Parenteral iron use in the management of anemia in end-stage renal disease patients.

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products.

Cough frequency and cough receptor sensitivity to citric acid challenge during a simulated ascent to extreme altitude.

The aim of this study was to determine the frequency of cough and the citric acid cough threshold during hypobaric hypoxia under controlled environmental conditions. Subjects were studied during Operation Everest 3. Eight subjects ascended to a simulated altitude of 8,848 m over 31 days in a hypobaric chamber.

Treatment of cancer of the exocrine pancreas.

Background: The incidence of cancer of the exocrine pancreas varies among populations, being the fourth or fifth cause of cancer death in the West. Outcome remains poor and opinions remain divided over the optimal management of the condition.

Method: A computer literature search was made of the MEDLINE database from January 1990 to December 1997 and selected other studies.

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain.

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects.

High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension.

The pathogenesis of pulmonary hypertension (PH) remains poorly understood. Vasoconstriction, although likely to be a major factor in the disease, varies between patients and studies of a variety of vasoactive substances have sometimes yielded conflicting results. Amongst these substances, alteration of the nitric oxide (NO) system has been cited as a possible pathogenic factor but both reduction and elevation of the expression of endothelial NO-synthase (eNOS) have been reported in pulmonary vessels.

Non-evidence of estrogen receptors in the rectal mucosa.

The aim of the study was to investigate whether estrogen receptors are present in the rectal mucosa of premenopausal women compared to postmenopausal women and men. Thirty biopsies obtained from the rectal mucosa at colonoscopy, performed to investigate inflammatory bowel disease in 23 patients and neoplasia in 7, were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen receptors. The study group (n = 10) were non-pregnant premenopausal women and the control group (n = 20) were postmenopausal women (n = 10) and men (n = 10).

Expression of inducible nitric oxide synthase and formation of peroxynitrite in posttransplant obliterative bronchiolitis.

Background: Obliterative bronchiolitis is characterized histologically by inflammation, epithelial cell damage and loss, fibrosis, and eventual obliteration of airways. Production of high levels of the potential cytotoxin nitric oxide by inducible nitric oxide synthase has been implicated in several inflammatory diseases. The damaging effects of nitric oxide are mediated by peroxynitrite, are formed from nitric oxide and superoxide, and can be demonstrated by the detection of nitrotyrosine.

Assessment of pelvic stabilization devices for improved field reproducibility.

The aim of this study was to evaluate the improvement in patient comfort and field positional accuracy provided by a new pelvic stabilization system when delivering multiple field radiotherapy to the pelvis. The Pelvic Cradle (BEHTS Manufacturing, Brisbane, Qld, Australia) is a stabilization device that provides reproducible patient positioning and levelling. Ninety patients were randomized into three groups.

Synthesis and 5-HT-3 receptor binding of 2- and 3-(halo)alkoxyl substituted (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chlorobenzamides as potential radioligands.

In an effort to develop selective, high-affinity radioligands for the 5-HT-3 receptor, a series of homologues of 5-chloro-2,3-dimethoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide (2b) was prepared in which individual methoxy groups were replaced by ethoxyl, (2-fluoroethoxyl), allyloxyl, propargyloxyl, or (3-iodoallyl)oxyl groups.

Synthesis and radiolabeling of (S)-4-amino-5-iodo-2-methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide, the active enantiomer of [125I]iodozacopride, and re-evaluation of its 5-HT3 receptor affinity.

We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)-iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to that obtained from (S)-3-amino-quinuclidine and 4-amino-2-methoxybenzoic acid via its corresponding 1-imidazole derivative.

Cough frequency and cough-receptor sensitivity are increased in man at altitude.

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher.

Hypoxia, hypocapnia and spirometry at altitude.

1. Both hypoxia and hypocapnia can cause broncho-constriction in humans, and this could have a bearing on performance at high altitude or contribute to altitude sickness. We studied the relationship between spirometry, arterial oxygen saturation and end-tidal carbon dioxide (ETCO2) concentration in a group of healthy lowland adults during a stay at high altitude, and then evaluated the response to supplementary oxygen and administration of a beta 2 agonist.

Nasal mucociliary transport is impaired at altitude.

There have been a number of anecdotal reports of rhinitis and nasal obstruction occurring at altitude. To quantify these reports, we investigated nasal obstruction and mucociliary transport in a group of healthy volunteers trekking to Mount Everest Base Camp, Nepal, altitude 5,300 m. Nasal obstruction was estimated by subjective scoring and mucociliary transport was determined by the saccharin method.

Human lung mononuclear cells induce nitric oxide synthase in murine airway epithelial cells in vitro: role of TNFalpha and IL-1beta.

Nitric oxide (NO) is a gas released by the airway epithelium, but the mechanism regulating NO release is unclear. We hypothesized that lung mononuclear cell release of tumor necrosis factor alpha (TNF) and interleukin-1beta (IL-1) would induce epithelial cells to release NO. Lung mononuclear cells were obtained from seven normal volunteers by bronchoalveolar lavage and cultured with Escherichia coli lipopolysaccharide for 24 h.

Calcitriol in the management of secondary hyperparathyroidism of renal failure.

Secondary hyperparathyroidism (HPT) is characterized by persistent hypersecretion of parathyroid hormone (PTH), and produces characteristics of hyperparathyroid bone disease and a variety of biochemical and hormonal derangements. Management of uremic secondary HPT involves both prevention and treatment. Among preventive measures are attempts to control serum phosphate and serum calcium concentrations through dietary restriction, administration of phosphate binders, and calcium supplementation.

Renal amyloidosis in related English foxhounds.

Renal amyloidosis was diagnosed in six related English foxhounds from two separate hunting kennels. There was no apparent age or sex predilection. All the dogs had clinical and laboratory findings compatible with renal disease.

3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor antagonists.

Early structure-activity studies on racemic tryptophan ester and amide NK-1 antagonists 5-7 led to the discovery that the potency of the series could be markedly increased by moving the carbonyl function in these molecules to an off-chain position as in the 3-aryl-1,2-diacetamidopropane 9. Further medicinal chemistry incorporating this change resulted in the discovery of a novel series of highly potent aryl amino acid derived NK-1 antagonists of the R stereoisomeric series (IC50's = 100 pM to > 5 microM). Compounds in this series were shown to be competitive antagonists using an in vitro NK-1 smooth muscle assay, and this data correlated well with observed human NK-1 binding affinities.

Effect of altitude on spirometric parameters and the performance of peak flow meters.

Background: Portable peak flow meters are used in clinical practice for measurement of peak expiratory flow (PEF) at many different altitudes throughout the world. Some PEF meters are affected by gas density. This study was undertaken to establish which type of meter is best for use above sea level and to determine changes in spirometric measurements at altitude.

Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist.

LY303870 [(R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4- (piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane] is a new, potent and selective nonpeptide neurokinin-1 (NK-1) receptor antagonist. LY303870 bound selectively and with high affinity to human peripheral (Ki = 0.15 nM) and central (Ki = 0.

Influence of cellulose triacetate hemodialyzers on vancomycin pharmacokinetics.

This study was designed to evaluate the pharmacokinetics of vancomycin during hemodialysis with cellulose triacetate (CT) high-flux dialyzers and to assess the influence of membrane surface area on intradialytic clearance. In a randomized crossover fashion, the pharmacokinetics of vancomycin were evaluated during dialysis with the CT 110 and CT 190 membranes. Six hemodialysis patients received 1 g of vancomycin immediately after the completion of a dialysis session, and subsequently, blood samples were obtained over a 5-day study period.