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Biomedical subjects

G Weiss

Publications and source records attributed to G Weiss.

At least 109 records · Page 6Linked to original sources
PubMed1999

The eosinophilic response and haematological recovery after treatment for Plasmodium falciparum malaria.

To examine a possible relationship between the immune response and haematological recovery after acute falciparum malaria, we followed peripheral blood eosinophil counts and haemoglobin concentrations for 4 weeks after starting effective treatment in 70 adult Thai patients. Eosinophils are induced by Th-2 cytokines as well as other stimuli. Eosinophil counts were elevated in only 8 (11%) of the subjects at presentation, but were increased in 65 (93%) by day 7. Eosinophil counts then decreased markedly by day 14, followed by a second increase until day 28. A significant positive correlation was found between peak eosinophil counts on day 7 and the haemoglobin concentration on day 28, both in 16 subjects without stool parasites (r = 0.65, P = 0.006) and in 54 patients with stool parasites (r = 0.32; P = 0.0019). These results suggest that a robust eosinophilic response shortly after completing antimalarial therapy predicts a good recovery from malaria-associated anaemia.

Adult↗
PubMed1999

Iron and anemia of chronic disease.

Anemia of chronic disease (ACD) is the most frequent anemia found in hospitalized patients, often occurring in subjects suffering from chronic inflammatory disorders. The underlying diversion of iron traffic leads to a withdrawal of the metal from the sites of erythropoiesis and the circulation to the storage compartment in the reticuloendothelial system, thus resulting, at the same time, in hypoferremia and hyperferritinemia. Proinflammatory and antiinflammatory cytokines, acute-phase proteins, and radicals are prominently involved in causing these disturbances of iron homeostasis. The role of these factors, as well as the pathophysiological reasons for the development of ACD, is discussed in this review.

Acute-Phase Proteins↗
PubMed1999

Associations between cellular immune effector function, iron metabolism, and disease activity in patients with chronic hepatitis C virus infection.

We studied the associations of macrophage activity, T-helper cell types 1 and 2 (Th-1/Th-2) responses, and iron status in 55 patients with hepatitis C virus (HCV)-related liver disease and 28 control patients with noninfectious liver disease. Serum concentrations of soluble tumor necrosis factor receptor type II (sTNFrec 75), a macrophage activation marker, were higher in cirrhotic than in noncirrhotic patients (P<.001) regardless of their HCV status, whereas levels of neopterin, interleukin (IL)-4 and IL-10 did not differ significantly. In HCV-positive patients, sTNFrec 75 levels and transferrin saturation (TfS) correlated positively with levels of aspartate transaminase (P<.001 for sTNFrec 75 and P=.028 for TfS) and alanine transaminase (P=.003 for sTNFrec 75 and P=.039 for TfS). Increased TfS correlated significantly with both advanced liver disease and a predominant Th-2 pattern in HCV patients. Our data suggest that an association exists between macrophage activation and hepatic dysfunction, and that iron status may affect the clinical course of HCV infection by modulating Th-1/Th-2 responses in vivo.

Antigens, CD↗
PubMed1999

Pattern of nucleotide substitution and rate heterogeneity in the hypervariable regions I and II of human mtDNA.

This study provides a comprehensive survey of the complex pattern of nucleotide substitution in the control region of human mtDNA, which is of central importance to the studies of human evolution. A total of 1229 different hypervariable region I (HVRI) and 385 different hypervariable region II (HVRII) sequences were analyzed using a complex substitution model. Moreover, we suggest a new method to assign relative rates to each site in the sequence. Estimates are based on maximum-likelihood methods applied to randomly selected subsets of sequences. Our results indicate that the rate of substitution in HVRI is approximately twice as high as in HVRII and that this difference is mainly due to a higher frequency of pyrimidine transitions in HVRI. However, rate heterogeneity is more pronounced in HVRII.

DNA, Mitochondrial↗
PubMed1999

Phase I and pharmacologic study of the tyrosine kinase inhibitor SU101 in patients with advanced solid tumors.

PURPOSE: To evaluate the clinical feasibility and pharmacologic behavior of the platelet-derived growth factor (PDGF) tyrosine kinase inhibitor SU101, administered on a prolonged, intermittent dosing schedule to patients with advanced solid malignancies. PATIENTS AND METHODS: Twenty-six patients were treated with SU101 doses ranging from 15 to 443 mg/m(2) as a 24-hour continuous intravenous (IV) infusion weekly for 4 weeks, repeated every 6 weeks. Pharmacokinetic studies were performed to characterize the disposition of SU101 and its major active metabolite, SU0020. Immunohistochemical staining of PDGF-alpha and -beta receptors was performed on malignant tumor specimens obtained at diagnosis. RESULTS: Twenty-six patients were treated with 52 courses (187 infusions) of SU101. The most common toxicities were mild to moderate nausea, vomiting, and fever. Two patients experienced one episode each of grade 3 neutropenia at the 333 and 443 mg/m(2) dose levels. Dose escalation of SU101 above 443 mg/m(2)/wk was precluded by the total volume of infusate required, 2.5 to 3.0 L. Individual plasma SU101 and SU0020 concentrations were described by a one-compartment model that incorporates both first-order formation and elimination of SU0020. SU101 was rapidly converted to SU0020, which exhibited a long elimination half-life averaging 19 +/- 12 days. At the 443 mg/m(2)/wk dose level, trough plasma SU0020 concentrations during weeks 2 and 4 ranged from 54 to 522 micromol/L. Immunohistochemical studies revealed PDGF-alpha and -beta receptor staining in the majority (15 of 19) of malignant neoplasms. CONCLUSION: SU101 was well tolerated as a 24-hour continuous IV infusion at doses of up to 443 mg/m(2)/wk for 4 consecutive weeks every 6 weeks. Although further dose escalation was precluded by infusate volume constraints, this SU101 dose schedule resulted in the achievement and maintenance of substantial plasma concentrations of the major metabolite, SU0020, for the entire treatment period.

Adult↗
PubMed1999

High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.

PURPOSE: To determine the short- and long-term efficacy and toxicity of the high-dose intravenous bolus interleukin 2 (IL-2) regimen in patients with metastatic melanoma. PATIENTS AND METHODS: Two hundred seventy assessable patients were entered onto eight clinical trials conducted between 1985 and 1993. IL-2 (Proleukin [aldesleukin]; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Data were analyzed through fall 1996. RESULTS: The overall objective response rate was 16% (95% confidence interval, 12% to 21%); there were 17 complete responses (CRs) (6%) and 26 partial responses (PRs) (10%). Responses occurred with all sites of disease and in patients with large tumor burdens. The median response duration for patients who achieved a CR has not been reached and was 5.9 months for those who achieved a PR. Twelve (28%) of the responding patients, including 10 (59%) of the patients who achieved a CR, remain progression-free. Disease did not progress in any patient responding for more than 30 months. Baseline performance status and whether patients had received prior systemic therapy were the only predictive prognostic factors for response to IL-2 therapy. Toxicities, although severe, generally reversed rapidly after therapy was completed. Six patients (2%) died from adverse events, all related to sepsis. CONCLUSION: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.

Adult↗
PubMed1999

[Percutaneous dilatational tracheostomy].

BACKGROUND: Tracheostomy provides a method for long-term ventilation in intensive care, which reduces the risk of necrotizing lesions of the pharyngeal and laryngeal mucosa. Since the introduction of the percutaneous dilatational tracheostomy, experienced physicians are able to perform bedside tracheostomies. This presentation reviews the complication rate and long-term outcome of percutaneous dilatational tracheostomy. PATIENTS AND METHOD: The method was applied in 57 patients following previous orotracheal intubation averaging 7.8 days (3 to 15 days). Underlying diseases were sepsis/SIRS in 29, stroke in 7, cerebral hypoxemia after cardiopulmonary resuscitation in 10, trauma in 7, prolonged weaning in 2, primary neurological diseases in 2. RESULTS: The following complications occurred during the procedure: 1 major and 7 minor bleedings. 2 subcutaneous emphysemas, 1 mediastinal emphysema following tracheal injury. No complication required surgical intervention. In the follow-up 17 patients (30%) died from their underlying disease, none from complications of the tracheostomy. After removed of the tracheal tube, in 39 patients the stoma closed spontaneously within 7 to 14 days. In 8 patients the tracheostoma persisted for more than 3 months, but no clinically relevant tracheal stenosis was found. CONCLUSION: Percutaneous dilatational tracheostomy is a safe procedure easy to perform in intensive care units. Bronchoscopic control is necessary to avoid complications.

Dilatation↗
PubMed1999

Senior living technology.

The pros and cons of long term care's shift to a prospective payment system will be debated well into the next millennium, but its effects have already been profound. Not least has been the role PPS has played in dragging providers into the information age. Providers who were once steadfast in their refusal to participate in the computer revolution are now eager converts, implementing innovative information and clinical technologies to operate more efficiently and improve quality of care. Major changes rarely happen overnight. The long process of upgrading information systems and integrating new clinical technologies will remain arduous for years to come. But innovative technologies (including non-computerized devices and equipment ranging from lift systems to weightlifting equipment) will play an ever-increasing role as the industry takes a more consumer-driven approach to delivery of care. While some providers complain that vendors have been slow to develop the level of sophisticated, integrative systems they require, vendors fault providers for not being able or willing to invest the capital necessary to upgrade their platforms to support state-of-the-art software. But partnering rather than finger-pointing appears to be winning the day as facilities and vendors intensify their efforts to create more and better technology for long term care. In the following pages, we look at a number of innovative providers--from Bronx, New York, to Oshkosh, Wisconsin, from big chains to mom-and-pops--who have come up with creative solutions to common problems.

Aged↗
PubMed1998

Elevated maternal serum relaxin concentrations throughout pregnancy in singleton gestations after superovulation.

OBJECTIVE: To test the hypothesis that superovulation results in elevated maternal circulating relaxin concentrations throughout the second and third trimesters of pregnancy, independent of the pattern of hCG secretion. METHODS: Two groups of women with singleton gestations were studied: a group of nine women who achieved pregnancy after stimulation with human menopausal gonadotropin and a group of six women who achieved pregnancy without prior stimulation. Peripheral blood samples were drawn approximately every 5 weeks throughout the second and third trimesters. Serum relaxin concentrations were measured using a human relaxin-specific enzyme-linked immunosorbent assay; hCG was measured by an immunofluorometric assay. RESULTS: The stimulated group had significantly higher relaxin levels throughout pregnancy (P=.007, multivariate analysis of variance) than did nonstimulated controls. The mean relaxin level in stimulated patients was 1.78 ng/mL (95% confidence interval [CI] 1.5, 2.17) and in nonstimulated subjects the level was 0.73 ng/mL (95% CI 0.59, 1.25). Spline fits demonstrated that stimulated patients had higher relaxin levels throughout the second and third trimesters. There was no significant difference in hCG concentrations between the two groups (P=.61). CONCLUSION: In singleton gestations after superovulation, maternal serum relaxin concentrations are significantly higher throughout the second and third trimesters of pregnancy. These differences are independent of the pattern of hCG secretion. It appears that luteal relaxin secretion is controlled by factors in addition to hCG.

Adult↗
PubMed1998

A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion.

In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels ( 14, 28, 46, and 70 mg/m2/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 1/hr/m2. Both plasma concentrations achieved during infusion (r2 = 0.9) and area under the curve (AUC) (r2 = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 1/hr/m2. Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.

Adult↗
PubMed1998

Prolonged macrophage activation and persistent anaemia in children with complicated malaria.

OBJECTIVE: To determine if prolonged immune activation may be associated with the persistence of anaemia after treatment for severe malaria, we measured serum concentrations of neopterin and interleukin-4 during one week of antimalarial therapy and determined haemoglobin levels one month later. Neopterin is a clinically valuable marker for monitoring activation of macrophages by gamma-interferon and thus reflects the TH-1 immune response. Interleukin-4 is a major cytokine that tends to be inhibited by TH-1 activity. METHOD: The study population consisted of 26 Zambian children < 6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. Six children (23%) were anaemic (haemoglobin < 11 g/dl) one month after completing antimalarial therapy. RESULTS: On admission, concentrations of neopterin were markedly elevated in all patients. During the seven days of anti-malarial therapy, neopterin levels remained elevated in the 6 children who proved to have persistent anaemia one month after finishing treatment but declined significantly (P = 0.008) in the 20 children who corrected their haemoglobin levels by that time. Conversely, interleukin-4 levels declined in the children with persistent anaemia (P = 0.043) but not in the other children. CONCLUSION: Persistence of the TH-1 mediated immune response and associated activation of macrophages may be involved in the pathogenesis of lingering anaemia after treatment of malaria.

Analysis of Variance↗
PubMed1998

Cerebrospinal fluid levels of biopterin, nitric oxide metabolites, and immune activation markers and the clinical course of human cerebral malaria.

Cerebrospinal fluid samples from 130 children who presented with cerebral malaria were investigated to elucidate the impact of biopterin production, NO formation, and local immune activation on the clinical course of this disease. Biopterin levels were significantly lower in patients who were in a deeper coma (P = .02). Cerebrospinal fluid concentrations of NO were significantly higher in children who died than in survivors (P = .037); however, this was not the case for macrophage activation markers, neopterin, and soluble tumor necrosis factor receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO concentrations were significantly related to each other. Low biopterin levels in deep coma are compatible with an impaired local Th1 response, but the low levels could also be due to the scavenging of radicals or to decreased neurotransmitter synthesis. Local production of NO, most likely by nonimmune mechanisms, may be detrimental in cerebral malaria; however, this appears not to be the case for local Th1-mediated immune pathways.

Biopterins↗
PubMed1998

Inference of population history using a likelihood approach.

We introduce an approach to revealing the likelihood of different population histories that utilizes an explicit model of sequence evolution for the DNA segment under study. Based on a phylogenetic tree reconstruction method we show that a Tamura-Nei model with heterogeneous mutation rates is a fair description of the evolutionary process of the hypervariable region I of the mitochondrial DNA from humans. Assuming this complex model still allows the estimation of population history parameters, we suggest a likelihood approach to conducting statistical inference within a class of expansion models. More precisely, the likelihood of the data is based on the mean pairwise differences between DNA sequences and the number of variable sites in a sample. The use of likelihood ratios enables comparison of different hypotheses about population history, such as constant population size during the past or an increase or decrease of population size starting at some point back in time. This method was applied to show that the population of the Basques has expanded, whereas that of the Biaka pygmies is most likely decreasing. The Nuu-Chah-Nulth data are consistent with a model of constant population.

Base Composition↗
PubMed1998

Endothelin stimulation of rat uterine segment contractility is estrogen-dependent.

To determine whether the effect of endothelin upon in vitro uterine contractility requires estrogen, immature female Long Evans rats were subcutaneously injected daily for 3 days with either estradiol benzoate or vehicle. The uterine contractile response to endothelin (5 or 100 nM) was measured. A response to endothelin in vehicle-treated animals exposed to physiologic (5.6 mM) or high (70.6 mM) potassium levels was also noted. Vehicle-treated uteri did not respond to endothelin; the contractions in estrogen-treated uteri increased by 288%. With high potassium, and without estrogen, no response to endothelin was seen. These data indicate that the contractile effect of endothelin on the uterus requires estrogen.

Animals↗
PubMed1998

Demonstration of a relaxin receptor and relaxin-stimulated tyrosine phosphorylation in human lower uterine segment fibroblasts.

To elucidate the mechanism of relaxin action, we studied the binding characteristics of human relaxin and its effects on intracellular concentrations of cAMP and tyrosine phosphorylation of cellular proteins in a model system of human cervix, human lower uterine segment fibroblasts. Human relaxin labeled with 125I bound specifically to a single class of high-affinity relaxin binding sites, distinct from insulin receptors, with a mean (+/-SEM) dissociation constant (Kd) of 4.36 +/- 1.7 x 10(-9) M and a mean of 3220 +/- 557 binding sites per cell in human lower uterine segment fibroblasts. Relaxin, in quantities that were shown previously to stimulate intracellular levels of cAMP in other cell types, had no effect on intracellular levels of cAMP in human lower uterine segment fibroblasts even in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX). Incubation of the cells with relaxin caused a significant increase in tyrosine phosphorylation of a protein with an apparent Mr of approximately 220 kDa in these cells. In concert with results of recent studies that demonstrated that the Mr of the relaxin receptor is approximately 220 kDa, our data suggest that the phosphorylated protein is likely to be the relaxin receptor.

1-Methyl-3-isobutylxanthine↗
PubMed1998

[The effect of different variables on the in vitro dissolution of a theophylline sustained-release preparation].

In vitro dissolution studies are valuable tools to judge quality and stability of sustained release dosage forms and are often utilised to predict the in vivo performance. For this reason, in vitro dissolution experiments with varying pH, osmolarity, rotation speed, and with addition of surfactants were performed with a sustained release theophylline (CAS 58-55-9) dosage form (Bronchoretard). In order to mimic the physiological situation of the gastrointestinal tract more closely, the pH of the dissolution media was changed and human bile was added at different time points. The results obtained show that the in vitro dissolution of the dosage form differs only slightly for the parameters pH, osmolarity and stirring speed and always lies within in vivo verified dissolution limits. However, the addition of sodium dodecyl sulphate to the dissolution medium markedly altered the dissolution rate whereas addition of the physiologically surface active human bile did not change the dissolution rate. A comparison with in vivo results indicated, that only the physiologically adapted model guarantees reliable results whereas the addition of synthetic surfactants cannot allow for the prediction of bile or food effects. The meaning of in vitro dissolution tests thus is limited to development studies of dosage forms and to routine quality and stability control testing. For judging the in vivo characteristics in vitro studies have only limited value and have to be verified by pharmacokinetic studies.

Anti-Asthmatic Agents↗