Brain beta-endorphin and spinal-cord enkephalin concentrations in experimental arachnoiditis

Arachnoiditis was produced experimentally in male albino ICR mice by intrathecal injection of meglumine iocarmate . A control group received intrathecal injection of an electrolyte solution resembling CSF. Eight weeks after injection, the brains and spinal cords were removed for brain beta-endorphin and spinal cord met-enkephalin measurement by radioimmunoassay, and the dural sacs were removed for histologic examination to confirm the presence or absence of arachnoiditis. Brain beta-endorphin content was significantly reduced and spinal-cord enkephalin concentration was significantly elevated in iocarmate-treated animals. The dura and arachnoid in the treated mice were thickened and infiltrated with lymphocytes. These studies indicate that arachnoiditis alters endogenous polypeptide concentrations.     

Ureteral neoplasms

The authors review primary and secondary neoplastic lesions of the ureter. Primary ureteral tumors are rare, although when they occur, they usually consist of transitional cell carcinoma. The most frequent symptoms are hematuria, frequency, dysuria, and pain. Secondary ureteral neoplasms are caused by direct extension from an adjacent extraureteral primary tumor or from a site of bulky metastasis and, rarely, by metastasis from a distant primary tumor. The most useful diagnostic modalities are retrograde pyelography for direct visualization of ureteral involvement--particularly in the presence of high-grade obstruction--and computed tomography for evaluation of extraureteral extent of tumors and the presence of lymphadenopathy and distant metastases.     

Population pharmacokinetics and pharmacodynamics of cefpirome in critically ill patients against Gram-negative bacteria

Objectives To develop a population pharmacokinetics model for cefpirome in ICU patients, to assess pharmacokinetic-pharmacodynamic profiles vs. MIC distribution of likely ICU pathogens, and to assess their expected cumulative fraction of response (CFR). Design and setting Prospective observational study in a multidisciplinary ICU. Measurements and results Twelve patients received 2 g cefpirome intravenously over 12 h. Thirteen blood samples were taken on two occasions. Demographic and creatinine clearance data were collected. Based on the final covariate model obtained using NONMEM, Monte Carlo simulations were undertaken to simulate free-drug concentrations for two administration methods: intermittent bolus administration (IBA) and continuous infusion (CI) with a loading dose of 0.5 g. Concentration-time profiles were evaluated by the probability of achieving free-drug concentrations above the MIC for more than 65% of dosing interval. Using MIC distributions from the EUCAST programme the CFR for each method was evaluated. A three-compartment model with zero-order input best described the concentration-time data. The CFR for Escherichia coli and Klebsiella spp. was greater than 97% in all IBA and CI doses but for Pseudomonas aeruginosa, and Acinetobacter spp. achieved target concentrations of 56% and 46%, respectively. High-dose CI cefpirome (6 g/day) for P. aeruginosa and Acinetobacter spp. was required to achieve CFR of 89%. Conclusion Measured creatinine clearance appears to be a good marker of cefpirome clearance and potentially could be used to individualise cefpirome therapy. When given as IBA or CI for E. coli and Klebsiella spp., cefpirome should be successful. Cefpirome fails to achieve the bactericidal target even when administered at high-doses such as 6 g/day for P. aeruginosa and Acinetobacter spp. Prospective clinical studies are needed to conclusively validate these findings.     

Pharmacokinetic Profiles of High-Dose Intravenous Ciprofloxacin in Severe Sepsis

The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6.01 ± 1.93 mg/liter; D2, 6.68 ± 2.01 mg/liter; and D6 to D8 6.45 ± 1.54 mg/liter. Trough levels were as follows: D0, 0.6 ± 0.5 mg/liter; D2, 0.7 ± 0.4 mg/liter; and D6 to D8 0.6 ± 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 ± 3.8 mg · h/liter; D2, 16.8 ± 5.4 mg · h/liter; and D6 to D8, 15.5 ± 4.7 mg · h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.     

Outcomes associated with 12 years of grant funding: the Pediatric Endocrinology Nursing Society grant program

In 1990, the Pediatric Endocrinology Nursing Society (PENS) developed a grant program to provide funding to advance pediatric endocrinology nursing practice through basic and applied research. Minimal data exist regarding the effect of grant funding on professional development and research dissemination. The purpose of this study was to determine the extent that PENS' grant funding has resulted in professional presentations, publications, and further research funding. Nineteen grants that received funding were identified. Survey questions included whether the results of the PENS-funded study were presented, published, and resulted in subsequent funding from other sources. Outcome data were available for 11 of 18 grants (61%). All funded studies were presented at PENS conference; 55% were presented at other national or international conferences. Sixteen publications resulted from seven funded studies; 64% of PENS' funded studies led to additional funding, and 18% resulted in additional research studies. In summary, the research grant program of PENS funded 19 grants, which resulted in numerous publications, presentations, and, in some cases, additional research funding from other sources. Many grant recipients acknowledged that PENS was their first source of research funding and gave them the opportunity to become experienced in their role as clinical researchers.