Modifying the baricity of local anesthetics for spinal anesthesia by temperature adjustment: model calculations

BACKGROUND: Although local anesthetics (LAs) are hyperbaric at room temperature, density drops within minutes after administration into the subarachnoid space. LAs become hypobaric and therefore may cranially ascend during spinal anesthesia in an uncontrolled manner. The authors hypothesized that temperature and density of LA solutions have a nonlinear relation that may be described by a polynomial equation, and that conversion of this equation may provide the temperature at which individual LAs are isobaric. METHODS: Density of cerebrospinal fluid was measured using a vibrating tube densitometer. Temperature-dependent density data were obtained from all LAs commonly used for spinal anesthesia, at least in triplicate at 5 degrees, 20 degrees, 30 degrees, and 37 degrees C. The hypothesis was tested by fitting the obtained data into polynomial mathematical models allowing calculations of substance-specific isobaric temperatures. RESULTS: Cerebrospinal fluid at 37 degrees C had a density of 1.000646 +/- 0.000086 g/ml. Three groups of local anesthetics with similar temperature (T, degrees C)-dependent density (rho) characteristics were identified: articaine and mepivacaine, rho1(T) = 1.008-5.36 E-06 T2 (heavy LAs, isobaric at body temperature); L-bupivacaine, rho2(T) = 1.007-5.46 E-06 T2 (intermediate LA, less hypobaric than saline); bupivacaine, ropivacaine, prilocaine, and lidocaine, rho3(T) = 1.0063-5.0 E-06 T (light LAs, more hypobaric than saline). Isobaric temperatures (degrees C) were as follows: 5 mg/ml bupivacaine, 35.1; 5 mg/ml L-bupivacaine, 37.0; 5 mg/ml ropivacaine, 35.1; 20 mg/ml articaine, 39.4. CONCLUSION: Sophisticated measurements and mathematic models now allow calculation of the ideal injection temperature of LAs and, thus, even better control of LA distribution within the cerebrospinal fluid. The given formulae allow the adaptation on subpopulations with varying cerebrospinal fluid density.     

Ventilator-associated pneumonia: gearing towards shorter-course therapy

PURPOSE OF REVIEW: The studies that are reviewed in this article have all concluded that a shorter duration of antibiotic therapy (7-8 days) may be adequate in the treatment of the majority of patients with ventilator-associated pneumonia, and does not confer an increased incidence of mortality. RECENT FINDINGS: Ventilator-associated pneumonia has traditionally been treated with at least 2 weeks of antimicrobial therapy. With the increasing emergence of multi-drug-resistant pathogens, however, efforts have been directed at minimizing the duration of therapy. Several studies have emerged over the last few years aiming to shorten the duration of antimicrobial therapy for ventilator-associated pneumonia. SUMMARY: The minimum effective duration of antibiotic therapy, however, remains unclear. Further studies geared towards determining this are needed.     

c‐Met signaling promotes IL‐6‐induced myeloma cell proliferation

Objectives: Hepatocyte growth factor (HGF) is a constituent of the myeloma microenvironment and is elevated in sera from myeloma patients compared to healthy individuals. Increased levels of serum HGF predict a poor prognosis. It has previously been shown by us and others HGF can act as a growth factor to myeloma cells in vitro although these effects have been moderate. We therefore wanted to investigate if HGF could influence the effects of interleukin (IL)‐6. Methods: Myeloma cell lines and primary samples were tested for the combined effects of IL‐6 and HGF in inducing DNA synthesis and migration. Expression levels of c‐Met protein were analysed by Western blotting and flow cytometry. Signaling pathways were examined by Western blotting using phosphospecific antibodies and a Ras‐GTP pull down assay. Results: HGF potentiated IL‐6‐induced growth in human myeloma cell lines and in purified primary myeloma cells. There was also cooperation between HGF and IL‐6 in induction of migration. There seemed to be two explanations for this synergy. IL‐6‐treatment increased the expression of c‐Met making cells HGF responsive, and IL‐6 was dependent on c‐Met signaling in activating both Ras and p44/42 MAPK by a mechanism involving the tyrosine phosphatase Shp2. Conclusions: The results indicate that besides from being a myeloma growth factor alone, HGF can also potentiate the effects of IL‐6 in myeloma proliferation and migration. Thus, c‐Met signaling could be a target for therapy of multiple myeloma.     

Violence and abuse among HIV-infected women and their children in Zambia: a qualitative study

HIV and violence are two major public health problems increasingly shown to be connected and relevant to international mental health issues and HIV-related services. Qualitative research is important due to the dearth of literature on this association in developing countries, cultural influences on mental health syndromes and presentations, and the sensitive nature of the topic. The study presented in this paper sought to investigate the mental health issues of an HIV-affected population of women and children in Lusaka, Zambia, through a systematic qualitative study. Two qualitative methods resulted in the identification of three major problems for women: domestic violence (DV), depression-like syndrome, and alcohol abuse; and children: defilement, DV, and behavior problems. DV and sexual abuse were found to be closely linked to HIV and alcohol abuse. This study shows the local perspective of the overlap between violence and HIV. Results are discussed in relation to the need for violence and abuse to be addressed as HIV services are implemented in sub-Saharan Africa.