Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous furosemide

Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed.     

Immunohistochemical analyses of gastric stromal tumors in Taiwanese.

BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs), identified by the presence of CD117 (KIT), were previously classified as gastric and intestinal smooth muscle tumors prior to the availability of immunohistochemical methods. This study evaluated the percentage of GISTs previously diagnosed as gastric smooth muscle tumors in our hospital during an 11-year period. METHODS: A total of 81 surgically resected gastric smooth muscle tumor specimens from 81 patients were collected from January 1986 to December 1997. Immunohistochemical studies were performed on these tumors with antibodies of CD34, CD117, smooth muscle actin (SMA), S-100, and desmin. RESULTS: Among the 81 tumors, 74 (91.4%) were CD117-positive and were classified as GISTs. Among the 74 GISTs, CD34 was positive in 72 tumors (97.3%), SMA was positive in 12 tumors (16.2%), desmin was positive in 5 tumors (6.7%), and S-100 was positive in 4 tumors (5.4%). The 7 tumors classified as non-GISTs had the following immunohistochemical characteristics: 1 was a CD117-negative CD34-positive stromal tumor (GINST) [1/81, 1.2%]; 3 were schwannomas with strong S-100-positive characteristics (3/81, 3.7%); and 3 were smooth muscle tumors with both SMA- and desmin-positive status (3/81, 3.7%). No clear relationship between CD117 or CD34 expression and prognosis was found for these tumors. CONCLUSIONS: The majority (91.4%) of gastric tumors originally diagnosed as gastric smooth muscle tumors were GISTs, except for small groups of smooth muscle tumors and schwannomas.     

Cosmetic orchiectomy for prostate cancer

With several effective therapeutic methods available for achieving androgen ablation, we must respect the psychological needs of our patients. The choice should ultimately be made by the patient after a thoughtful discussion of the advantages and disadvantages of various approaches. Cosmetic orchiectomy has the advantages of having the minimal morbidity of a simple operation, achieving the reliable result of androgen ablation and preserving the physical male organ without the risk of drug side effects and the dependence on patient compliance. In our experience, the operation is satisfactory both in achieving the therapeutic goal of androgen deprivation and in meeting the psychological needs of patients.     

A randomized controlled trial of electromagnetic therapy in the primary care management of venous leg ulceration

OBJECTIVE: The aim was to establish the potential efficacy, tolerabilityand side-effect profile of electromagnetic therapy as an adjunctto conventional dressings in the treatment of venous leg ulcers. METHOD: A prospective, randomized, double blind controlled clinicaltrial was carried out in a dedicated leg ulcer clinic basedin one urban general practice. Nineteen patients with leg ulcersof confirmed venous aetiology were assessed. The main outcomemeasures were rate and scale of venous leg ulcer healing, changesin patient-reported pain levels, quality of life, degree ofmobility, side effect profile and acceptability to patientsand staff. RESULTS: Sixty-eight per cent of patients attending this dedicated clinicachieved improvements in the size of their ulcer (4, 21%, healedfully) and in reduced pain levels (P < 0.05) during the trial,despite the chronicity of ulcer histories. Patients treatedwith electromagnetic therapy at 800 Hz were found at day 50to have significantly greater healing (P < 0.05) and paincontrol (P < 0.05) than placebo therapy or treatment with600 Hz. All patients reported improved mobility at the end ofthe study. The electromagnetic therapy was well tolerated bypatients, with no differences between groups in reporting adverseevents, and proved acceptable to staff. CONCLUSION: Despite the small numbers in this pilot study, electromagnetictherapy provided significant gains in the healing of venousleg ulcers and reduction in pain. Keywords. Electromagnetic therapy, RCT, leg ulcers, primary care.     

Effect of pulley integrity on excursions and work of flexion in healing flexor tendons

Effect of pulley integrity on excursions and work of flexion in healing flexor tendons@Wang YH @Gu YT @Chen F     

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.