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Biomedical subjects

M Fried

Publications and source records attributed to M Fried.

At least 145 records · Page 8Linked to original sources

Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial.

PURPOSE: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. RESULTS: Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. CONCLUSION: TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.

Adult↗

The role of laparoscopy in the treatment of morbid obesity.

BACKGROUND: Laparoscopic surgery was established as a regular surgical technique 11 years ago. There are still some controversies among surgeons about the benefits of this method. METHOD: A retrospective 3-year analysis of immediate and long-term complication rates, hospitalization length, and weight loss following laparotomic and laparoscopic nonadjustable gastric banding in 150 and 145 patients, respectively, was undertaken. Some of the criteria usually used for comparison of results in laparotomy and laparoscopy in general surgery were used in this analysis as background for the comparison of the two groups of obese patients. One example of the different results of the laparotomic and laparoscopic approaches in bariatric surgery was provided by obese monozygotic twins who underwent surgery the same day in our department, one by laparotomy and the other by laparoscopy. There was a significant difference in hospitalization length, in required postoperative analgesia, and in levels of c-reactive protein. RESULTS: There was no statistical difference in intraoperative complication rates in the two groups, but there was a significant difference in immediate and long-term postoperative complications of wound discharge and incisional hernias. The obese twins illustrate the significant difference in postoperative c-reactive protein levels and in length of operating time and hospitalization in favor of laparoscopy, and this difference supports our results in much larger groups of genetically unrelated patients who were studied. CONCLUSION: At the end of the 10-year period of laparoscopic surgery for bariatric procedures, the results were impressive. The laparoscopic approach to surgery for morbid obesity was of considerable value in terms of low morbidity and mortality.

Adult↗

Assessment of the outcome of laparoscopic nonadjustable gastric banding and stoma adjustable gastric banding: surgeon's and patient's view.

BACKGROUND: The results of nonadjustable gastric banding (NAGB) and stoma adjustable gastric banding (SAGB) in the treatment of morbid obesity are compared. Of 300 patients operated laparoscopically with NAGB since 1993 and of 25 with SAGB since 1994, 65 in the NAGB and 11 in the SAGB group were available for a 3-year follow-up study. METHODS: For assessment of the outcome of our laparoscopic approach in terms of weight loss, length of hospitalization, immediate and late postoperative wound complications, postoperative changes in the band and pouch area, were compared in patients from both groups. The patient's opinion on the outcome of the operation and the quality of postoperative digestion was recorded. RESULTS: There was no significant difference in the length of hospital stay and wound complication rate in the two groups or the weight loss at 36 months after surgery. There was a statistically significant lower incidence of postoperative food intolerance and vomiting and a lower rate of immediate and long-term reoperation rate in the SAGB group. CONCLUSION: SAGB is a method with less postoperative complications in food intolerance and vomiting in comparison with NAGB.

Follow-Up Studies↗

Clinical guidelines for diagnosis and management of obesity in the Czech Republic.

Guidelines for the management of obesity include recommendation about diet, exercise, behavioral modification, drug therapy and bariatric surgery in the comprehensive management of an obese patient. It is emphasized that the treatment of obesity should be individually tailored according to the age of the patient, degree and phase of obesity, body fat distribution and an expression of risk factors and comorbidities. The new realistic goals in obesity management do not focus on the weight loss per se but mainly on the risk factors reduction which accompanies even modest weight loss. The system of obesity management introduced in the Czech Republic includes obesity management centres attached to major teaching hospitals, obesity out-patient clinics (led by an obesity specialist), primary care physicians and weight reduction clubs. Postgraduate training in obesity management should be recognized by health authorities as a function specialty. A time demanding therapeutic strategy in obesity management should be taken into account by both health policy makers and health insurance companies.

Czech Republic↗

Long-term results of aggressive weight reduction treatment.

We have checked weight changes in 11 patients eight years after 2-weeks in-patient weight reduction treatment and weight changes of another group of 11 patients three years after gastric banding. Using multiple linear regression we've looked for factors which could influence the aforementioned weight changes. For weight reduction regimens we confirmed only the following connection: BMI reduction in 8 years = 12.256 - 2.827 x BMI reduction in 2 weeks. For gastric banding it was: BMI reduction in 3 years = -7.880 + 2.383 x BMI reduction in 6 months. We therefore conclude that the long term effects of reduction regimens is not influenced by any hormonal or metabolic characteristics of the patient, but can be predicted by the early weight loss of the patient. Patients who lose too much during the reduction regimen will find it more difficult to keep the weight down, whereas patients who lose weight rapidly after gastric banding have the best long term prognosis.

Adult↗

Long-term treatment of obesity in the obesity unit.

A group of 318 obese patients followed-up at the Obesity Unit in Prague in 1995-1997 was included into a study. Their treatment was based on the standard combination of a weight reduction diet, physical activity and behavioural intervention. In patients with more severe degrees of óbesity VLCD in one daily portion, pharmacotherapy, in-patient regimen lasting 24 days, including VLCD (1,500 kJ/day), exercise and group psychotherapy; or bariatric surgery (mostly laparoscopic gastric banding) were used, if necessary. Patients were divided into two groups according to their compliance to the weight reducing regimen. Group A dropped out before 2 years of follow-up, group B was followed-up 2 years or more. The groups did not differ significantly in their mean age, initial body weight, initial BMI and fat content and in percentage of males and females. Weight, BMI, fat content, essential anthropometric indices (waist circumference, WHR, subscapular and triceps skinfolds) and blood pressure are presented in this study. The maximum weight loss was significantly higher in group B. We did not find any other significant differences between group A and group B. The most significant predictor of compliance expressed as duration of follow-up (evaluated by multiple regression with stepwise variable selection) was the maximum BMI decrease (p < 0.005). The most significant predictors of the weight loss at the end of the follow-up were maximum weight loss and maximum decrease of BMI (p < 0.001). Family history of obesity (obese one or both parents) was significantly more often in group B (p < 0.05). This trend was expressed predominantly in females (p < 0.01), where also family history of obesity in mother was significantly more often in group B (p < 0.05). The frequency of methods used in individual patients was estimated. Standard combination of diet, enhanced physical activity and behavioural intervention was used in all patients. All other methods were used significantly more frequently in group B. In group A in-patient treatment was significantly more often used in men. The in-patient treatment promotes the compliance with the therapeutic regimen in women significantly more effectively than in men.

Adult↗

Bariatric surgery at First Surgical Department in Prague--Czech Republic--history and some technical aspects of the procedures.

BACKGROUND: There is an increasing number of obese population in the Czech Republic in last twenty years. In 1983 we were one of the first surgical departments in the country who started with bariatric surgery on regular basis. METHODS: In the period from 1983 to 1986 we performed vertical banded gastroplasties (VBG) in our department. Because of high rate of various complications arising both from the stomach and from the wound we switched in 1986 to less "aggressive" non-adjustable gastric banding. In 1993 we performed the first round the world laparoscopic non-adjustable banding. In 1994 we started with laparoscopic placement of adjustable gastric bands. RESULTS: In the group of 52 patients who underwent VBG and were followed-up, acceptable weight loss results (-40.5 kg) were achieved in 24 months following surgery. The postoperative complications were high, 17.3% of gastric staple line disruption and 15.3% of wound complications--incisional hernias, discharge etc. Since 1986 we performed non-adjustable gastric banding in 150 patients with the weight loss of -38.4 kg in 24 months following surgery. There was no change in the wound complications rate, but the complications arising from the stomach and the band decreased to 6.3%. Since June 1993 we performed 268 procedures laparoscopically either with non-adjustable bands or since 1994 with the adjustable bands. The wound complication rate decreased to 0.9% and one complication (6.6%) was connected with the adjustable band. CONCLUSIONS: Because of the high rate of postoperative complications connected in our experience with VBG we started with gastric bandings in 1986. Since than the number of complications arising from the stomach decreased substantially. With the laparoscopic technique used in bariatric surgery there was another decrease in wound healing problems. With the adjustable GB a significant decrease in the stomach related complications occurred. Shorter hospital stay is related to the laparoscopic technique. The long-term weight loss results are not significantly different among the procedures mentioned above.

Gastroplasty↗

p53 in polyoma virus transformed REF52 cells.

While cellular transformation by small DNA tumour viruses usually involves targeting the product of the p53 tumour suppressor gene by a virally encoded protein, none of the three polyoma virus (Py) specified T antigens have been observed to interact with p53. We show that primary mouse embryo fibroblasts and REF52 cells, which resemble primary cells in requiring co-operating oncogenes for transformation, cannot be transformed by the Py oncogene, middle T-antigen (PyMT), alone. These cells can be transformed by the complete Py early region, which encodes the Py large, middle and small T-antigens. We find that PyMT can transform rodent cells lacking a functional p53 protein (p53 null mouse embryo fibroblasts and DN-REF52 cells which contain a dominant negative p53). In Py transformed REF52 cells (Py-REF52) there is no significant accumulation of p53 protein, as opposed to SV40 transformed REF52 cells (SV-REF52) in which the amount of steady state p53 protein is elevated. However accumulation of p53 is observed following exposure of Py-REF52 cells to u.v. Treatment of Py-REF52 cells with X-rays results in a rapid increase in the levels of the p53-induced proteins p21/WAF1 and MDM2. In untransformed REF52 cells, X-irradiation causes p53 activation, which results in induction of both G1/S and G2/M blocks. In SV-REF52 and DN-REF52 cells, p53 abrogation results in the absence of both the G1/S and G2/M blocks. Only the absence of a G1/S block is observed in Py-REF52 cells exposed to X-irradiation. Together these results indicate that in contrast to most other DNA tumour viruses, Py does not appear to interfere with the DNA damage induced transactivation activities of the p53 protein but absence of a functional p53 protein can mediate transformation by the PyMT oncogene in the absence of other co-operating oncogenes. Possible modes of transformation by Py are discussed.

Animals↗

Preliminary assessment of three-dimensional magnetic resonance imaging for various colonic disorders.

BACKGROUND: Improvements in magnetic resonance imaging (MRI) technology have enabled the acquisition of three-dimensional MRI datasets in a single breath hold. We adopted this technique to make a three dimensional intraluminal and extraluminal assessment of the colon in three patients with various colonic disorders. METHODS: One patient was studied after having a double-contrast barium enema. Two patients had MRI scans after colonoscopy, which showed three colonic tumours in one and multiple polyps in the ascending colon of the other. The process of rectal filling with 1.5-2.0 L water mixed with 15-20 mL 0.5 mol/L gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) was monitored with MR fluoroscopic sequence. Three-dimensional datasets of the contrast-filled colon were taken with patients in prone (before and after intravenous administration of 0.1 mmol/kg bodyweight Gd-DTPA) and supine positions. 64 sections with a voxel-resolution of 2.0 x 2.0 x 1.25 mm3-were taken during a 28 s breath hold. Three-dimensional maximum intensity projection, multiplanar reconstruction, and virtual colonoscopic images of the colon were created from these. FINDINGS: Analysis of the coronal source images in conjunction with multiplanar reconstructions revealed all relevant abnormalities, including diverticula, carcinomas, and polyps. Three dimensional maximum-intensity projections gave a morphological overview of the whole colon. Targeted projections, made up of a limited number of coronal source images, showed diverticula and smaller polyps more clearly. After patients were given intravenous contrast all colonic mass lesions were enhanced. Datasets obtained in prone patients gave the best intraluminal views of the colon. Virtual magnetic resonance colonoscopy showed colonic haustra as well as the ileocaecal valve, but did not show clearly the diverticula. All intraluminal mass lesions, on the other hand, were easy to see. INTERPRETATION: The potential of three-dimensional colonic MRI to provide accurate, minimally invasive, cost-effective polyp screening, as well as comprehensive colonic tumour staging, warrants further investigation.

Aged↗

[Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer].

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters.

BACKGROUND: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS: Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS: In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopist's clinical judgement.

Adult↗

Underutilization of upper gastrointestinal endoscopy.

BACKGROUND & AIMS: Efforts to reduce costs in health care may raise concerns about underuse of medical procedures. This study prospectively assessed underuse of upper gastrointestinal endoscopy in a cohort of patients in whom we have recently published data on overuse of endoscopy. METHODS: Underuse was identified by formal necessity criteria for endoscopy, obtained by an explicit panel process. Outpatients were consecutively included in two clinical settings. Setting A consisted of 20 primary care physicians and 7215 patient visits that occurred within 1 month. Setting B consisted of 920 visits that occurred during 3 weeks at an outpatient clinic. RESULTS: During these 8135 visits, 611 patients complained of upper digestive symptoms; 63 of them underwent endoscopy. Underuse was identified in 72 patients (11.8%). The two clinical situations mainly responsible for underuse of endoscopy were uninvestigated peptic symptoms resistant to treatment and dysphagia. At first follow-up, 29 of the patients with initial underuse still fulfilled criteria of necessity (underuse rate, 4.7%). One-year follow-up showed underuse of endoscopy in 5 patients. CONCLUSIONS: This prospective evidence shows that underuse of a medical procedure exists. The estimated overuse and underuse of endoscopy in this cohort were approximately equal (5%). Improving quality of care will require reductions of both overuse and underuse of medical procedures.

Adolescent↗

The comparative genomic structure and sequence of the surfeit gene homologs in the puffer fish Fugu rubripes and their association with CpG-rich islands.

The puffer fish Fugu rubripes (Fugu) has a compact genome approximately one-seventh the size of man, mainly owing to small intron size and the presence of few dispersed repetitive DNA elements, which greatly facilitates the study of its genes at the genomic level. It has been shown previously that, whereas the Surfeit genes are tightly clustered at a single locus in mammals and birds, the genes are found at three separate loci in the Fugu genome. Here, Fugu gene homologs of all six Surfeit genes (Surf-1 to Surf-6) have been cloned and sequenced, and their gene structure has been compared with that of their mammalian and avian homologs. The predicted protein products of each gene are well conserved between vertebrate species, and in most cases their gene structures are identical to their mammalian and avian homologs except for the Fugu Surf-6 gene, which was found to lack an intron present in the mouse gene. In addition, we have identified conserved regulatory elements at the 5' and 3' ends of the Surf-3/rpL7a gene by comparison with the mammalian and chicken Surf-3/rpL7a gene homologs, including the presence of a polypyrimidine tract at the extreme 5' end of this ribosomal protein gene. The Fugu Surfeit gene homologs appear to be associated with CpG-rich islands, like the Surfeit genes in higher vertebrates, but these Fugu CpG islands are similar to the nonclassical islands characteristic of other fish species. Our observations support the use of the Fugu genome to study vertebrate gene structure, to predict the structure of mammalian genes, and to identify vertebrate regulatory elements. [The sequence data described in this paper have been submitted to the data library under accession nos. Y15170 (Surf-2, Surf-4), Y15171 (Surf-3, Surf-1, Surf-6), and Y15172 (Surf-5.)]

Amino Acid Sequence↗

Gastroenteropancreatic effects of xenin in the dog.

Xenin is a 25 amino acid peptide detected in the gastric mucosa of various mammals. It has since been found in low concentrations in other tissues. Xenin plasma concentrations increase after meals. The present study reports some gastroenteropancreatic effects of this peptide in the dog. Intravenous infusion of 64 pmol/kg min synthetic xenin significantly inhibited pentagastrin-stimulated gastric acid secretion and stimulated exocrine pancreatic secretion of volume and protein. Further, intravenous infusion of xenin in a dose of 1.0 pmol/kg min stimulated jejunal motility in the anaesthetized dog. An intravenous infusion of 32 pmol/kg min xenin raised plasma concentrations of pancreatic polypeptide, vasoactive intestinal polypeptide, insulin and glucagon. The present experiments therefore indicate manifold bioactive properties of intravenously infused xenin in the dog, with jejunal motility the most sensitive target. Conclusions as to the physiological role of xenin cannot be drawn from the present experiments. The release of other hormonal peptides indicates a complex action of xenin.

Animals↗

Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide.

BACKGROUND: Exogenous cholecystokinin (CCK) inhibits antral motility and slows gastric emptying (GE) but the effect of endogenous CCK on the gastric motor mechanisms responsible for GE remains unclear. METHODS: The effect of the CCK-A antagonist loxiglumide (LOX) on GE and motility was studied using magnetic resonance imaging in six healthy volunteers after ingestion of 500 ml Intralipid 10% (550 kcal). Subjects were studied in the supine position on two occasions during intravenous infusion of LOX (66 mumol/kg/h for 10 min followed by 22 mumol/kg/h) or placebo. GE was determined every 15 minutes using transaxial abdominal scans and motility was studied by means of 120 coronal scans, 1.2 seconds apart. For each coronal image the proximal and distal (antral) diameters were measured at a fixed point in the stomach to determine contraction frequency (ACF) and amplitude (AMP). RESULTS: GE was faster during LOX infusion than placebo (t1/2 31 (22) versus 115 (67) minutes, p < 0.03). There was little variation in the diameter of the proximal stomach with either LOX or placebo. In the distal stomach marked contractile activity was observed during LOX (ACF 2.9 (0.2) versus 1.5 (2.9) during placebo, p < 0.01). AMP also increased during LOX compared with placebo (56 (22)% versus 27 (16)%, p < 0.001). CONCLUSION: The increases in antral motility are likely to contribute to the acceleration of GE and suggest that CCK may regulate GE by acting on the distal stomach although an effect on the proximal stomach cannot be excluded.

Adult↗