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Biomedical subjects

S Eckhardt

Publications and source records attributed to S Eckhardt.

At least 19 recordsLinked to original sources
PubMed2000

Interaction of the G protein beta 3 subunit T825 allele and the IRS-1 Arg972 variant in type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus is a common late-onset disease with a strong genetic component. It is characterized by insulin resistance which results from alterations in insulin signal transduction. The G protein beta 3 subunit 825T allele was recently found to be associated with hypertension and obesity which makes it a sensible candidate gene for type 2 diabetes. METHODS: In a case-control study on 320 male patients and 962 male healthy controls we investigated the association of two candidate genes with diabetes, i.e. (i) the GNB3 825T allele, associated with a G protein beta 3 subunit splice variant and enhanced intracellular signal transduction, and (ii) the insulin receptor substrate-1 (IRS-1) 972Arg variant, which encodes a protein variant associated with cellular insulin resistance. RESULTS: The GNB3 825T allele and the IRS-1 972Arg variant were significantly associated with diabetes (odds ratios for either variant 1.4 1.8). Odds ratios were 3 4 in males carrying both alleles. CONCLUSIONS: The results document an association of a hypertension susceptibility gene with type 2 diabetes which may partially explain the frequent coexistence of both disorders.

Adult↗
PubMed2000

The efficacy of a combination of etoposide, ifosfamide, and cisplatin in the treatment of patients with soft tissue sarcoma.

BACKGROUND: Successful chemotherapy for patients with soft tissue sarcoma (STS) has been limited by a lack of active drugs. The most effective single agents are doxorubicin, dacarbazine, and, more recently, ifosfamide. Previously the most widely used combination has been CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). In one randomized trial, ifosfamide was superior to cyclophosphamide; two nonrandomized studies also reported favorable results. Etoposide monotherapy was successful in 8%; the effectiveness of cisplatin was 5-23%. In view of these findings, the authors treated STS patients with an etoposide, cisplatin, and ifosfamide (VIP) combination. METHODS: The eligibility criteria included histologically confirmed, inoperable, metastatic or locally recurrent STS; a World Health Organization (WHO) performance status of 0-2; a maximum age of 75 years; and progressive, measurable disease. A total of 104 patients were treated from January 1990 to June 1997. The median age of the patients was 42.4 years. The patients were treated with a combination of etoposide (100mg/m(2) for 5 days), ifosfamide (2000 mg/m(2) for 2 days), and cisplatin (20mg/m(2) for 5 days) once a month via a peripheral vein. The treatment response and the toxicity were assessed according to WHO criteria. RESULTS: Of 104 evaluable patients, 47 responded. The overall response rate was 46% (complete response: 10%; partial response: 36%). In 43 patients the disease remained stable (41%). Remission duration was 4.6 months. Toxicity was moderate. The main adverse events were alopecia (100%), nausea and vomiting (73%), and leukopenia (29%). CONCLUSIONS: This new combination is promising for the treatment of patients with advanced STS.

Adult↗
PubMed2000

Early detection for colorectal cancer: new aspects in fecal occult blood screening.

The authors report on promising diagnostic methods of occult intestinal bleeding and discusses the potential new strategy of early detection of colorectal carcinomas in respect to old and new diagnostic measures available. Because of the limited sensitivity and specificity of classical methods used for the demonstration of occult fecal blood, the authors recommend the introduction of new techniques and markers in screening practice. It is presumed that new discoveries in molecular biology will improve the accuracy of early colorectal cancer prevention. Their implementation into routine screening, however, will not take place in the near future. Until their realization, improved screening efficacy is expected from the use of more specific and sensitive blood tests.

Colorectal Neoplasms↗
PubMed1999

Reflections on oncology in central and eastern Europe.

In the last two decades cancer mortality dramatically increased in the majority of Central and Eastern European countries. In the period from 1992 to 1995, the Hungarian male population had the highest death rate (265.0 of 100,000) due to malignancies among 46 countries worldwide. Hungarian women ranked third in cancer death rate among these countries (138.0 of 100,000). Several factors might be responsible for these figures: a) increases in environmental carcinogenic risk factors, b) unfavourable lifestyle changes in the population especially related to high tobacco consumption and dangerous drinking habits, c) lack or insufficiency detection, d) delay in diagnosis, e) inadequate therapeutic patient management, f) shortage of manpower, and g) unsatisfactory financial support. Efforts have been made to overcome these difficulties by: a) detail analysis of exogenous risk factors, b) review of lifestyle of the population, c) public education efforts for effective prevention, d) introduction of model screening programs, e) reorganization of cancer diagnosis and treatment services, and f) design and establishment of a National Cancer Control Program.

Europe, Eastern↗
PubMed1998

[The effect of docetaxel on malignant tumors].

In recent years numerous molecular biological discoveries enlightened the various steps of the neoplastic transformation. Based on new targets, this development made it possible to synthetize new tumour inhibitory substances. Among them taxanes capable to block depolymerization of tubulin--which is an essential molecule in cell division--play an important role. Docetaxel (Taxotere) belongs to this group and is an active drug in the treatment of breast cancer. Moreover, platinum-resistant tumours may also respond to the therapy. It is important to note that even visceral (hepatic) metastases may express chemosensitivity. Results of combination chemotherapy seem to be also promising. The antitumour effect of Taxotere in NSCLC and other malignant neoplasms in under investigation. The toxicity of Taxotere may be successfully reduced by premedication of steroids. The necessary protective measures render the Taxotere therapy safe and of being perspectivistic.

Alopecia↗
PubMed1997

Guanidinoacetate methyltransferase deficiency: new clinical features.

Guanidinoacetate methyltransferase deficiency is a recently described inborn error of creatine biosynthesis that responds to treatment with oral creatine supplementation. The previously reported clinical features consist of developmental arrest and an extrapyramidal movement disorder. We describe a patient who presented with epilepsy, global developmental delay, and a persistently low plasma creatinine level. The diagnosis was established by measuring urinary guanidinoacetate and by demonstrating absence of the creatine/phosphocreatine peak in the patient's basal ganglia in 1H magnetic resonance spectroscopy. The clinical and biochemical abnormalities responded to creatine replacement.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.

Blood Glucose↗
PubMed1995

[Use of taxol in the management of malignant tumors].

Taxol is a novel cytostatic agent which inhibits the depolymerisation of microtubulin. The stabilization of this important substance leads to cellular arrest and consecutively apoptosis. Accordingly, taxol is capable to influence neoplastic growth in several malignancies. At present the following standard regimen is recommended: 175 mg/m2 taxol in a 3-hour i. v. infusion following corticosteroid + diphenhydramine + cimetidine premedication. Its antitumour activity has been proved especially in advanced ovarian and breast cancer. Encouraging results have been reported in various bronchial, testicular malignancies, lymphomas and leukemias. Clinical investigations in several other malignancies are ongoing.

Antineoplastic Agents↗
PubMed1995

Interferon-alpha for induction and maintenance in multiple myeloma: results of two multicenter randomized trials and summary of other studies.

BACKGROUND: Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. PATIENTS AND METHODS: 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. RESULTS: The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. CONCLUSIONS: Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.

Adult↗
PubMed1995

Bartter's syndrome associated with severe retinopathy and presenting as pseudohypoaldosteronism in a newborn.

Various pathophysiological explanations for Bartter's syndrome have been put forward since the condition was first described in 1962. It is currently thought that reduced reabsorption of sodium chloride in the distal tubule of the loop of Henle and the collecting ducts leads to secondary hyperkaluria and hypokalaemic metabolic alkalosis. We describe a 9 1/2-year-old boy with Bartter's syndrome and severe retinopathy whose features may be those of a previously unrecognized disorder.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Randomized comparison of fluorouracil and leucovorin therapy versus fluorouracil, leucovorin, and cisplatin therapy in patients with advanced colorectal cancer.

BACKGROUND: Because of experimental and preliminary clinical evidence that additional modulation of the biochemical pharmacology and cytotoxicity of 5-fluorouracil (5-FU) and leucovorin (LV) may be possible by combination of these agents with cisplatin (CDDP), the authors undertook a prospective randomized trial in patients with colorectal cancer. METHODS: Between 1989 and 1992, 138 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either 5-FU (425 mg/m2) and LV (20 mg/m2) for 5 days, or the combination of 5-FU and LV in the same daily dose plus cisplatin (20 mg/m2), each drug given for 4 consecutive days. In both treatment arms, courses were administered every 28 days, if toxicity allowed, for a total of 6 months or until evidence of tumor progression. RESULTS: The overall responses (complete and partial response) were 19% and 28% for the 5-FU/LV and the 5-FU/LV/CDDP treatment arms, respectively. Although the three-drug combination appeared superior to 5-FU/LV for time to progression or death (8.5 versus 5.2 months; P = 0.042), there was no evidence that the adoption of cisplatin will translate into a definite survival advantage. A comparative analysis of the toxicities experienced by the patients in the two treatment groups showed a comparable rate, although severe side effects (P < 0.05), specifically stomatitis (P = 0.013), were noticed more frequently in patients treated with 5-FU/LV for 5 days. CONCLUSIONS: These results suggest that the therapeutic index of 5-FU/LV in metastatic colorectal cancer may be improved with the addition of cisplatin. However, the somewhat better therapeutic activity and lower incidence of severe gastrointestinal side effects have to be weighed against additional pharmaceutical charges and the need for a more intense antiemetic regimen.

Adult↗
PubMed1994

Isolated dihydroxyacetonephosphate acyltransferase deficiency presenting with developmental delay.

A boy aged 21 months who was being investigated for developmental delay and failure to thrive was found to have punctate epiphyseal calcification. He had no evidence of rhizomelic shortening of the limbs or cataracts. Investigation revealed defective plasmalogen synthesis due to isolated deficiency of dihydroxyacetonephosphate acyltransferase (DHAP-AT). The parents were consanguineous and a sister was similarly affected, suggesting autosomal recessive inheritance. Hitherto, recessively inherited isolated DHAP-AT deficiency has only been described in patients with a phenotype similar to that of rhizomelic chondrodysplasia punctata. This report indicates that the same biochemical disorder can be associated with a less severe phenotype.

Acyltransferases↗
PubMed1994

Influence of toremifene on the endocrine regulation in breast cancer patients.

In a combined phase I-II study, the hormonal effects of toremifene (TOR) were investigated in 30 patients. Half of the patients received continuous therapy of TOR 60 mg and half 300 mg of TOR orally daily. Serum concentrations of oestradiol (E2), progesterone (PROG), testosterone (TE), follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), human growth hormone (hGH) and sex hormone binding globulin (SHBG) were monitored prior to the treatment and at the second, sixth, eighth and twelfth weeks. The influence of TOR upon the hypothalamo-hypophyseal axis was investigated by the TRH (thyroid-stimulating hormone releasing hormone) functional test using 400 micrograms intravenous injection of TRH for stimulation of PRL secretion. The concentration of E2 decreased during the TOR therapy with 60 mg and 300 mg causing 82 and 71% decreases, respectively (non-significant). PRL was significantly (P < 0.001) suppressed. Both these effects reflect the anti-oestrogenic action of TOR. SHBG increased significantly at both doses of TOR, probably due to a direct oestrogen-like effect of TOR in the liver. TE decreased as a consequence of the elevated SHBG. The TRH-induced PRL release was suppressed by both doses of TOR. There were 17 and 27% reductions at 12 weeks in the 60 and 300 mg groups, respectively. Other hormones measured were not significantly affected by TOR. The hormonal effects of 60 and 300 mg doses of TOR did not differ significantly. Anti-oestrogenic (i.e. decrease of E2), and partially oestrogenic (i.e. increase of SHBG) properties as well as the antiprolactinic effects of TOR may have an overall beneficial effect in the clinical management of breast cancer patients.

Adult↗