Appropriate nitroxoline dosage regimen design

Clinically used dosage regimen of nitroxoline, three times 100 mg daily, was proved to be inappropriate because the successfulness of medical treatment was rarely sufficient. Nitroxoline, used as urinary antiseptic, exhibits its antibacterial activity in concentrations higher than 6 mg/l, as demonstrated in many "in vitro" experiments. This work deals with the most appropriate nitroxoline dosage form as well as with the optimal dosage regimen design. The data were obtained by the aid of the suitable pharmacokinetic model and multiple dosing simulation on analog-hybrid computer EAI 580. From the several studied alternatives two usable dosage forms with the necessary dose and corresponding dosage interval were selected.     

Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-elevation acute myocardial infarction (STEMI). In comatose survivors of cardiac arrest, mild induced hypothermia (MIH) improves neurological recovery. In the present study, we investigated feasibility and safety of combining primary PCI and MIH in comatose survivors of ventricular fibrillation with signs of STEMI after reestablishment of spontaneous circulation. Forty consecutive patients undergoing primary PCI and MIH from November 1, 2003 to December 31, 2005 were compared to 32 consecutive patients who underwent primary PCI but no MIH between January 1, 2000 and November 1, 2003. There were no significant differences between the MIH and no MIH groups in general characteristics, cardiac arrest circumstances and angiographic features. Except for decreases in heart rate during hypothermia interval, there was no difference between the MIH and no MIH groups in arterial pressure, peak arterial lactate (5.1 mmol/l versus 5.7 mmol/l; p = .56), need for vasopressors (65% versus 53%; p = .44), inotropes (48% versus 59%; p = .44), aortic balloon counterpulsation (20% versus 22%; p = .92), repeat cardioversion/defibrillation (30% versus 34%; p=.89) and use of antiarrhythmics (33% versus 53%; p = .13). There was also no difference in inspired oxygen requirements during mechanical ventilation and in renal function. Hospital survival with cerebral performance category 1 and 2 was significantly better in MIH group (55% versus 16%; p=.001). Our preliminary experience indicates that primary PCI and MIH are feasible and may be combined safely in comatose survivors of ventricular fibrillation with signs of STEMI. Such a strategy may improve survival with good neurological recovery.     

Dissociation of the metal inlay from the polyethylene liner in an uncemented threaded cup

We describe a case of spontaneous dissociation of the metal inlay from the polyethylene cup of a sandwiched metal-on-metal total hip prosthesis manufactured from Co-28Cr-6Mo SM 21 alloy. The patient, a 51-year-old active woman, started to feel groin pain 50 months postoperatively. The pain progressed after a slight trauma and led to final revision after 66 months in situ. No signs of impingement were observed. The polyethylene cup showed an approximately 2 mm-deep groove in the superior wall, and the head was heavily worn on the lateral side. In addition to the typically observed abrasive wear patterns, several types of severe wear defects were noticed. Extensive metallosis and necrosis were observed histologically. This unusual case of substantial deformation of the head and the cup was presumed to have occurred as a result of the increased friction and consequent high wear of the metal head.     

Mixture design of theophylline retard formulation

Three different cellulose derivatives (hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC) and microcrystalline cellulose (MC)) were used to prepare tablets containing 10% of theophylline with the aid of wet granulation. The retardation effect of different compositions of these cellulose derivatives was investigated. Using mixture design, the formulations with the best retardation properties were selected. On the basis of these results, tablets with different compositions containing 60% (300 mg) of theophylline were prepared. The simulation was performed on a personal computer with the implemented digital simulation language SIMCOS to predict steady-state plasma levels. It was established that formulation C, composed of 34.6% of MC 4.7% of HPMC 0.7% of HPC and 60% of theophylline exhibits in vivo the same retardation effect as commercially available theophylline tablets.     

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.     

Treatment of chronic wounds by means of electric and electromagnetic fields part 1 literature review

The healing of a cutaneous wound is accompanied by endogeneous electrical phenomena. Not knowing whether they represent merely a side-effect of the physiological processes which take course during healing or whether they play a much more important role as mediators of healing, externally applied electricity was examined as a therapeutic tool for the enhancement of natural regenerative processes. In the present review a historical literature survey dealing with human applications of electric current for wound healing acceleration is given. It presents a complete palette of heterogeneous studies, differing in the parameters of applied electric current, in delivery modes as well as in the types of wounds being stimulated. Because of all these differences, comparing the efficacy of the described methods is difficult and could hardly be objective. Therefore greater stress was laid upon the discussion concerning the problems in designing clinical studies (size of the sample observed, control group, ethics of the procedures), rationales for the employment and possible underlying mechanisms of particular methods, and problems of evaluating their efficacy. In spite of the extensive work performed in the field of electrical wound healing we remain only part way towards explaining the mechanisms by which electricity reinforces the regenerative capabilities of injured tissue as well as only part way towards the selection of the optimal stimulation method from among the published reports.     

Kinetic model of drug distribution in the urinary bladder wall following intravesical instillation

Intravesical administration of cytotoxic agents is commonly used in urological practice for treatment of superficial bladder cancer. The leading motive is optimisation of drug delivery near the site of action and reduction of systemic toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The objectives of this work were to develop a kinetic model of drug distribution in the bladder wall following intravesical instillation and to study the effect of various parameters on tissue and systemic drug exposure and explore the potential benefits of permeability enhancing effects of chitosan (CH) and polycarbophil (PC) through simulation. Key elements of the model are variable urinary drug concentration due to urine formation and voiding, biphasic diffusion in the bladder tissue and systemic absorption. Model parameters were estimated from bladder-tissue concentration profiles obtained in previous in vitro experiments with pipemidic acid (PPA) as a model drug. The results support further investigations on application of CH and PC in intravesical drug delivery. Both polymers increase permeability of the bladder wall by diffusion enhancement in the urothelium and presumably by improving the contact with the bladder surface. The developed mathematical model could serve for optimisation of intravesical drug delivery and future development of intravesical drug delivery systems.     

Gripping-force identification using EEG and phase-demodulation approach

In this paper we investigate the fuzzy identification of brain-code during simple gripping-force control tasks. Since the synchronized oscillatory activity and the phase dynamics between the brain areas are two important mechanisms in the brain’s function and information transfer, we decided to examine whether it is possible to extract the encoded information from the EEG signals using the phase-demodulation approach. The EEG was measured during the performance of different visuomotor tasks and the information we were trying to decode was the gripping force as applied by the subjects. The study revealed that it is possible, by using simple beta-rhythm filtering, phase demodulation, principal component analysis and a fuzzy model, to estimate the gripping-force response by using EEG signals as the inputs for the proposed model. The presented study has shown that even though EEG signals represent a superposition of all the active neurons, it is still possible to decode some information about the current activity of the brain centers. Furthermore, the cross-validation showed that the information about the gripping force is encoded in a very similar way for all the examined subjects. Thus, the phase shifts of the EEG signals seem to have a key role during activity and information transfer in the brain, while the phase-demodulation method proved to be a crucial step in the signal processing.     

Human skeletal muscle: Phasic type of electrical stimulation increases its contractile speed

Skeletal muscles, exposed to a prolonged period of specific functional demands, respond adaptively. Electrical stimulation, when employed as a technique for subjecting selected muscles to altered use, enables precise entrainment of the pattern of functional activity. In this investigation, the vastus lateralis muscle in a group of volunteers was stimulated. The stimulation program typical of a phasic type of activity (high frequency, high current amplitude, short pulse duration) intermittently subjected the stimulated muscles to brief periods of intense activity, followed by relatively long pauses. The activation-relaxation time ratio chosen was 1 to 13. It was determined to prevent the muscles from fatiguing. The effects of the chronic stimulation program were established by measurements of the time course of contraction and relaxation and fatigue of the vastus lateralis muscle. Chronic phasic electrical stimulation increased the speed of muscle contraction by 15% while the fatigue characteristics remained unchanged.