A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer.

Purpose: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer.

Patients And Methods: A total of 317 neutropenic patients (<500 cells/mm3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily).

Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects.

Several studies suggest that dietary supplementation with antioxidants can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents. Administration of antineoplastic agents results in oxidative stress, i.e.

Nociception in cyclooxygenase isozyme-deficient mice.

Prostaglandins formed by cyclooxygenase-1 (COX-1) or COX-2 produce hyperalgesia in sensory nerve endings. To assess the relative roles of the two enzymes in pain processing, we compared responses of COX-1- or COX-2-deficient homozygous and heterozygous mice with wild-type controls in the hot plate and stretching tests for analgesia. Preliminary observational studies determined that there were no differences in gross parameters of behavior between the different groups.

Thermal probes alone or with epinephrine for the endoscopic haemostasis of ulcer haemorrhage.

In the last two decades, significant progress has been made in the diagnosis, prognostication and treatment of patients with severe peptic ulcer haemorrhage. Patients can now be risk stratified by clinical presentation and endoscopic stigmata of ulcer haemorrhage. The purposes of this chapter are to discuss: (1) the techniques of thermal probe with or without epinephrine for haemostasis of ulcers with major stigmata of haemorrhage and (2) the outcomes of treatment of patients with ulcer haemorrhage treated with endoscopic thermal probes or other therapies, medical therapy and/or surgery.

Striatal kinetic modeling of FDOPA with a cerebellar-derived constraint on the distribution of volume of 30MFD: a PET investigation using non-human primates.

The peripherally born metabolite of FDOPA, 3-O-Methyl-FDOPA (3OMFD), crosses the blood-brain barrier, thus complicating positron emission tomography-FDOPA (PET-FDOPA) data analysis. In previous reports the distribution volume (DV) of 3OMFD was constrained to unity. We have recently shown that the forward transport rate-constant of FDOPA (K(S1)) and the cerebellum-to-plasma ratio (C(b)/C(p)), a measure for the DV of 3OMFD, are functions of plasma large neutral amino acid (LNAA) concentration.

Nitric oxide: a unique endogenous signaling molecule in vascular biology.

The properties of nitric oxide as an endogenous cell signaling molecule in vascular biology are described.

Effects of nitric oxide on the copper-responsive transcription factor Ace1 in Saccharomyces cerevisiae: cytotoxic and cytoprotective actions of nitric oxide.

Previous studies indicate that nitric oxide (NO) can serve as a regulator/disrupter of metal-metabolizing systems in cells and, indeed, this function may represent an important physiological and/or pathophysiological role for NO. In order to address possible mechanisms of this aspect of NO biology, the effect of NO on copper metabolism and toxicity in the yeast Saccharomyces cerevisiae was examined. Exposure of S.

Making history: Thomas Francis, Jr, MD, and the 1954 Salk Poliomyelitis Vaccine Field Trial.

This article focuses on the poliomyelitis vaccine field trial directed by Thomas Francis,Jr, MD, of the University of Michigan Vaccine Evaluation Center and sponsored by the National Foundation for Infantile Paralysis (NFIP) or, as it was better known to the public, the March of Dimes. It was a landmark in the widescale testing of a vaccine and the ethical use of human subjects. Millions of American parents readily volunteered their healthy children to participate.

rTLE3, a newly identified transducin-like enhancer of split, is induced by depolarization in brain.

The transducin-like enhancers of split are a family of mammalian proteins that share sequence homology with the Drosophila protein Groucho. Using representational difference analysis, we isolated the cDNA for a previously unidentified gene, rTLE3 (rat transducin-like enhancer of split 3), as a sequence induced by depolarization and forskolin, but not by neurotrophins or growth factors, in PC12 pheochromocytoma cells. rTLE3 encodes the protein rTLE3, a 764-amino acid orthologue of mouse and human TLE3.

Combined revascularization and microvascular free tissue transfer for limb salvage: a six-year experience.

Atherosclerotic vascular disease causing extensive tissue loss of the lower extremities often results in primary amputation. Combined revascularization and free tissue transfer has been described as a method of extending limb salvage to these patients. The durability of this combined procedure remains unknown, thus the objective of this report is to describe the immediate and long-term results in a series collected over 6 years.

The interaction of nitric oxide (NO) with the yeast transcription factor Ace1: A model system for NO-protein thiol interactions with implications to metal metabolism.

Nitric oxide (NO) was found to inhibit the copper-dependent induction of the yeast CUP1 gene. This effect is attributable to an inhibition of the copper-responsive CUP1 transcriptional activator Ace1. A mechanism is proposed whereby the metal binding thiols of Ace1 are chemically modified via NO- and O(2)-dependent chemistry, thereby diminishing the ability of Ace1 to bind and respond to copper.

D1 dopamine receptor signalling defect in spontaneous hypertension.

Dopamine modulates cardiovascular function by actions in the central and peripheral nervous system, by altering the secretion/release of prolactin, pro-opiomelanocortin, vasopressin, aldosterone, and renin, and by directly affecting renal function. Dopamine produced by the renal proximal tubule exerts an autocrine/paracrine action via two classes of dopamine receptors, D1-like (D1 and D5) and D2-like (D2, D3, and D4), that are differentially expressed along the nephron. The autocrine/paracrine function of dopamine, manifested by tubular rather than by haemodynamic mechanisms, becomes most evident during extracellular fluid volume expansion.

The University of Michigan Medical School, 1850-2000: "an example worthy of imitation".

The 150th anniversary of the University of Michigan Medical School affords occasion for both celebration and reflection, not just in Ann Arbor but throughout the world, as we consider its contributions to medical education, research, and health care over the past century and a half. This article explores the medical school's origins as a frontier medical outpost and describes the vital reforms in medical education implemented in Ann Arbor long before the landmark Flexner Report on Medical Education of 1910. It also depicts how and why the medical school developed as it did and what features are distinctive or typical about the school during this period.

Manipulating the host to study bacterial virulence.

The ability to manipulate animal hosts as well as bacterial pathogens greatly expands the utility of in vivo models of infection. For example, the construction of mice that harbor human tissues or express specific transgenes can provide ligand-receptor interactions that are essential for pathogenesis. Interactions between virulence factors and specific host defenses can sometimes be resolved by challenging selectively immuno deficient mice with bacteria containing virulence gene mutations.

Transcriptional regulation of the cyclooxygenase-2 gene in activated mast cells.

Activation of mast cells by aggregation of their IgE receptors induces rapid and transient synthesis of cyclooxygenase-2 (COX-2). In this study we investigated (i) the cis-acting response elements and transcription factors active at the COX-2 promoter and (ii) the signal transduction pathways mediating COX-2 induction following aggregation of mast cell IgE receptors. Transient transfection assays with COX-2 promoter/luciferase constructs suggest that a consensus cyclic AMP response element is essential for induced COX-2 expression.

Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage.

Background: Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain.

Methods: We studied the role of urgent colonoscopy in the diagnosis and treatment of 121 patients with severe hematochezia and diverticulosis. All patients were hospitalized, received blood transfusions as needed, and received a purge to rid the colon of clots, stool, and blood.

The urokinase plasminogen activator receptor (UPAR) is preferentially induced by nerve growth factor in PC12 pheochromocytoma cells and is required for NGF-driven differentiation.

Nerve growth factor (NGF)-driven differentiation of PC12 pheochromocytoma cells is a well studied model used both to identify molecular, biochemical, and physiological correlates of neurotrophin-driven neuronal differentiation and to determine the causal nature of specific events in this differentiation process. Although epidermal growth factor (EGF) elicits many of the same early biochemical and molecular changes in PC12 cells observed in response to NGF, EGF does not induce molecular or morphological differentiation of PC12 cells. The identification of genes whose expression is differentially regulated by NGF versus EGF in PC12 cells has, therefore, been considered a source of potential insight into the molecular specificity of neurotrophin-driven neuronal differentiation.

Nitric oxide as a signaling molecule in the vascular system: an overview.

In retrospect, basic research in the fields of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) during the past two decades appears to have followed a logical course, beginning with the findings that NO and cGMP are vascular smooth muscle relaxants, that nitroglycerin relaxes smooth muscle by metabolism to NO, progressing to the discovery that mammalian cells synthesize NO, and finally the revelation that NO is a neurotransmitter mediating vasodilation in specialized vascular beds. A great deal of basic and clinical research on the physiologic and pathophysiologic roles of NO in cardiovascular function has been conducted since the discovery that endothelium-derived relaxing factor (EDRF) is NO. The new knowledge on NO should enable investigators in this field to develop novel and more effective therapeutic strategies for the prevention, diagnosis, and treatment of numerous cardiovascular disorders.

Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells.

Activation of mast cells by aggregation of their high-affinity IgE receptors stimulates prostaglandin (PG) D(2) synthesis and secretion. An immediate phase of PGD(2) synthesis, complete within 30 min, is followed by a delayed, second phase of PGD(2) production that reaches a maximum 4 to 8 h after activation. Activation of mast cells from COX-2 (-/-) mice stimulates the release of PGD(2) during the first 30 min, whereas activation of mast cells from COX-1 (-/-) mice does not generate any PGD(2) in the first 2 h.

Treatment of hereditary and acquired thrombophilic disorders.

The treatment of hereditary and acquired thrombophilic disorders is based on an understanding of the disease pathophysiology, prevalence, associated morbidity and mortality, and available therapeutic options. Genetic mutations are identified that result in activated protein C (APC) resistance and hyperhomocyst(e)inemia. The underlying etiologies are less well-defined; however, the disorders of factor XII deficiency, dysfibrinogenemia, Wien-Penzing platelet defect, and sticky platelet syndrome (SPS) are treatable inherited thrombophilias.