Genetic analysis of host responses in sepsis

During much of the past century, the microbe itself stood at the heart of microbial pathogenesis. Little thought was devoted to the host per se, though it was granted that differences in susceptibility to certain infections did exist between individuals, and between different ethnic groups. During the past 20 years, extraordinary strides in our grasp of mammalian genetics have made the host side of the equation far more approachable. A restricted collection of genes now presents itself as the likely repository for genetic differences that foretell susceptibility to infectious disease. The Toll-like receptors, of which 10 are presently known to exist in humans, offer an excellent example of this genetic reductionism, in that they embody the afferent component of the innate immune system, and strongly influence the containment of an infection from its earliest stages. The Toll-like receptors were identified as the culmination of a long and relentless inquiry into the yet-unsolved clinical problem of sepsis.     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Simultaneous assessment of blood flow in UVB-inflamed human skin by laser Doppler flowmetry and the 133-xenon washout technique.

The purpose of the study was to compare skin blood flow by laser Doppler flowmetry (LDF) and the 133-Xenon washout technique in UVB-inflamed human skin. Six healthy subjects participated in the study. Forearm skin blood flow was measured prior to irradiation and then 8, 24, 48 and 72 h after the exposure to twice the minimal erythema dose of UVB. Baseline blood flow as measured by the 133-Xenon washout method was 5.2 (range 3.0 to 10.4) ml/100g/min and LDF flux was 3.1 (range 2.7 to 5.7) arbitrary units. Following irradiation, maximum blood flow increase as evaluated by the 133-Xenon washout was 10.8 (95% confidence interval 3.7 to 11.3) times baseline blood flow, corresponding to an absolute blood flow of 47.5 (range 33.8 to 56.3) ml/100g/min. Maximum increase after induction of inflammation as assessed by LDF was 34.6 (95% confidence interval 24.6 to 56.5) times baseline flux. The two methods showed comparable time courses in all subjects. A significant correlation between the two methods was found, Spearman's rho = 0.54, p = 0.006. The relative LDF blood flow increase was 4.2-fold (95% confidence interval 2.7 to 5.0) greater than the increase measured by the 133-Xenon washout method. These results are at variance with previous comparative studies of the two methods. Some explanations are discussed.     

In vivo Intracellular Recording of Neurons in the Supraoptic Nucleus of the Rat Hypothalamus

Intracellular recordings were made from cells in the hypothalamic supraoptic nucleus in the urethane-anaesthetized male rat using the ventral surgical approach. Impalements lasted from 5 min to 1 h and recorded cells had an input resistance of 55 to 170 megohms. Spikes of over 50 mV were recorded from 14 cells which could be antidromically activated by stimulation of the neural stalk. The spikes showed a hyperpolarizing afterpotential and the broadening characteristic of rapidly firing magnocellular neurons, which recovered rapidly (<200 ms). When depolarized, the cells showed evidence of a transient potassium current. Recurrent synaptic coupling between the recorded cell and adjacent cells would be expected to alter the hyperpolarizing afterpotential of an antidromic spike as compared with a spontaneous spike; no perceptible difference in the waveforms of the different types of spike could be detected in 11 spontaneously active cells. Application of just subthreshold stimuli to the neural stalk did not evoke depolarizing or hyperpolarizing potentials. Suprathreshold shocks to the neural stalk, when the antidromic spike was prevented by collision, also had no discernible effect on membrane potential. Thus intracellular recordings from magnocellular neurons in vivo revealed electrophysiological properties similar to those seen in vitro. No evidence for synaptic interconnection between magnocellular neurons was found in male rats.