Computer simulation of ciprofloxacin pharmacokinetics in patients on CAPD

Continuous ambulatory peritoneal dialysis (CAPD) has become an accepted alternative to chronic hemodialysis in the treatment of end-stage renal disease. The method utilizes the diffusion of drugs from the blood through the peritoneal membrane to the peritoneal cavity if administered intravenously (IV) and perorally (PO) and in the opposite direction if applied intraperitoneally (IP). The present work uses an open, two-compartment pharmacokinetic model reversibly linked with the compartment representing the peritoneal cavity and an analog-hybrid computer to simulate drug levels in sampled and unsampled compartments under conditions of various routes of administration (IV, IP and sequential IV, IP and PO) and different clinical status (presence and absence of peritonitis). The drug chosen for simulation was ciprofloxacin (CIP), a new synthetic antibacterial agent of the 4-quinolone group. Eight patients were included in the study, and CIP concentrations in plasma and dialysate were obtained by HPLC analysis to assess the reliability of the model and the efficiency of the sequential dosing scheme. CIP plasma and dialysate levels were adequate for the majority of microbes causing CAPD peritonitis. The proposed regimen was efficient in 85% of cases.     

Amphetamine regulation of acetylcholine and gamma-aminobutyric acid in nucleus accumbens.

In situ hybridization histochemistry and in vivo microdialysis were combined to study the effect of amphetamine on the expression of choline acetyltransferase and glutamate decarboxylase67 mRNA and in vivo release of acetylcholine and GABA in rat medial nucleus accumbens. Differential effects on acetylcholine and GABA neurons by a single challenge injection of amphetamine (1.5 mg/kg, s.c.) were apparent in saline-pretreated and amphetamine-pretreated (same dose, twice daily for the previous seven days) rats. Extracellular acetylcholine levels were increased up to 50% over a prolonged period following both single and repeated amphetamine. In contrast, extracellular concentrations of GABA were gradually decreased to half the control values, but only in rats receiving repeated amphetamine. Although the increase of acetylcholine release was not associated with any change in choline acetyltransferase mRNA levels, the number of neurons expressing high levels of glutamate decarboxylase67 mRNA was decreased (28%) following repeated injections. Thus we suggest that amphetamine decreases extracellular GABA levels by a slow mechanism, associated with the decreased expression of glutamate decarboxylase67 mRNA in a subpopulation of densely labeled neurons in the medial nucleus accumbens. The delayed response by GABA to amphetamine may reflect supersensitivity in the activity of postsynaptic gamma-aminobutyric acid-containing neurons in nucleus accumbens as a consequence of the repeated amphetamine treatment.     

The contribution of risk factors to the effect of early otitis media with effusion on later language, reading, and spelling

A cohort of 946 children who were screened for otitis media with effusion (OME) from the ages of 2 to 4 were studied for language, reading, and spelling at 7 years of age. The effects of OME in combination with single risk factors and with increasing numbers of risk factors were investigated. An interaction with an additional risk factor was found only for gender and OME, with boys' spelling influenced negatively by a history of OME. OME in combination with preterm birth and low birthweight also appears to put children at risk for later langauage and educational problems. Although a negative linear relation between the number of risk factors and later functioning was found, it is suggested that OME, even when combined with a number of other risk factors, produces only minor effects on later language, reading, and spelling.     

Gallbladder and bile duct stones: percutaneous therapy with primary MTBE dissolution and mechanical methods

The authors describe percutaneous treatment of gallbladder or bile duct stones in 18 patients who were poor surgical candidates or in whom conventional therapy failed. Dissolution was performed in most cases with methyl tert-butyl ether (MTBE) because of its potent dissolution properties; other solvents used included monooctanoin or chelating solutions. Gallbladder stones were eliminated in 11 of 13 patients (six of seven with dissolution alone, four of four with dissolution and basket extraction, one with basket removal alone). In five patients with stones in the common bile duct (n = 3), cystic duct remnant (n = 1), and intrahepatic bile ducts (n = 1), stones were eliminated with dissolution alone in two and with dissolution plus basket extraction in one. In two patients percutaneous therapy failed due to complications (vagal hypotension with bile peritonitis and transient respiratory arrest) that occurred during catheter placement. Preliminary results suggest that MTBE is effective for dissolution of many gallbladder stones and some bile duct stones. Noncholesterol solvents and adjuvant mechanical maneuvers are valuable adjuncts to achieve complete stone elimination.     

Control of Tetranychus urticae Koch by extracts of three essential oils of chamomile,marjoram and Eucalyptus

Objective

To evaluate the acaricidal activity of extracts of three essential oils of chamomile, marjoram and Eucalyptus against Tetranychus urticae (T. urticae) Koch.

Methods

Extracts of three essential oils of chamomile, marjoram and Eucalyptus with different concentrations (0.5%, 1.0%, 2.0%, 3.0% and 4.0%) were used to control T. urticae Koch.

Results

The results showed that chamomile (Chamomilla recutita) represented the most potent efficient acaricidal agent against Tetranychus followed by marjoram (Marjorana hortensis) and Eucalyptus. The LC₅₀ values of chamomile, marjoram and Eucalyptus for adults were 0.65, 1.84 and 2.18, respectively and for eggs 1.17, 6.26 and 7.33, respectively. Activities of enzymes including glutathione-S-transferase, esterase (α-esterase and β-esterase) and alkaline phosphatase in susceptible mites were determined and activities of enzymes involved in the resistance of acaricides were proved. Protease enzyme was significantly decreased at LC₅₀ of both chamomile and marjoram compared with positive control. Gas chromatography-mass spectrometer (GC-MS) proved that the major compositions of Chamomilla recutita are α-bisabolol oxide A (35.251%), and trans-β-farersene (7.758%), while the main components of Marjorana hortensis are terpinene-4-ol (23.860%), p-cymene (23.404%) and sabinene (10.904%).

Conclusions

It can be concluded that extracts of three essential oils of chamomile, marjoram and Eucalyptus possess acaricidal activity against T. urticae.     

Dialysis patients after kidney graft failure: Slovenian experience

Increased mortality has been reported in patients starting dialysis after kidney graft failure. In this study we analyzed this subgroup of dialysis patients based on the data from the Slovenian Renal Replacement Therapy Registry. Patients starting dialysis after graft failure in the period between 2004 and 2008 were identified from the registry. Demographic, clinical and treatment data, as well as survival were compared to incident dialysis patients, who were on the waiting list or preparing for enrollment. There were 49 patients starting dialysis after 7.9 ± 6.4 years spent with a functioning graft and a total of 13.7 ± 7.4 years on renal replacement therapy. Their mean age was 48.3 ± 11.0 years (vs. 48.2 ± 13.9 years in incident patients, P = 0.96), 53% were male, and all were on hemodialysis. By the end of 2008, 8 (16%) patients had been re-transplanted (after a median of 27.5 months) and 11 (23%) had died (after a median of 1.4 months of dialysis). The cause of death was infection in five patients, a cardiovascular event in three, malignancy in two, and a cerebrovascular event in one patient. Deceased patients were significantly older, but similar to survivors in other parameters. Unadjusted one- and three-year survival rates after graft failure were both 77%, which was significantly worse than in incident patients (P < 0.001). To conclude, patients after graft failure have increased mortality in the first year after starting dialysis, but patients surviving the first year have good survival thereafter. Studies focusing on the early period after graft failure are necessary to improve outcomes.