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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 199 records · Page 11Linked to original sources
PubMed1993

Neopterin and prognosis in patients with adenocarcinoma of the colon.

Concentrations of neopterin, a sensitive indicator for the activation of cellular immunity, were measured in urine samples of 44 patients with adenocarcinoma of the colon at diagnosis. To judge the relative predictive value of neopterin concentrations, other routine clinical and laboratory variables were concomitantly determined. The patients were then followed up to 10 yr, and the abilities of all variables to predict death from cancer were assessed. Neopterin concentrations were not correlated with either tumor stage or Dukes' stage. In univariate analyses using the product-limit approach, four variables were significant indicators of poor prognosis: presence of distant metastases (P = 0.0001); high Dukes' stage (P = 0.0009); high urinary neopterin concentration (P = 0.0034); and advanced stage (P = 0.030). Presence versus absence of lymph node metastases was not associated with prognosis. Multivariate survival analyses by the proportional hazards technique demonstrated that neopterin provided statistically independent predictive information in addition to either presence versus absence of distant metastases or Dukes' stage. When neopterin and tumor stage were investigated for joint prediction, stage failed to be included in the model. Thus, neopterin concentrations provide valuable and statistically independent prognostic information in patients with adenocarcinoma of the colon.

Adenocarcinoma↗
PubMed1993

Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway.

Nitric oxide (NO) produced from L-arginine by NO synthases (NOS) is a transmitter known to be involved in diverse biological processes, including immunomodulation, neurotransmission and blood vessel dilatation. We describe a novel role of NO as a signaling molecule in post-transcriptional gene regulation. We demonstrate that induction of NOS in macrophage and non-macrophage cell lines activates RNA binding by iron regulatory factor (IRFs), the central trans regulator of mRNAs involved in cellular iron metabolism. NO-induced binding of IRF to iron-responsive elements (IRE) specifically represses the translation of transfected IRE-containing indicator mRNAs as well as the biosynthesis of the cellular iron storage protein ferritin. These findings define a new biological function of NO and identify a regulatory connection between the NO/NOS pathway and cellular iron metabolism.

Amino Acid Oxidoreductases↗
PubMed1993

Weight loss in patients with hematological neoplasias is associated with immune system stimulation.

Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon-gamma and tumor necrosis factor-alpha are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon-gamma activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon-gamma activity.

Biomarkers↗
PubMed1993

Phase II trial of 6-thioguanine administered as 120 hour continuous infusion for refractory or recurrent small cell lung cancer. A Southwest Oncology Group study.

Nineteen eligible patients with recurrent small cell lung cancer were treated with a 120 hour continuous infusion of 6-thioguanine at a starting dose of 35 mg/m2/day. There were no responses in these 19 patients. Toxicity was acceptable with the primary toxicity being hematologic. Based on this trial, 6-thioguanine is not felt to have significant antitumor activity in this patient population.

Aged↗
PubMed1993

A phase II trial of piroxantrone in adenocarcinoma of the pancreas. A Southwest Oncology Group study.

Thirty-five evaluable patients with advanced adenocarcinoma of the pancreas were treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. No objective responses were observed (95% confidence interval 0%-10%). Toxicities of grade > or = 3 were primarily hematologic and were seen in 28 patients. Piroxantrone is inactive in pancreatic cancer and no further investigation of this agent in this tumor is recommended.

Adenocarcinoma↗
PubMed1993

Serum soluble tumour necrosis factor receptor 55 is increased in patients with haematological neoplasias and is associated with immune activation and weight loss.

Enhanced concentrations of soluble forms of the receptor for tumour necrosis factor (TNF)-alpha have been detected in the serum of cancer patients. We determined serum concentrations of soluble TNF receptor p55 (sTNF-R55) in patients with haematological neoplasias, 50 patients suffering from non-Hodgkin's lymphoma (n = 35), Hodgkin's disease (n = 10) and multiple myeloma (n = 5). Compared with healthy controls and with patients with potential thyroid disease, significantly elevated concentrations of sTNF-R55 were found (mean +/- standard error: 2.68 +/- 0.22 vs. 1.23 +/- 0.21 ng/ml, P < 0.0001 and 2.18 +/- 0.32 ng/ml, P = 0.03). Likewise, neopterin concentrations were raised (19.6 +/- 3.66 vs. 5.3 +/- 0.25 nmol/l in controls, P < 0.0001). We found a significant correlation between sTNF-R55 and neopterin concentrations (Rs = 0.544, P < 0.001). Patients with weight loss showed higher sTNF-R55 concentrations than patients with stable weight. Our results confirm the relevance of sTNF-R55 concentrations in serum of patients with cancer.

Biopterins↗
PubMed1993

Gonadotropin-releasing hormone agonist administration in early human pregnancy is associated with normal outcomes.

OBJECTIVE: To evaluate the reproductive outcomes of early human gestations exposed to GnRH agonist (GnRH-a). Gonadotropin-releasing hormone agonist is commonly used as an adjunct to ovulation induction regimens, and sometimes early pregnancies are inadvertently exposed to the drug. There has been concern regarding possible teratogenic effects of GnRH-a on these gestations, but there is a paucity of data regarding human subjects. DESIGN: Identified pregnancies were followed for obstetric and fetal outcomes. PATIENTS, PARTICIPANTS: Over 4 years 18 early pregnancies among 17 women were found to be exposed to GnRH-a. During the month of conception, daily injections were begun on menstrual day 22 after documenting an ovulatory P level on day 21. Gonadotropin-releasing hormone agonist was discontinued from 10 to 24 days later, immediately after pregnancy was recognized. Obstetric and fetal outcomes were ascertained by chart review and telephone follow-up with mothers. RESULTS: Five first trimester losses were observed in 18 hCG confirmed pregnancies for a loss rate of 28%. Thirteen pregnancies produced apparently normal babies. One normal fetus was lost at 20 weeks' gestation because of cervical incompetence. CONCLUSION: There does not appear to be an increased risk of birth defects or pregnancy wastage in human pregnancies exposed to daily low-dose GnRH-a therapy in the first weeks of gestation.

Abnormalities, Drug-Induced↗
PubMed1993

Increased immune activation during and after physical exercise.

The present study has been performed to examine the pattern of immune response during and following a long-duration of physical exercise. We have measured plasma concentrations of serum soluble immune activation markers namely soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8), soluble intercellular adhesion molecule 1 (sICAM-1), soluble CD23 (sCD23), soluble tumor necrosis factor receptor (sTNF-R) and neopterin in 18 individuals before, during (ascent: 3 h, descent: 2 h) and after an alpine tour. Compared to baseline levels, all the parameters were significantly increased on top of the mountain and/or after descent. Within 36 hours after the tour sIL-2R, sCD8 and sICAM-1 decreased. In contrast, sTNF-R and neopterin levels remained higher than baseline throughout the study, only partially decreasing 24 and 36 hours from start. These data show immune system activation induced by physical exercise. The increase of parameters sTNF-R and neopterin, reflecting activation of macrophages, was sustained. The data suggest that immune activation phenomena may be involved in the pathogenesis of impaired immune function after exercise and the exercise-induced asthma.

Adult↗
PubMed1993

Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection.

The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-gamma, serum and urine neopterin, and beta 2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-gamma, neopterin and beta 2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-gamma-inhibiting erythropoiesis may be one underlying cause of anaemia in these patients.

Adolescent↗
PubMed1993

Neopterin, biochemistry and clinical use as a marker for cellular immune reactions.

Large amounts of neopterin are produced and released from human macrophages on stimulation with interferon-gamma. Neopterin is biologically stable, and it can be easily quantified in human body fluids. Neopterin measurements are useful to monitor allograft recipients to detect immunological complications. In autoimmune diseases, neopterin concentrations reflect the extent and activity of the disease. In infectious syndromes and in patients with cancer, neopterin concentrations provide prognostic information. In addition to providing clinically useful information, neopterin monitoring allows insight into the immunopathogenesis of a variety of diseases.

Biomarkers↗
PubMed1993

Parent training and social skills training for children with attention-deficit hyperactivity disorder: how can they be combined for greater effectiveness?

Attention-deficit hyperactive disorder (ADHD) is a chronic and treatment-refractory syndrome affecting academic, social and emotional adjustment in children. Stimulant medication is the treatment of choice and is often paired with psychosocial treatment. However, no single treatment modality alleviates the symptoms or improves the negative peer status of these children in their social ecology over the long term. This article reviews two psychosocial treatments used for ADHD, parent training and social skills training and suggests ways that these two components may be combined for greater effectiveness by encouraging the parent to: 1. learn more about the importance of developing social competence and positive peer status; 2. use incidental teaching and self-evaluation strategies; 3. become strategic organizers of the child's social life; and 4. become case managers to facilitate more consistency between the significant adults in the child's social environment.

Attention Deficit Disorder with Hyperactivity↗