Continuous infusion versus intermittent administration of cefepime in patients with Gram-negative bacilli bacteraemia

The objective of this study was to compare the pharmacokinetics of cefepime administered by continuous infusion and intermittent injection regimens. A prospective, randomized, cross-over study of ten patients with Gram-negative bacilli bacteraemia was conducted. All patients were randomized to receive cefepime either as a 4-g continuous infusion over 24 h for 48 h or a 2-g bolus administered intermittently intravenously every 12 h for 48 h. After 48 h the patients received the alternative dose regimen. Cefepime pharmacokinetic studies were carried out during hours 36-48 after the start of both regimens. All of the pathogens isolated from the blood in 7 patients had a minimum inhibitory concentration (MIC) < 1 microg mL(-1). In both regimens, the serum cefepime concentrations at all time points were higher than the MIC for the pathogens isolated from this study. For the continuous infusion arm, the highest steady-state concentration was 49.80+/-18.40 microg mL(-1) and the lowest steady-state concentration was 41.42+/-16.48 microg mL(-1). The steady-state concentrations were greater than 4 times the MIC of 8 microg mL(-1). For the intermittent injection regimen, the mean trough concentration was 4.74+/-3.99 microg mL(-1). The mean serum cefepime concentration was above 8 microg mL(-1) for 81.66% of the dosing interval. Therefore, we conclude that either continuous infusion or intermittent injection can be used as an effective mode of cefepime administration to achieve bactericidal activity.     

Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia

The bactericidal activity of β-lactams is determined by the time that concentrations in tissue and serum are above the minimum inhibitory concentration (T > MIC) for the pathogen. The aim of this study was to compare the probability of target attainment (PTA) and the cumulative fraction of response (CFR) for meropenem between administration by bolus injection and a 3-h infusion. The study was a randomised, three-way, cross-over design in eight febrile neutropenic patients with bacteraemia. Each subject received meropenem in three regimens consecutively: (i) a bolus injection of 1 g every 8 h (q8h) for 24 h; (ii) a 3-h infusion of 1 g q8h for 24 h; and (iii) a 3-h infusion of 2 g q8h for 24 h. For pathogens with an MIC of 4 μg/mL, the PTA of achieving 40% T > MIC following administration of meropenem by a bolus injection of 1 g q8h, a 3-h infusion of 1 g q8h and a 3-h infusion of 2 g q8h was 75.7%, 99.24% and 99.96%, respectively. Only the 3-h infusion of 2 g q8h achieved a PTA >99% for 40% T > MIC for a MIC of 8 μg/mL. By referral to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC distributions, the three regimens of meropenem were predicted to achieve a CFR ≥ 90% against Escherichia coli and Klebsiella spp. In conclusion, a 3-h infusion of 2 g of meropenem q8h resulted in the highest PTA rates. The three regimens of meropenem had high probabilities of achieving optimal impact against E. coli and Klebsiella spp.     

Quaternary polymethacrylate–sodium alginate films: effect of alginate block structures and use for sustained release tablets

The objectives in this study were to characterize quaternary polymethacrylate–sodium alginate (QPM–SA) films prepared using high G block or high M block SA (GSA or MSA, respectively), and to investigate the effects of QPM–SA ratios, film-coating levels and SA block structures on propranolol HCl (PPN) released from coated tablets. The results demonstrated that GSA and MSA shared a similar interaction mechanism with QPM. The QPM–GSA films had higher puncture strength than the QPM–MSA films in dry and wet states, whereas the % elongations were not different. The drug permeability of the QPM–GSA films was lower than that of the QPM–MSA films in both acidic and neutral media, but higher water uptake of the QPM–GSA films was found at neutral pH. Moreover, the QPM–MSA-coated tablets had a greater PPN release rate than the QPM–GSA-coated tablets, and drug release was dependent on the film-coating levels. In addition, the QPM–SA films at a ratio of 4:0.5 produced a stronger film and could sustain PPN release. These results indicate that the QPM–GSA films had greater film strength and lower drug permeability than the QPM–MSA films. Additionally, the QPM–SA films have a strong potential for use in sustained-release tablets.     

Optical mapping study of blebbistatin-induced chaotic electrical activities in isolated rat atrium preparations

We have studied the spatiotemporal pattern of blebbistatin-induced anomalous electrical activities in isolated rat atrial preparations using the optical mapping of excitation spread. Atrial preparations including the right or left auricle were dissected from adult rat hearts. Each preparation was then stained with a fast merocyanine–rhodanine voltage-sensitive dye (NK2761). Using a multi-element (16 × 16) photodiode array, we assessed the spread of excitation optically by timing the initiation of the action potential-related extrinsic absorption changes. The contraction-related optical signals were suppressed by adding (S)-(−)-blebbistatin (10–100 μM) to the bathing solution. Blebbistatin had an effective delay time of about 1.5 h following its application, at which time anomalous electrical activities occurred. These took the form of triggered activities and rhythmical spontaneous excitations. We optically mapped the spatiotemporal patterns of the excitation spread during these anomalous electrical activities. When the triggered activities occurred, the site of ectopic focus, where the triggered action potential first appeared, and the area of excitation spread varied in every event. When the rhythmical spontaneous excitations occurred, the excitation spread from the anomalous pacemaker and, occasionally, their spatial shift was observed. In addition, the combination pattern of the spontaneous excitations and triggered activities was also observed. We suggest that these phenomena are due to the disturbed intracellular calcium dynamics induced by the application of blebbistatin.     

The efficacy of hydroxyapatite composite impregnated with amphotericin B

We investigated the efficacy of local biodegradable composites composed of hydroxyapatite-plaster of paris and either chitosan or alginate binder impregnated with amphotericin B. Antifungal activity was tested for Candida albicans using a modified disc diffusion technique for 6 weeks and compared with similarly impregnated polymethylmethacrylate. The physicochemical properties of each preparation were evaluated using scanning electron microscopy and Fourier transform infrared spectroscopy. The antifungal activity of amphotericin B eluted from the hydroxyapatite composites was significantly greater than the polymethylmethacrylate after 7 days. The hydroxyapatite composites and the polymethylmethacrylate system sustained their antifungal activity for at least 1 month. However, after 5 weeks, the antifungal activities of the polymethylmethacrylate systems rapidly lessened, while the hydroxyapatite composites sustained their activities at a much higher level. We found no difference in antifungal activity between the hydroxyapatite composite using either the chitosan or alginate binder. Scanning electron microscopy and Fourier transform infrared spectroscopy revealed the drug release profile. The hydroxyapatite composites impregnated with amphotericin B showed superior antifungal efficacy over those loaded in polymethylmethacrylate in an in vitro study, but additional in vivo research is needed to confirm this result.     

Effects of garlic on the induction of ventricular fibrillation

OBJECTIVE: Previous studies have shown that oral and intravenous administrations of garlic provide a significant antiarrhythmic effect and improve defibrillation efficacy. We tested the hypothesis that garlic could decrease the inducibility of ventricular arrhythmia. METHODS: Twenty-one pigs (25-30 kg) were divided into three groups. In each group, the ventricular fibrillation threshold (VFT) and the upper limit of vulnerability (ULV) were determined. After the control VFT and ULV values were obtained, solutions containing 20 mg/kg (group 1, n = 7) and 40 mg/kg (group 2, n = 7) of garlic (1.3% allicin) were administered intravenously. The VFT and ULV were determined again at the end of garlic infusion. In group 3 (n = 7), 100 mL of normal saline was administered instead of garlic. RESULTS: The VFT values in groups 1 and 2 were not different from the control VFT. The ULV in group 1 was not different from the control ULV. However, the ULV in group 2 (328 +/- 58 V, 8 +/- 3 J) was significantly lower than the control ULV (415 +/- 24 V, 13 +/- 2 J), thus accounting for the reduction of approximately 21% by peak voltage and approximately 38% by energy. The effective refractory period and diastolic pacing threshold were not altered after garlic infusion. Saline did not alter VFT or ULV. CONCLUSION: Garlic cannot alter the VFT, but it significantly decreases the ULV in a dose-dependent pattern, indicating that it can reduce the range of the stimulation strength between the VFT and ULV (vulnerability window) during the vulnerable period of a cardiac cycle.     

The malaris muscle: its morphological significance for sustaining the intraorbital structures

The orbicularis oculi muscle, an important mimetic muscle, was investigated to ascertain its anatomical relation to facial aging—especially its orbital part (Oo). Previous studies of the distinct muscle bundles frequently found inferior to the Oo have provided various definitions, including that of the malaris muscle. This study aimed to examine these muscle bundles and clarify their function in facial aging. Twelve heads of Japanese cadavers (average age: 82.5 years old) were dissected to observe the muscles, focusing in particular on those in the periorbital region. Six specimens were further dissected from the inner surfaces to examine the patterns of facial nerve branches under the operating microscope. Histological examinations of two head halves were carried out to investigate the relationship between the muscle bundles and the intraorbital structures. Muscle bundles consisting of lateral, medial, and U-shaped suspending bundles were observed in the region inferior to the Oo. Lateral and suspending bundles were found in all specimens, while the medial bundles were noted in only 9 of 22 specimens. Some branches of the facial nerve penetrated through the lateral, medial, and suspending bundles. The relationship between the suspending bundles and the protruding orbital fat was assessed. The muscle bundles found in this study were regarded as the malaris muscle—a transitional muscle between the superficial and deep facial layers. The suspending bundle may play a role in sustaining the intraorbital structures.     

Heart rate variability in myocardial infarction and heart failure

The need to refine the identification of patients who might benefit from implantation of an implantable cardioverter defibrillator has been risen by the results of many clinical trials on ICD therapy. Traditional parameters such as left ventricular ejection fraction and the presence of non-sustained ventricular tachycardia were not strong enough to achieve this goal with reasonable cost-effectiveness. Heart rate variability (HRV) is one of the most popular parameters used to assess the autonomic tone. HRV has been reported as a strong predictor of cardiovascular mortality. Currently, three different categories of methods in HRV analysis are being used; the time domain, frequency domain, and non-linear dynamic analysis. Both time domain and frequency domain analyses of HRV have been investigated extensively regarding their use as a prognostic marker for cardiovascular mortality. The non-linear dynamic analysis is the latest tool that has shown to have an even higher predictive value than any of the traditional parameters. However, standardized and supporting evidence on this new technique is still lacking. In this article, the current role of HRV in the prediction of cardiovascular mortality in myocardial infarction and heart failure patients has been reviewed.