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Biomedical subjects

Jose A Martinez

Publications and source records attributed to Jose A Martinez.

6 recordsLinked to original sources

Diabetes, leukoencephalopathy and rage.

Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood vessels, but brain is not usually considered a primary target. We describe direct involvement of the brain, particularly white matter, in long-term (9 months) experimental diabetes of mice, not previously modeled, correlating magnetic resonance (MR) imaging with quantitative histological assessment. Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic humans, developed in diabetic mice and was accompanied by time-related development of cognitive changes in behavioural testing. Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. RAGE null diabetic mice had significantly less neurodegenerative changes when compared to wild-type diabetic mice. Our findings identify a robust and novel model of cerebral, particularly white matter, involvement with diabetes associated with abnormal RAGE signaling.

Animals↗

CD8+ lymphocyte-mediated injury of dorsal root ganglion neurons during lentivirus infection: CD154-dependent cell contact neurotoxicity.

Neuronal damage in dorsal root ganglia (DRGs) with accompanying axonal injury is a key feature of human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP). In a model of HIV-related DSP, we observed numerous CD3+ T lymphocytes (p < 0.05) in DRGs from feline immunodeficiency virus (FIV)-infected animals, which also exhibited low CD4+ and high CD8+ lymphocyte levels in blood accompanied by a selective loss of small-diameter sural nerve axons (p < 0.05). FIV-infected lymphocytes cocultured with syngeneic DRGs caused neuronal damage, indicated by neurite retraction, neuronal soma atrophy, and loss (p < 0.05). In contrast, supernatants from FIV-infected or uninfected lymphocytes were minimally neurotoxic, despite high FIV virion levels. Among lymphocyte subsets cocultured with DRG cultures, CD8+ T cells from both FIV-infected and uninfected lymphocytes selectively caused DRG neuronal injury (p < 0.05). FIV-infected CD8+ T cells showed markedly increased CD154 expression (p < 0.05), whereas neurons were the predominant cells expressing CD40 in DRGs. Blocking CD154 on activated CD8+ T cells protected DRG neurons (p < 0.05). These findings indicated that CD8+ T cells were principal effectors of DRG neuronal injury after FIV infection through a CD40-CD154 interaction in a cell contact-dependent manner.

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Recombinant human growth hormone increases thyroid hormone-binding sites in recovering severely burned children.

Thyroxine (T4), Tri-iodothyronine (T3), and total serum protein levels are reduced in severely burned children. T4 and T3 are carried on serum transport proteins via thyroid hormone-binding sites (THBS). Treatment of bums with recombinant human growth hormone (rhGH) increases albumin (Alb) and prealbumin (PreAlb), which bind nearly 30% of circulating T4 and T3. This study investigated the effect of rhGH on THBS sites in burned children. Records of 11 acutely burned children with a total body surface area burned >40% who were randomized to either a daily subcutaneous injection of rhGH at 0.05 mg/kg/day or placebo for 6 months after discharge from hospital were reviewed. Thyroxine uptake percentage (TU%), Total T4 levels (TT4), free thyroxine index, Alb and PreAlb, and height and weight measurements taken at discharge and 6 months later were compared in both groups. In the six children who received rhGH, mean TU% had decreased from 41 +/- 1 to 33 +/- 1% by 6 months postdischarge, (P < 0.001), mean TT4 increased from 5.8 +/- 0.3 to 8.1 +/- 0.8 microg/dL, (P < 0.02), mean Alb increased from 2.0 +/- (0.6) to 3.5 +/- (0.1) g/dL (P < 0.0001), and mean PreAlb increased from 8.7 +/- 0.7 to 16.5 +/- 2.1 mg/dL, (P < 0.006). There were no significant changes in the five children in the placebo (control group), and height and weight did not significantly change in either group. rhGH significantly increases THBS in severely burned children, possibly through increases in serum Alb and PreAlb. The increases in circulating thyroxine observed in this group may be involved in the attenuation of growth arrest.

Blood Glucose↗

Clinical utility of blood cultures drawn from central venous or arterial catheters in critically ill surgical patients.

OBJECTIVE: To determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture. DESIGN: Retrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through a central venous or arterial catheter and peripheral venipuncture. SETTING: Tertiary-care, university-affiliated medical center. PATIENTS: Two hundred seventy-one patients hospitalized on a surgical and a cardiothoracic intensive care unit between November 1994 and August 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blinded assessments of culture results done by two physicians were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from catheters and culture of blood from peripheral venipuncture. Of 499 observations, 426 were catheter-negative/venipuncture-negative, 19 were catheter-positive/venipuncture-positive, 18 were catheter-negative/venipuncture-positive, and 36 were catheter-positive/venipuncture-negative pairs. For catheter draws compared with peripheral venipuncture, sensitivity was 78% (confidence interval [CI], 65% to 90%) and 65% (CI, 50% to 79%) (p = .2), specificity was 95% (CI, 94% to 97%) and 98% (CI, 97% to 99%) (p = .002), positive predictive value was 63% (CI, 51% to 76%) and 78% (CI, 64% to 91%) (p = .1) and negative predictive value was 98% (CI, 96% to 99%) and 97% (CI, 95% to 98%) (p = .3). When central venous specimens as differentiated from arterial catheter specimens were compared with peripheral venipuncture, the difference between positive predictive values reached statistical significance (61% and 82%; p = .04). CONCLUSIONS: In critically ill surgical patients, cultures of blood drawn through a catheter are less specific than those obtained from a peripheral venipuncture. Both types of cultures have an excellent negative predictive value. Positive predictive value of cultures of blood drawn through a catheter is low and, when obtained from a central line, statistically less than from a peripheral venipuncture. Additional cultures seem to be necessary for the proper interpretation of a positive culture drawn through a catheter in critical care patients.

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