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Biomedical subjects

K Simon

Publications and source records attributed to K Simon.

At least 37 records · Page 2Linked to original sources
PubMed1998

Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity.

The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.

Adipose Tissue↗
PubMed1998

Phase I clinical and pharmacokinetic trial of penclomedine using a novel, two-stage trial design for patients with advanced malignancy.

PURPOSE: A novel phase I trial design was used to determine the maximum-tolerated dose (MTD) and pharmacokinetics for penclomedine when administered as an intravenous (i.v.) infusion over 1 hour daily for 5 days, repeated every 28 days. This study also tests the feasibility of a novel two-stage design for phase I trials. PATIENTS AND METHODS: Twenty-eight patients with advanced malignancy who met standard eligibility criteria were treated with i.v. penclomedine. The initial daily dose was 50 mg/m2. Dose escalations were planned using a modified Fibonacci sequence. One patient was enrolled on each dose level during the first stage of this trial. In the second stage, patients were enrolled in cohorts of three, proceeding in an up-and-down manner based on toxicities observed. MTD was determined by logistic regression analysis. Pharmacokinetic assessment was performed during the first cycle of treatment. RESULTS: Dose-limiting toxicities (DLT) observed during this trial were principally neurologic and were self-limited. Although hematologic toxicity was rare, the few patients with significant hematologic changes experienced late nadirs with prolonged time to recovery. The MTD was estimated as 381 mg/m2 (80% CI, 343 to 415 mg/m2). Although there was a long elimination half-life, accumulation of penclomedine over the 5 days of administration was negligible. CONCLUSION: The novel trial design used in this study was safe and appeared effective in limiting the numbers of patients treated at lower-dose levels. Reversible neurotoxicity was dose-limiting. Although the estimated MTD was 381 mg/m2, any dose within the CI would be reasonable for phase II study.

Adult↗
PubMed1998

[Therapeutic efficacy of low-dose alpha interferon therapy in liver cirrhosis associated with HBV].

The aim of this study was the assessment the efficacy and safety of therapy with interferon alpha (Intron A) administered s.c. 3 MU x 3/week for 12 weeks for patients with HBV related liver cirrhosis (Child's class A). Fifteen patients completed therapy and 12 months follow-up. At the end of follow-up sustained response to the therapy, defined by clearance of HBV-DNA, normalization of ALAT activity in serum and improvement in the liver histology was achieved in 46.6% of treated patients. Moreover, among few patients from group of nonresponders (patients without sustained clearance of HBV-DNA) decrease of HBV-DNA level, ALAT activity in serum and improvement in the liver histology were observed. Adverse effects of IFN alpha therapy were typical, but in any case were no necessity terminate the therapy.

Adult↗
PubMed1998

Regression of left ventricular hypertrophy in hypertensive patients after 1 year of treatment with rilmenidine: a double-blind, randomized, controlled (versus nifedipine) study.

OBJECTIVE: To assess the effect of 1-year treatment with rilmenidine, an oxazoline compound that exerts its antihypertensive effects through binding to imidazoline receptors in the brainstem, on left ventricular hypertrophy (LVH) secondary to essential, mild-to-moderate hypertension [supine diastolic blood pressure (DBP)95-115 mmHg]. METHODS: We performed a double-blind, randomized, controlled (versus slow-release nifedipine) trial. Adjustment of treatment took place every month (M) between inclusion (MO) and an evaluation after 6 months (M6), then during M9 and after 1 year (M12) to achieve supine DBP values < or = 90 mmHg. Patients were dropped from our study if they had DBP> 95mmHg during two consecutive visits or DBP>115 mmHg on one occasion. The daily dosage of rilmenidine was 1 mg, and could be increased to 2 mg/day. The daily dosage of slow-release nifedipine was started from the beginning at the maximum dosage of 40 mg/day, so that there was no true adjustment of treatment despite the allocation of patients to a different unit in the case of DBP> 95 mmHg. The primary criterion was the change in left ventricular mass index (LVMI, g/m2), assessed by echocardiography, between MO and M12 for patients who completed the trial. RESULTS: After a 1-month placebo run-in period, 76 patients were selected and 73 were included (35 treated with rilmenidine and 38 treated with nifedipine). Fifteen patients withdrew from the study and two completed the study with a major deviation from protocol, leaving 56 patients (24 treated with rilmenidine and 32 treated with nifedipine) for a per-protocol analysis. Baseline demographic characteristics and history of arterial hypertension for the rilmenidine and nifedipine groups were similar, for included patients and for those taken into account for the per-protocol analysis. Between MO and M12, DBP in members of the per-protocol population was adequately controlled for those in the rilmenidine group (102.7+/-4.6 versus 88.5+/-7.1 mmHg, respectively) and for those in the nifedipine group (102.7+/-5.1 versus 85.6+/-79 mmHg, respectively). During MO, LVMI of patients in the rilmenidine group (176.9+/-41.3 g/m2) was slightly higher than that of patients in the nifedipine group (172.6+/-35.1 g/m2). During M12, LVMI was observed to have decreased both for patients in the rilmenidine group (to 154.8+/-40.2 g/m2, a decrease of 22.1+/-23.3 g/m2, P< 0.001) and for those in the nifedipine group (to 145.6+/-36.4 g/m2, a decrease of 26.9+/-29.5 g/m2, P< 0.001) but the difference between these two groups was not significant (P= 0.5). CONCLUSION: One-year treatment with a daily dosage of 1 or 2 mg rilmenidine achieves a significant reduction of left ventricular mass, which is not statistically different than that occurring with a daily dosage of 40 mg of slow-release nifedipine.

Adult↗
PubMed1998

A randomized, placebo-controlled trial of low-dose alpha-difluoromethylornithine in individuals at risk for colorectal cancer.

DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO 0.5 g/m2/day as a single oral dose on polyamine and ODC levels in rectal, rectosigmoidal, and cecal colonic mucosae of individuals at risk for colon cancer because of a personal history of adenomatous polyps of the colon or a family history of colon cancer in at least one first-degree relative. A second goal was to determine toxicity of this treatment given over 1 year. Forty-five randomized subjects had a flexible sigmoidoscopy with no preparation and a colonoscopy after lavage preparation at baseline, a sigmoidoscopy with no preparation after 3 months, and both procedures (as at baseline) after 12 months, with mucosal biopsies taken from the rectosigmoid area (sigmoidoscopy) or rectal and cecal areas (colonoscopy) for evaluations of ODC and polyamine levels. Significantly decreased levels of putrescine and spermidine were found in rectosigmoid colonic mucosae of DFMO-treated (n = 24) compared with placebo (n = 21) subjects at 3 months (P = 0.03 and 0.04) and 12 months (P = 0.005, P = 0.004). Similar trends, none reaching statistical significance, were found for individual polyamine levels in rectal and cecal mucosae. No significant differences in ODC levels were detected marginally. There was evidence of global suppression of ODC and polyamine levels in the treatment group (P = 0.035). Three DFMO recipients (12.5%) developed clinically noticeable and audiologically demonstrated hearing loss, which was reversible and attributed to DFMO after 3 months (two subjects) and 12 months (one subject). The tissue polyamine changes demonstrated in this study are consistent with findings in other studies in colon and other tissues. The ototoxicity findings here suggest that investigation of other DFMO schedules, such as ones with a drug "holiday," will be a necessary step before Phase III chemoprevention studies can be pursued.

Adult↗
PubMed1997

[Tumors of the papilla of Vater--diagnostic and therapeutic dilemmas].

Benign and malignant tumors of papilla Vateri are rare diagnoses in the endoscopic practice. Sixteen patients with benign and 22 cases of malignant tumors are presented. In all of them endoscopic cholangiopancreatography with or without papillotomy followed by biopsy and operation in 13 cases was performed. Biopsy confirmed the endoscopy in 71%. Adenomyosis, supposed by endoscopy was proved by repeated histology in only 2/9 cases although invasive component of the tumor was found in 3/9 patients at operation underlying precancerous nature of this entity. Among 5 cases of villous adenoma one developed malignant alterations during 4 years of follow-up. Biopsy was not more effective after papillotomy than without it, and 5-7 days of delay for recovery of thermic lesion did not ameliorate success rate of histology. For malignant diseases surgical therapy should be considered if staging of tumor and general condition of the patient permits. In unresectable cases endoscopic palliation (papillotomy or polypectomy with or without drainage) can increase survival. In patients with benign tumors operative endoscopy followed by regular ultra-sonography and endoscopy seems to be necessary.

Adenocarcinoma↗
PubMed1997

[Change of trend in the treatment of type 2 non-insulin-dependent diabetics].

Medical opinion about the significance of non-insulin-dependent diabetes has been recently changed for three reasons: epidemiological evidence about the continuously increasing disease-prevalence, accumulation of new intriguing details on the pathophysiology of the disease, and the growing clinical evidence about the importance of accelerated atheromatosis related to any stage of the disease. The new theoretical approach resulted in some new aspects of therapeutical management as well. There is an emphasis on the early recognition, the very strict metabolic control and the individualized form of the therapy. Well organized regular medical care for the diabetics, recognition and effective treatment of comorbidities (dyslipidemia, high blood pressure), self-involvement of the patients in the management (ie. patient education) are the corner stones of this approach. The authors give a short review about the armamentura of the therapy available nowadays, including rules of indication for different sulfonylurea drugs, combined sulfonylurea-insulin treatment and single insulin regimes as well.

Arteriosclerosis↗
PubMed1997

Effect of endotoxin administration on the severity of acute pancreatitis in two experimental models.

CONCLUSIONS: Endotoxemia can transform acute pancreatitis (AP) into a more severe form of the disease in models of AP provoked by common pancreatico-biliary duct ligation or L-arginine injection. BACKGROUND: It has been shown that systemic endotoxemia is a common feature in severe AP. The effect of endotoxemia on the course of experimental pancreatitis is unknown. METHODS: AP was induced by common pancreatico-biliary duct ligation (experiment 1) and i.p. injection of 250 mg/100 g body wt of L-arginine (experiment 2). Test animals of both experiments received i.p. injections of 0.5 and 1.0 mg/100 g body wt of endotoxin at the induction of AP. Saline-treated and only endotoxin-dosed animals served as controls for both experiments. Mortality rates and pancreatic histology were investigated at 48 h. RESULTS: The mortality rate was significantly elevated (60%, p < 0.05) in experiment 1 when 1.0 mg/100 g of endotoxin was given. In experiment 2, the mortality rate was also increased (30%) at this dose of endotoxin without reaching significance. Histologic changes were more severe in both groups of AP treated by the two doses of endotoxin than without it. Acinar necrosis and hemorrhage were highly elevated (p < 0.01) in both experiments when AP was combined with 1.0 mg/100 g body wt of endotoxin. The animals receiving only endotoxin showed only slight inflammatory and necrotic changes.

Acute Disease↗
PubMed1996

[Calcium antagonists and ischemic heart disease].

The authors give a short account about the significance, basic rules in regulation of intracellular (cytosolic) calcium homeostasis, distribution of calcium channels in different organs and characteristics of L channels in cardiovascular system. The different types of calcium channel blockers (dihydropyridines, phenylalkilamines, benzothiazepines), their similarities, dissimilarities (cardio, -vascular selectivity) are discussed. Differences in calcium homeostasis, in sympathetic innervation between vascular smooth- and heart muscle in briefly disputed. The basic role of endothel cell dysfunction in development of ischemic heart disease, the possible mechanisms (potential anti-remodeling, antifissuring, antiischemic, cardioprotective, sympaticolytic effects) of different calcium antagonists in the treatment of patients with ischemic heart disease are reviewed. Potential adverse effects of calcium channel blockers (proischemic, proarrhythmic, procongestive, prohaemorrhagic effects) are also mentioned. Finally the up-date preventive and therapeutic indications of different calcium channel blockers in the clinical management of patients with stable, unstable angina pectoris, silent myocardial ischemia, vasospastic angina, acute myocardial infarction is shortly reported.

Angina, Unstable↗
PubMed1996

Ipriflavone, an antiostheophorotic agent.

The antiostheophorotic agent ipriflavone [7-(1-methyl-ethoxy)-3-phenyl-4H-1-benzopyran-4-one, C18H16O3] is an important member of the isoflavone family. The structure of the molecule is dominated by the dihedral angle (50 degrees) between the planes of the phenyl and benzo-pyran moieties. A structural comparison with other related published structures is represented.

Analgesics↗
PubMed1996

Biphasic effect of prostaglandin E1 on the severity of acute pancreatitis induced by a closed duodenal loop in rats.

The effect of prostaglandin E1 (PGE1) on the severity of acute pancreatitis induced by a closed duodenal loop in the rat was tested. PGE1 was administered subcutaneously at various doses (3, 6, 12, and 24 microgram/kg) at hourly intervals, from the induction of acute pancreatitis up to the 24th hour. A saline-treated group served as the control. The mortality rate was recorded, and pancreatic histology was evaluated by a scoring system. Serum amylase activity and pancreatic amylase, trypsin, protein, and desoxyribonucleic acid (DNA) contents were determined at 24 h. Administration of PGE1 influenced the severity of acute pancreatitis biphasically. Serum amylase was reduced significantly (p < 0.01) at a dose of 12 microgram/kg/h, but less at 24 microgram/kg/h. Pancreatic weights did not differ in the groups. Pancreatic amylase, trypsin, and protein contents showed significant elevations (p < 0.01), yet the mortality rate was reduced using 6 and 12 microgram/kg/h doses of PGE1 compared to controls, but not at higher and lower doses. The DNA content was significantly higher at the 6 microgram/kg/h dose, compared to the control. The extent of necrosis and the severity of hemorrhage were reduced significantly (p < 0.05) at doses of 6 and 12 microgram/kg/h of PGE1, but less at 24 microgram/kg/h. Leukocyte infiltration was not affected. In conclusion, optimal doses of PGE1 can ameliorate, but higher doses increase, the severity of acute pancreatitis in this experimental model.

Acute Disease↗