Investigation of altered heart rate variability, nonlinear properties of heart rate signals, and organ dysfunction longitudinally over time in intensive care unit patients

PURPOSE: To investigate longitudinally over time heart rate dynamics and relation with mortality and organ dysfunction alterations in patients admitted to a multidisciplinary intensive care unit. METHODS: Data from 53 patients were used, with heart rate recorded from monitors and analyzed on a daily basis (every morning) for 600 seconds and sampling rate at 250 Hz, from admission to the intensive care unit until final discharge from the unit. Variance, which is a measure of heart rate variability; exponent alpha2; and approximate entropy (ApEn), which assess long-range correlations and periodicity within a signal, respectively; were measured and compared with every day Sequential Organ Failure Assessment Score (SOFA) and mortality. RESULTS: Nonsurvivors had lower ApEn mean (greater periodicity in their signals) and minimum values compared to survivors (0.53 +/- 0.25 vs 0.62 +/- 0.23, P = .04; 0.24 +/- 0.23 vs 0.48 +/- 0.23, P = .01, respectively). Patients in better conditions with SOFA of less than 7 (mean value) had higher variance and ApEn (more variable, less periodic signals) than those with SOFA of 7 or higher (0.47 +/- 0.51 vs 0.10 +/- 0.65, P < .001; 0.67 +/- 0.28 vs 0.49 +/- 0.24, P < .001, respectively). The alpha2 exponent and variance were correlated with length of stay (r = 0.55, P = .02, and r = 0.53, P = .02, respectively) and minimum ApEn with mortality (r = 0.41, P = .01). CONCLUSIONS: Loss of variability and increase in periodicity in heart rate of critically ill patients are linked with parallel deterioration of organ dysfunction and high mortality.     

Biliary calculi fragmentation by a 308 nm excimer laser: a preliminary study

The use of a 308-nm XeCl excimer laser for biliary stone fragmentation is reported. The 130-nsec laser pulses are delivered via UV grade fused silica fibers to the target stones immersed in normal saline solution and placed in direct contact with the fiber. Sixty biliary calculi, 20 cholesterol and 40 pigment, were fragmented in vitro. The energy delivered per unit mass of the stone is kept constant at 50 mJ/mg. The effect of laser repetition rate, energy fluence, and fiber core size on stone fragmentation was studied. Fragmentation thresholds for a variety of biliary calculi of known composition were measured. It was found that higher fragmentation efficiency was obtained with larger fluence, lower repetition rate, and fiber of larger core. Our study indicates that the 308-nm excimer laser may be effective as a laser lithotriptor with low threshold and good efficiency for biliary stone fragmentation.     

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

The burden of illness of osteoporosis in Canadian men

There is a dearth of information about the burden of osteoporosis in Canadian men. To fill this gap, we conducted a burden of illness study aimed at estimating the economic burden attributable to osteoporosis in Canadian men aged 50 years and older. Five national data sources were used to estimate health care resource utilization and costs (in 2010 Canadian dollars) associated with osteoporosis in men. Any information gap was supplemented by using data from provincial and community sources. Direct medical costs included costs associated with hospitalizations, same day surgeries, emergency room visits, rehabilitation, chronic care, long-term care, home care, physician visits, and prescribed medications. The value of lost productivity from patients and informal caregivers was also determined to provide a societal perspective. Sensitivity analyses were conducted to evaluate the impact of key assumptions on the results. In fiscal year 2007/2008, the total economic burden of treating and rehabilitating male osteoporotic fractures was estimated at $570 million per year, where direct medical costs accounted for 86%. Acute care utilization was responsible for 70% of all direct costs. About 51% of all hospitalizations were for hip fractures and hip fractures alone accounted for 54% of the acute care spending. If a proportion of Canadian men were assumed to live in long-term care facilities due to osteoporosis, the overall annual cost of osteoporosis would increase from $570 million to $910 million. Male osteoporosis has a substantial economic burden on the Canadian society.     

Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3)

Iron overload may predominantly involve parenchymal or reticuloendothelial cells, the prototype of parenchymal iron overload being HFE-related genetic haemochromatosis. We studied a family with autosomal dominant hyperferritinaemia in whom the proband showed selective iron accumulation in the Kupffer cells on liver biopsy. Analysis of L and H ferritin genes excluded mutations responsible for hereditary hyperferritinaemia/cataract syndrome or similar translational disorders. Sequence analysis of the ferroportin gene (SLC11A3) in four individuals with hyperferritinaemia singled out a three base pair deletion in a region that contains four TTG repeats. This mutation removes a TTG unit from 780 to 791, and predicts the loss of one of three sequential valine residues 160-162. Denaturing high performance liquid chromatography can be used for its detection. SLC11A3 polymorphism analysis indicates that this probably represents a recurrent mutation due to slippage mispairing. Affected individuals may show marginally low serum iron and transferrin saturation, and young women may have marginally low haemoglobin concentration levels. Serum ferritin levels are directly related to age, but are 10-20 times higher than normal. Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias.