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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 55 records · Page 3Linked to original sources

Interaction of insulin, glucagon-like peptide 1, gastric inhibitory polypeptide, and appetite in response to intraduodenal carbohydrate.

The relation between gastrointestinal incretin hormones in the control of insulin release and short-term satiety by intestinal carbohydrate was investigated in 8 fasted, healthy male volunteers. Insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and appetite ratings were measured during, and food intake was measured after, intraduodenal infusions of glucose or saline. Studies were conducted under hyperinsulinemic and euglycemic conditions. Raising plasma insulin with intravenous insulin infusion to concentrations slightly above usual postprandial concentrations (356.4 +/- 4.8 pmol/L) had no effect on GIP, GLP-1, or appetite ratings before the intraduodenal infusions began. Intraduodenal glucose infusion resulted in a further increase in plasma insulin to a peak of 779.4 +/- 114.0 pmol/L, caused an early increase in plasma GIP and a later increase in GLP-1 concentrations (P < 0.01), suppressed appetite (P < 0.05), and reduced energy intake (P < 0.01) compared with intraduodenal infusion of saline. There was a close association between the increase in GLP-1 and decrease in appetite. Infusion of octreotide to suppress the release of gastrointestinal hormones prevented the rise in insulin, GIP, and GLP-1 induced by intraduodenal glucose infusion and reversed the suppression of appetite and reduction in energy intake. These results suggest that 1) when infused to result in plasma concentrations slightly above usual postprandial concentrations, insulin does not inhibit its own release and 2) the effects of intraduodenal glucose on appetite may be mediated through the release of GLP-1 and not insulin.

Adult

The Koyanagi-Nonomura 1-stage bucket repair of severe hypospadias with and without penoscrotal transposition.

PURPOSE: We report our experience with 1-stage Koyanagi-Nonomura hypospadias repair, which may be performed even when penoscrotal transposition is present. Repair involves bilateral parameatal skin flaps based on the meatus and urethral plate. MATERIALS AND METHODS: A total of 14 boys 10 to 20 months old underwent 1-stage Koyanagi-Nonomura repair for severe hypospadias. The meatus was proximal to the penoscrotal junction in all patients, and in 8 penoscrotal transposition was corrected during the same operation. RESULTS: In 7 of the 14 boys 1 or more fistulas developed that were subsequently repaired. In all cases the fistula was on the proximal shaft and/or penoscrotal junction. In no case was there stenosis or breakdown of the distal neourethra. CONCLUSIONS: The Koyanagi-Nonomura 1-stage repair provides excellent cosmetic results in severe hypospadias while preserving the available urethral plate tissue. It is particularly suitable when there is associated penoscrotal transposition. Most if not all 1-stage repairs are inappropriate in patients with severe hypospadias and penoscrotal transposition. In other repairs vascular supply to Byar's flaps and the neourethra may be compromised by mobilization of the anteriorly transposed scrotal tissue. We expect that the fistula rate will decrease with experience but now it is acceptable, considering the severity of hypospadias.

Humans

Posteroinferior cerebellar artery aneurysms: surgical results for 38 patients.

OBJECTIVE: Posteroinferior cerebellar artery aneurysms have an incidence of approximately 0.49%. Reports in the literature are sparse concerning outcomes in this patient population. We report our results for 38 consecutive patients who were treated during the last 6.5 years. METHODS: All patients (n = 38) with posteroinferior cerebellar artery aneurysms that were surgically treated at Zale-Lipshy University Hospital between January 1990 and May 1997 were retrospectively reviewed. Data were collected and analyzed relating to demographics, condition at presentation, lesion characteristics, associated medical problems, postsurgical complications, and outcome. RESULTS: Sixty-six percent of the patients (n = 25) experienced neurological sequelae, which included symptomatic vasospasm, hydrocephalus, dysarthria, paresis, diplopia, ataxia, and facial paralysis. Many, however, showed significant improvement during their hospitalization and during the course of the ensuing year. Seventy-four percent of the patients had a Glasgow Outcome Scale score of 1 or 2 at the time of discharge, 91% at 6 months after surgery, and 89% at 1 year after surgery. CONCLUSION: This review summarizes the presentations and outcomes of 38 consecutive surgical cases during a 6.5-year period and concludes that posteroinferior cerebellar artery aneurysms are not benign entities. The study does, however, also demonstrate that patients have significant recuperative potential after the treatment of these lesions.

Adult

The effect of aging on bone mineral metabolism and bone mass in Native American women.

OBJECTIVE: To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women. DESIGN: A cross-sectional study. SETTING: The Sac and Fox Nation in rural Oklahoma MEASUREMENTS: Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry. PARTICIPANTS: A total of 77 Native American women aged 19 to 85 years. RESULTS: Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women. CONCLUSIONS: In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.

Adult

Motor function of the proximal stomach and visceral perception in gastro-oesophageal reflux disease.

BACKGROUND: The abnormally high postprandial rate of transient lower oesophageal sphincter relaxations seen in patients with reflux disease may be related to altered proximal gastric motor function. Heightened visceral sensitivity may also contribute to reporting of symptoms in these patients. AIMS: To assess motor function of the proximal stomach and visceral perception in reflux disease with a barostat. METHODS: Fasting and postprandial proximal gastric motility, sensation, and symptoms were measured in nine patients with reflux disease and nine healthy subjects. Gastric emptying of solids and liquids was assessed in six of the patients on a different day (and compared to historical controls). RESULTS: Minimal distending pressure and gastric compliance were similar in the two groups, whereas the patients experienced fullness at lower pressures (p < 0.05) and discomfort at lower balloon volumes (p < 0.005) during isobaric and isovolumetric distensions respectively. Maximal gastric relaxation induced by the meal was similar in the two groups. Late after the meal, however, proximal gastric tone was lower (p < 0.01) and the score for fullness higher (p < 0.01) in the reflux patients, in whom the retention of both solids and liquids in the proximal stomach was greater (p < 0.05). CONCLUSIONS: Reflux disease is associated with delayed recovery of proximal gastric tone after a meal and increased visceral sensitivity. The former may contribute to the increased prevalence of reflux during transient lower oesophageal sphincter relaxations and the delay in emptying from the proximal stomach, whereas both may contribute to symptom reporting.

Adult

Effect of glucose supplementation on appetite and the pyloric motor response to intraduodenal glucose and lipid.

The effects of different macronutrients on appetite and pyloric motility and the impact of short-term dietary glucose supplementation on these responses were evaluated. Ten males (aged 19-38 yr) received isocaloric (2.9 kcal/min) intraduodenal infusions of glucose and lipid while antropyloroduodenal motility and appetite were assessed by manometry and visual analog scales, respectively. Effects of each intraduodenal nutrient on appetite and motility were evaluated before and after 7 days of dietary supplementation with glucose (400 g daily). Initially, both nutrients caused a similar rise in pyloric tone, but intraduodenal lipid was a more potent stimulus of phasic pyloric motility (P = 0.05) and suppressed appetite more (P = 0.013) than intraduodenal glucose. After dietary glucose supplementation, the increase in pyloric tone during intraduodenal glucose was attenuated. Although intraduodenal lipid remained a more potent stimulant of phasic pyloric motility (P = 0.016), it no longer decreased appetite. We conclude that in healthy young males 1) intraduodenal infusion of lipid is a more potent stimulus of phasic pyloric motility and suppresses appetite more than intraduodenal glucose and 2) dietary glucose supplementation alters both the appetite suppressant effect of intraduodenal lipid and the pyloric motor response to intraduodenal glucose infusion.

Adult

Physiological changes in blood glucose affect appetite and pyloric motility during intraduodenal lipid infusion.

We evaluated the effects of varying blood glucose concentration within the normal postprandial range and its interaction with small intestinal nutrients on antropyloric motility and appetite. Eight healthy males (19-40 yr) underwent paired studies, with a blood glucose level of 5 or 8 mmol/l. Manometry and visual analog scales were used to assess motility and appetite, during fasting and intraduodenal lipid infusion (1.5 kcal/min). In the fasting state, antral waves were suppressed at 8 mmol/l compared with 5 mmol/l (P = 0.018). However, pyloric motility was no different between the two blood glucose concentrations. Hunger was no different at 5 mmol/l compared with 8 mmol/l, but fullness was greater at 8 mmol/l (P = 0. 01). During intraduodenal lipid infusion, antral waves were suppressed (P < 0.035) and isolated pyloric pressure waves (IPPWs) were stimulated (P < 0.02) compared with during the fasting state, with no difference between blood glucose concentrations, although the temporal patterning of IPPWs varied between blood glucose concentrations. The amplitude of IPPWs was greater at 5 mmol/l compared with 8 mmol/l (P < 0.001), and hunger decreased at 8 mmol/l compared with 5 mmol/l (P = 0.02). We conclude that "physiological" hyperglycemia modifies gastric motor and sensory function and that synergy exists between blood glucose concentration and small intestinal nutrients in modulating gastric motility and appetite.

Adult

Effects of nitroglycerin on liquid gastric emptying and antropyloroduodenal motility.

The effects of the nitric oxide donor nitroglycerin on gastric emptying and antropyloroduodenal motility were evaluated in nine healthy male subjects (ages 19-36 yr). Antropyloroduodenal pressures were recorded with a manometric assembly that had nine side holes spanning the antrum and proximal duodenum and a pyloric sleeve sensor; gastric emptying was quantified scintigraphically. In each subject, the emptying of 300 ml of 25% glucose labeled with 99mTc was assessed on two separate days during intravenous infusion of either nitroglycerin (5 micrograms/min in 5% dextrose) or 5% dextrose (control). Studies were performed with the subject in the supine position; blood pressure and heart rate were monitored. Nitroglycerin had no significant effect on blood pressure or heart rate. Nitroglycerin slowed gastric emptying (P < 0.02), and this was associated with greater retention of the drink in the proximal stomach (P < 0.05). In both nitroglycerin and control studies, ingestion of the drink was associated with an increase in the number of isolated pyloric pressure waves (P < 0.05) and antral pressure wave sequences (P < 0.05). Nitroglycerin reduced the number of isolated pyloric pressure waves (P < 0.05), basal pyloric pressure (P < 0.05), and the number of antral pressure wave sequences (P < 0. 05), but not the total number of antral pressure waves. The rate of gastric emptying and the number of isolated pyloric pressure waves were inversely related during control (P = 0.03) and nitroglycerin (P < 0.05) infusions. We conclude that in normal subjects, 1) gastric emptying of 300 ml of 25% glucose is inversely related to the frequency of phasic pyloric pressure waves, and 2) nitroglycerin in a dose of 5 micrograms/min inhibits pyloric motility, alters the organization but not the number of antral pressure waves, and slows gastric emptying and intragastric distribution of 25% glucose.

Adult

Effect of intravenous glucose and euglycemic insulin infusions on short-term appetite and food intake.

To investigate the short-term effects of insulin on feeding, 14 fasting, young adults received 150-min euglycemic intravenous infusions of control (C), low-dose (LD, 0.8 mU.kg-1.min-1), and high-dose (HD, 1.6 mU.kg-1.min-1) insulin and ate freely from a buffet meal during the last 30 min. Steady-state preprandial plasma insulin concentrations were 5.9 +/- 0.7 (C), 47 +/- 2 (LD), and 95 +/- 6 (HD) microU/ml and increased 56-59 microU/ml during the meal. No effect of treatment type of hunger or fullness ratings, duration of eating, or the weight, energy content (1,053 +/- 95 kcal, C; 1,045 +/- 101 kcal, LD; 1,066 +/- 107 kcal, HD; P = 0.9), and composition of food eaten was observed. On a fourth study day, 12 of the subjects received an intravenous infusion of glucose only (Glc) that was identical to the glucose infusion on their HD insulin day. Mean venous glucose concentration was 9.3 +/- 0.5 mmol [P < 0.001 vs. C (5.3 +/- 0.1), LD (5.2 +/- 0.2), and HD (5.2 +/- 0.2)], and plasma insulin increased to 45 +/- 2.3 microU/ml at the start and 242 +/- 36 microU/ml at the end of the meal. Energy intake during the meal was (approximately 15%) reduced (1,072 +/- 97 kcal, C; 1,086 +/- 102 kcal, LD; 1,088 +/- 105 kcal, HD; 919 +/- 115 kcal, Glc; P < 0.05 Glc vs. C, LD, and HD). Plasma insulin normally increases to approximately 100 microU/ml after a mixed meal in lean subjects. Therefore, in the absence of altered blood glucose concentrations, physiological concentrations of insulin are unlikely to play a role in meal termination and the short-term control of appetite.

Adult

Effects of meal volume and posture on gastric emptying of solids and appetite.

The effects of volume and posture on gastric emptying and intragastric distribution of a solid meal and appetite were evaluated. Eight normal volunteers were studied on four occasions, on each of which a meal comprising ground beef mixed with tomato sauce of either 650 g ("large") or 217 g ("small") was eaten. Two studies were performed while the subject was lying in the left lateral decubitus position, and two studies were performed while the subject was sitting so that in each subject data were available for both meals and in both postures. Hunger and fullness were evaluated using a visual analog questionnaire. In both postures and after both meals, gastric emptying approximated a linear pattern after an initial lag phase. The lag phase was shorter for the large meal when compared with the small meal [sitting: large 13 +/- 5 vs. small 29 +/- 7 min; left lateral: large 16 +/- 3 vs. small 24 +/- 3 min, F(1, 7) = 46.3, P < 0.0005]. In both postures the contents of the total [F(1,7) = 1794.5, P < 0.0001], proximal [F(1,7) = 203.7, P < 0.0001], and distal [F(1,7) = 231.5, P < 0.0001] stomach were greater after the large meal when compared with the small meal. Although the 50% emptying time was greater with the large than the small meal [F(1,7) = 40.8, P < 0.001], the postlag emptying rate (g/min) was more rapid with the large meal [sitting: large 1.7 +/- 0.2 vs. small 1.1 +/- 0. 1 g/min; left lateral: large 1.8 +/- 0.1 vs. small 1.3 +/- 0.04 g/min, F(1,7) = 44.7, P < 0.0005]. There was a significant interaction between meal volume and posture for retention in the distal stomach [F(1,7) = 7.14, P < 0.05]. Contrasts were used to evaluate the effects of volume and posture between the four studies and demonstrated an effect of posture for the large [F(1,21) = 18.7, P < 0.005] but not the small [F(1,21) = 0.30, P = 0.60] meal so that the retention was greater in the sitting when compared with the left lateral position. The magnitude of the postprandial increase in fullness [F(1,7) = 7.8, P < 0.05] and reduction in hunger [F(1,7) = 5.9, P < 0.05] was greater with the large meal. We conclude that meal volume has a major effect on gastric emptying; in contrast posture has only a minor impact on intragastric meal distribution, which is observed only after a large meal, and no effect on gastric emptying.

Adolescent

Field trial of a diagnostic axis for defense mechanisms for DSM-IV.

Following critiques that the DSM multiaxial system lacks psychodynamic information useful for treatment, an axis for defense mechanisms was developed for DSM-IV, including up to 7 individual defenses from a glossary of 27, and 3 predominant defense levels from a list of 7. We tested the feasibility, reliability, and discriminability of the proposed axis. Clinician and psychiatric resident volunteers were trained at two U.S. and one Norwegian sites. After conducting initial interviews on 107 patients, they rated the DSM-III-R and defense axes, as did a second blind rater. Median kappa reliabilities were .42 (individual defenses), and .47 (defense levels). A summary measure, Overall Defensive Functioning (ODF), had similar reliability to current GAF (IR .68 vs. .62), similar 1-month stability (.75 vs. .78), but greater 6-month stability (.51 vs. .17). Independent of Axis III, ODF had small to moderate associations with other Axes and symptoms. Our findings indicate that the defense axis is a feasible, acceptably reliable, and nonredundant addition to DSM-IV, which may prove useful for planning and conducting treatment.

Adult

Modification and validation of a single-isotope radiocalcium absorption test.

UNLABELLED: This study was done to establish and allow for the influence of body weight on plasma radioactivity after administering radiocalcium to measure calcium absorption. METHODS: We administered 5 microCi 45Ca in 20 mg of calcium carrier in 250 ml distilled water to 103 premenopausal volunteers over the age of 40 yr, after an overnight fast. Venous blood was withdrawn when the dose was given (to serve as a blank) and exactly 60 min later, and the counts were determined in a liquid scintillation counter. After the exclusion of three outliers, the fraction of the administered dose per liter of plasma at 60 min was a curvilinear inverse function of body weight and a positive linear function of the reciprocal of body weight, with an r value of 0.45 (p < 0.001). This latter relationship then was used to correct the plasma radioactivity to a standard body weight of 65 kg, in which the volume of distribution of the dose was assumed to be 10 liters. This yielded the estimated fraction of the dose circulating at 1 hr, which then was converted into a fractional absorption rate from our previously published equation. RESULTS: In the 100 volunteers, the mean value of the radiocalcium absorption rate (termed alpha2, to distinguish it from our original calculation) was 0.75/hr, with 98 of the 100 values falling between 0.30 and 1.20. The value alpha2 was significantly related to serum calcitriol in these 100 volunteers (r = 0.29; p = 0.003) and in 89 normal postmenopausal women (r = 0.46; p < 0.001). It also was significantly related to the 24-hr urine calcium in the same 89 women (r = 0.48; p < 0.001) and to net calcium absorption corrected for intake in balance studies on another 103 postmenopausal women (r = 0.44; p < 0.001). In most respects, alpha2 was marginally superior to alpha1 but, unlike alpha1, was independent of body weight. CONCLUSION: The modified low-carrier radiocalcium absorption test is a valid indicator of calcium absorption status over a wide range of calcium intakes and is independent of body weight.

Body Weight

Effect of recent alcohol intake on parathyroid hormone and mineral metabolism in men.

The mechanisms by which alcohol intake, particularly moderate alcohol intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with liver function tests, including serum bilirubin (r = 0.30, p = 0.002), alkaline phosphatase (r = 0.30, p = 0.004), and aspartate aminotransferase (SGOT) (r = 0.29, p = 0.006). SRAI correlated with serum calcium corrected for albumin (r = -0.39, p < 0.001), estradiol (r = 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r = -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r = 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 +/- 3.4 and 39.9 +/- 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 +/- 0.05 vs. 8.88 +/- 0.07 mg/dl, respectively). In addition, urinary calcium (corrected per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 +/- 0.4 vs. 8.4 +/- 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 +/- 38 vs. 530 +/- 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (beta = 0.215, p = 0.025), SRAI (beta = -0.281, p = 0.003), 250-hydroxyvitamin D (beta = -0.309, p = 0.002), and testosterone (beta = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.

Adult

Decreased glucose utilisation does not increase food intake in the marsupial Sminthopsis crassicaudata.

The marsupial Sminthopsis crassicaudata increases food intake following a fast. However, the role of metabolic fuel availability, in particular glucose, in the regulation of food intake in this animal is unknown. In this study, we have demonstrated that neither insulin-induced hypoglycaemia nor metabolic blockade of glucose utilisation with 2-deoxy-D-glucose effects food intake compared to saline-treated controls, suggesting that mechanisms other than glucose availability are important in the regulation of food intake in this marsupial. These data are discussed in the context of the role of glucoprivation in feeding in other mammals.

Animals

Spatial patterns of fasting and fed antropyloric pressure waves in humans.

1. Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with individual gastric contractions. 2. In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum. 3. Pressure wave sequences that occurred during phase II fasting contractions (n = 221) and after food (n = 778) were evaluated. 4. The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade-29% after food and 42% during fasting (P < 0.05); purely synchronous-23% fed and 17% fasting; and purely retrograde-6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences 'skipped' individual recording points. 5. The spatial patterning of gastric pressure wave sequences is diverse, and may explain the differing mechanical outcomes among individual gastric contractions. 6. Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during individual gastric contraction sequences.

Adult

Food intake and food choice: the role of the endogenous opioid peptides in the marsupial Sminthopsis crassicaudata.

Endogenous opioid peptides activate food seeking behaviour and influence macronutrient choice in a number of animal species and previous studies have suggested that the palatability of food is strongly modulated by the opioid feeding system. The effect of opioid peptides on appetite and food choice in marsupials has not been evaluated. The aim of these studies was to determine the effect of mu, delta and K opioid receptors on food intake and food choice in the marsupial Sminthopsis crassicaudata. When offered a choice of mealworms or laboratory diet after 24 h food deprivation, S. crassicaudata ate predominantly mealworms. After a 24 h fast, adult male S. crassicaudata were injected peripherally with opioid receptor antagonists or saline. Animals were re-fed with either their laboratory diet alone, or a choice of laboratory diet and mealworms. In animals re-fed with laboratory diet alone, naloxone at doses of 15 and 10 mg/kg produced a 31% (P < 0.05) and 38% (P < 0.05) respectively reduction in food intake in the first 30 min after laboratory diet was re-introduced, but lower doses had no effect. The selective delta antagonist naltrindole at 20 mg/kg resulted in a 65% (P < 0.01) reduction in food intake compared to controls between 30 and 60 min. The selective kappa opioid antagonist nor-binaltorphimine had no effect on the intake of laboratory diet. In animals offered a choice of laboratory diet and mealworms, naloxone doses of 1, 5, 10, 15 and 20 mg/kg significantly decreased intake in the first 0.5 h after re-feeding, due to a preferential suppression of the intake of mealworms. Naltrindole and nor-binaltorphimine had no effect on food choice. These studies demonstrate that endogenous opioid peptides influence both food intake and choice in S. crassicaudata and that the role of the opioid feeding system is in part modulated by food palatability. In S. crassicaudata these effects appear to occur predominantly by a mu opioid receptor mechanism.

Animals

Allogeneic blood stem cell transplantation: considerations for donors.

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

Adult