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Biomedical subjects

Michael Schwartz

Publications and source records attributed to Michael Schwartz.

13 recordsLinked to original sources
PubMed2003

Straight talk. New approaches in healthcare. Hospital/physician partnerships are key to growth of market share.

UNLABELLED: Do you know who your biggest competitor is? It's probably your most loyal physician group. That's because up to 80% of hospitals are competing with their own medical staffs, according to PricewaterhouseCoopers' research. Physicians are launching revenue enhancement and diversification strategies to combat declining reimbursement and respond to the surge in demand for outpatient services. THE SOLUTION: Hospital administrators need to aggressively develop economic partnerships with their medical staff. In this installment of Straight Talk, we discuss how two institutions have crafted viable hospital and physician ventures. Modern Healthcare and PricewaterhouseCoopers present Straight Talk. The session on growth strategies was held on May 6, 2003. Charles S. Lauer, publisher of Modern Healthcare, was the moderator.

Attitude of Health Personnel↗
PubMed2003

The effect of tibial torsion on the dynamic function of the soleus during gait.

An induced acceleration analysis (IAA) model was used to investigate the effect of tibial torsion on the ability of the soleus to support and propel the body during gait. The IAA approach is well suited for this study because it allows soleus action to be quantified in the presence of varying amounts of tibial torsion, while other factors such as body configuration and muscle activation are held constant. The results of the analysis showed that excess tibial torsion shifts the induced knee joint accelerations toward flexion, valgus and external rotation, and diminishes body center-of-mass support and propulsion. This analysis supports the concept that bony mal-alignment can lead to 'lever arm dysfunction'. The objective data correlate with previous clinical observations related to valgus stress, crouch and the role of the soleus in level walking. The IAA model provides a tool for examining various aspects of abnormal gait independently and quantitatively.

Adaptation, Physiological↗
PubMed2003

Effects of amphotericin B and caspofungin on histamine expression.

STUDY OBJECTIVE: To determine the effects of amphotericin B deoxycholate and caspofungin on the release of histamine from human peripheral blood cells, mononuclear cells, and mast cells. DESIGN: In vitro cell culture experiments. SETTING: University medical center. MATERIAL: Cultured human mononuclear (THP-1) and mast (HMC-1) cells from five healthy volunteers. MEASUREMENTS AND MAIN RESULTS: The cultured cells were incubated with increasing concentrations of amphotericin B deoxycholate, diphenhydramine, amphotericin B deoxycholate plus diphenhydramine, caspofungin, caspofungin plus diphenhydramine, and the calcium ionophore A23187 for up to 24 hours. Histamine concentrations and histamine N-methyltransferase activity were determined at various time points throughout exposure. Cell viability was assessed by exclusion of erythrocin B. The A23187 increased histamine concentrations from baseline in peripheral blood and HMC-1 cells. No change in histamine concentrations was observed in response to amphotericin B deoxycholate, whereas caspofungin induced a significant increase in histamine release in peripheral blood cells and HMC-1 cells. No change in histamine concentrations was observed in THP-1 cells in response to any pharmacologic agent tested. Similarly, histamine N-methyltransferase activity in peripheral blood was not affected by amphotericin B deoxycholate, but was significantly decreased by caspofungin. CONCLUSION: Amphotericin B deoxycholate does not affect histamine concentrations or histamine N-methyltransferase activity in whole blood or HMC-1 cells, suggesting that the amphotericin B-induced infusion-related reaction is not a histamine-mediated event. Conversely, caspofungin increased histamine concentrations in whole blood and HMC-1 cells and inhibited histamine N-methyltransferase activity. These data suggest that infusion-related reactions associated with caspofungin may be mediated by histamine release secondary to caspofungin.

Amphotericin B↗
PubMed2002

A1 adenosine receptor activation induces ventriculomegaly and white matter loss.

A1 adenosine receptors (A1ARs) are widely expressed in the brain during development. To examine whether A1AR activation can alter postnatal brain formation, neonatal rats from postnatal days 3 to 14 were treated with the A1AR agonist N6-cyclopentyladenosine (CPA) in the presence or absence of the peripheral A1AR antagonist 8-(p-sulfophenyl)-theophylline (8SPT). CPA or CPA + 8SPT treatment resulted in reductions in white matter volume, ventriculomegaly, and neuronal loss. Quantitative electron microscopy revealed reductions in total axon volume following A1AR agonist treatment. We also observed reduced expression of myelin basic protein in treated animals. Showing that functional A1ARs were present over the ranges of ages studies, high levels of specific [3H]CCPA binding were observed at PD 4, 7 and 14, and receptor-G protein coupling was present at each age. These observations show that activation of A1ARs with doses of CPA that mimic the effects of high adenosine levels results in damage to the developing brain.

Adenosine↗
PubMed2002

Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer.

PURPOSE: To evaluate safety and pharmacokinetics (PK), and determine the recommended dose for efficacy studies, of L-377202, a novel peptide conjugate of doxorubicin (Dox) that releases the active metabolites leucine-doxorubicin (Leu-Dox) and Dox on cleavage by membrane-bound prostate-specific antigen (PSA). PATIENTS AND METHODS: Nineteen patients with advanced hormone-refractory prostate cancer were treated intravenously with 71 cycles of L-377202 at escalating dose levels of 20 (n = 1), 40 (n = 3), 80 (n = 4), 160 (n = 3), 225 (n = 6), and 315 mg/m(2) (n = 2) once every 3 weeks. Toxicity, response, and PK of L-377202 were assessed. RESULTS: L-377202 was well tolerated. Dose-limiting grade 4 neutropenia was noted in two of two patients administered 315 mg/m(2) (both patients were able to resume therapy at 225 mg/m(2)). The recommended dose for efficacy studies was 225 mg/m(2), which induced grade 4 neutropenia in one of six patients. PK studies demonstrated that L-377202 was metabolized to Leu-Dox and Dox. PK were linear; after administration of single doses of 225 mg/m(2), the mean area under the concentration-time profiles of L-377202, Leu-Dox, and Dox were 6 micromol x L/h, 4 micromol x L/h, and 1 micromol x L/h, and peak concentrations were 14 micromol/L, 5 micromol/L, and 120 nmol/L, respectively. At 225 and 315 mg/m(2), five patients completed at least three cycles of therapy; two patients had a greater than 75% decrease in PSA, and one patient had a stabilized PSA. No response was noted at dose levels less than 225 mg/m(2). CONCLUSION: This is the first study of selective drug delivery in humans using a novel PSA-activated agent. L-377202 was cleaved to produce detectable levels of the active metabolites Leu-Dox and Dox. L-377202 was well tolerated and established a safe dose level for further study.

Aged↗
PubMed2002

A positive-strand RNA virus replication complex parallels form and function of retrovirus capsids.

We show that brome mosaic virus (BMV) RNA replication protein 1a, 2a polymerase, and a cis-acting replication signal recapitulate the functions of Gag, Pol, and RNA packaging signals in conventional retrovirus and foamy virus cores. Prior to RNA replication, 1a forms spherules budding into the endoplasmic reticulum membrane, sequestering viral positive-strand RNA templates in a nuclease-resistant, detergent-susceptible state. When expressed, 2a polymerase colocalizes in these spherules, which become the sites of viral RNA synthesis and retain negative-strand templates for positive-strand RNA synthesis. These results explain many features of replication by numerous positive strand RNA viruses and reveal that these viruses, reverse transcribing viruses, and dsRNA viruses share fundamental similarities in replication and may have common evolutionary origins.

Bromovirus↗
PubMed2002

Precursor B-cell lymphoblastic lymphoma/leukemia presenting as osteoblastic bone lesions.

Lymphoblastic lymphoma is a neoplasm of precursors lymphoid cells morphologically indistinguishable from those of acute lymphoblastic leukemia. Approximately 10% to 20% of cases are of the precursor B-cell (P-BLL) phenotype. This type of lymphoma most often manifests in the skin and lymph nodes. In recent years more case reports of P-BLL presenting as lytic bone lesions have appeared in the literature. We describe an interesting case of P-BLL/leukemia that initially presented as an osteoblastic bone lesion and discuss the differential diagnosis from a pathologic-radiologic standpoint.

Adult↗
PubMed2002

Single- and multiple-dose pharmacokinetics of caspofungin in healthy men.

Caspofungin, a glucan synthesis inhibitor, is being developed as a parenteral antifungal agent. The pharmacokinetics of caspofungin following 1-h intravenous infusions in healthy men was investigated in four phase I studies. In an alternating two-panel (six men each), rising-single-dose study, plasma drug concentrations increased proportionally with the dose following infusions of 5 to 100 mg. The beta-phase half-life was 9 to 10 h. The plasma drug clearance rate averaged 10 to 12 ml/min. Renal clearance of unchanged drug was a minor pathway of elimination (approximately 2% of the dose). Multiple-dose pharmacokinetics were investigated in a 2-week, serial-panel (5 or 6 men per panel) study of doses of 15, 35, and 70 mg administered daily; a 3-week, single-panel (10 men) study of a dose of 70 mg administered daily; and a parallel panel study (8 men) of a dose of 50 mg administered daily with or without a 70-mg loading dose on day 1. Moderate accumulation was observed with daily dosing. The degree of drug accumulation and the time to steady state were somewhat dose dependent. Accumulation averaged 24% at 15 mg daily and approximately 50% at 50 and 70 mg daily. Mean plasma drug concentrations were maintained above 1.0 microg/ml, a target selected to exceed the MIC at which 90% of the isolates of the most clinically relevant species of Candida were inhibited, throughout therapy with daily treatments of 70 or 50 mg plus the loading dose, while they fell below the target for the first 2 days of a daily treatment of 50 mg without the loading dose. Caspofungin infused intravenously as a single dose or as multiple doses was generally well tolerated. In conclusion, the pharmacokinetics of caspofungin supports the clinical evaluation of once-daily dosing regimens for efficacy against fungal infections.

Adult↗
PubMed2002

Expression of melanoma antigen gene by cells from inflamed joints in juvenile rheumatoid arthritis.

OBJECTIVE: To determine if synovial fluid (SF) cells from inflamed joints of patients with juvenile rheumatoid arthritis (JRA) express melanoma antigen gene (MAGE) RNA and protein. METHODS: The pattern of MAGE-A1 expression was analyzed in inflammatory synovial tissue and peripheral blood mononuclear cells (PBMC) from patients with JRA by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry. RESULTS: MAGE-A1, previously detected only in tumor cells, is strongly expressed in SF cells from patients with JRA. Immunocytochemistry revealed strong staining of SF cells in all of 22 specimens tested. PBMC from patients (7 of 7) also expressed MAGE-A1, but not as strongly as SF cells. Two-color immunofluorescence showed colocalization with CD4 and CD14. Flow cytometry on 3 samples of SF cells confirmed the presence of MAGE-A1 on the cell surface and intracellularly. Five of 5 SF cell samples were positive for MAGE-A1 by RT-PCR. CONCLUSION: Mononuclear cells from inflamed joints and blood from patients with JRA express MAGE-A1. MAGE family proteins were previously thought to be expressed only by certain tumors and presented by HLA Class I, resulting in tumor cell lysis by cytotoxic T cells. The observation of MAGE-A1 expression in JRA suggests an association with autoimmune disease and a possible causal role for MAGE antigen in the chronic inflammation of JRA.

Adolescent↗
PubMedDate not supplied

Cutaneous anthrax.

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Adult↗