Nitrogen oxide in the treatment of oxygenation failure in neonates

Oxygenation problems are common in very sick infants, and involve a high risk of mortality or residual morbidity. We describe two infants with severe oxygenation difficulties. In one baby these were caused by meconium aspiration, while in the second, premature (1,500 g birth weight) infant Escherichia coli septicemia had precipitated persistent pulmonary hypertension. Inhaled nitric oxide led to immediate improvement in oxygenation, and the one infant was weaned off mechanical ventilatory support after four days, the other after ten days. There were no discernible side effects in either baby. Nitric oxide treatment should be considered for infants with life-threatening oxygenation problems who do not respond adequately to conventional management.     

Anti-C1q receptor/calreticulin autoantibodies in patients with systemic lupus erythematosus (SLE)

We report a case of acute glomerulonephritis associated with acute Q fever. An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy. Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis. Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody. Other known causes of glomerulonephritis were excluded. Most reports of renal complications of C. burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever. Renal involvement in patients with acute C. burnetii infection has been rarely described. Glomerulonephritis should be recognized as a complication of acute C. burnetii infection and endocarditis due to chronic Q fever.     

Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF

We employed a morphological assay of outer segment collapse to determine if growth factors or other supplements directly affect dissociated rod photoreceptors in vitro. The morphological changes in outer segments were correlated with the light responsiveness of rods. Time-lapse video microscopy was used to observe the collapse of rod outer segments from isolated single cells and small clumps of cells. A consistent pattern of outer segment collapse into the inner segment was observed, yielding a convenient assay of the effects of neurotrophic factors on photoreceptor functional maintenance. The functional state of rods, defined as light-responsiveness, was measured with suction electrode recordings and matched with the various stages of outer segment collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived neurotrophic factor (GDNF) at a high concentration, yielded statistically significant improvements in rat outer segment survival times. Basic fibroblast growth factor (bFGF), which rescues photoreceptors in several rodent models of retinal degeneration, produced a significant increase in survival time in the presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF also yielded a significant increase in survival times. When brain-derived neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times did not change. Outer segments collapsed more quickly when either pigment epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal) were present. Our results show that rod photoreceptors can respond to bFGF, GDNF and CNTF in vitro and provide evidence for a direct effect of these neurotrophic factors on rods. The rapid collapse of isolated photoreceptors in this model provides a convenient means for testing various neurotrophic agents and the induced cellular responses.     

Biological and virologic characteristics of primary HIV infection

BACKGROUND: The clinical events surrounding acute HIV-1 infection have been well described, but little is known about whether the virologic course of acute HIV-1 infection influences the subsequent progression of disease. OBJECTIVE: To define the virologic natural history of acute and very early HIV infection. DESIGN: Prospective, longitudinal cohort study. SETTING: University of Washington Research Clinic PARTICIPANTS: 74 adults enrolled soon after acquisition of HIV (mean, 69 days). MEASUREMENTS: Plasma HIV-1 RNA levels; quantitative cell cultures; CD4 cell counts; and detailed clinical assessments done at study entry, biweekly for 1 month, monthly for 2 months, and quarterly thereafter. RESULTS: In the first 30 days after acquisition of HIV, HIV-1 RNA levels varied greatly among participants (range, 27,200 to 1.6 x 10(6) copies per mL of plasma). Levels of HIV-1 RNA decreased by a mean of 6.5% per week for the first 120 days and then increased by a mean of 0.15% per week. CD4 cell counts decreased by a mean of 5.2 cells/mm3 per week for the first 160 days and by a mean of 1.9 cells/mm3 per week thereafter (P < 0.01). Disease progressed faster in participants who sought medical care for their acute seroconversion syndrome (P = 0.01) and those who had high plasma HIV-1 RNA levels 120 to 365 days after acquisition (P < 0.01). Peak levels in the first 120 days were not predictive of disease progression. CONCLUSIONS: The variability in viral RNA levels associated with acute HIV-1 infection is greater than previously appreciated. Within 120 days of acquisition, plasma HIV RNA levels rapidly decrease to an inflection point, after which they gradually increase. Virus-host interactions soon after acquisition seem to have a major influence on the long-term outcome of HIV-1 disease.     

Evaluation of brain injury related behavioral disturbances in community mental health centers

As a result of improved emergency trauma services, more individuals suffering a traumatic brain injury are surviving. Unfortunately, most of these survivors suffer chronic neuropsychiatric sequelae related to both the brain damage and the psychosocial impact of the injury on self-esteem, self-image, primary role, and vocational function. Current community supports are often inadequate to deal with the complex array of neurologic and psychiatric difficulties. This article outlines common features of brain injury, explores the link between these features and the common neuropsychiatric sequelae of brain injury, and suggests some principles helpful in the evaluation of the behaviorally challenged brain injured patient.     

Nitric oxide, the biological mediator of the decade: fact or fiction?

Nitric oxide (NO), an atmospheric gas and free radical, is also an important biological mediator in animals and humans. Its enzymatic synthesis by constitutive (c) and inducible (i) isoforms of NO synthase (NOS) and its reactions with other biological molecules such as reactive oxygen species are well characterized. NO modulates pulmonary and systemic vascular tone through its vasodilator property. It has antithrombotic functions and mediates some consequences of the innate and acute inflammatory responses; cytokines and bacterial toxins induce widespread expression of iNOS associated with microvascular and haemodynamic changes in sepsis. Within the lungs, a diminution of NO production is implicated in pathological states associated with pulmonary hypertension, such as acute respiratory distress syndrome: inhaled NO is a selective pulmonary vasodilator and can improve ventilation-perfusion mismatch. However, it may have deleterious effects through modulating hypoxic pulmonary vasoconstriction. Inhibitors of NOS may be of benefit in inotrope-refractory septic shock, but toxicity of newly developed selective iNOS inhibitors have prevented clinical trials of efficacy. An expanding literature on the origins and measurement of NO in exhaled breath implicates NO as a potentially useful marker of disease activity in respiratory tract inflammation in the future. This report reviews some aspects of research into the clinical importance of nitric oxide.