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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 217 records · Page 12Linked to original sources
PubMed1993

Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group.

PURPOSE: To test the concept that cisplatin dose-intensity is important in the treatment of non-small-cell lung cancer (NSCLC), the Southwest Oncology Group (SWOG) performed a randomized trial comparing standard-dose cisplatin (SDCP) 50 mg/m2 days 1 and 8 on a 28-day cycle for eight cycles, high-dose cisplatin (HDCP) 100 mg/m2 days 1 and 8 for four cycles, and high-dose cisplatin plus mitomycin (HDCP-M) 8 mg/m2 day 1. To isolate the effects of dose-intensity versus total dose, the planned cumulative cisplatin dose was 800 mg/m2 in each arm. PATIENTS AND METHODS: Between July 1988 and April 1990, 356 patients were enrolled and 323 were eligible and assessable. All patients had metastatic, measurable disease, were chemotherapy-naive, and had a performance status (PS) of 0 to 2. RESULTS: Confirmed complete plus partial response rates were SDCP, 12%; HDCP, 14%; and HDCP-M, 27% (P < .05). Complete responses were uncommon (HDCP, 3%; HDCP-M, 4%) and were observed only in the high-dose arms. Progressive disease occurred more frequently in the SDCP arm (57%) compared with HDCP (38%) or HDCP-M (34%) (P < .05). However, there were no significant differences in median survival times (SDCP, 6.9 months; HDCP, 5.3 months; HDCP-M, 7.2 months; P = .53). The mean delivered dose-intensity for cisplatin was significantly greater in the high-dose arms: HDCP 41 mg/m2/wk and HDCP-M 39 mg/m2/wk, versus SDCP 23 mg/m2/wk (P = .05). The high-dose arms resulted in an increased incidence of ototoxicity, emesis, and myelosuppression, but similar degrees of renal toxicity and neuropathy compared with SDCP. CONCLUSION: This study does not confirm evidence of a steep clinical dose-response curve for cisplatin in NSCLC at the cisplatin dose-intensities achieved. The addition of mitomycin increases the response rate, but does not improve survival. Continued evaluation of new agents in this disease is warranted.

Adult↗
PubMed1993

Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion.

PURPOSE: To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization. PATIENTS AND METHODS: Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule. RESULTS: Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours. CONCLUSION: The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.

Adult↗
PubMed1993

Self-organizing neural networks as a means of cluster analysis in clinical chemistry.

Connectionist systems (often termed "neural networks") are an alternative way to solve data processing tasks. They differ radically from conventional "von-Neumann" computing devices. Recent work on neural networks in clinical chemistry was done using supervised learning schemes, resulting in models which resemble classical discriminant analysis. The aim of the present study is to make clinical chemists familiar with basic concepts of self-organizing neural networks employing unsupervised learning schemes. Using a benchmark data set on the composition of milk from 22 different mammals, it is demonstrated that self-organizing neural networks are capable of performing tasks similar to classical cluster analysis and principal component analysis. Self-organizing neural networks could be envisaged to provide an alternative way for reducing the dimensionality of complex multivariate data sets, thus producing easily comprehensible low-dimensional "maps" of essential features.

Animals↗
PubMed1993

Comparative effects of heme and metalloporphyrins on interferon-gamma-mediated pathways in monocytic cells (THP-1).

Previous results have demonstrated links between cell-mediated immunity, interferon (IFN)-gamma and neopterin production with heme, porphyrins, and iron metabolism. In this study, we compared the effects of heme, several metalloporphyrins, protoporphyrin IX, and iron on the signal or IFN-gamma-mediated pathways, such as the expression of major histocompatibility complex class II antigens, neopterin formation, and the degradation of tryptophan. Using the human monocytic cell line, THP-1, we found that heme, Zn-mesoporphyrin, Zn-deuteroporphyrin, Co-protoporphyrin, and iron reduced the efficiency of the IFN-gamma signal. In addition, Zn-mesoporphyrin almost fully inhibited IFN-gamma-induced degradation of tryptophan by the heme protein, indoleamine 2,3-dioxygenase. In contrast, tin-protoporphyrin enhanced the IFN-gamma effects as seen by increased neopterin production, enhanced tryptophan degradation, and elevated HLA-DR antigen expression on cells. These effects are considered to be due to the action of heme, metalloporphyrins, iron, or heme byproducts on the IFN-gamma signal, rather than to direct effects on IFN-gamma-induced enzymatic pathways. Heme and metalloporphyrins were previously shown to affect heme oxygenase activity, T cell growth, and lipid peroxidation and to modulate interleukin 2 activity. These pathways are also known to be influenced by IFN-gamma, and our data suggest that heme and metalloporphyrins may directly modulate the efficiency of the IFN-gamma signal.

Biopterins↗
PubMed1993

Biliary and urinary neopterin concentrations in monitoring liver-allograft recipients.

Biliary neopterin concentrations were measured daily in nine liver-transplant recipients during the early post-transplant period (on average, 25 days). Concentrations increased strongly during rejection episodes and decreased quickly after successful antirejection therapy. Contrary to the changes of urinary neopterin, cytomegalovirus infection and hepatitis were not associated with an increase in biliary neopterin concentrations. Therefore, measurement of neopterin in bile fluid and in urine may aid in distinguishing rejection from infectious complications in liver-allograft recipients.

Adult↗
PubMed1993

Elevated first-trimester serum relaxin concentrations in pregnant women following ovarian stimulation predict prematurity risk and preterm delivery.

OBJECTIVE: To determine whether ovarian stimulation would result in higher circulating relaxin concentrations and whether this hyperrelaxinemia would be associated with prematurity. METHODS: Two groups of women were studied: 1) women achieving pregnancy after ovarian stimulation (n = 114) and 2) women achieving pregnancy without treatment (n = 37). Serum was obtained at 6-12 weeks' gestational age; fetal number was determined by transvaginal ultrasound. Prematurity risk or preterm delivery was determined from the obstetric record. A specific human relaxin enzyme-linked immunosorbent assay was used to measure serum relaxin concentrations. Hyperrelaxinemia was defined as levels greater than 3 standard deviations above the weighted mean of levels in normal unstimulated singleton pregnancies at 6-12 weeks' gestation. RESULTS: An association was found between prematurity risk or premature delivery and peripheral relaxin concentrations during weeks 6-12 of pregnancy in women having ovarian stimulation and in women having multiple gestations. Circulating relaxin concentrations greater than 16 ng/mL in women having ovarian stimulation and levels greater than 7 ng/mL in women who had multiple gestations predicted prematurity risk or premature delivery in 50% of the women. CONCLUSIONS: These data demonstrate that after ovarian stimulation, some women have highly elevated circulating first-trimester relaxin concentrations. First-trimester hyperrelaxinemia identifies a group of women at risk for prematurity who can be monitored aggressively.

Adolescent↗
PubMed1993

The role of neopterin in assessing disease activity in Crohn's disease: classification and regression trees.

Neopterin, a product of human monocytes/macrophages stimulated by gamma-interferon, was previously found to be correlated with clinical activity of Crohn's disease. The present investigation attempted to identify more precisely the role of neopterin for assessment of clinical activity in a multivariate setting. A broad panel of clinical and laboratory variables was obtained on 76 patients. Neopterin was determined in urine by high performance liquid chromatography. Using a 4-point clinical activity score as dependent variable, multivariate linear discriminant analyses were performed in order to identify subsets of statistically independent laboratory activity indices. Neopterin was shown to be an independent indicator for clinical activity. The significant variables were then tested together with the eight constituent variables of the Crohn's Disease Activity Index. The resulting model, which consisted of the three laboratory variables--erythrocyte sedimentation rate, serum protein and neopterin, together with pain score--was further subjected to two multivariate techniques for comparison: polychotomous logistic regression analysis and the technique of classification and regression trees. By all methods, neopterin was included into the multivariate models, confirming that its determination aids in the assessment of clinical activity in Crohn's disease.

Adult↗
PubMed1992

Critical study of consensus analysis.

Consensus analysis has been proposed as a statistical method by which the efficacy of clinical and laboratory tests of inflammatory activity can be assessed. This technique is claimed to overcome the need for an external "gold standard" as a reference method; instead, the consensus of all tests is used as the gold standard. We have evaluated the reliability of consensus analysis using data collected from patients with Crohn's disease. Our results demonstrate that the technique depends strongly on the correlation structure underlying the set of measures of disease used for analysis. This observation was supported by a series of conventional cluster analyses of the same set of variables. Furthermore, slight modifications of the algorithm had profound effects on the final result. We conclude that for the evaluation of tests of inflammatory activity, an external reference method, albeit an imperfect one, remains indispensable.

Clinical Laboratory Techniques↗
PubMed1992

Biliary neopterin for differentiation between liver allograft rejection and viral graft infection.

Differential diagnosis between rejection and infection of a liver graft still represents a major problem. Rising concentrations of neopterin in serum or urine sensitively indicate rejection or infectious complications after renal, cardiac or bone marrow transplantation. Neopterin has been shown to be even more sensitive when measured locally, e.g. in the pancreatic juice of patients after pancreas allotransplantation. In the present study, we measured urinary and, for the first time, biliary neopterin concentrations in nine liver allograft recipients during the early post-transplant period.

Bile↗
PubMed1992

Association between serum-soluble CD8 levels and parameters of immune activation in patients with human immunodeficiency virus infection.

We compared the serum concentrations of soluble CD8 with the immune activation markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4, and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency virus (HIV) infection. The majority of patients had increased concentrations of soluble CD8, interferon-gamma and neopterin, and various significant correlations existed between them. Our results support the view that enhanced soluble CD8 levels indicate activated CD8+ T cells in patients with HIV infection.

Adult↗
PubMed1992

Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study.

A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicities were nausea and vomiting and anemia. On the basis of this trial, Didemnin-B is not felt to have significant effect with epithelial ovarian cancer.

Aged↗
PubMed1992

Controlled micromanipulation of human sperm in three dimensions with an infrared laser optical trap: effect on sperm velocity.

Individual human sperm can be micromanipulated in three dimensions using a 1.06 microns Nd:YAG laser trap. Single sperm swimming with velocities in the range of 65 to 85 microns/sec can be trapped with 40 mW of power through 120 seconds without a deleterious effect on velocity. Even though it will be necessary to further evaluate the effects of laser light on specific functions of sperm, our data suggest that decreasing the time of manipulation to a minimum will increase the safety of the micromanipulation procedures. Laser traps may play a role in assisted reproductive technology by facilitating the selective transport of individual sperm.

Analysis of Variance↗