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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 37 records · Page 2Linked to original sources

Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans.

Gastric lipase (HGL) contributes significantly to fat digestion. However, little is known about its neurohormonal regulation in humans. We studied the role of CCK and cholinergic mechanisms in the postprandial regulation of HGL and pancreatic lipase (HPL) secretion in six healthy subjects. Gastric emptying of a mixed meal and outputs of HGL, pepsin, acid, and HPL were determined with a double-indicator technique. Three experiments were performed in random order: intravenous infusion of 1) placebo, 2) low-dose atropine (5 micrograms.kg-.h-1), and 3) the CCK-A receptor antagonist loxiglumide (22 mumol.kg-.h-1). Atropine decreased postprandial outputs of HGL, pepsin, gastric acid, and HPL (P < 0.03) while slowing gastric emptying (P < 0.05). Loxiglumide markedly increased the secretion of HGL, pepsin, and acid while distinctly reducing HPL outputs and accelerating gastric emptying (P < 0.03). Plasma CCK and gastrin levels increased during loxiglumide infusion (P < 0.03). Atropine enhanced gastrin but not CCK release. Postprandial HGL, pepsin, and acid secretion are under positive cholinergic but negative CCK control, whereas HPL is stimulated by cholinergic and CCK mechanisms. We conclude that CCK and cholinergic mechanisms have an important role in the coordination of HGL and HPL secretion to optimize digestion of dietary lipids in humans.

Adult

Role of lipase in the regulation of upper gastrointestinal function in humans.

The role of lipase in the regulation of upper gastrointestinal function is poorly understood. We studied the effect of orlistat, a new, potent, and highly specific lipase inhibitor, on gastric emptying, cholecystokinin (CCK) release, and pancreaticobiliary secretion. Three groups of studies were performed in nine healthy volunteers, using the double-indicator technique with a triple-lumen duodenal tube, polyethylene glycol 4000 as a duodenal perfusion marker, and 99mTc-diethylenetriamine pentaacetic acid as a meal marker. Gastric emptying, pancreaticobiliary output, and postprandial plasma CCK levels were measured after ingestion of the following isocaloric 500-ml liquid meals with or without 200 mg orlistat: 1) a pure fat meal (10% Intralipid), 2) a meal containing free fatty acids, or 3) an albumin-glucose meal. All experiments were performed in a randomized, placebo-controlled, crossover design. Orlistat markedly inhibited lipase activity in all three experiments. Orlistat given with the fat meal reduced CCK release and output of lipase, trypsin, and bilirubin and accelerated the rate of gastric emptying (P < 0.05). After ingestion of the free fatty acid or albumin-glucose meal, orlistat had no significant effect on any of these parameters. We conclude that lipase plays an important, nutrient-specific role in the regulation of gastric emptying and pancreaticobiliary secretion after ingestion of fatty meals in humans.

Adult

Effects of a specific CCK-A antagonist, Loxiglumide, on postprandial mood and sleepiness.

Previous studies have demonstrated that feelings of sleepiness increase after ingestion of a fat-rich meal. The aim of the study was to test the hypothesis that postprandial sleepiness is mediated by cholecystokinin (CCK) acting on CCK-A receptors. A double-blind crossover study was conducted. Twelve male volunteers ate a high-fat morning meal [54% energy fat, 41% energy carbohydrate (CHO)]. On one day they received an i.v. infusion of Loxiglumide, a CCK-A receptor antagonist (30 mg/kg/h for 10 min then 10 mg/kg/h for 3 h 10 min). On another day the protocol was repeated except a saline placebo infusion was given at similar rates as the Loxiglumide, starting 20 min before the meal. Subjects' mood and sleepiness were monitored throughout using questionnaires and performance tasks. The results indicate that ratings of vigour were significantly lower during the Loxiglumide infusion than during the saline infusion, [F(1,10) = 6.65; p = 0.027]. Subjects who were infused with Loxiglumide on their first test day felt significantly (p < 0.05) more fatigued, sleepy and tense and less vigorous, less efficient and had lower energetic arousal during the Loxiglumide infusion than during the saline infusion. In conclusion, the results suggest that the postprandial decline in feelings of alertness after a fat-rich meal is not mediated solely by CCK acting through CCK-A receptors.

Adult

Overuse of upper gastrointestinal endoscopy in a country with open-access endoscopy: a prospective study in primary care.

BACKGROUND: This prospective observational study was aimed at evaluating the appropriateness of use of upper gastrointestinal endoscopy (UGE) in primary care in a country with open access to and high availability of the procedure. METHODS: Outpatients were consecutively included in two clinical settings: Setting A (20 primary care physicians during 4 weeks) and B (university-based outpatient clinic during 3 weeks). In patients undergoing UGE, appropriateness of referral was judged by explicit Swiss criteria developed by the RAND/UCLA panel method. RESULTS: Patient visits (8135) were assessed. Six hundred eleven patients complained of upper gastrointestinal symptoms. Physicians decided to perform UGE in 63 of these patients. Twenty-five (40%) of the endoscopies were rated appropriate, 7 (11%) equivocal, and 31 (49%) inappropriate. Overuse of UGE occurred in 5.1% (setting A: 4.7%; setting B:6.5%; p = 0.39) of the patients who presented with upper gastrointestinal symptoms. The decision to perform UGE in previously untreated dyspeptic patients was the most common clinical situation resulting in overuse. CONCLUSIONS: Inappropriate use of UGE is high in Switzerland. However, to better reflect primary care decision making, overuse should be related not only to patients referred for a medical test, but also to the number of patients who complain of the symptoms that would be investigated by the procedure.

Adolescent

Primary biliary cirrhosis associated with antiphospholipid syndrome.

A 47-year-old female was admitted for severe pain of 1 month's duration in the third and fourth toes of the right foot, culminating in gangrene. Laboratory findings revealed liver enzyme abnormalities, and anti-mitochondrial, anti-phospholipid and antinuclear and doubtful anti-DNA antibodies. Systemic lupus erythematosus (SLE) was excluded on clinical grounds after a 6-year follow-up. Therefore, a diagnosis was made of the primary antiphospholipid syndrome, complicated by microvasculopathy, and associated with primary biliary cirrhosis.

Antiphospholipid Syndrome

[An unusual cause of intestinal obstruction in the puerperal period (case report)].

The authors present a case report of acute intestinal obstruction which manifested itself on the fourth day after the delivery of twins by Caesarian section. Compression of the rectosigmoid colon by the enlarged uterus--which was as big as a pregnant uterus in its fourth month--was established as the cause of ileus. Acute intestinal obstruction was obviously caused by sudden enormous enlargement of the antero-posterior dimension of the contracting uterus at the aditus pelvis level. The situation was successfully surgically resolved by the employment of temporary tube cecostomy.

Acute Disease

[Gastroesophageal reflux].

Gastroesophageal reflux disease (GERD) is a common, typically chronic recurring disorder. The majority of patients with heartburn and regurgitation have intermittent symptoms for which they do not consult their physicians. The main long-term risk of esophagitis is adenocarcinoma arising from Barrett's metaplasia. There are two principle therapeutic strategies in the treatment of GERD. The use of prokinetic drugs aims at treating the primary motility disorder leading to reflux, whereas acid-suppressive therapy targets at the reduction of gastric acid production to prevent symptoms and complication of GERD. The cornerstone in the treatment of GERD are proton pump inhibitors (PPI). Patients with mild symptoms and rarely relapsing disease may be best treated intermittently. Longterm maintenance acid-suppressive therapy with PPIs is necessary in GERD patients with immediate and severe relapse. At present, eradication of Helicobacter pylori in GERD patients is not recommended. Antireflux surgery is an effective treatment to control gastroesophageal reflux. However, surgery is associated with a low, but still substantial morbidity, a low mortality of up to 0.5% and is only indicated in patients with pharmacological refractory reflux disease.

Anti-Ulcer Agents

[Functional dyspepsia].

The term "functional dyspepsia" describes a complex of symptoms which are related to the upper gastrointestinal tract and frequently experienced by the patients after food intake. The pathophysiology of functional dyspepsia is still poorly understood. There are no organic causes found nor are there any functional changes observed that correlate with symptom occurrence and intensity and which could offer a satisfactory explanation for the symptoms and a basis for successful therapy. Mechanisms discussed include a disturbance of gastric motility and emptying, an increased sensitivity of the stomach to or hypersecretion of gastric acid, and infection by Helicobacter pylori. Recent research indicates visceral hypersensitivity of the gastroduodenal region to mechanical (distension) and chemical (nutrients or neuromodulators) stimulation to be a major factor in the aetiology of functional dyspepsia, potentially offering an explanation why dyspeptic symptoms are often related to food intake. The occurrence of dyspeptic symptoms in relation to food ingestion frequently prompts the gastroenterologist to the diagnosis of a motility disorder and subsequent therapy with prokinetic drugs. These substances may result in an improvement of gastric emptying, but not necessarily symptoms. It is apparent that the incompletely understood pathophysiology of functional dyspepsia is one of the main reasons for the lack of an effective therapy for this common condition.

Diagnosis, Differential

The amplicons in HL60 cells contain novel cellular sequences linked to MYC locus DNA.

We have previously determined that the amplified DNA present in the HL60 promyelocytic leukaemia cell line contained 70 kb of continuous DNA sequences around the c-myc gene. In the work presented here we have further defined the HL60 amplicon and find it to be of the order of 160 kb and to contain a large region of DNA from chromosome 8q24 that is located at least 260 kb telomeric to the c-myc gene, joined to the 70 kb of DNA from the c-myc gene region. The novel chromosome 8 DNA coamplified sequences are not lost during multiple passage of HL60 cells since the composition of the chimeric amplicon is the same in both early passage HL60 cells containing only double minutes (DMs) and late passage isolates containing homogeneous staining regions (HSRs) at different chromosomal locations. This shows that the HL60 HSRs found in late passage cells are not generated anew but are directly derived from the precursor DMs. The HL60 cells contain two copies of chromosome 8, each with different polymorphic markers. Both these chromosome 8 homologues retain a c-myc gene as well as the region containing the coamplified DNA sequences indicating that the HL60 amplicons were not generated by simple DNA deletion. The constraint to maintain the novel DNA sequences coamplified with c-myc gene DNA suggests that these sequences may play some role in maintaining the growth potential and/or differentiation capacity of the HL60 cells.

Chromosomes, Human, Pair 8

[Helicobacter pylori and ulcer disease: diagnosis and treatment 1995].

The association between Helicobacter pylori infection and type-B gastritis as well as peptic ulcer disease is established. Eradication of this organism effectively eliminates ulcer recurrence. Furthermore, seroepidemiologic studies suggest a role for Helicobacter pylori in gastric malignancies. For patients with peptic ulcer disease, the determination of Helicobacter pylori infection is recommended and, if positive, should be followed by an eradication therapy.

Algorithms

[Effect of non-steroidal antirheumatic agents on the gastrointestinal tract: clinical aspects and pathophysiology].

The major gastrointestinal side effects of non-steroidal antiinflammatory drugs (NSAID) mainly occur in the stomach and duodenum. Acute mucosal lesions are almost always seen but only 50% of patients complain of upper abdominal discomfort. NSAIDs elevate the risk of ulcerations of the stomach or duodenum 4 to 5 fold. Side effects in the small bowel are due to elevated intestinal permeability which may lead to inflammatory reactions, chronic blood loss and iron deficiency. Ulceration, perforation and strictures of the small and large bowel may also occur in rare cases.

Anti-Inflammatory Agents, Non-Steroidal

[Prevention and therapy of NSAID-induced ulcers: fact versus myth].

Non-steroidal antiinflammatory drugs (NSAIDs) are responsible for dyspeptic symptoms in more than 50% of patients. Symptomatic ulcers and ulcer complications occur in less than 5%. In order to avoid these complications during prolonged treatment, the lowest possible NSAID dose should be chosen. Furthermore, NSAIDs can often be replaced by paracetamol. Prophylaxis of NSAIDs and ulcers with misoprostol is only indicated in a small risk group of patients (eg: advanced age, history of ulcer and for gastrointestinal bleeding, concurrent corticosteroid treatment and significant comorbidity) and only if NSAIDs are given for several months. NSAIDs-induced ulcers should be treated with omeprazole in a dose of 20-40 mg daily.

Anti-Inflammatory Agents, Non-Steroidal

[Detection of RET-proto-oncogene mutations in the diagnosis of Type 2 endocrine neoplasia (MEN 2)].

We have analyzed 95 blood- and 25 paraffin-derived DNA samples of 120 individuals from Switzerland (MEN 2 family members and patients with medullary thyroid carcinoma or pheochromocytoma) for the presence of RET protooncogene mutations in exons 10, 11, 13, 14 and 16, where recently germline point mutations have been identified in more than 95% of patients with MEN 2A, familial medullary thyroid carcinoma (FMTC) and MEN 2B. Molecular DNA screening of samples was performed by non-radioactive single strand conformation polymorphism (SSCP) and heteroduplex gel electrophoresis method followed by mutation analysis of PCR products by direct cycle sequencing using an automated DNA sequencer. We identified 12 MEN 2A/FMSC and 6 MEN 2B families with 29 gene carriers. Ten different types of mutations were identified in the MEN 2A/FMTC families (620 Cys-->Arg, 618 Cys-->Ser, Gly, 611 Cys-->Tyr; 634 Cys-->Arg, Tyr, Trp, Phe, Ser, Gly) and all 6 MEN 2B families had a 918 Met-->Thr point mutation. Our results indicate that PCR-based DNA testing for RET point mutations is a rapid, accurate and reproducible method of identifying MEN 2 gene carriers using blood or tissue DNA. Early detection of gene carriers allows preventive thyroidectomy without neck dissection or parathyroid transplantation, and non-gene carriers can be released from biochemical testing. Furthermore, it is shown that the distribution and localization of RET mutations in MEN 2 families from Switzerland concur with combined results of larger series and that a "founder effect" of MEN 2 can be excluded for this country.

Adrenal Gland Neoplasms

Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta.

Women are particularly susceptible to malaria during first and second pregnancies, even though they may have developed immunity over years of residence in endemic areas. Plasmodium falciparum-infected red blood cells (IRBCs) were obtained from human placentas. These IRBCs bound to purified chondroitin sulfate A (CSA) but not to other extracellular matrix proteins or to other known IRBC receptors. IRBCs from nonpregnant donors did not bind to CSA. Placental IRBCs adhered to sections of fresh-frozen human placenta with an anatomic distribution similar to that of naturally infected placentas, and this adhesion was competitively inhibited by purified CSA. Thus, adhesion to CSA appears to select for a subpopulation of parasites that causes maternal malaria.

Adhesiveness

cDNA sequence analysis and expression of the expression of the ribosomal protein S24 during oogenesis and embryonic development of the sea urchin Paracentrotus lividus.

A gene for the Paracentrotus lividus ribosomal protein S24, called P1-S24, has been isolated and sequenced. Ribosomal protein P1-S24 consists 130 amino acids and has a molecular weight of 14869 Da. Sequence analysis shows a high percentage (90%) identity with the corresponding gene of Strongylocentrotus purpuratus. Hybridization of the cDNA to digested sperm DNA suggests that P1-S24 is represented in no more than two copies. Studies of the temporal expression of P1-S24 gene indicate a good correlation between this and the expression of the rRNA genes both during oogenesis and embryonic development.

Amino Acid Sequence