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Biomedical subjects

Michael Horowitz

Publications and source records attributed to Michael Horowitz.

At least 19 recordsLinked to original sources
PubMed2007

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.

OBJECTIVE: Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Level 3, mixed medical and surgical intensive care unit. SUBJECTS: A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). INTERVENTIONS: Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. MEASUREMENTS AND MAIN RESULTS: Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. CONCLUSIONS: Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.

APACHE↗
PubMed2006

Intravenous CCK-8, but not GLP-1, suppresses ghrelin and stimulates PYY release in healthy men.

We have investigated the effects of exogenous CCK-8 and GLP-1, alone and in combination, on ghrelin and PYY secretion. Nine healthy males were studied on four occasions. Plasma ghrelin and PYY concentrations were measured during 150 min intravenous infusions of: (i) isotonic saline, (ii) CCK-8 at 1.8 pmol/kg/min, (iii) GLP-1 at 0.9 pmol/kg/min or (iv) CCK-8 and GLP-1 combined. CCK-8 markedly suppressed ghrelin and stimulated PYY when compared with control between t=0-120 min (P<0.001 for both). GLP-1 had no effect on ghrelin, but decreased PYY slightly at 120 min (P<0.05). During infusion of CCK-8+GLP-1, there was comparable suppression of ghrelin (P<0.001), but the stimulation of PYY was less (P<0.001), than that induced by CCK-8, between t=20-120 min. In conclusion, in healthy subjects, in the doses evaluated, exogenous CCK-8 suppresses ghrelin and stimulates PYY, and exogenous GLP-1 has no effect on ghrelin and attenuates the effect of CCK-8 on PYY.

Adolescent↗
PubMed2006

Upper gastrointestinal function and glycemic control in diabetes mellitus.

Recent evidence has highlighted the impact of glycemic control on the incidence and progression of diabetic micro- and macrovascular complications, and on cardiovascular risk in the non-diabetic population. Postprandial blood glucose concentrations make a major contribution to overall glycemic control, and are determined in part by upper gastrointestinal function. Conversely, poor glycemic control has an acute, reversible effect on gastrointestinal motility. Insights into the mechanisms by which the gut contributes to glycemia have given rise to a number of novel dietary and pharmacological strategies designed to lower postprandial blood glucose concentrations.

Blood Glucose↗
PubMed2006

Reduced pretreatment ipsilateral middle cerebral artery cerebral blood flow is predictive of symptomatic hemorrhage post-intra-arterial thrombolysis in patients with middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) can be a devastating complication associated with thrombolytic therapy for acute ischemic stroke. We hypothesized that patients with lower prethrombolysis cerebral blood flow (CBF) were at a higher risk of symptomatic ICH (sICH). METHODS: Twenty-three patients who underwent quantitative CBF assessment with Xenon CT studies for acute stroke before intra-arterial (IA) thrombolysis for a middle cerebral artery (MCA) or internal carotid artery terminus occlusion within 6 hours of symptom onset were studied. Univariate and multivariate analysis were carried out to determine predictors of sICH post-IA thrombolysis. Receiver operating characteristic curves were generated to determine the association between mean ipsilateral CBF and the occurrence of sICH. RESULTS: The mean age of our cohort was 68+/-12 years and a mean National Institutes of Health Stroke Scale (NIHSS) score of 18+/-3. In univariate analysis, patients with higher percent of core infarct, hyperglycemia, and reduced mean ipsilateral CBF were at risk of sICH. In multivariate analysis only mean ipsilateral CBF was associated with higher rates of sICH (odds ratio 1.58; 95% CI, 1.01 to 2.51; P<0.04). The area under the receiver operating characteristic curve was 0.87 (95% CI, 0.76 to 0.97; P<0.005). CONCLUSIONS: Patients with lower pre-IA thrombolysis mean ipsilateral MCA CBF are at significantly higher risk for sICH in the setting of a MCA or carotid terminus occlusion. The threshold identified in this study may be useful for selection of patients with acute MCA occlusions for acute stroke thrombolysis.

Aged↗
PubMed2006

Effects of posture on gastric emptying, transpyloric flow, and hunger after a glucose drink in healthy humans.

Previous studies suggest that posture has relatively little effect on gastric emptying of high-nutrient liquids; these studies have, however, only assessed overall rates of gastric emptying, whereas gastric emptying is known to be predominantly a pulsatile phenomenon. In healthy subjects perceptions of appetite, such as hunger, are inversely related to antral area and content; hence, changes in intragastric meal distribution induced by posture may affect appetite. Gastric emptying is a major determinant of postprandial glycemia. The aims of this study were to evaluate the effects of posture on patterns of transpyloric flow (TF), gastric emptying (GE), antral area (AA), hunger, and the glycemic response to oral glucose. Eight healthy young subjects (five males, three females; mean age, 24.0 +/- 2.4 years; BMI, 21.2 +/- 0.6 kg/m2) were studied twice in random order, once in the sitting position and once in the lying (supine) position. After consuming 600 ml water with 75 g glucose, labeled with 20 MBq 99mTc-sulfur colloid, subjects had simultaneous measurements of (i) TF during consumption of the drink by Doppler ultrasonography, (ii) GE with scintigraphy, (iii) AA at t = -5 and t = 30 min by ultrasonography, and (iv) perceptions of appetite with a visual analogue scale. During drink ingestion TF was greater in the sitting, compared with the lying, position (586 +/- 170 vs. 177 +/- 65 [cm/sec] x sec; P < 0.05). Posture affected intragastric distribution; more of the drink was retained in the distal stomach in the sitting position (e.g., at 30 min: sitting, 29 +/- 3%, vs. lying, 12 +/- 3%; P < 0.0001) but had no effect on the overall rate of GE or the blood glucose response. AA at t = 30 min (P < 0.005) was greater in the sitting position; there was an inverse relationship between hunger and AA at 30 min (r = -0.53, P < 0.05). We conclude that posture influences initial TF and intragastric distribution, but not the overall rate of GE of, or the glycemic response to, a large-volume nutrient liquid. The increases in AA and content in the sitting position are associated with a reduction in hunger.

Administration, Oral↗
PubMed2006

The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed.

Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18-59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine ("short-segment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long-segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P < 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long- than during the short-segment infusion (P < 0.05). During the long- but not the short-segment infusion, antral pressure waves (PWs) were suppressed (P < 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon >60 cm of the intestine being exposed to glucose.

Adolescent↗
PubMed2006

Effect of fatty acid chain length on suppression of ghrelin and stimulation of PYY, GLP-2 and PP secretion in healthy men.

We have evaluated the effects of fatty acid chain length on ghrelin, peptide YY (PYY), glucagon-like peptide-2 (GLP-2) and pancreatic polypeptide (PP) secretion and hypothesized that intraduodenal administration of dodecanoic ("C12"), but not decanoic ("C10"), acid would decrease plasma ghrelin and increase PYY, GLP-2 and PP concentrations. Plasma hormone concentrations were measured in seven healthy men during 90-min intraduodenal infusions of: (i) C12, (ii) C10 or (iii) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10) and after a buffet-meal consumed following the infusion. C12 markedly suppressed plasma ghrelin and increased both PYY and GLP-2 (all P < 0.05) compared with control and C10, while C10 had no effect. Both C10 and C12 increased PP concentrations slightly (P < 0.05). We conclude that the effects of intraduodenal fatty acids on ghrelin, PYY and GLP-2 secretion are dependent on their chain length.

Adult↗
PubMed2006

Effects of fat on gastric emptying of and the glycemic, insulin, and incretin responses to a carbohydrate meal in type 2 diabetes.

CONTEXT: Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to carbohydrate. OBJECTIVE: The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes. DESIGN: This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d. SETTING: The study was performed at the Royal Adelaide Hospital. PATIENTS: Six males with type 2 diabetes were studied. INTERVENTION: Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil). MAIN OUTCOME MEASURES: GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures. RESULTS: GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil. CONCLUSIONS: Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.

Aged↗
PubMed2006

Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses.

CONTEXT: The inhibitory action of glucagon-like peptide-1 (GLP-1) on gastric emptying (GE) is likely to be important in mediating its effects on postprandial glycemia, appetite, and gastrointestinal symptoms. OBJECTIVE: The objective of the study was to evaluate the effects of "low" and "high" doses of iv GLP-1 on GE, intragastric meal distribution, glycemia, insulinemia, and appetite. DESIGN: Ten healthy males were studied on 3 d. GE of a solid (ground beef)/liquid (glucose) meal, blood glucose, plasma insulin, glucagon and glucose-dependent insulinotropic peptide, appetite perceptions, and gastrointestinal symptoms were evaluated during iv infusion of: 1) GLP-1 at 0.3 pmol x kg(-1) x min(-1) (GLP-1 0.3); 2) GLP-1 at 0.9 pmol x kg(-1) x min(-1) (GLP-1 0.9); and 3) 0.9% saline. RESULTS: GLP-1 0.3 and 0.9 slowed GE of solid (intragastric retention at t = 100 min; saline: 28 +/- 5%; GLP-1 0.3: 53 +/- 6%; GLP-1 0.9: 58 +/- 7%; P < 0.001) and liquid (time for 50% of the liquid to empty, saline: 28 +/- 2 min; GLP-1 0.3: 42 +/- 7 min; GLP-1 0.9: 50 +/- 9 min; P < 0.001). Both doses of GLP-1 induced gastroparesis in about half the cohort and increased meal retention in the distal stomach (P < 0.05). GLP-1 attenuated the rises in glucose, insulin, and glucose-dependent insulinotropic peptide (P < 0.05). There was an inverse relationship between blood glucose at t = 15 min and the time for 50% of the liquid to empty (r = -0.70, P < 0.001). CONCLUSIONS: In healthy subjects exogenous GLP-1 increases meal retention in the distal stomach and, even when administered in a "low" dose, frequently induces "gastroparesis," and the effects of GLP-1 on postprandial glycemia are predictable on the basis of its effect on GE, supporting the concept that GE is a major target mechanism for the clinical use of incretin mimetics.

Adult↗
PubMed2006

Effects of intraduodenal glucose concentration on blood pressure and heart rate in healthy older subjects.

The aims of this study were to determine whether the hypotensive and heart rate responses to small intestinal glucose infusion are dependent on the glucose concentration. Eight healthy subjects, aged 65-78 years, were studied on 3 separate days in random order. Each subject received intraduodenal infusions of 50 g of glucose in either 300 mL (16.7%), 600 mL (8.3%), or 1200 mL (4.1%) of saline (0.9%) at a rate of 3 kcal/min for 60 minutes (t = 0-60 minutes), followed by saline (0.9%) for a further 60 minutes (t = 60-120 minutes). During the infusions, blood pressure (systolic and diastolic) and heart rate were measured every 3 minutes, and blood glucose concentrations every 15 minutes. Systolic and diastolic blood pressure fell (P < .0001), and heart rate and blood glucose increased (P = .0001 for both) over time, during all 3 infusions. Between t = -2-120 minutes, there was no difference in systolic blood pressure (P = .20), diastolic blood pressure (P = .61), or heart rate (P = .09) over the study days. There was also no significant difference in the glycemic response to the infusions. We conclude that in healthy older subjects, glucose concentration does not affect the blood pressure or heart rate responses to intraduodenal glucose and that, therefore, the magnitude of the postprandial fall in blood pressure induced by oral glucose is likely to depend primarily on the small intestinal glucose load.

Age Factors↗
PubMed2006

An update on autonomic neuropathy affecting the gastrointestinal tract.

Gastrointestinal symptoms and disordered gut motility occur frequently in the diabetic population and are generally regarded as manifestations of gastrointestinal "autonomic dysfunction," although the relationships between both symptoms and dysmotility with abnormal cardiovascular autonomic function are weak. It is now recognized that the blood glucose concentration is both a determinant of and determined by gastrointestinal function. An improved definition of the underlying pathophysiology should facilitate the development of therapies that are targeted more effectively.

Animals↗
PubMed2006

Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption.

BACKGROUND: Mixed alcoholic drinks are increasingly being consumed in "diet" varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with "regular" versions containing sugar. METHODS: We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose (total 478 kcal), or "diet" mixer (225 kcal). RESULTS: Gastric half-emptying time measured by ultrasound (mean+/-standard deviation) was less for the "diet" than the "regular" drink (21.1+/-9.5 vs 36.3+/-15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053+/-0.006 vs 0.034+/-0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2+/-0.7 vs 3.2+/-0.7 units, P <.001) were greater with the "diet" drink. CONCLUSIONS: Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.

Absorption↗
PubMed2006

Clinical and anatomic outcomes after endovascular coiling of middle cerebral artery aneurysms: report on 30 treated aneurysms and review of the literature.

BACKGROUND: Endovascular treatment of middle cerebral artery (MCA) aneurysms has not been extensively studied. We report our experience on a select group of patients that underwent coil embolization of an MCA bifurcation aneurysm. METHODS: From August 1999 to January 2005, 29 patients harboring 30 MCA aneurysms were treated with coil embolization. These patients were felt to have favorable characteristics for endovascular therapy including absence of thrombus in the aneurysm, absence of an efferent artery off of the aneurysm, and ability to reconstruct the wide neck with stent reconstruction. We retrospectively reviewed their records and angiographic images to evaluate for technical result and complications. RESULTS: The mean age of our cohort was 59 +/- 13 years with 19 patients presenting with a ruptured aneurysm. Complete obliteration was achieved in 24 (80%) of 30 of aneurysms on postprocedural angiography and no patient showed aneurysm regrowth at 6-month follow-up. Twenty-seven (93%) of 29 patients had no change in baseline neurological function post-embolization. There were two procedural-related complications: one intraprocedural rupture of an aneurysm and one thromboembolic stroke in the ipsilateral MCA territory. CONCLUSIONS: Coil embolization of MCA bifurcation aneurysms has a high rate of complete obliteration with acceptable morbidity in our selected group of patients.

Aged↗
PubMed2006

Effects of lipase inhibition on gastric emptying and alcohol absorption in healthy subjects.

The rate of alcohol absorption is dependent on gastric emptying (GE). As the slowing of GE by fat is dependent on lipolysis, orlistat may increase the rise in blood alcohol when alcohol is consumed with, or after, fat. The aim of the study was to evaluate the effects of orlistat on GE and blood alcohol after an alcohol-containing drink following a fat 'preload', in healthy subjects. Ten healthy males consumed 120 ml cream with or without 120 mg orlistat, 30 min before an alcohol-containing drink labelled with 20 MBq [(99 m)Tc]sulfur colloid on 2 d. GE, plasma alcohol and blood glucose were measured. GE was slightly faster with orlistat (P<0.05) compared with control. Plasma alcohol at 15 min was slightly higher with orlistat (0.034 (SEM 0.006) g/100 ml) v. control (0.029 (SEM 0.005) g/100 ml) (P<0.05), but there was no effect on the area under the curve 0-240 min. The increase in blood glucose was greater with orlistat, for example, at 15 min (1.07 (SEM 0.2) mmol/l) v. control (0.75 (SEM 0.2) mmol/l) (P=0.05). The rise in blood glucose and plasma alcohol were related (for example, at 15 min r 0.49; P=0.03). In conclusion, lipase inhibition accelerates GE of an alcohol-containing drink following a fat 'preload' with a minor increase in the initial rise in plasma alcohol.

Absorption↗
PubMed2006

The hypotensive response to oral fat is comparable but slower compared with carbohydrate in healthy elderly subjects.

The objective of the present study was to determine the comparative hypotensive responses to drinks containing predominantly fat and carbohydrate (CHO) in healthy elderly subjects. Using a randomised, cross-over study, the participants, twelve elderly subjects, six of them female (72.2 (sd 5.7) years), were investigated. On three separate days, blood pressure (BP) and heart rate were measured following ingestion of 300 ml drinks containing: (1) CHO (75 g glucose and 93 g Polyjoule (CHO polymer) providing 2732 kJ (653 kcal)); (2) 88 % fat (cream blended with milk providing 2732 kJ (653 kcal)); (3) water. Systolic BP decreased following the CHO drink (P<0.001) and the high-fat drink (P<0.001) but not water; there was no difference in the magnitude of the decrease between the CHO drink and the drink containing fat (13.4 v. 15.6 mmHg). However, the onset of the fall was slower after the fat-containing drink (13.0 v. 26.5 min (P=0.01); area under the curve for 0-30 min for CHO drink -6.5 v. fat-containing drink 125.4 mmHg x min (P=0.043)). We conclude that ingestion of a high-fat drink results in a comparable fall in BP to a CHO drink although the onset is relatively slower. These observations may have implications for the management of postprandial hypotension.

Administration, Oral↗
PubMed2006

Resection of a recurrent paraganglioma via an endoscopic transnasal approach to the jugular fossa.

OBJECTIVE: To present a novel endoscopic, transnasal approach to a recurrent paraganglioma of the jugular fossa (glomus jugulare). STUDY DESIGN: Case report and review of the literature. SETTING: The study was carried out at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, U.S.A. PATIENT: A 64-year-old woman presented to the University of Pittsburgh Medical Center with a 9-month history of left otalgia, occasional vertigo, facial pain, and recurrent epistaxis. She had undergone two previous procedures over the past 35 years for a glomus tympanicum. Physical examination revealed a mass in the left nasopharynx originating from the eustachian tube. A computed tomographic scan revealed an expansive mass in the left jugular foramen extending into the posterior parapharyngeal space suggestive of a large jugular paraganglioma. INTERVENTION: The patient underwent preoperative embolization of the paraganglioma. An endoscopic, transnasal approach along the eustachian tube, the ascending parapharyngeal carotid artery, and into the jugular fossa was used to remove the tumor. Intraoperative image guidance assisted in the identification of key anatomic landmarks. RESULTS: Postoperative magnetic resonance imaging revealed a thin rim of enhancement at the posterior aspect of the jugular fossa consistent with residual tumor. The patient was discharged to home on postoperative Day 1 in stable condition. There have been no complications with 4 months of follow-up, and the left facial paralysis secondary to preoperative embolization has resolved. CONCLUSION: We report the successful subtotal resection of a recurrent paraganglioma via a novel endoscopic, transnasal, transclival, transpetrous approach with image guidance. This approach allowed the near-total resection of a recurrent glomus jugulare with minimal surgical morbidity. Technological advances and surgical experience with nasal endoscopy and image guidance allow minimally invasive surgical management of select extracranial lesions of the lateral cranial base.

Embolization, Therapeutic↗
PubMed2006

Gastrointestinal motility and glycemic control in diabetes: the chicken and the egg revisited?

Upper gastrointestinal dysfunction occurs frequently in diabetes and potentially contributes to both abdominal symptoms and impaired glycemic control; conversely, variations in blood glucose concentration reversibly affect gut motility in humans. In this issue of the JCI, Anitha et al. report apoptosis of rodent enteric neurons under hyperglycemic conditions, both in vitro and in vivo, associated with impaired PI3K activity and preventable by glial cell line-derived neurotrophic factor. These observations add to recent insights gained from animal models regarding the etiology of diabetic gastrointestinal dysfunction, but investigators must strive to translate animal data to human diabetes.

Animals↗