Severe hypoglycaemic unawareness in a patient with insulinoma.
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Adult↗
Biomedical subjects
M Horowitz
Publications and source records attributed to M Horowitz.
A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies.
Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3-5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor tumor response was observed in a patient with a GRP-expressing progressive medullary carcinoma of the thyroid. Due to problems with the analytical method, plasma pharmacokinetic data was obtained only from two patients included at the highest dose level. In these patients, RC-3095 reached plasma concentrations >100 ng/mL for about 8 h, which were within therapeutic levels on the basis of prior data obtained in mice and rats. The plasma elimination half-life was between 8.6-10.9 h. Due to the occurrence of local toxicity at the injection site, the dose escalation procedure could not be fully evaluated up to a maximum tolerated dose. Thus, a recommended dose of RC-3095 for Phase II trials could not be clearly established. Considering the novelty of its mechanism of action and impressive preclinical anti-tumor activity, further studies exploiting new formulations of RC-3095 for human use, such as slow-release preparations, and analogues with a more favorable pharmacokinetics are warranted.
Adult↗
Dietary factors in functional dyspepsia.
Functional dyspepsia (FD) is characterized by upper gastrointestinal symptoms, which are frequently exacerbated by meal ingestion. While subgroups of FD patients exhibit a range of disturbances in upper gastrointestinal motor function, including delayed gastric emptying and abnormal intragastric meal distribution, which may reflect impaired proximal gastric relaxation and/or antral dysmotility, the association between symptoms and abnormalities in motor function appears to be relatively weak. More recently, the concept of visceral hypersensitivity to mechanical and chemical/nutrient stimuli has been promoted as important in the aetiology of dyspeptic symptoms. Somewhat surprisingly, the role of 'dietary' factors, that is, those factors, related directly to food ingestion, including patterns of nutrient intake, potential intolerance to specific foods or macronutrients, as well as cognitive factors, have been largely ignored. Moreover, presently available treatments fail to take into account the fact that symptoms are frequently induced by eating. This review focuses on the relevance of 'dietary' factors to FD.
Animals↗
'Gastric' hypoglycaemia--an important concept in diabetes management.
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Blood Glucose↗
Measurements of gastric emptying of low- and high-nutrient liquids using 3D ultrasonography and scintigraphy in healthy subjects.
Scintigraphy represents the 'gold standard' for the measurement of gastric emptying. Recent studies suggest that three-dimensional (3D) ultrasonography may allow a precise measure of gastric emptying, given the capacity for accurate volume calculations of the stomach. The aim of this study was to compare measurements of gastric emptying of both low- and high-nutrient drinks by 3D ultrasonography with scintigraphy. Ten healthy young subjects (6M, 4F, age 23.5 +/- 1.5 years) were studied on 2 days. Concurrent measurements of gastric emptying by scintigraphy and 3D ultrasonography were performed after ingestion of 500 mL beef soup (12 kcal) or 300 ml dextrose (25% w/v) (314 kcal) labelled with 20 MBq (99m)Tc-sulphur colloid. There was no significant difference between scintigraphic and ultrasonographic 50% emptying times (T50s) (soup: 27.7 +/- 4.8 min vs 23.8. +/- 4.8 min; dextrose: 122.2 +/- 13.3 min vs 131.9 +/- 10.2 min). There was a close correlation between scintigraphic and ultrasonographic T50s for both soup (r = 0.92, P = 0.0005) and dextrose (r = 0.88, P = 0.0007). For the T50s, the limits of agreement were -15.2 min and +8.1 min for the soup (mean difference -3.6 min) and -35.3 min and +47.6 min for dextrose (mean difference +6.2 min). 3D ultrasonography provides a valid measure of gastric emptying of liquid meals in healthy subjects.
Adult↗
To be or not to be--an incretin or enterogastrone?
Glucagon-like peptide 1 does not comfortably fulfil the criterion of a gut derived factor responsible for an enhanced meal related insulin response; it appears logical to add the definition of a "physiological incretin hormone".
Blood Glucose↗
Cavernous carotid origin aneurysm rupture with intracerebral intraparenchymal hemorrhage after treatment of a traumatic Barrow type A cavernous carotid artery fistula.
This case report demonstrates delayed rupture of a cavernous carotid fistula and aneurysm into the temporal lobe 12 years after treating a direct cavernous carotid artery fistula using detachable silicon balloons. The ultimate treatment was performed using arterial endovascular sacrifice. Successful treatment of cavernous carotid fistulas may ultimately lead to formation of cavernous aneurysms. Although these lesions rarely cause intraparenchymal hemorrhage, the risk for such an event must be taken into consideration when patients are treated for the initial lesion.
Adult↗
Initial experience with the use of intravenous eptifibatide bolus during endovascular treatment of intracranial aneurysms.
BACKGROUND AND PURPOSE: Despite systemic heparinization, thromboembolic complications remain a major concern related to endovascular treatment of intracranial aneurysms. We assessed the safety of intravenous eptifibatide administered during aneurysm coiling procedures to prevent such complications. METHODS: From August 2001 to November 2004, 298 coil embolization procedures were performed to treat intracranial aneurysms; eptifibatide was used in 84 endovascular coil embolization procedures to treat 79 aneurysms in 74 patients. We retrospectively reviewed medical charts, radiographic images, and procedure notes to evaluate periprocedural complications related to eptifibatide. RESULTS: The mean age of the 74 patients in our cohort was 55 +/- 9 years (range, 31-84) harboring 79 aneurysms (32 ruptured/47 unruptured). Eptifibatide was given prophylactically in 77 procedures, whereas in 7 procedures, it was given for treatment of a thromboembolic event (visualization of an arterial branch occlusion). A total of 5 (5.9% [total cohort]) bleeding complications related to eptifibatide occurred during 84 procedures. Two patients (2.4% [total cohort]/6.3% [ruptured group]) developed intracerebral hemorrhagic complications exacerbated by eptifibatide. The other 3 (3.6% [total cohort]) patients had groin hematomas requiring blood transfusions but had no surgical intervention. One thromboembolic event occurred in the 77 patients receiving eptifibatide prophylactically. CONCLUSIONS: Intravenous infusion of eptifibatide seems to be safe to administer in patients undergoing endovascular repair of an unruptured cerebral aneurysm. Caution must be used in patients harboring ruptured aneurysms as intracranial bleeding complications may occur. Further study is required to delineate the group of patients most likely to benefit from this therapy.
Adult↗
Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients.
BACKGROUND: Gastric emptying is frequently delayed in critical illness which compromises the success of nasogastric nutrition. The underlying motor dysfunctions are poorly defined. AIMS: To characterise antro-pyloro-duodenal motility during fasting, and in response to gastric and duodenal nutrient, as well as to evaluate the relationship between gastric emptying and motility, in the critically ill. SUBJECTS: Fifteen mechanically ventilated patients from a mixed intensive care unit; 10 healthy volunteers. METHODS: Antro-pyloro-duodenal pressures were recorded during fasting, after intragastric administration (100 ml; 100 kcal), and during small intestinal infusion of liquid nutrient (6 hours; 1 kcal/min). Gastric emptying was measured using a (13)C octanoate breath test. RESULTS: In healthy subjects, neither gastric nor small intestinal nutrient affected antro-pyloro-duodenal pressures. In patients, duodenal nutrient infusion reduced antral activity compared with both fasting and healthy subjects (0.03 (0-2.47) waves/min v 0.14 (0-2.2) fasting (p = 0.016); and v 0.33 (0-2.57)/min in healthy subjects (p = 0.005)). Basal pyloric pressure and the frequency of phasic pyloric pressure waves were increased in patients during duodenal nutrient infusion (3.12 (1.06) mm Hg; 0.98 (0.13)/min) compared with healthy subjects (-0.44 (1.25) mm Hg; p<0.02 after 120 minutes; 0.29 (0.15)/min; p = 0.0002) and with fasting (-0.06 (1.05) mm Hg; p<0.03 after 160 minutes; 0.49 (0.13)/min; (p = 0.0001). Gastric emptying was delayed in patients (gastric emptying coefficient 2.99 (0.2) v 3.47 (0.1); p = 0.015) and inversely related to the number of pyloric pressure waves (r = -0.563, p = 0.029). CONCLUSIONS: Stimulation of pyloric and suppression of antral pressures by duodenal nutrient are enhanced in the critically ill and related to decreased gastric emptying.
Adult↗
Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.
AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.
Adult↗
The role of endoscopic assisted microneurosurgery (image fusion technology) in the performance of neurosurgical procedures.
The use of endoscopic techniques has gained significant popularity over the past decade. The potential advantages of angled lenses to visualize around tight corridors without retracting have proven to be an attractive feature. The limitation of endoscopy has been the inability to obtain a true three-dimensional perspective for which microscopy is ideal. Therefore we postulated that for complex intradural lesions the merger of the two technologies would prove to be ideal. In this paper we report our experience with simultaneous microscopy and endoscopy, using picture-in-picture technology, for intracranial vascular and oncological surgery. We have found it useful to offer enough visualization to allow for performing surgery and not just for inspection.
Adult↗
The effects of drinks made from simple sugars on blood pressure in healthy older people.
The objective of the research was to determine the blood pressure (BP) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a randomised, cross-over study with ten (six females) healthy older subjects (mean age 72.20 (sem 1.50) years). BP, heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient content (glucose, sucrose and fructose). A significant decline in BP over the first 60 min was seen following glucose (systolic BP (SBP) P<0.01, diastolic BP (DBP) P<0.01, mean arterial BP (MAP) P=0.03) and sucrose (SBP P<0.01, DBP P<0.01, MAP P<0.01) ingestion, although the decrease occurred earlier after glucose than sucrose ingestion (SBP 7.33 (sem 2.19) v. 21.00 (sem 4.30) min (P=0.03) and MAP 11.22 (sem 3.10) v. 17.00 (sem 3.78) min (P=0.03)). BP increased after water ingestion (SBP P=0.04, DBP P=0.18, MAP P=0.02) but did not change after fructose ingestion (SBP P=0.36, DBP P=0.81, MAP P=0.34). Post hoc analyses revealed that the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion. Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In contrast to this, fructose ingestion causes no change in BP. Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postprandial hypotension.
Aged↗
Role of cholecystokinin in appetite control and body weight regulation.
Summary Cholecystokinin (CCK), a peptide that is distributed widely throughout the gastrointestinal tract and the central nervous system, has a number of physiological effects including the stimulation of gallbladder contraction and pancreatic and gastric acid secretion, slowing of gastric emptying and suppression of energy intake. This review focuses on current knowledge relating to (i) the effects of CCK on energy intake; (ii) the role for CCK in the pathophysiology of obesity; and (iii) the therapeutic potential for strategies which modulate the action or secretion of CCK in the management of obesity. While CCK plays a role in the acute regulation of appetite and energy intake, there is little evidence to suggest that specific CCK receptor agonists, or modulation of the actions of endogenous CCK by dietary manipulation, have sustainable inhibitory effects on energy intake. Hence, it appears unlikely that manipulating the pathways by which CCK modulates energy intake will prove to be an effective strategy in the long term management of obesity.
Animals↗
Repeat microvascular decompression for hemifacial spasm.
OBJECTIVE: To report our experience with repeat microvascular decompression (MVD) for hemifacial spasm (HFS) in patients who have failed their first operation. METHODS: The authors describe 41 redo MVDs for HFS in 36 patients performed over a 3 year period. Seven patients underwent early re-operation after an aborted seventh nerve decompression. Eight patients underwent early re-operation for clinical failure. Eighteen patients underwent late re-operation for spasm recurrence long after their original MVD. Eight MVDs were performed on patients who had already undergone at least two prior operations. RESULTS: Twenty four patients experienced complete spasm resolution (70.6%), eight patients had near total resolution (23.5%), and two patients failed re-operation (5.9%). Two patients were lost to follow up (5.6%). A favourable outcome was reported by 82.4% of patients at a mean follow up interval of 18 months. A total of 91.7% of patients 50 years of age or younger were cured at follow up versus 59.1% of patients older than 50 (p = 0.04). Patients undergoing early re-operation were significantly more likely to be cured or improved than patients undergoing late re-operation (p = 0.03). CONCLUSIONS: Repeat MVD for HFS is effective in experienced hands. Younger patients respond better to repeat MVD. Late repeat MVD for HFS is a reasonable treatment option, although results are less favourable than for early re-operation.
Adult↗
Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes.
AIMS/HYPOTHESES: We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients. METHODS: Eight type 2 diabetic patients, who were aged 62 years (median range: 49-68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq (99m)Tc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device. RESULTS: Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean +/- SEM], 61+/-8 min vs 98+/-5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not. CONCLUSIONS/INTERPRETATION: Inhibition of fat digestion by orlistat may-as a result of more rapid gastric emptying-exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.
Aged↗
Heat acclimation affects the neuromodulatory role of AngII and nitric oxide during combined heat and hypohydration stress.
We studied the effect of heat acclimation on the neuromodulatory role of angiotensin (AngII) and nitric oxide during combined heat (39 degrees C) and hypohydration (water deprivation, -10% body weight) stress. Rats were divided into control (C), short (2d-STHA) or long (30d-LTHA) acclimation (34 degrees C) groups. AngII, 7-nitroindazole (7NI)-nNOS blocker, or both were centrally administered (5 mul, bolus) under light chloroform anesthesia prior to each experimental paradigms: (1) In vivo: measurements of skin-vasodilatation (VTsh) and salivation-cooling (STsh) thresholds, and heat endurance in conscious heat/hypohydrated stressed rats; (2) expression of AT(1) and AT(2) AngII receptors and nNOS were measured in the hypothalamus (Western blot); (3) transcript levels of the coding genes were measured using real-time PCR. A synthesis of the results shows a biphasic acclimatory profile of VTsh, STsh, and transcript levels of all studied genes, with transient up/down-regulatory changes on STHA. AngII affected the physiological integrative outcome primarily during euhydration, although AT membranal changes (except in LTHA) were confined to hypohydration. 7NI had an impact during hypohydration. Evidence is provided that AngII and 7NI modulate thermoregulation primarily via AT(1) and AT(2) receptors, with predominance of AT(2) signaling following LTHA and/or hypohydration, opposing a drop in AT(1)-mediated thresholds. The final shaping of AngII signaling depends on cross-talk between nNOS and AngII receptors at both molecular and protein levels. Hypohydration induces transcriptional responses but desensitizes AngII receptors signaling, attenuating their effect on VTsh and STsh, and abolishing the beneficial thermoregulatory effects achieved by heat acclimation. nNOS, AngII receptor-independent pathway is also implicated.
Acclimatization↗
Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis.
BACKGROUND: KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans. AIM: To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis. METHODS: Twenty-nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and 'meal-related' symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days. RESULTS: KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal. KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo. The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05). CONCLUSIONS: KC 11458, in a dose of 8 mg t.d.s. for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis. The absence of efficacy may relate to an effect of hyperglycaemia.
Autonomic Nervous System Diseases↗