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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 73 records · Page 4Linked to original sources

Endovascular management of a basilar artery false aneurysm secondary to endoscopic third ventriculostomy: case report.

OBJECTIVE AND IMPORTANCE: Third ventriculostomy for the management of noncommunicating hydrocephalus is a commonly performed procedure with a 5% complication rate. One of the known complications is basilar artery injury. CLINICAL PRESENTATION: We report a case of basilar artery injury, intraventricular hemorrhage, and false aneurysm formation in a 30-month-old boy after third ventricle floor fenestration. INTERVENTION: The false aneurysm was managed with endovascular trapping by use of Guglielmi detachable coils without morbidity. CONCLUSION: Endovascular therapy can be used successfully to manage vascular injury after third ventriculostomy.

Aneurysm, False↗

Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life.

OBJECTIVES: Morbidity from GI symptoms in diabetes is considered to be high, but no studies have quantified the impact of GI symptoms in diabetes on health-related quality of life. We hypothesized that diabetics reporting increased GI symptoms would experience more impaired quality of life. METHODS: Subjects from the community with diabetes (n = 892) and outpatients with diabetes (n = 209) were recruited for this study. Subjects were divided into type 1 (diabetes diagnosed at age <30 yr and requiring insulin) and type 2. A validated questionnaire measuring GI symptoms and diabetes status and the Short Form-36 were completed. The results were compared with Australian normal data. GI symptom groups measured were frequent abdominal pain, bowel-related abdominal pain, reflux, dyspepsia, constipation, diarrhea, and fecal incontinence. RESULTS: There was a clinically significant decrease in quality-of-life scores in diabetics compared with population norms across all subscales. The impact on quality of life in diabetes was predominantly observed in type 2 diabetics. The quality-of-life scores in all subscales decreased markedly with increasing numbers of distinct GI symptom groups, and this was similar in community and outpatient diabetics. For all the Short Form-36 subscales, GI symptom groups were significantly (all p < 0.0001) associated with poorer quality of life in diabetes, independent of age, gender, smoking, alcohol use, and type of diabetes. CONCLUSIONS: GI symptoms impact negatively on health-related quality of life in diabetes mellitus.

Adult↗

Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus.

OBJECTIVE: The association between Helicobacter pylori (H. pylori) infection and diabetes mellitus is controversial. We aimed to determine the prevalence of H. pylori infection in patients with diabetes and nondiabetic controls, and assess whether H. pylori infection was associated with upper gastrointestinal (GI) symptoms in diabetes mellitus. METHODS: A total of 429 patients with type 1 (n = 49) or type 2 (n = 380) diabetes mellitus (48.6% women, mean age 60.7 yr) and 170 nondiabetic controls (34.7% women, mean age 60.4 yr) were evaluated. All subjects completed a validated questionnaire (the Diabetes Bowel Symptom Questionnaire) to determine upper GI symptoms, and a blood sample was tested for H. pylori infection using a validated ELISA kit (sensitivity 96%, specificity 94%). RESULTS: Seroprevalence of H. pylori was 33% and 32%, respectively, in patients with diabetes and controls (NS). In both groups, the seroprevalence was significantly higher in men than in women; 39% vs 25% (p = 0.002) in diabetic patients, and 40% vs 20% (p = 0.01) in controls. Patients with diabetes had a significantly higher prevalence of early satiety (OR = 2.30), fullness (OR = 3.15), and bloating (OR = 1.50) compared with controls. Upper GI symptoms were present in 49% of H. pylori-positive and 53% of H. pylori-negative patients with diabetes (OR = 0.87, 95% CI 0.58-1.31, p = 0.56). H. pylori infection was also not associated with any of the individual upper GI symptoms before or after adjustment for potential confounding factors. However, patient age and female gender were identified as independent risk factors for upper GI symptoms. Smoking was a risk factor for bloating and early satiety. CONCLUSIONS: H. pylori infection appears not to be associated with diabetes mellitus or upper GI symptoms in diabetes mellitus.

Diabetes Complications↗

Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus.

OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients with long-standing diabetes mellitus, but the pathogenesis is controversial. We aimed to determine if GI symptoms are linked to psychological distress in diabetes. METHODS: A consecutive sample of outpatients with diabetes mellitus (n = 209) and a random sample of community diabetics (n = 892) completed a validated questionnaire measuring GI symptoms, the Hospital Anxiety and Depression (HAD) Scale for anxiety and depression, and the Eysenck short neuroticism scale. RESULTS: Overall, 42% reported one or more GI symptoms: bloating, abdominal pain, loose stools, and urgency were most common. The mean HAD and neuroticism scores were significantly higher for most GI symptoms (11 of 14, all p < 0.05), and a dose-response relationship was observed. GI symptoms were, in general, approximately twice as frequent in cases with anxiety or depression (HAD > or = 11). Anxiety, depression, and neuroticism were each independently associated with the number of GI symptoms, adjusting for age, gender, duration and type of diabetes, and self-reported glycemic control. CONCLUSIONS: Increased levels of state anxiety and depression and neuroticism are associated with upper and lower GI symptoms in diabetes mellitus. It is uncertain whether psychological distress is causally linked to symptoms, or whether GI symptoms per se increase levels of anxiety and depression.

Anxiety↗

Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men.

OBJECTIVE: The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity. METHODS: Thirteen older (65-84 yr) and 13 young (18-32 yr) healthy men received isovolumetric, intraduodenal (i.d.) infusions of saline (control), lipid, and glucose for 120 min, on separate days. The energy content of the lipid and glucose infusions was identical at 2.86 kcal/min. Immediately after the i.d. infusions, each subject was offered a buffet meal, and ad libitum food intake was quantified. Blood glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide were measured. Gastric myoelectrical activity was measured by surface electrogastrography (EGG). RESULTS: I.d. lipid suppressed food intake in both the young and older men (p < 0.05), whereas i.d. glucose suppressed food intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin (p < 0.05) responses to i.d. glucose were greater in older than young men. However, there were no differences in glucagon-like peptide 1 or glucose-dependent insulinotropic peptide responses to any of the infusions. There was a greater increase in the EGG power ratio both during and after i.d. glucose infusion in the young (p < 0.05) than the older men, and an attenuation of EGG frequency by nutrient infusions in older, but not young, men. CONCLUSIONS: Our findings indicate that aging is associated with nutrient-specific changes in appetite, hormonal, and gastric myoelectrical (EGG) responses to i.d. nutrients. An enhanced satiating effect of small intestinal carbohydrates may potentially contribute to the anorexia of aging.

Adolescent↗

Nutrient-induced spatial patterning of human duodenal motor function.

The spatiotemporal patterning of duodenal motor function has been evaluated comprehensively for the first time in humans, with a novel 21-lumen manometric assembly. In nine young, healthy volunteers (6 male, 3 female), duodenal motility was recorded during fasting and three 45-min intraduodenal (ID) nutrient infusion periods (Intralipid at 0.25, 0.5, and 1.5 kcal/min). Pressures were recorded along the length of the duodenum with an array of 18 sideholes at 1.5-cm intervals. Pressure patterns were compared for the final 20 min of each of the four periods. Compared with fasting, ID lipid was associated with regional variation in pressure wave (PW) sequences, with fewer proximally and more distally; this was not observed during fasting (P < 0.001). During fasting and all rates of lipid infusion, most (87-90%) PW sequences were short (1.5-4.5 cm), with a small number (2-4%) of 10.5 cm or longer. At all times, antegrade PW sequences occurred more frequently than retrograde sequences over all distances examined (3, 4.5, and >6 cm), and the proportion of antegrade sequences increased with greater PW sequence length (P = 0.0001). Increasing ID lipid rates appeared to produce dose-related suppression of PW sequences (P < 0.001). The frequency and spatial patterning of human duodenal motor function show substantial variability in response to different nutrient delivery rates. These complex patterns are likely to be involved in duodenal modulation of flow and gastric emptying rate.

Adult↗

Relationship between ultrasonically detected phasic antral contractions and antral pressure.

The relationships between gastric wall motion and intraluminal pressure are believed to be major determinants of flows within and from the stomach. Gastric antral wall motion and intraluminal pressures were monitored in five healthy subjects by concurrent antropyloroduodenal manometry and transabdominal ultrasound for 60 min after subjects drank 500 ml of clear soup. We found that 99% of antral contractions detected by ultrasound were propagated aborally, and 68% of contractions became lumen occlusive at the site of the ultrasound marker. Of the 203 contractions detected by ultrasound, 53% were associated with pressure events in the manometric reference channel; 86% of contractions had corresponding pressure events detectable somewhere in the antrum. Contractions that occluded the lumen were more likely to be associated with a pressure event in the manometric reference channel (P < 0.01) and to be of greater amplitude (P < 0.01) than non-lumen-occlusive contractions. We conclude that heterogeneous pressure event patterns in the antrum occur despite a stereotyped pattern of contraction propagation seen on ultrasound. Lumen occlusion is more likely to be associated with higher peak antral pressure events.

Adolescent↗

Effects of glucose supplementation on gastric emptying, blood glucose homeostasis, and appetite in the elderly.

The aims of this study were to evaluate the effects of dietary glucose supplementation on gastric emptying (GE) of both glucose and fat, postprandial blood glucose homeostasis, and appetite in eight older subjects (4 males, 4 females, aged 65--84 yr). GE of a drink (15 ml olive oil and 33 g glucose dissolved in 185 ml water), blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and appetite (diet diaries, visual analog scales, and food intake at a buffet meal consumed after the GE study) were evaluated twice, after 10 days on a standard or a glucose-supplemented diet (70 g glucose 3 times a day). Glucose supplementation accelerated GE of glucose (P < 0.05), but not oil; there was a trend for an increase in GIP (at 15 min, P = 0.06), no change in GLP-1, an earlier insulin peak (P < 0.01), and a subsequent reduction in blood glucose (at 75 min, P < 0.01). Glucose supplementation had no effect on food intake during each diet so that energy intake was greater (P < 0.001) during the glucose-supplemented diet. Appetite ratings and energy intake at the buffet meal were not different. We conclude that, in older subjects, glucose supplementation 1) accelerates GE of glucose, but not fat; 2) modifies postprandial blood glucose homeostasis; and 3) increases energy intake.

Aged↗

Heat acclimation and heat stress have different effects on cholinergic-induced calcium mobilization.

There is evidence that the signal transduction array responsible for the secretion of water in evaporative cooling by the submaxillary gland of the rat is subject to heat acclimatory responses. The objectives of the present study were 1) to examine whether heat acclimation affects intracellular Ca(2+) mobilization and, in turn, submaxillary glandular responsiveness; 2) to assess whether the acclimatory responses differ from those evoked on heat stress (HS). Experiments were conducted on submaxillary glands of rats acclimated at 34 degrees C for 0, 2 [short-term heat acclimation (STHA)], and 30 [long-term heat acclimation (LTHA)] days. The resting cytosolic calcium concentration ([Ca(2+)](c)) and the carbamylcholine-evoked calcium signal ([Ca(2+)](s)) of dispersed glandular cells were measured using the fluorescent dye fura 2 AM. Inositol-1,4,5-trisphosphate (IP(3))-sensitive endoplasmic reticulum Ca(2+) stores were determined in permeabilized cells using fura 2 potassium salt. STHA resulted in a drop in both [Ca(2+)](s) and IP(3)-sensitive Ca(2+) stores. On LTHA, the [Ca(2+)](s) amplitude reverted to the preacclimation value, whereas the IP(3)-sensitive Ca(2+) stores remained low. The drop in [Ca(2+)](s) on STHA is in accord with the decreased glandular output (measured by (86)Rb efflux) observed during this acclimation phase. However, after LTHA the enhanced glandular output despite reduced [Ca(2+)](s) levels suggests an increased efficiency of cellular secretory mechanisms in that group. Collectively, the alterations in [Ca(2+)](s) support our biphasic acclimation model (Horowitz M, Kaspler P, Marmari Y, and Oron Y. J Appl Physiol 80: 77--85, 1996.). In nonacclimated glands, HS caused an elevation in [Ca(2+)](s) coincidentally with a decrease in the IP(3) Ca(2+) stores. In contrast, [Ca(2+)](s) in both STHA and LTHA glands was not affected by HS, despite a marked increase in the IP(3)-sensitive Ca(2+) stores in the LTHA glands. The opposing responses to HS and heat acclimation in calcium signaling and stores confirm the specificity of each process.

Acclimatization↗

Gastroparesis: prevalence, clinical significance and treatment.

The application of novel techniques to quantify gastric motor function and gastric emptying has yielded important insights into the prevalence, pathogenesis and clinical sequelae of gastroparesis. Both acute and chronic gastroparesis occur frequently; gastric emptying of solids is delayed in 30% to 50% of patients with diabetes mellitus, functional dyspepsia and gastroesophageal reflux disease. While many patients with gastroparesis experience upper gastrointestinal symptoms that adversely affect quality of life, the concept that symptoms are inevitably the direct outcome of delay in gastric emptying is now recognized to be overly simplistic. In contrast, the potential impact of gastroparesis on oral drug absorption and blood glucose control in patients with diabetes mellitus has probably been underestimated. While the use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy in symptomatic patients with gastroparesis, a number of novel pharmacological therapies are being evaluated, and preliminary studies using gastric pacing show promise.

Gastric Emptying↗

Endovascular particulate and alcohol embolization for near-fatal epistaxis from a skull base vascular malformation.

A three-year old girl who initially presented at 16 months with epistaxis from an anterior skull base vascular anomaly returned with near-fatal epistaxis despite embolization of the internal maxillary artery at the time of initial presentation. Repeat angiography demonstrated blood supply to the vascular lesion coming from branches of both the external and internal carotid arteries. The patient underwent four sessions of endovascular embolization with polyvinyl alcohol, alcohol, and gelatin microspheres. At the conclusion of treatment, her epistaxis had resolved and the only residual blood supply to the lesions came from bilateral ophthalmic arteries intentionally not sacrificed to prevent loss of vision. Endovascular embolization of both the internal and external carotid arteries is a challenging but important treatment option for life-threatening epistaxis resulting from vascular lesions of the skull base.

Carotid Artery, External↗

Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.

Healthy aging is associated with reductions in appetite and food intake--the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on the satiating effects of CCK, 12 young and 12 older healthy subjects received 25-min iv infusions of saline (control) and CCK-8, 1 ng/kg per min or 3 ng/k per min, on 3 separate days before a test meal. Older subjects ate less than young subjects, and food intake was suppressed 21.6% by CCK-8, compared with the control day (P < 0.05). The suppression of energy intake by CCK-8 in older subjects was twice that in young subjects (32 +/- 6% vs. 16 +/- 6% SEM, P < 0.05) and was related to plasma CCK-8 concentrations, which were higher at baseline (P < 0.05) and increased more during CCK-8 infusions in older than young subjects (P < 0.01). The extent of suppression of food intake per given rise in plasma CCK-8 concentrations did not differ between the two age groups (P = 0.35). Endogenous CCK concentrations were higher at baseline in older subjects (P < 0.001) and decreased during the CCK-8 but not control infusions (P < 0.01), suggesting that CCK suppresses its own release. Plasma leptin concentrations were not affected by CCK infusion, whereas postprandial insulin concentrations were lowered and the peak postprandial glucose concentration was delayed but not affected by CCK-8 infusion. Because older people retain their sensitivity to the satiating effects of exogenous CCK and plasma endogenous CCK concentrations are higher in older people, increased CCK activity may contribute to the anorexia of aging.

Adult↗

Relationships of upper gastrointestinal motor and sensory function with glycemic control.

Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.

Blood Glucose↗

Predictors of delayed gastric emptying in diabetes.

OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.

Animals↗

[Sepsis associated cholestasis in adults].

Hepatic injury presenting as jaundice, hypglycemia, encephalopathy, coagulation disturbances and a significant increase in transaminases in a late well recognized complication of sepsis. Less known is a cholestatic liver injury, which can precede sepsis. This type of early liver injury is characterized by a rise of direct bilirubin and less prominent increase in liver enzymes. Experimental work in animal models demonstrates that sepsis associated cholestasis is mediated by a variety of gram negative bacterial endotoxins and cytokines which interfere with the function of bile acid intracellular transporters. Although sepsis associated cholestasis is quite common, its clinical and prognostic characteristics are not widely appreciated. This often results in performance of unnecessary procedures and delayed diagnosis. Here we review the relevant updated literature regarding the pathophysiological basis of this phenomenon and its clinical presentation and implications.

Adult↗

Inhibition of bone resorption by divided-dose calcium supplementation in early postmenopausal women.

We have previously shown that a calcium (Ca) supplement of 1000 mg given in the evening reduces the overnight and early morning, but not the daytime, excretion of bone resorption markers in postmenopausal women within five years of the menopause. In the present study, we have looked at the effect of splitting the Ca into two doses of 500 mg each given in the morning and evening. We studied 19 healthy women (median age 53 years) who were all within 5 years of the menopause. On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection), and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine sample was obtained at 9 a.m. at the end of the night collection. The first day was a control day; on the second day the subjects ingested 500 mg Ca as the carbonate at 9 a.m. and 9 p.m. We measured pyridinoline cross-links excretion in all the samples, as well as hydroxyproline in the fasting urine. The Ca supplements lowered urinary excretion of the markers during the day (P < 0.01), had only a marginal effect during the night, but reduced excretion significantly in the fasting urine (P < 0.001). In the whole 24-hour period, the falls in resorption markers were small but comparable to those seen after the ingestion of 1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca in the morning and evening reduced the markers of bone resorption in early postmenopausal women during the day but not during the following night, whereas the single 1 g supplement had the reverse effect. Over the 24-hour period, there was nothing to choose between the two regimes. Women at this stage in their life cycle probably require a larger Ca supplement if they are not taking estrogen.

Amino Acids↗