The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

Weichteilemphysem ungewöhnlichen Ausmaßes

Streptococcus agalactiae, known as a pathogen that causes meningitis and septicemia in neonates, emerges as an invasive organism in nonpregnant adults. This case report describes the fulminant course of a necrotizing fasciitis (NF) with streptococcal toxic shock-like syndrome (STSS) in a 76-year-old diabetic patient caused by S. agalactiae, serotype V. Chronic diseases and immunodeficiency are considered to be risk factors for the acquisition of group B streptococcal disease. Since early surgical treatment in conjunction with antimicrobial and intensive care therapy is critical for the outcome of patients with NF and/or STSS, clinicians should be aware of invasive S. agalactiae infections in adults with subcutaneous emphysema.     

Association of psychological and physiological measures of stress in health‐care professionals during an 8‐week mindfulness meditation program: mindfulness in practice

Work stress, burnout, and diminished empathy are prevalent issues for health‐care professionals. Mindfulness meditation (MM) is one commonly used strategy to manage stress. Measuring salivary cortisol allows for the assessment of serum cortisol level, a known stress level indicator. This study evaluated the association of subject‐reported stress symptoms and salivary cortisol in health‐care professionals, in an 8‐week MM program, with data collected prospectively at baseline and 8 weeks after program completion. Questionnaires [Profile of Mood States—Short Form (POMS‐SF), Maslach Burnout Inventory (MBI), and Interpersonal Reactivity Index (IRI)] measured mood, burnout and empathy. A paired t‐test between groups for pre/post‐salivary cortisol yielded no significant change. The POMS‐SF was most sensitive to change (mean increase 12.4; p = 0.020). Emotional exhaustion, measured in the MBI, was also affected by MM (mean decrease 4.54; p = 0.001). Changes in empathy may not have been captured due to either absence of effect of MM on empathy, subject number or scale sensitivity. Baseline and 8‐week correlations between salivary cortisol and survey results, and correlations between changes in these measures, were weak and not statistically significant. Nevertheless, psychometric results present a strong case for additional clinical trials of MM to reduce stress for health‐care professionals. Copyright © 2005 John Wiley & Sons, Ltd.     

Comparison of the Different Approaches to Saphenous Nerve Block

Background: The authors compared the efficacy of the different approaches to saphenous nerve block.

Methods: The following approaches to saphenous nerve block were compared in 10 volunteers: perifemoral, transsartorial, block at the medial femoral condyle, below-the-knee field block, and blockade at the level of the medial malleolus. Each volunteer underwent all five blocks, and the interval between blocks was 3-7 days. The sequence of injection was randomized by Latin square design. Sensory blockade at the medial aspects of the leg and foot and the strength of the anterior thigh muscles were noted.

Results: The transsartorial, perifemoral, and below-the-knee field block approaches were more effective than block at the medial femoral condyle in providing sensory anesthesia to the medial aspect of the leg. The transsartorial approach was more effective than block at the medial femoral condyle and below-the-knee field block in providing sensory anesthesia to the medial aspect of the foot. Compared with the perifemoral approach, the transsartorial approach did not cause weakness of the hip flexors and the knee extensors. In volunteers with partial numbness in the medial aspect of the foot, supplemental block of the medial dorsal cutaneous branch of the superficial peroneal nerve resulted in complete sensory blockade.     

Chemical equivalence of two polyetherpolyurethane foams as a vehicle for povidone-iodine solution: kinetic model for the loss of available iodine

The loss of available iodine from povidone-iodine solution stored in contact with two different polyetherpolyurethane foams was monitored as a function of time and temperature. Statistical evaluation of the results for the four temperatures studied [ambient (25 degrees), 30, 45 and 55 degrees C] indicated the chemical equivalence of the two foams as storage and delivery systems for povidone-iodine solution in terms of solution stability. In addition, application of a first-order kinetic model to the data produced an acceptable fit. An Arrhenius-type evaluation of the resulting rate constants yielded a linear relationship which was shown to be useful for predicting loss of available iodine under ambient temperature conditions of storage.     

Non-clastogenicity in mouse bone marrow of fructose/lysine and other sugar/amino acid browning products with in vitro genotoxicity

Heated sugar/amino acid reaction mixtures, known to contain products that are clastogenic and/or mutagenic to cells in vitro, were evaluated for clastogenic activity in mouse bone marrow using the erythrocyte micronucleus assay. Heated (i.e. browned) fructose/lysine reaction mixtures were also evaluated in the Salmonella his-reversion assay and the Chinese hamster ovary (CHO) cell chromosomal aberration assay to confirm and extend previous in vitro observations. Significant mutagenicity of fructose/lysine mixtures was observed in Salmonella typhimurium strains TA100, TA2637, TA98 and TA102, with greater activity in mixtures heated at pH 10 than at pH 7. S-9 decreased the activity in strains TA100, TA2637 and TA98, but increased the activity in strain TA102. Both pH 7 and pH 10 reaction mixtures of the fructose/lysine browning reaction were highly clastogenic in CHO cells. Heated mixtures of fructose and lysine, and of glucose or ribose with lysine, histidine, tryptophan or cysteine, did not increase the frequency of micronucleated erythrocytes in mice when administered by the oral route. This indicates the absence of chromosomal aberrations in erythrocyte precursor cells, and indicates that the genotoxic components of the browned mixtures are not absorbed and distributed to bone marrow cells in amounts sufficient to induce micronuclei when given orally. Because sugar/amino acid browning reactions occur commonly in heated foods, it is important to evaluate further the in vivo genotoxicity of browning products in cell populations other than bone marrow.     

An in-vitro study of the interactions between intravenous induction agents and the calcium antagonists verapamil and nifedipine

Thiopentone, propofol and etomidate inhibit the contractions of the rat isolated atria and portal vein. The actions of thiopentone and propofol summate with those of verapamil and nifedipine. Verapamil potentiates the action of etomidate on both preparations. The depressant actions of thiopentone and propofol on the portal vein are associated with a reduced response to calcium. Etomidate does not reduce the response to calcium in this preparation.