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G Weiss

Publications and source records attributed to G Weiss.

At least 37 records · Page 2Linked to original sources
PubMed2002

The Koebner phenomenon: review of the literature.

First described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma, the Koebner phenomenon has since been described in numerous diseases. Other authors have tried to implicate either infections or parasitic causes as the pathogenesis of this phenomenon. Subsequent research by many authors have contributed to our poor understanding of this reaction in the hope of understanding the pathogensis of psoriasis. We present a review of the literature covering the following topics as they relate to the Koebner phenomenon: diseases that koebnerize and their possible causes, predisposing and provoking factors, type, site, depth and degree of trauma, the all or none phenomenon, time lag, site preference, medications, inhibition of koebnerization and reverse koebnerization.

Humans↗
PubMed2002

Immunomodulation by perioperative administration of n-3 fatty acids.

It has been increasingly reported that administration of n-3 fatty acids is beneficial in patients with inflammatory processes. This effect is most likely caused by different biological characteristics, including an immunomodulating effect of the products derived from n-3 fatty acids through eicosanoid metabolism. The aim of this study was to investigate the effect of perioperative administration of n-3 fatty acids on inflammatory and immune responses as well as on the postoperative course of patients with extended surgical interventions of the abdomen. In particular, the effect of n-3 fatty acids on interleukin-6 release and on granulocyte/monocyte function (HLA-DR expression) was studied. There was a downregulation of the inflammatory response, and, simultaneously, a smaller postoperative immune suppression in the n-3 fatty acid group. In addition, we observed shorter postoperative periods in the intensive care unit and on the regular medical wards as well as lower rates of severe infections. The results suggest that perioperative administration of n-3 fatty acids may have a favourable effect on outcome in patients with severe surgical interventions by lowering the magnitude of inflammatory response and by modulating the immune response.

Abdomen↗
PubMed2002

Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma.

BACKGROUND: Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon gamma (IFN-gamma). AIMS: To investigate this in humans, we studied the effects of human recombinant IL-10 administration on IFN-gamma production by patient leucocytes. Furthermore, we assessed the IFN-gamma inducible molecule neopterin and nitrite/nitrate serum levels, which are indicative of endogenous nitric oxide formation. METHODS: As part of two placebo controlled double blind studies, we analysed patients with chronic active Crohn's disease (CACD) who received either subcutaneous recombinant human IL-10 (n=44) or placebo (n=10) daily for 28 days, and patients with mild to moderate Crohn's disease (MCD) treated with either subcutaneous IL-10 (n=52) or placebo (n=16) daily for 28 days. Neopterin and nitrite/nitrate concentrations were measured in serum, and ex vivo IFN-gamma formation by lipopolysaccharide or phytohaemagglutinin (PHA) stimulated whole blood cells were investigated before, during, and after IL-10 therapy. RESULTS: In patients with CACD, the highest dose of 20 microg/kg IL-10 caused a significant increase in serum neopterin on days +15 and +29 of therapy compared with pretreatment levels. No changes were observed for nitrite/nitrate levels under either condition. In MCD, treatment with 20 microg/kg IL-10 resulted in a significant increase in PHA induced IFN-gamma production. CONCLUSIONS: High doses of IL-10 upregulate the production of IFN-gamma and neopterin. This phenomenon may be responsible for the lack of efficacy of high doses of IL-10 in the treatment of CACD and MCD.

Administration, Cutaneous↗
PubMed2002

Infiltration and inflow in combined sewer systems: long-term analysis.

A study was conducted on 34 German combined sewer systems including combined sewer overflow (CSO) tanks and treatment plant to show up actual hidden reserves and bottlenecks in stormwater treatment. The study gave also a general insight into the water pathways in urban hydrology. A special focus was given to undesired non-polluted water infiltrating into the sewer, labelled infiltration and inflow (I/I) or infiltration inflows, which is widely underestimated. It leads to a bad performance of the drainage system although the parasite waters are themselves non-polluted. In existing combined systems, pollution control can be considerably improved by reducing I/I. It is equivalent to the reduction of surface runoff e.g. by a separate drainage as frequently proposed alternative. Artificial infiltration of surface runoff may even increase infiltration inflows.

Cities↗
PubMed2001

Outpatient biochemotherapy with interleukin-2 and interferon alfa-2b in patients with metastatic malignant melanoma: results of two phase II cytokine working group trials.

PURPOSE: The Cytokine Working Group performed a randomized phase II trial of two outpatient biochemotherapy regimens to identify an outpatient regimen with high antitumor activity and less toxicity than inpatient regimens which might be compared with chemotherapy or inpatient biochemotherapy regimens in future phase III trials. PATIENTS AND METHODS: Eighty-one patients with metastatic malignant melanoma received dacarbazine 250 mg/m(2)/d intravenously (IV) and cisplatin 25 mg/m(2)/d IV on days 1, 2, and 3, plus interferon (IFN) alfa-2b 5 mU/m(2) subcutaneously (SC) on days 6, 8, 10, 13, and 15, given every 28 days. Interleukin-2 (IL-2) was given daily on days 6 to 10 and 13 to 15. In group 1, IV IL-2 was given at 18.0 MU/m(2), and in group 2, SC IL-2 was given at 5.0 mU/m(2). RESULTS: In group 1 (IV IL-2), there were five complete responses (CRs) and 11 partial responses (PRs) among 44 patients (objective response rate [ORR], 36%; 95% confidence interval [CI], 22% to 51%). In group 2 (SC IL-2), there was one CR and five PRs among the 36 patients (ORR, 17%; 95% CI, 4% to 29%). The median survival was 10.7 months in group 1 and 7.3 months in group 2. Eleven patients in group 1 and four patients in group 2 remain alive as of the last follow-up. Toxicities in both groups were similar. No patient required hospitalization for neutropenic fever. CONCLUSION: Biochemotherapy has activity in these outpatient regimens with acceptable toxicity. The antitumor activity observed with the IV IL-2 regimen seems similar to that of inpatient biochemotherapy regimens. If inpatient biochemotherapy regimens develop an established role in the management of melanoma, future phase III trial comparisons with this outpatient IV IL-2 regimen would be appropriate.

Adult↗
PubMed2001

Phase I and pharmacokinetic study of NSC 655649, a rebeccamycin analog with topoisomerase inhibitory properties.

PURPOSE: To assess the feasibility of administering NSC 655649, a water-soluble, rebeccamycin analog with topoisomerase inhibitory properties, as a brief intravenous (IV) infusion once every 3 weeks and to determine the maximum-tolerated dose (MTD) of NSC 655649, characterize its pharmacokinetic behavior, and seek preliminary evidence of antitumor activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of NSC 655649 administered over 30 to 60 minutes IV once every 3 weeks. An accelerated dose-escalation method was used to guide dose escalation. After three patients were treated at the first dose level, doses were escalated in increments that ranged up to 150% using single patient cohorts until moderate toxicity was observed, when a more conservative dose-escalation scheme was invoked. MTD was defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%. MTD was determined for both minimally pretreated (MP) and heavily pretreated (HP) patients. Plasma and urine were sampled to characterize the pharmacokinetic and excretory behavior of NSC 655649. RESULTS: Forty-five patients were treated with 130 courses of NSC 655649 at doses ranging from 20 mg/m(2) to 744 mg/m(2). Myelosuppression was the principal toxicity. Severe neutropenia, which was often associated with thrombocytopenia, was unacceptably high in HP and MP patients treated at 572 mg/m(2) and 744 mg/m(2), respectively. Nausea, vomiting, and diarrhea were common but rarely severe. The pharmacokinetics of NSC 655649 were dose dependent and fit a three-compartment model. The clearance and terminal elimination half-lives for NSC 655649 averaged 7.57 (SD = 4.2) L/h/m(2) and 48.85 (SD = 23.65) hours, respectively. Despite a heterogeneous population of MP and HP patients, the magnitude of drug exposure correlated well with the severity of myelosuppression. Antitumor activity was observed in two HP ovarian cancer patients and one patient with a soft tissue sarcoma refractory to etoposide and doxorubicin. CONCLUSION: Recommended phase II doses are 500 mg/m(2) and 572 mg/m(2) IV once every 3 weeks for HP and MP patients, respectively. The absence of severe nonhematologic toxicities, the encouraging antitumor activity in HP patients, and the unique mechanism of antineoplastic activity of NSC 655649 warrant further clinical development.

Adult↗
PubMed2001

Phase I and pharmacokinetic study of BMS-184476, a taxane with greater potency and solubility than paclitaxel.

PURPOSE: To assess the feasibility, toxicity, pharmacokinetics, and preliminary activity of BMS-184476 administered as a 1-hour intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of BMS-184476 as a 1-hour IV infusion every 3 weeks without premedication to prevent hypersensitivity reactions (HSR). Plasma sampling and urine collections were performed to characterize the pharmacokinetics and pharmacodynamics of BMS-184474. RESULTS: Thirty-four patients were treated with 78 courses of BMS-184476 at five dose levels ranging from 20 to 80 mg/m2. Dose-limiting toxicity (DLT), consisting of severe neutropenia with fever, severe diarrhea, and/or severe mucositis, was experienced during course 1 by six of nine minimally pretreated patients treated at the 70 and 80 mg/m2 dose level. In contrast, of 15 assessable patients treated at the 60 mg/m2 dose level, which is the maximum-tolerated dose (MTD) of BMS-184476 on this administration schedule, only one heavily pretreated patient developed DLT (grade 4 neutropenia with fever and grade 3 diarrhea). One patient developed a grade 2 HSR during a second course of BMS-184476 at the 40 mg/m2 dose level. A previously untreated patient with an advanced cholangiocarcinoma experienced a partial response, and a patient with an untreated carcinoma of the gastroesophageal junction had a minor response. The pharmacokinetics of BMS-184476 seemed linear in the dose range studied. Mean +/- SD values for clearance, volume of distribution at steady-state, and terminal half-life were 220 +/- 89 mL/min/m2, 402 +/- 231 L/m2, and 40.8 +/- 21.8 hours, respectively. CONCLUSION: The MTD and recommended dose for phase II evaluations of BMS-184476 is 60 mg/m2 as a 1-hour IV infusion every 3 weeks. The results of this study suggest that BMS-184476 may have several advantages compared with paclitaxel in terms of toxicity, pharmacokinetics, pharmaceutics, and administration and warrants further clinical development.

Adult↗
PubMed2001

Regulatory interactions between iron and nitric oxide metabolism for immune defense against Plasmodium falciparum infection.

Iron chelation therapy of Plasmodium falciparum infection alleviates the clinical course of cerebral malaria in children. This study assessed the underlying mechanisms of this therapy. Cytokine stimulation of human (intestinal cell line DLD-1) or murine cells (murine macrophage cell line RAW 264.7) resulted in increased nitric oxide (NO) formation and decreased survival of plasmodia within cocultured human erythrocytes. The addition of desferrioxamine (DFO) before cytokine treatment increased both NO formation and parasite killing but had no effect in the presence of the inhibitor of NO formation, L-N6-(1-iminoethyl)-lysine. Moreover, peroxynitrite, which is formed after chemical reaction of NO with superoxide, appears to be the principal effector molecule for macrophage-mediated cytotoxicity toward P. falciparum, and interferon-gamma is a major regulatory cytokine for this process. The effect of DFO on the clearance of plasmodia appears to be due to enhanced generation of NO, rather than to limitation of iron availability to the parasite.

Animals↗
PubMed2001

Modulation of cellular iron metabolism by hydrogen peroxide. Effects of H2O2 on the expression and function of iron-responsive element-containing mRNAs in B6 fibroblasts.

Cellular iron uptake and storage are coordinately controlled by binding of iron-regulatory proteins (IRP), IRP1 and IRP2, to iron-responsive elements (IREs) within the mRNAs encoding transferrin receptor (TfR) and ferritin. Under conditions of iron starvation, both IRP1 and IRP2 bind with high affinity to cognate IREs, thus stabilizing TfR and inhibiting translation of ferritin mRNAs. The IRE/IRP regulatory system receives additional input by oxidative stress in the form of H(2)O(2) that leads to rapid activation of IRP1. Here we show that treating murine B6 fibroblasts with a pulse of 100 microm H(2)O(2) for 1 h is sufficient to alter critical parameters of iron homeostasis in a time-dependent manner. First, this stimulus inhibits ferritin synthesis for at least 8 h, leading to a significant (50%) reduction of cellular ferritin content. Second, treatment with H(2)O(2) induces a approximately 4-fold increase in TfR mRNA levels within 2-6 h, and subsequent accumulation of newly synthesized protein after 4 h. This is associated with a profound increase in the cell surface expression of TfR, enhanced binding to fluorescein-tagged transferrin, and stimulation of transferrin-mediated iron uptake into cells. Under these conditions, no significant alterations are observed in the levels of mitochondrial aconitase and the Divalent Metal Transporter DMT1, although both are encoded by two as yet lesser characterized IRE-containing mRNAs. Finally, H(2)O(2)-treated cells display an increased capacity to sequester (59)Fe in ferritin, despite a reduction in the ferritin pool, which results in a rearrangement of (59)Fe intracellular distribution. Our data suggest that H(2)O(2) regulates cellular iron acquisition and intracellular iron distribution by both IRP1-dependent and -independent mechanisms.

Amino Acid Sequence↗
PubMed2001

Pronounced postprandial lipemia impairs endothelium-dependent dilation of the brachial artery in men.

OBJECTIVE: Pronounced postprandial lipemia has been established as a risk factor for cardiovascular disease, but reports regarding its effect on endothelial function have been controversial. In the present study the influence of a standardized fatty meal with its ensuing postprandial lipemia of highly varying magnitude on endothelium-dependent dilation (EDD) was investigated. METHODS: In 17 healthy, normolipidemic men EDD of the brachial artery was quantified in two series of three measurements each. In both series initial measurements were performed at 08:00 h after an overnight fast followed by measurements at 12:00 and 16:00 h, in the first series with continued fasting and in the second following the ingestion of a standardized fatty test meal 4 and 8 h postprandially. RESULTS: Measurements of EDD in the fasting state revealed the recently appreciated diurnal variation with higher values in noon and afternoon hours compared with morning values (2.5+/-1.6% at 08:00, 7.5+/-2.7% at 12:00, and 7.0+/-2.1% at 16:00 h, P<0.001 by analysis of variance). Postprandial EDD values measured at 12:00 h were, at the average, lower than fasting EDD values measured at 12:00 h and correlated inversely with the magnitude of postprandial triglyceridemia (r=-0.81, P<0.001). In multivariate analysis, higher postprandial lipemia was associated with impaired postprandial EDD (P<0.001) independent of fasting triglycerides, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, insulin, age and body mass index. CONCLUSION: We conclude that pronounced postprandial lipemia is associated with transient impairment of endothelial function. Our findings support the notion that impaired triglyceride metabolic capacity plays an important role in atherogenesis.

Adult↗
PubMed2001

Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches.

AIM: In the present 6-month multicentre trial, the outcome of 2 different approaches to non-surgical treatment of chronic periodontitis, both involving the use of a locally delivered controlled-release doxycycline, was evaluated. MATERIAL AND METHODS: 105 adult patients with moderately advanced chronic periodontitis from 3 centres participated in the trial. Each patient had to present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth (PPD) of > or =5 mm and bleeding following pocket probing (BoP), out of which at least 2 sites had to be > or =7 mm and a further 2 sites > or =6 mm. Following a baseline examination, including assessments of plaque, PPD, clinical attachment level (CAL) and BoP, careful instruction in oral hygiene was given. The patients were then randomly assigned to one of two treatment groups: scaling/root planing (SRP) with local analgesia or debridement (supra- and subgingival ultrasonic instrumentation without analgesia). The "SRP" group received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia. In addition, at a 3-month recall visit, a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided. This was followed by subgingival application of an 8.5% w/w doxycycline polymer at sites with a remaining PPD of > or =5 mm. The patients of the "debridement" group were initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia, and followed by application of doxycycline in sites with a PPD of > or =5 mm. At month 3, sites with a remaining PPD of > or =5 mm were subjected to scaling and root planing. Clinical re-examinations were performed at 3 and 6 months. RESULTS: At 3 months, the proportion of sites showing PPD of < or =4 mm was significantly higher in the "debridement" group than in the "SRP" group (58% versus 50%; p<0.05). The CAL gain at 3 months amounted to 0.8 mm in the "debridement" group and 0.5 mm in the "SRP" group (p=0.064). The proportion of sites demonstrating a clinically significant CAL gain (> or =2 mm) was higher in the "debridement" group than in the "SRP" group (38% versus 30%; p<0.05). At the 6-month examination, no statistically significant differences in PPD or CAL were found between the two treatment groups. BoP was significantly lower for the "debridement" group than for the "SRP" group (p<0.001) both at 3- and 6 months. The mean total treatment time (baseline and 3-month) for the "SRP" patients was 3:11 h, compared to 2:00 h for the patients in the "debridement" group (p<0.001). CONCLUSION: The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis.

Adult↗
PubMed2001

Great ape DNA sequences reveal a reduced diversity and an expansion in humans.

The extent of DNA sequence variation of chimpanzees is several-fold greater than that of humans. It is unclear, however, if humans or chimpanzees are exceptional among primates in having low and high amounts of DNA sequence diversity, respectively. To address this, we have determined approximately 10,000 bp of noncoding DNA sequences at Xq13.3 (which has been extensively studied in both humans and chimpanzees) from 10 western lowland gorillas (Gorilla gorilla gorilla) and 1 mountain gorilla (Gorilla gorilla beringei; that is, from 2 of the 3 currently recognized gorilla subspecies), as well as 8 Bornean (Pongo pygmaeus pygmaeus) and 6 Sumatran (Pongo pygmaeus abelii) orang-utans, representing both currently recognized orang-utan subspecies. We show that humans differ from the great apes in having a low level of genetic variation and a signal of population expansion.

Animals↗