗
PubMed1984

Nutrient intake of patients with cystic fibrosis.

Nutrient intake, anthropometric measurements, and pulmonary function were assessed in 26 young adult patients with cystic fibrosis (CF). Mean nutrient intakes, excluding those from vitamins and nutrient supplements, were less than the Recommended Dietary Allowances for folate for men and women and for iron and vitamin B-6 for women. Male cystic fibrosis patients consumed significantly more of 11 of 16 nutrients in comparison with men with Crohn's disease and men with functional gastrointestinal complaints. Female cystic fibrosis patients consumed significantly more of 9 of 16 nutrients than did women with gastrointestinal complaints. The relative body weight was less than 85% of standard in 65% of men and 50% of women with CF. Relative body weight was correlated with variables indicative of airflow obstruction, reduced vital capacity, and hyperinflation of lung volumes.

Adolescent↗
PubMed1983

The effect of the opioid-benzodiazepine, tifluadom, on ingestive behaviors.

A large body of evidence has suggested a role for the endogenous opiates and their receptors in the regulation of appetite. In this study, we report on the effects of tifluadom, a noval opiate with a benzodiazepine-like structure and preferential activity at the kappa opiate receptor, on ingestive behaviors. Tifluadom increases food intake in rats without altering water intake. Tifluadom's effect on feeding is more potent than that of morphine or ketocyclazocine and equivalent to that of butorphanol. The effect is partially resistant to naloxone antagonism. Tifluadom is more potent when administered subcutaneously than when given intraperitoneally. These data provide further support for the concept that kappa opiate receptors represent an important component of the natural feeding drive.

Animals↗
PubMed1983

Effects of dietary manipulation on vascular status of patients with peripheral vascular disease.

In a one-year, double-blind clinical trial, 45 patients with peripheral vascular disease (PVD) were randomly assigned to either the American Heart Association Hyperlipidemia Diet C (n = 20) or a low-fat, high-fiber, complex carbohydrate diet similar to the Pritikin Maintenance Diet (n = 25). Vascular status and blood lipid levels were monitored at 0, 2, 4, 6, and 12 months. Walking distance increased significantly in both groups, with no difference between groups. No vascular parameters changed significantly, suggesting that increased walking distance was due to improved metabolic capacity of the muscle. A trend toward lower blood lipid values was observed, with no significant differences within or between groups. We conclude that while patients with PVD benefit from a program of diet and exercise, there is no apparent advantage to the more difficult complex carbohydrate diet.

Aged↗
PubMed1983

Patterns of cancer in geographic and endogamous subdivisions of the Hutterite Brethren of Canada.

The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar.

Canada↗
PubMed1983

Effect of centrally administered neurotensin on multiple feeding paradigms.

Recent studies have suggested that the tridecapeptide, neurotensin, may be an endogenous satiety factor. The present study was undertaken to examine the effects of neurotensin on multiple paradigms known to stimulate feeding. Following a 30 hour starvation period, neurotensin suppressed feeding at the 20 microgram and 10 microgram dose, but not at the 1 microgram dose when compared to saline controls. Norepinephrine (20 micrograms ICV) induced feeding was suppressed at the 20 microgram neurotensin dose but not at the 10 microgram or 1 microgram dose. In contrast, neurotensin did not suppress muscimol induced feeding at any of the doses. Insulin induced feeding (10 units SC) also was not suppressed by neurotensin. Neurotensin suppressed dynorphin induced feeding at the 20 microgram and 10 microgram but not at the 1 microgram dose. Neurotensin suppressed spontaneous feeding (p less than 0.01) in vagotomized rats (2.5 +/- 0.3 g/2 hr) when compared with saline controls (4.2 +/- 0.5 g/2 hr) suggesting that an intact vagus is not necessary for neurotensin's anorectic effect. We conclude that neurotensin may play a role in short-term appetite regulation by a complex interaction with monoamines and neuropeptides, particularly norepinephrine and the kappa opiate agonist, dynorphin.

Animals↗
PubMed1983

The effect of peripherally administered satiety substances on feeding induced by butorphanol tartrate.

Endogenous opioid peptides appear to play a role in the initiation of feeding. Butorphanol, an exogenous opiate which preferentially generalizes to the kappa-sigma opiate receptors, is a potent initiator of feeding. In these studies, we examined the effect of peripherally administered putative satiety substances, cholecystokininoctapeptide, somatostatin, bombesin, gastrin-releasing peptide, thyrotropin-releasing hormone, calcitonin and glucagon on butorphanol induced feeding. With the exception of bombesin, all the other putative satiety factors required 2 to 32 times as high a dose to significantly suppress feeding following butorphanol compared to the dosages required to suppress starvation or tail pinch induced feeding. Bombesin appeared to be approximately equipotent in all systems tested. Haloperidol and atropine both suppressed butorphanol induced feeding supporting our previous hypothesis of an integral relationship between acetylcholinergic-dopaminergic and opioid mechanisms in the initiation of feeding. The findings reported here are compatible with an important role for opioid mechanisms in the initiation of feeding.

Acetylcholine↗
PubMed1983

Computed tomography of the craniocervical junction in rheumatoid arthritis.

Thirty-three patients with rheumatoid arthritis had computed tomographic examination of the craniocervical junction. This demonstrated soft tissue features which have not previously been described in published reports. A low attenuation lesion between the odontoid and the transverse ligament shown in 11 patients was considered a premonitory sign of rupture of the transverse ligament or a manifestation of active disease. Computed tomography revealed spinal cord compression in 3 patients and ligamentous changes in the transverse ligament and the alar and spinal ligaments in 26 patients. Erosion of the odontoid was shown in 19 patients and subluxation in 20 patients. No relationship could be found between the clinical signs and symptoms and the radiological abnormalities except in the case of cord compression.

Adolescent↗