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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 73 records · Page 4Linked to original sources

Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia.

BACKGROUND/AIMS: We aimed to evaluate the role of fat and cholecystokinin (CCK) in the pathophysiology of functional dyspepsia (FD) by investigating symptoms and plasma CCK levels following increasing doses of duodenal lipid during gastric distension, and the effect of CCK-A receptor blockade. SUBJECTS/METHODS: In study A, six FD patients were studied on three occasions during duodenal infusion of saline or lipid (1.1 (L-1) or 2 kcal/min (L-2)) and proximal gastric distensions. Six healthy subjects were also studied as controls during L-2 only. In study B, the effect of the CCK-A antagonist dexloxiglumide (5 mg/kg/h) on L-2 induced symptoms was studied in 12 FD patients. Changes in gastric volume at minimal distending pressure and plasma CCK (study A) were assessed, gastric distensions were performed using a barostat, and dyspeptic symptoms were monitored. RESULTS: Lipid increased gastric volume compared with saline (DeltaV (ml): saline 15 (20), L-1 122 (42), L-2 114 (28)) in patients and even more so in controls (221 (37); p<0.05). During distensions, symptoms were greater during L-2 than during saline or L-1, and greater in patients than in controls, while gastric compliance was smaller in patients than in controls (p<0.05). Lipid increased plasma CCK levels in patients and controls (p>0.05). Dexloxiglumide abolished the increase in gastric volume (DeltaV (ml): dexloxiglumide 17 (9), placebo 186 (49)) and dyspeptic symptoms (sum of scores: dexloxiglumide 24 (7), placebo 44 (19)) during duodenal lipid infusion. Dexloxiglumide also reduced gastric compliance (ml/mm Hg: dexloxiglumide 51 (7), placebo 72 (11)) and symptoms (sum of scores: dexloxiglumide 101 (17), placebo 154 (21)) during gastric distension. CONCLUSION: CCK-A receptors are involved in the generation of dyspeptic symptoms by duodenal lipid during gastric distension.

Adult↗

Modulation of gastric distension-induced sensations by small intestinal receptors.

Duodenal lipid exacerbates gastrointestinal sensations during gastric distension. Using luminal application of the local anesthetic benzocaine, we investigated the role of intestinal receptors in the induction of these sensations. Nine healthy subjects were studied on five occasions, during which isotonic saline or 20% lipid (2 kcal/min), combined with (duodenal or jejunal) 0.75% benzocaine or vehicle at 2.5 ml/min, was infused intraduodenally before and during gastric distension. Intragastric pressures and volumes, gastrointestinal sensations, and plasma CCK levels were determined. Duodenal lipid combined with vehicle increased gastric volume (in ml: saline, -10 +/- 18; lipid/vehicle, 237 +/- 30) and plasma CCK [mean levels (pmol/l): saline, 2.0 +/- 0. 2; lipid/vehicle, 8.0 +/- 1.6] and, during distensions, induced nausea (scores: saline, 3 +/- 2: lipid/vehicle, 58 +/- 19) and decreased pressures at which fullness and discomfort occurred. Duodenal but not jejunal benzocaine attenuated the effect of lipid on gastric volume, plasma CCK, and nausea during distension (135 +/- 38 and 216 +/- 40 ml, 4.6 +/- 0.6 pmol/l and not assessed, and 37 +/- 12 and 64 +/- 21 for lipid + duodenal benzocaine and lipid + jejunal benzocaine, respectively) and on pressures for sensations. In conclusion, intestinal receptors modulate gastrointestinal sensations associated with duodenal lipid and gastric distension. There is also the potential for local neural mechanisms to regulate CCK release and thereby reduce afferent activation indirectly.

Adult↗

Pressure-geometry relationship in the antroduodenal region in humans.

Understanding of the control mechanisms underlying gastric motor function is still limited. The aim of the present study was to evaluate antral pressure-geometry relationships during gastric emptying slowed by intraduodenal nutrient infusion and enhanced by erythromycin. In seven healthy subjects, antral contractile activity was assessed by combined dynamic magnetic resonance imaging and antroduodenal high-resolution manometry. After intragastric administration of a 20% glucose solution (750 ml), gastric motility and emptying were recorded during intraduodenal nutrient infusion alone and, subsequently, combined with intravenous erythromycin. Before erythromycin, contraction waves were antegrade (propagation speed: 2.7 +/- 1.7 mm/s; lumen occlusion: 47 +/- 14%). Eighty-two percent (51/62) of contraction waves were detected manometrically. Fifty-four percent of contractile events (254/473) were associated with a detectable pressure event. Pressure and the degree of lumen occlusion were only weakly correlated (r(2) = 0.02; P = 0.026). After erythromycin, episodes of strong antroduodenal contractions were observed. In conclusion, antral contractions alone do not reliably predict gastric emptying. Erythromycin induces strong antroduodenal contractions not necessarily associated with fast emptying. Finally, manometry reliably detects ~80% of contraction waves, but conclusions from manometry regarding actual contractile activity must be made with care.

Duodenum↗

Does the laparoscopic approach significantly affect cardiac functions in laparoscopic surgery? Pilot study in non-obese and morbidly obese patients.

BACKGROUND: Laparoscopy in bariatric surgery represents a modern method generally associated with lower morbidity and mortality, compared with the traditional surgical approach. However, in patients with impaired cardiovascular function, the laparoscopic approach is limited by the potential adverse hemodynamic impact. We assessed the influence of some laparoscopic procedures on selected cardiac functions in significantly obese patients and in subjects with normal body weight, using transesophageal echocardiography (TEE). PATIENTS AND METHODS: Six subjects with normal body weight (mean BMI 25.3 +/- 3.6 kg/m2), and six patients undergoing laparoscopic gastric banding for morbid obesity (mean BMI 45.8 +/- 7.5 kg/m2) were studied. Heart rate (HR), blood pressure (BP), ejection fraction, cardiac output (CO) and transmitral flow were measured. Parameters were recorded at baseline before the operation (BL), after installation of capnoperitoneum (CP), and after positioning the patient for surgery (SP). RESULTS: Compared to BL, CP and SP were characterized by an increase in HR and BP in both groups of patients. As ejection fraction did not change significantly, the HR changes were accompanied by an increase in CO: (BL 5.8 +/- 2.2 l/min, CP 6.5 +/- 2.6 l/min, SP 6.7 +/- 2.7 l/min, p < 0.05 BL vs CP and SP). Transmitral flow parameters did not change significantly. Hemodynamic changes in subgroups with normal body build and in the obese patients were comparable. There was an increase in CO and pressure-rate product in obese individuals. CONCLUSIONS: Our results suggest that the hemodynamic response to laparoscopic surgery is characterized by an increase in CO (due to increased HR) and BP. In subjects without a manifest cardiovascular disease, neither systolic nor diastolic performance was significantly affected by the introduction of capnoperitoneum and positioning of the patient for surgery. Similar results were observed in obese and non-obese subjects. Phase II of this on-going study is focusing on impact and safety of laparoscopy in obese patients with known cardiovascular disease.

Adult↗

Leptin as an acute phase reactant after non-adjustable laparoscopic gastric banding.

BACKGROUND: Leptin is a hormone that regulates food intake; its concentrations are elevated in the majority of obese individuals. During inflammation, plasma leptin is usually increased and may contribute to the anorexia and cachexia of infection. The purpose of this study was to characterize the dynamics of circulating leptin in the early postoperative period in relation to the acute phase response in extremely obese patients undergoing laparoscopic non-adjustable gastric banding (LNAGB). We compared plasma leptin changes with 4 proinflammatory cytokines and BMI. METHODS: The prospective study was performed on 18 patients with 3rd degree obesity. Plasma concentration of leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, soluble IL-2 receptor (sIL-2R), and IL-6 were estimated before operation and 24, 48, and 72 h after NALGB. RESULTS: We demonstrate statistically significant elevation of plasma leptin concentration (32.2 +/- 10.2 micrograms/l) 24 h after operation compared with preoperative status (18.4 +/- 5.2 micrograms/l, p < 0.05). There was diminished correlation of plasma leptin and BMI in this period. Leptin levels +48 and +72 h after banding quickly returned to preoperative levels. The regression coefficient was the highest for leptin and TNF-alpha 24 h after surgery (r = 0.40, p < 0.05), and for leptin and IL-6 24 h after surgery (r = 0.29, p < 0.05). There was no significant correlation between leptin and IL-1 and between leptin and sIL-2R respectively. CONCLUSIONS: During the non-infectious stress response (as with abdominal surgery), leptin shows itself as an acute phase reactant. Proinflammatory cytokines can be the main regulatory factors of leptin in this period. Significant correlation between leptin and TNF-alpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNF-alpha can be a crucial regulator of leptin generation in the early postoperative period.

Acute-Phase Reaction↗

[The development of bariatric surgery and the role of the First Surgical Clinic of the General Medical School Hospital and the First Medical School of Charles University in Prague in this specialty].

The authors discuss the development of bariatric surgery in Europe and the USA from its beginnings at the onset of the fifties. More detailed attention is paid in particular to the development of the method of gastric bandings and the role at the First Surgical Department in this field in "classical" as well as miniinvasive surgery. Results of gastric banding are summarized in 683 patients operated since 1983, in particular the numbers of early and late complications after laparotomies and laparoscopic operations, similarly as complications which are directly associated with gastric banding itself. In the conclusion it is stated that the First Surgical Department of the General Faculty Hospital and First Medical Faculty Charles University in Prague belong as regards their results in surgical treatment of obese subjects and the position in the field of bariatric surgery on an international scale to the foremost departments in this field worldwide.

Czech Republic↗

[Percutaneous electrogastrography in the perioperative period in laparoscopic gastric banding at the First Surgical Clinic of the General Faculty Hospital in Prague].

Percutaneous electrogastrography (EGG) is a method which makes non-invasive follow-up of the myoelectric gastric activity possible. The authors present the results of assessment of the myoelectric gastric activity during the perioperative period in patients undergoing, at the First Surgical Clinic General Faculty Hospital, laparoscopic non-adjustable gastric banding. The data were recorded using a Microdigittrapper and evaluated using spectral analysis and Fourier's transformation. The authors mention also briefly conditions which must be met to ensure the study, and the physiological and pathophysiological background of the method. In 14 patients the ECG record was made 24 hours prior to surgery and then 5 hours, 24 and 48 hours after surgery on fasting and after a fluid bolus. The assembled results of the dynamics of perioperative changes on the EGG were compared with results obtained in a group of healthy volunteers. The most frequent finding during the early postoperative period was bradygastria, the return to preoperative values occurred on average 48 hours after surgery. Percutaneous electrogastrography is a non-invasive method which can provide the surgeon during the early postoperative period with information on myoelectric gastric activity.

Adult↗

[History and present status of surgical treatment of morbid obesity].

Problems of extreme and morbid obesity take on constantly considerable relevance in 21st century. The prevalence of the obesity (BMI--Body Mass Index > 30 kg/m2) is still on the increase worldwide. In the Czech Republic approximately 16% of male and 20% of female in the age of 20-65 years are obese (BMI > 30 kg/m2). To begin with the effective cure is always indicate in case of the obesity over BMI > 30. The bariatric surgery is indicating in the occurrence of failure of conservative care of morbidly obese patients with recurrences of overweight. The morbid obesity with serious associate health complications often represents the vital danger of the patient's life. The development of the bariatric surgery passed from resections of the bowel, gastric bypasses, biliopancreatic diversions, horizontal gastroplasties to in the present the most frequently used methods as the vertical bandage gastroplasty (VBG) and the gastric bandage (GB). The standard applications of the miniinvasive laparoscopic methods with significant decrease of postoperative complications radical changes of the bariatric surgery in the present years.

Biliopancreatic Diversion↗

[Surgical treatment of morbid obesity--gastric banding].

Approximately 16% of male and 20% of female of the age from 20 to 65 years are obese in the Czech Republic. The restrictive bariatric procedure of stomach--gastric banding (GB) is one of possibilities to cure the morbid obese patients after failure of conservative therapy. The ratio of complications (5-18%) after GB presenting in various papers is comparable with the ratio of complications (4-23%) in others bariatric procedures. From 1993 to 1999, 517 morbid obese patients (mean BMI 51.1) underwent laparoscopic nonadjustable gastric banding (LNGB) at 1st Surgical Department, Charles University Teaching Faculty Hospital in Prague. As the early complications (during hospitalization) offered swelling of the gastric mucous in the place of GB in 5.6% (n = 29), the oesophagitis, the gastritis or the gastric ulcer in 1.5% (n = 9) and perforation of the stomach wall in 0.6% (n = 3). As the late complications offered the bleeding from peptic ulcer in 0.4% (n = 2), sequential migration of gastric band through the stomach wall inside in 0.6% (n = 3) and the slippage of anterior stomach wall or the dilatation of the pouch above gastric bandage in 5.1% (n = 26). The serious complications in 6.3% (n = 32) claimed surgical procedures. Other complications in 7.5% (n = 39) have been treated conservatively. The 86% (n = 446) of obese patients after LNGB were without complications.

Adult↗

Phase I chemotherapy study of biochemical modulation of folinic acid and fluorouracil by gemcitabine in patients with solid tumor malignancies.

PURPOSE: This phase I biochemical modulation study evaluated the maximum-tolerated dose (MTD), toxicity, and effectiveness of the combination of folinic acid (FA)/fluorouracil (5-FU) followed by escalated dose levels of gemcitabine (FFG) in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were refractory to primary treatment and/or without effective treatment options. Twenty-eight patients received an intravenous (IV) infusion of FA 100 mg/m(2) over 1 hour and a 5-FU 450 mg/m(2) IV bolus in the middle of the FA infusion. After the FA infusion, gemcitabine was administered at a steady rate of infusion of 10 mg/m(2)/min over initially 30 minutes and with increases of an additional 15 minutes at each given level. One cycle consisted of six weekly treatments followed by a 2-week rest. RESULTS: The MTD of gemcitabine was established at 900 mg/m(2) given over 90 minutes. Eight patients of 21 with metastatic colorectal cancer achieved responses (one complete response; seven partial responses), for a response rate of 38%. Responses were seen across the gemcitabine doses of 300 to 900 mg/m(2). One patient had prior treatment with FA/5-FU for advanced disease. Patients with colorectal carcinoma had a median survival of 18 months, and the patient with lung carcinoma has been alive for 24+ months. CONCLUSION: The combination chemotherapy of FFG was well tolerated and may benefit patients with advanced colorectal carcinoma. A phase II evaluation in this patient population is in progress.

Adult↗

[Cyanosis and cirrhosis of liver: hepatopulmonary syndrome].

A 66-year-old man with Child-B alcoholic cirrhosis presented with melaena due to hemorrhagic gastritis. Clinical examination revealed cyanosis and clubbing accompanied by severe hypoxaemia without signs of obstructive or restrictive lung disease. Contrast-enhanced echocardiography showed right to left shunt due to intrapulmonary shunting leading to the diagnosis of hepatopulmonary syndrome. Hypoxaemia in patients suffering from chronic liver disease can have different causes but in the presence of cyanosis and clubbing without signs of lung disease the hepatopulmonary syndrome should be suspected. When presence of intrapulmonary shunts has been proven by contrast-enhanced echocardiography, a 100% oxygen test can determine the need for pulmonary angiography and thus determine the indication for interventional therapy or liver transplantation. The patient described was treated supportively with long-term oxygen therapy 6 l/min. Three months later his clinical condition was stable. An attempt to reduce the need for nasal oxygen failed.

Aged↗

Isolation and genomic analysis of the human surf-6 gene: a member of the Surfeit locus.

The human Surfeit locus contains at least six tightly clustered genes (Surf-1 to Surf-6) of which five (Surf-1 to Surf-5) have been characterised and found not to share any sequence homology. The organisation and juxtaposition of the Surfeit genes are conserved between human and mouse. The Surf-6 gene that encodes a novel nucleolar-matrix protein with nucleic-acid binding properties has been characterised in mouse. In this work, we have isolated and analysed the human Surf-6 homologue and determined its genomic organisation in the Surfeit locus. The human Surf-6 gene has five exons spread over a distance of 4.3kb and has features of a housekeeping gene being ubiquitously expressed, having its 5' end located within a CpG rich island and lacking a canonical TATA box. The intragenic region between the 3' end of the Surf-5 gene and the 5' end of the Surf-6 gene is 3.2kb and contains a pseudogene of the ribosomal protein gene rpL21. The putative human Surf-6 protein is 361 amino acids long and includes motifs found in both the mouse and fish Surf-6 homologues, which may underlie the functions of Surf-6. Three amino acid polymorphisms have been detected at codons 163, 175 and 311 by SSCP analysis.

Alleles↗

Cost analysis of antibiotic prophylaxis for PEG.

BACKGROUND: There are conflicting recommendations regarding the prophylactic use of antibiotics in patients undergoing placement of percutaneous endoscopic gastrostomy tubes. The purpose of this decision analysis was to assess the cost-effectiveness of antibiotic prophylaxis in percutaneous endoscopic gastrostomy. METHODS: A decision tree was modeled using the data of 7 published prospective placebo-controlled trials. Infectious complications were classified as grade I (requiring local care), grade II (requiring intravenous antibiotics), or grade III (requiring surgery). Medication costs were estimated from the United States average wholesale prices of the 1998 Red Book. Physician and facility costs were estimated based on the 1998 Medicare costs. A one-way sensitivity analysis was performed by varying the probability rates of the complications associated with percutaneous endoscopic gastrostomy and the costs of their treatment. RESULTS: The average cost of prophylactic antibiotics was $13.10. Antibiotic prophylaxis led to expected cost savings of $76.72 per percutaneous endoscopic gastrostomy. A sensitivity analysis suggested that antibiotic prophylaxis for percutaneous endoscopic gastrostomy was the preferred strategy unless the average probability of grade III complications dropped below an improbably low threshold value of 0.09%. CONCLUSION: Antibiotic prophylaxis in percutaneous endoscopic gastrostomy is a cost-effective strategy.

Antibiotic Prophylaxis↗

In-vivo real-time magnetic resonance monitoring of endoscopic laser applications in the porcine gastrointestinal tract.

BACKGROUND AND STUDY AIMS: Endoscopic laser therapy involves a risk of perforation, mainly because the depth of tissue destruction is not visible. Magnetic resonance (MR) imaging is capable of showing temperature changes, and is therefore suitable for monitoring thermal therapies such as laser. This animal study assessed the feasibility of real-time MR monitoring of endoscopic laser applications in the gastrointestinal tract. MATERIALS AND METHODS: The procedures were carried out using an MR-compatible endoscope in three live pigs in a 0.5-Tesla interventional MR system. Nd:YAG laser applications were performed in the lower gastrointestinal tract (n = 7) and upper gastrointestinal tract (n = 5), and were monitored using real-time color-coded T1-weighted gradient echo sequences. The postmortem macroscopic tissue coagulation sizes were compared with the lesion diameters seen on real-time MR. RESULTS: The endoscope did not cause any artifacts during continuous MR imaging. Ten of the twelve laser lesions were visible with temperature-sensitive MR imaging, and their sizes correlated well with the diameters of the postmortem macroscopic coagulation zones (r = 0.76, P = 0.009). Two laser lesions were not visible on MR due to technical limitations inherent with the healthy animal model. CONCLUSIONS: The formation of endoscopic laser lesions in the porcine gastrointestinal tract can be accurately visualized using real-time temperature-sensitive MR imaging. This new technique has the potential to spare healthy tissue while ensuring full treatment coverage of the targeted lesion with fewer therapy sessions.

Animals↗