PubMed Health⌕ Search

Biomedical subjects

D Wexler

Publications and source records attributed to D Wexler.

At least 19 recordsLinked to original sources
PubMed2006

Circulating adiponectin concentrations in patients with congestive heart failure.

OBJECTIVES: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF). METHODS: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n = 175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1beta, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor alpha and CD-40 ligand were determined. The association of adiponectin with the clinical severity of CHF was sought as well as the predictive value of this adipokine on mortality, CHF hospitalisations or the occurrence of each of these end points. RESULTS: Concentrations of adiponectin were significantly increased in patients with CHF. Patients with higher New York Heart Association class had significantly higher serum concentrations of adiponectin. Adiponectin serum concentrations were lower in patients with diabetes and CHF as well as in patients with ischaemic cardiomyopathy. Serum adiponectin concentration was positively associated with age and NT-proBNP but was negatively correlated with C reactive protein concentrations. Serum adiponectin above the 75th centile was found to be an independent predictor of total mortality, CHF hospitalisations or a composite of these end points over a two-year prospective follow up. CONCLUSION: Adiponectin is increased in CHF patients and predicts mortality and morbidity.

Adiponectin↗
PubMed2006

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

Adult↗
PubMed2004

Correction of anemia in patients with congestive heart failure increases resting energy expenditure.

BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND METHODS: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls. RESULTS: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively). CONCLUSION: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.

Aged↗
PubMed2004

Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study.

Posaconazole is an antifungal with a wide-spectrum of activity against common and emerging fungal pathogens. In this randomised, open-label, two-way crossover study, the potential for drug interactions with posaconazole via the cytochrome P450 (CYP450) enzyme pathway was evaluated. Thirteen subjects received posaconazole tablets (2 x 100 mg) once daily for 10 days or no treatment; following a 14-day washout period, subjects were crossed over to the alternate treatment. The inhibition spectra of posaconazole were examined using a cocktail of the following probe substrates: caffeine (CYP1A2), tolbutamide (CYP2C8/9), dextromethorphan (CYP2D6 and total CYP3A4), chlorzoxazone (CYP2E1), and midazolam (hepatic CYP3A4). Except for midazolam, which was intravenously infused on Day 10, the cocktail probes were administered simultaneously on Day 9 during both treatment periods. Blood and urine samples were collected at specified times to quantitate probe substrates and/or metabolites. Based on insignificant differences in mean probe ratios, posaconazole did not inhibit CYP1A2, 2C8/9, 2D6, or 2E1. However, the midazolam AUC((tf)) was higher in the posaconazole than no-treatment group (93.4 n gh/ml versus 51.4 ng h/ml, P<0.01), indicating inhibition of hepatic CYP3A4. Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however these results suggest that posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.

Adult↗
PubMed2003

Anemia in chronic kidney disease and congestive heart failure.

Anemia is seen in chronic kidney insufficiency (CKI), dialysis patients, congestive heart failure (CHF), and renal transplantation. Anemia can lead to progressive cardiac damage as well as progressive renal damage. It is not generally appreciated that CHF itself may be a very common contributor to both the production of anemia as well as to the progression of the renal failure. Correction of the anemia with erythropoietin and, as necessary, intravenous iron, may prevent the deterioration of both the heart and the kidneys. We suggest that there is a triangular relationship, a vicious circle, between CHF, CKI and anemia where each of these three can both cause and be caused by the other. We call this syndrome the cardio-renal anemia (CRA) syndrome. All physicians, especially cardiologists and internists who treat CKI and CHF, should be made aware of the dangers of anemia in CKI and CHF and should work with nephrologists to correct it.

Anemia↗
PubMed2003

The cardio renal anemia syndrome: correcting anemia in patients with resistant congestive heart failure can improve both cardiac and renal function and reduce hospitalizations.

Anemia (Hemoglobin of < 12 to 13 g/dl) is frequently encountered in patients with congestive heart failure (CHF). This anemia may be partly due to hemodilution, partly to the associated reduction in renal function, and partly to the use of ACE inhibitors and aspirin. However, there is evidence that CHF alone--through excessive cytokine production may also reduce the bone marrow and cause anemia. In several recent studies anemia has been found to be associated with a more severe degree of CHF, a higher rate of death, renal failure, hospitalization and evidence of malnutrition. In both uncontrolled and controlled studies correction of anemia with erythropoietin with or without the addition of i.v. iron has been attempted. The correction of anemia has been associated with a marked improvement in New York Heart Association (NYHA) functional cardiac class and Left Ventricular Ejection Fraction, a marked reduction in the need for hospitalization and high dose oral and i.v. diuretics, and an improvement in exercise capacity, peak exercise oxygen utilization and quality of life. The serum creatinine, which had been increasing steadily before treatment, stabilized with the correction of anemia. All this suggests that control of anemia in CHF could become a valuable addition to the therapeutic armamentarium of CHF and might also play a major role in the prevention of progressive renal failure.

Anemia↗
PubMed2002

Mechanical milling assisted by electrical discharge.

Mechanical milling is an effective technique for the preparation of fine metallic and ceramic powders and can also be used to drive a wide range of chemical reactions. Milling devices include planetary machines, attritors and vibrational mills; products include amorphous, nanocrystalline and quasicrystalline materials, supersaturated solid solutions, reduced minerals, high-surface-area catalysts and reactive chemicals. During milling, solid-solid, solid-liquid and solid-gas reactions are initiated through repeated deformation and fracture of powder particles. A separate materials synthesis and processing technique involves reacting a material in a gas atmosphere under an electrical discharge. Here we show that the application of low-current, high-voltage electrical impulses during milling can result in both faster reactions and new synthesis and processing routes. We demonstrate the effects of glow (cold) and spark (hot) discharge milling on particle fracture for brittle, low-conductivity materials and ductile metals. Glow discharge milling was found to promote solid-gas reactions whereas spark discharge milling promotes fast fracturing, recrystallization, mineral reduction and solid-solid reactions.

Journal Article↗
PubMed2002

The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization.

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia.

Aged↗
PubMed2001

The effect of correction of mild anemia in severe, resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a randomized controlled study.

OBJECTIVES: This is a randomized controlled study of anemic patients with severe congestive heart failure (CHF) to assess the effect of correction of the anemia on cardiac and renal function and hospitalization. BACKGROUND: Although mild anemia occurs frequently in patients with CHF, there is very little information about the effect of correcting it with erythropoietin (EPO) and intravenous iron. METHODS: Thirty-two patients with moderate to severe CHF (New York Heart Association [NYHA] class III to IV) who had a left ventricular ejection fraction (LVEF) of < or =40% despite maximally tolerated doses of CHF medications and whose hemoglobin (Hb) levels were persistently between 10.0 and 11.5 g% were randomized into two groups. Group A (16 patients) received subcutaneous EPO and IV iron to increase the level of Hb to at least 12.5 g%. In Group B (16 patients) the anemia was not treated. The doses of all the CHF medications were maintained at the maximally tolerated levels except for oral and intravenous (IV) furosemide, whose doses were increased or decreased according to the clinical need. RESULTS: Over a mean of 8.2+/-2.6 months, four patients in Group B and none in Group A died of CHF-related illnesses. The mean NYHA class improved by 42.1% in A and worsened by 11.4% in B. The LVEF increased by 5.5% in A and decreased by 5.4% in B. The serum creatinine did not change in A and increased by 28.6% in B. The need for oral and IV furosemide decreased by 51.3% and 91.3% respectively in A and increased by 28.5% and 28.0% respectively in B. The number of days spent in hospital compared with the same period of time before entering the study decreased by 79.0% in A and increased by 57.6% in B. CONCLUSIONS: When anemia in CHF is treated with EPO and IV iron, a marked improvement in cardiac and patient function is seen, associated with less hospitalization and renal impairment and less need for diuretics.

Aged↗
PubMed2001

The pathological consequences of anaemia.

Many patients with chronic diseases such as chronic renal failure, chronic inflammatory bowel disease and rheumatoid arthritis are anaemic. Recently congestive heart failure (CHF) has also been found to be associated with anaemia. In all these diseases this anaemia or chronic disease is at least partially due to excessive production of cytokines and leukotrines that interfere both with the effect of erythropoietin (EPO) at the bone marrow and the release of stored iron in the reticuloendothelial system. Treating this anaemia with subcutaneous EPO and IV iron improves the weakness, fatigue, cachexia, nutritional state, mood, cognitive function and quality of life. In the case of CHF it also improves cardiac function and patient functional class, prevents deterioration of renal function and markedly reduces hospitalization. Very few agents in medicine improve so many aspects of the patient so well and so quickly. Unfortunately (for the suffering patient) this anaemia is often ignored and goes untreated.

Anemia↗
PubMed2001

Frontal and lateral cephalometry in patients with sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: The traditional lateral-view cephalometric analysis is limited because it provides only two-dimensional analysis of the three-dimensional craniofacial structure. The objectives were to analyze lateral and frontal cephalometric radiographs in a series of normal patients and those with varying degrees of sleep-disordered breathing and to define the degrees of narrowing or other unfavorable anatomical changes that might differentiate the patients with sleep-disordered breathing from normal subjects. STUDY DESIGN: A prospective study of 100 adult patients with sleep-disordered breathing and 60 age-matched normal subjects. METHODS: An analysis of the lateral and frontal cephalometric measurements was performed to assess velopharyngeal anatomical features. A comparison was made between the patients' polysomnographic and cephalometric analyses. RESULTS: The compromised cephalometric parameters that may be found in patients with sleep-disordered breathing include acute skull-base and bony nasopharynx angles, inferior hyoid position, thickening of the velum, reduced retrovelar posterior air space along with thickening of the velum, thickening of the posterior pharyngeal wall, and narrowing of the velopharyngeal lumen. Worsening of sleep-disordered breathing was generally associated with increased numbers of compromised cephalometric parameters. As body mass index increases, there is reduced velopharyngeal width, the velum thickness is increased, and the posterior pharyngeal wall thickness is increased. CONCLUSIONS: Sleep-disordered breathing is associated with statistically significant changes in a number of cephalometric measurements. Frontal cephalometric analysis adds further information regarding the anatomical assessment of patients with upper airway obstruction, enhancing the traditional lateral cephalometric view.

Body Mass Index↗
PubMed2001

The plasma concentration and LDL-C relationship in patients receiving ezetimibe.

Ezetimibe is a novel selective inhibitor of intestinal cholesterol absorption, which has been shown to significantly decrease low-density lipoprotein cholesterol (LDL-C). In this article, the relationship between plasma ezetimibe concentrations and lowering of LDL-C is determined using Emax and regression models. Data from two phase II double-blind placebo-controlled studies (n = 232 and 177) were used in which daily doses of ezetimibe ranging from 0.25 to 10 mg were administered for 12 weeks. Ezetimibe concentrations correlated significantly with percentage change in LDL-C from baseline (%LDL-C). Reductions in %LDL-C of 10%, 15%, and 20% were achieved with concentrations in the ranges 0 to 2, 2 to 15, and > 15 ng/ml, respectively, as compared with placebo. To achieve > 15% reduction in LDL-C, patients need to maintain trough concentrations > 15 ng/ml, taking plasma concentrations as a surrogate for concentrations at the enterocyte. Based on the doses administered, the 10 mg dose had the highest likelihood of sustaining such concentrations, confirming that a daily 10 mg dose of ezetimibe is an optimal therapeutic dose in the treatment of hypercholesterolemia.

Adolescent↗
PubMed2001

Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases.

The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.

Aged↗
PubMed2000

Anatomical basis of sleep-related breathing abnormalities in children with nasal obstruction.

OBJECTIVE: To define, in a group of children with nasal obstruction, the anatomical differences that differentiate those with quiet, unobstructed nocturnal respiration from those with obstructive sleep-related breathing abnormalities (snoring and obstructive sleep apnea). DESIGN: Case series. PATIENTS: Fifty-nine children aged 3 to 13 years (35 boys and 24 girls) with nasal obstruction and without tonsillar hypertrophy, known craniofacial syndromes, or neuromuscular diseases were included in the study. MAIN OUTCOME MEASURES: Each patient was categorized as to severity of nocturnal obstructive breathing symptoms. Angular and linear cephalometric measurements were used for assessment of craniofacial features. Clinical symptom scores were correlated with the cephalometric measurements. RESULTS: Significant craniofacial abnormalities were identified in patients prone to obstructive breathing patterns: increased flexure of the cranial base and bony nasopharynx, opening of the gonial angle, shortened mandibular length, dorsocaudal location of the hyoid, reduced posterior airway space, and increased velar thickness. CONCLUSIONS: A number of anatomical abnormalities may contribute to sleep-related abnormal breathing in otherwise normal children with nasal obstruction. Our results suggest that symptomatic children show some of the same skeletal and soft-tissue configurations that are found in adults with obstructive sleep apnea. While adenoidectomy is generally an effective treatment in children with obstructive sleep-related breathing abnormalities, the underlying craniofacial variances that remain after adenoidectomy may predispose these patients to redevelopment of obstructive breathing abnormalities in adulthood.

Adolescent↗
PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗
PubMed1999

Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis.

The design, fabrication, and operation of a radial capillary array electrophoresis microplate and scanner for high-throughput DNA analysis is presented. The microplate consists of a central common anode reservoir coupled to 96 separate microfabricated separation channels connected to sample injectors on the perimeter of the 10-cm-diameter wafer. Detection is accomplished by a laser-excited rotary confocal scanner with four color detection channels. Loading of 96 samples in parallel is achieved using a pressurized capillary array system. High-quality separations of 96 pBR322 restriction digest samples are achieved in < 120 s with the microplate system. The practical utility and multicolor detection capability is demonstrated by analyzing 96 methylenetetrahydrofolate reductase (MTHFR) alleles in parallel using a noncovalent 2-color staining method. This work establishes the feasibility of performing high-throughput genotyping separations with capillary array electrophoresis microplates.

Electrophoresis, Capillary↗