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G Klein

Publications and source records attributed to G Klein.

At least 37 records · Page 2Linked to original sources
PubMed2004

Temozolomide and interferon alpha 2b in metastatic melanoma stage IV.

BACKGROUND: A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-alpha 2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV. OBJECTIVES: The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-alpha 2b were documented. PATIENTS/METHODS: Twenty-nine male and 18 female patients (mean age 57.6 years, range 34-74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m(-2) on days 1-5 orally every 28 days in combination with IFN-alpha 2b 10 MIU m(-2) every other day and 27 patients received temozolomide 150 mg m(-2) on days 1-5 every 28 days in combination with IFN-alpha 2b in a fixed dose of 10 MIU every other day. RESULTS: We observed an overall response rate of 27.6% comprising five complete remissions (10.6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4.3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6.4%, two patients in group A, one patient in group B). Three patients showed stable disease (6.4%: one patient in group A, two patients in group B). Mean survival was 14.5 months [95% confidence interval (CI) 10-19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P < 0.03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30.6 months (95% CI 19.1-42) compared with 25 patients who did not respond (13.7 months 95% CI 9.2-18.3). In total, patients with at least one complete remission showed the longest survival (37.1 months 95% CI 26.3-47.9), followed by patients with at least one partial response (17.4 95% CI 10.9-23.9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths. CONCLUSIONS: The combination of temozolomide and IFN-alpha 2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Adult↗
PubMed2004

Analysis of gyrA mutations in quinolone-resistant and -susceptible Campylobacter jejuni isolates from retail poultry and human clinical isolates by non-radioactive single-strand conformation polymorphism analysis and DNA sequencing.

AIMS: The aims of this study were to characterize the molecular variations in the quinolone resistance-determining region (QRDR) of gyrA among quinolone-resistant and -susceptible Campylobacter jejuni isolates originating from foods of animal origin and human infections and to evaluate the suitability of the single-strand conformation polymorphism (SSCP) method as a screening method for molecular characterization of fluoroquinolone resistance. METHODS AND RESULTS: Alterations in QRDR of gyrA from 182 C. jejuni isolates were determined by nonradioisotopic SSCP analysis and direct sequencing. A total of 13 types of nucleic acid sequence combinations within the QRDR of the gyrA gene resulted in 11 different SSCP patterns. All nalidixic acid resistant strains possessed nucleotide substitution at either codon Thr-86 or Asp-90. Silent mutations were detected additionally. Thr-86 to Ile mutation was detected in all 139 ciprofloxacin resistant strains, which showed cross-resistance to nalidixic acid. CONCLUSIONS: The SSCP method is suitable for a molecular screening of quinolone resistant C. jejuni isolates and in combination with DNA sequencing suitable to detect genetic variations of the QRDR of gyrA. SIGNIFICANCE AND IMPACT OF STUDY: This study provides data of the genetic variations of the QRDR of gyrA from C. jejuni isolates of foods and human beings.

Animals↗
PubMed2004

[Test schemes for evaluation of the effect of a probiotic feed additive on the gut microflora of young calves and newly hatched turkeys].

Probiotic feed additives have to undergo a strict assessment according to EU regula-tions, including the evaluation of the influence on the gut microflora of the host animal. A probiotic strain of the genus Enterococcus faecium and two different host animal species, young calves and newly hatched turkeys, were chosen as a test model for the establishment of schemes for feeding trials. Investigations included faeces samples and pooled swab samples of faeces as well as samples from gut sections derived from diagnostic slaughtering. The samples were tested for aerobic total count, for enterococci count and for Enterobacteriaceae and E. coli. The test schemes were appropriate for the evaluation of the influence of the probiotic feed additive on the physiological gut microflora of the host animals. Additional information could be gathered concerning safety aspects and effectiveness.

Animal Feed↗
PubMed2004

[Spread of viruses through the food chain].

Food associated viruses are responsible for a high number of infectious diseases in man, mainly gastroenteritis and hepatitis. The three most important viral agents are noroviruses (NV) (formerly known as Norwalk-like viruses), Rotavirus (RV) and Hepatitis A-Virus (HAV). The numbers of infections in man were in 2002 according to the Robert Koch-Institut for NV and RV 50,000, respectively, and for HAV 1,500, slightly decreasing in 2003. The rate of foodborne infections caused by viruses can only be estimated (appr. 20% of total cases). On the other hand only a very small part of viral gastroenteritis can be diagnosed and notified. Besides the direct infection through contaminated food the human to human infection is the most important source, also responsible for outbreaks. There is at the moment no routine diagnostic tool available for the detection of viruses in food because of the lack of standardized methods. For NV, one of the most important foodborne (live bivalve molluscs) viral pathogens, indicator organisms are in use. There is a scientific evaluation in different member states concerning the value of bacterial indicators vs. bacteriophages. In addition to foodborne viruses (via faecal contamination present in the food chain) there are emerging zoonotic viral agents. Food may be a vector for this agents depending on the production structures (e.g. SARS or influenca).

Animals↗
PubMed2003

Second malignant neoplasms after treatment of childhood cancer.

The aim of this study was to determine therapy-related risk factors for the development of second malignant neoplasm (SMN) after childhood cancer. The German Childhood Cancer Registry (GCCR) registers all childhood malignancies since 1980 including SMN. A nested case-control study with 238 SMN cases and 450 controls was conducted. A confirmatory, as well as an explorative, analysis was performed. Radiotherapy showed a small effect on the risk of SMN for doses >or=65 Gy. Regarding the chemotherapeutical agents, we saw increased Odds Ratios (OR) for high doses of cyclophosphamide (CP >8000 mg/m(2) OR=6.3 (95% Confidence Interval (CI): 1.3-30.2)), cisplatinum (DDP >435 mg/m(2) OR=2.8 (95% CI: 1.1-6.7)) and mercaptopurine (MP >5000 mg/m(2) OR=4.5 (95% CI: 1.1-18.9)). Patients jointly receiving high doses of MP (>5000 mg/m(2)) and dexamethasone (DEXA >or=1200 mg/m(2)) had an OR=6.9 (95% CI: 1.2-40.3). Our results could be added to those of other investigations to give indications for modifying future therapeutic strategies for childhood cancer.

Adolescent↗
PubMed2003

Endogenous nitric oxide synthase inhibitors and renal perfusion in patients with heart failure.

BACKGROUND: Patients with heart failure are characterized by impaired nitric oxide-dependent endothelial vasodilation and, in addition, by reduced renal perfusion. DESIGN: We assessed blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal haemodynamics to compare normotensive patients with mild heart failure (n = 12, seven males, 70 +/- 1 years, 72.0 +/- 2.7 kg, 92 +/- 2 mmHg, NYHA I/II) and healthy subjects matched with respect to gender, age and body weight (n = 12, seven males, 69 +/- 2 years, 72.7 +/- 2.5 kg, 88 +/- 2 mmHg). RESULTS: Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P < 0.01) and effective renal plasma flow (ERPF) significantly lower (P < 0.01) in the patients with heart failure (ADMA 4.18 +/- 0.42 micro mol L-1, RVR 159 +/- 12 mmHg mL-1 min-1, ERPF 381 +/- 26 mL min-1 1.73 m-2) as compared with the healthy controls (ADMA 2.38 +/- 0.11 micro mol L-1, RVR 117 +/- 8 mmHg mL-1 min-1, ERPF 496 +/- 19 mL min-1 1.73 m-2). In contrast, plasma concentrations of l-arginine, homocysteine, symmetric dimethylarginine (i.e. the biologically inactive stereoisomer of ADMA) and plasma renin activity were not significantly different in both groups studied. In the multiple regression analysis, only plasma ADMA concentrations independently predicted reduced ERPF (r = -0.57; P < 0.003). CONCLUSIONS: In normotensive patients with heart failure plasma ADMA concentrations are markedly increased and related to reduced renal perfusion. Thus accumulation of this endogenous nitric oxide inhibitor may play a role in renal pathology in these patients.

Aged↗
PubMed2003

Validation of a short questionnaire to qualitatively assess the intake of total fat, saturated, monounsaturated, polyunsaturated fatty acids, and cholesterol.

BACKGROUND: To validate a self-administered 20-item short questionnaire (SQ) for classifying individuals according to their intake of total fat, saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA), as well as cholesterol. METHODS: The SQ was sent to a randomly selected subsample of 300 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg. The SQ was sent back by 244 participants (52.5% women, 47.5% men). Intake of total fat, SFA, MUFA, PUFA, and cholesterol was calculated from a 148-item food frequency questionnaire (FFQ). The intake was compared with the scores computed from the SQ. RESULTS: Spearman's correlation coefficient between the intake estimated from the FFQ and the score from the SQ ranged from r = 0.29 (PUFA) to r = 0.56 (cholesterol). When the participants were assigned to quartiles of intake according to both methods 29-42% were classified into the same quartile, 1-7% of the participants were grossly misclassified. CONCLUSIONS: The SQ demonstrated a good validity with respect to SFA and cholesterol and an acceptable validity with respect to total fat and MUFA, while the results are less good for PUFA. The SQ can be used to classify persons according to their intake into categories of intake.

Adult↗
PubMed2003

K(+) transport in Malpighian tubules of Tenebrio molitor L: is a K(ATP) channel involved?

The presence of ATP-regulated K(+) (K(ATP)) channels in Tenebrio molitor Malpighian tubules was investigated by examining the effect of glibenclamide on both fluid secretion and basolateral membrane potentials (V(bl)). Glibenclamide, a K(ATP) channel blocker, slowed fluid secretion of Tenebrio tubules. In low bath K(+) concentration (5 mmol l(-1)), glibenclamide either hyperpolarized or depolarized V(bl), resembling the effect seen with Ba(2+). Subsequent addition of 6 mmol l(-1) Ba(2+) caused a further hyper- or depolarization of V(bl). In control Ringer (50 mmol l(-1) KCl, 90 mmol l(-1) NaCl), glibenclamide had no visible effect on V(bl). The effect of ouabain was investigated in low bath [K(+)] in the presence of Ba(2+). V(bl) responded by a small but significant hyperpolarization from -51+/-4 mV to -56+/-4 mV (n=16, P<0.001) in response to 1 mmol l(-1) ouabain. Repeating the experiments in the presence of both glibenclamide and Ba(2+) resulted in a depolarization of V(bl) when ouabain was added. In low bath [K(+)] (high Na(+)), the Na(+)/K(+)-ATPase is expected to function at a high rate. In the presence of Ba(2+), replacing Na(+) by K(+) rapidly depolarized V(bl), but this was followed by a repolarization. Repeating the experiments in the presence of glibenclamide markedly reduced the depolarizing effect and abolished the repolarization, with a gradual decrease in the sensitivity of V(bl) to the surrounding [K(+)]. These results suggest the presence of K(ATP) channels in the basolateral membrane. Glibenclamide had no visible effect on V(bl) in high K(+) or in the absence of Ba(2+), indicating that other highly conductive K(+) channels may mask the effect on K(ATP) channels. This is the first demonstration of the presence of K(ATP) channels in an insect epithelium.

Adenosine Triphosphate↗
PubMed2003

Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip.

CONTEXT: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or selective inhibitors of cyclooxygenase-2 (COX-2). OBJECTIVE: This clinical trial aimed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen, named dexibuprofen (S(+)-ibuprofen) in a special crystal form, and the selective COX-2 inhibitor celecoxib in adults with OA of the hip. Moreover, the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested. METHODS: The investigation was a randomized, parallel-group, double-blind, active controlled clinical trial, conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria. 148 inpatients were randomly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily. The primary criterion was the improvement in the Western Ontario and' McMasters osteoarthritis index (WOMAC OA index) after 15 days of therapy. RESULTS: Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d. is not inferior to celecoxib 100 mg b.i.d. with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95% confidence interval equal to 0.4409. The overall incidence of adverse drug reactions was 12.16% in the dexibuprofen group and 13.51% in the celecoxib group. 8.1% of patients on dexibuprofen and 9.5% on celecoxib suffered from gastrointestinal disorders. CONCLUSION: In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip.

Adult↗
PubMed2002

Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns.

BACKGROUND: Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease (CHD) is far from optimal. The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels. METHODS: Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication. Data are derived from a multicenter, randomized, open-label, parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany. Medical history, physical examination, and serum lipid levels were obtained at the beginning of the washout phase (Week -6) and at the end of the washout phase (Week -1, i.e., 5 weeks after the discontinuation of all prior lipid-lowering medications). The data at Week -6 represented the lipid levels under real life conditions. The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at Week -6 was 173.4 +/- 42.5 mg/dl. Only 176 (6.2%) of 2,856 CHD patients were found to meet the target LDL-C level of <115 mg/dl at Week -6, only 76 (2.7%) patients had LDL-C levels <100 mg/dl, and 363 (12.7%) patients had LDL-C levels <130 mg/dl. After discontinuation of all prior lipid-lowering medications, mean LDL-C increased to 187.2 +/- 44.0 mg. This means that only a marginal 7.4% reduction in LDL-C level was achieved under real life treatment conditions. This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment (65.5% of patients did not receive any medication at all) and inadequate dosing. With respect to the effect on LDL-C and total cholesterol, statins alone were superior to fibrates. CONCLUSION: The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany. Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians. Available treatment guidelines should be better implemented.

Adult↗
PubMed2002

[Cardiovascular manifestations in inflammatory rheumatic diseases].

Inflammatory rheumatic diseases show an increased cardiovascular mortality. The reasons for this are unclear. Possible associations between atherosclerosis and autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus can be illustrated.

Arthritis, Rheumatoid↗
PubMed2002

Arterial occlusion after total knee arthroplasty: successful management of an uncommon complication by percutaneous thrombus aspiration.

Management of arterial occlusion after total knee arthroplasty is controversial in the literature, in part because of the relatively small number of reported cases. We report a case of perioperative popliteal artery thrombosis after total knee arthroplasty that was treated successfully with percutaneous thrombus aspiration and balloon dilation. Immediate intervention prevented ischemic muscular necrosis, resulting in full recovery of the limb.

Aged↗
PubMed2002

[Combination of heterozygote blood coagulation factor V Leiden carriage with erythrocytosis as a cause of the hip deep vein thrombosis].

AIM: To reject one of the variants of inherited thrombophylia in a 64-year-old patient with deep thrombosis of leg veins and high hemoglobin and red cell levels. MATERIAL AND METHODS: The study was made of antithrombin III and protein C, protein S levels; resistance to activated protein C; molecular structure of DNA coding factor 5; methylenetetrahydrofolate reductase. RESULTS: The patient was diagnosed to have heterozygote factor V Leiden mutation. The replacement of arginine by glutamine in position 506 of factor V molecule raises the risk of thrombosis. This risk was aggravated by high hemoglobin, red cells, hematocrit, low volume of circulating plasma, smoking. The patient had normal levels of leukocytes and platelets, normal spleen size, slightly lowered level of erythropoietin. CONCLUSION: The presence of thrombosis in patients with erythremia or erythrocytosis rejects one of the thrombophilia forms.

Factor V↗
PubMed2002

Effect of nimesulide on metalloproteinases and matrix degradation in osteoarthritis: a pilot clinical study.

In osteoarthritis (OA) the balance between cartilage degeneration and repair is disturbed. The aim of this pilot clinical study was to examine the effects of a nonsteroidal anti-inflammatory drug, nimesulide, on the synthesis of matrix metalloproteinases (MMPs) which are important enzymes in cartilage proteolysis. Cartilage oligomeric matrix protein (COMP), a component of the extracellular matrix, was used as an indicator of accelerated joint erosion. Radiologically proven painful OA of the knee or hip was treated with 100 mg nimesulide twice daily for 3 weeks. MMP-1, -3 and -8 and COMP were measured by immunoassays, and clinical investigations were made on pain, and on disease intensity using the WOMAC scale. During treatment with nimesulide, in addition to clinical improvement and less pain, serum levels of MMP-3, MMP-8 and COMP fell indicating a beneficial effect on cartilage catabolism.

Acute Disease↗
PubMed2001

Nipple aspirate cytology and pathologic parameters predict residual cancer and nodal involvement after excisional breast biopsy.

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type of ductal carcinoma in situ (DCIS) or invasive cancer (IC), grade of DCIS or IC, tumour and specimen size, tumour and biopsy cavity location, presence or absence of extensive DCIS, and biopsy scar distance from the nipple were evaluated bivariately and then by logistic regression (LR) for their association with RC and involved LN (> or = 1 (+) LN, useful to determine chemotherapy need, and > or = 4 (+) LN, useful to determine radiation need to the chest and axilla). Data were analysed using NAF cytology alone, pathologic parameters alone, and NAF cytology and pathologic parameters combined. The combined LR model was superior in predicting residual cancer (94%) to LR models using NAF cytology (36%) or pathologic parameters (75%) alone. When only subjects with normal NAF cytology were evaluated by LR, the model was 92% sensitive in predicting RC. Tumour size and NAF cytology predicted which patients had > or = 1 (+) LN, whereas tumour and specimen size predicted which patients had > or = 4 (+) LN. We propose an algorithm which, if confirmed in a larger study, may allow clinicians to be more selective in their recommendations of re-excision breast biopsy or mastectomy.

Adult↗