Ten years of prophylactic treatment with fresh-frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of a congenital deficiency of von Willebrand factor-cleaving protease

We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpura (TTP), in whom a severe congenital von Willebrand factor (VWF)-cleaving protease deficiency has been documented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of protease activity and platelet count after FFP infusion led us to conclude tentatively that 5% may be sufficient to degrade very large and adhesive VWF multimers.     

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.     

Suicidality among nonadherent patients living with HIV in Buenos Aires,Argentina: prevalence and correlates

Of those in the general population hospitalized for suicidal ideation and suicide attempts in Argentina, many reattempt suicide and are readmitted. However, few studies in Argentina have examined suicidal ideation and suicide-related behaviors among people living with HIV (PLHIV) and none have examined these factors among nonadherent PLHIV, though the prevalence of suicidal ideation in this group may be higher than in the general population and also than in other groups of PLHIV. This study of PLHIV in Buenos Aires, Argentina, examined the correlates of suicidal ideation in nonadherent PLHIV. Nonadherent patients with HIV (N?=?118) were recruited from two clinics providing outpatient healthcare services to PLHIV in Buenos Aires, Argentina. Participants completed assessments on demographic characteristics, depression and suicidality, stigma, and self-efficacy. Participants were HIV-infected men (51%) and women (49%) with a median age of 40 years (IQR?=?11). About half had completed high school or more, two-thirds were employed, and had a mean monthly income of 4196.79 (SD?=?3179.64) Argentine pesos (USD$221). Thirty-three (28% [95% CI 20.3, 37.3]) participants reported suicidal ideation in the past two weeks, and one-third (35.6% [27.1, 44.9]) reported lifetime suicidal ideation. In bivariate analyses, attending a public clinic, being female, younger, unemployed, and experiencing greater stigma and depression were associated with suicidal ideation. In multivariable logistic regression, stigma interacted with the number of years since HIV diagnosis to predict suicidal ideation. The impact of stigma on suicidal ideation decreased with time since HIV diagnosis, suggesting that suicidal ideation may arise following HIV diagnosis due to perception of HIV-related stigma. Interventions to reduce perceived stigma during the period following HIV diagnosis may reduce suicidal ideation in this population. Organizational initiatives that explore HIV stigma microagressions in the healthcare setting may be needed to optimize health outcomes.     

Activation profile of dorsal root ganglia Iba-1 (+) macrophages varies with the type of lesion in rats

The interactions between neurons, immune and immune-like glial cells can initiate the abnormal processes that underlie neuropathic pain. In the peripheral nervous system the resident macrophages may play an important role. In this study we investigated in experimental adult Sprague-Dawley rats how Iba-1 (ionized calcium binding adaptor molecule 1) (+) resident macrophages in the dorsal root ganglion (DRG) are activated after a spinal nerve ligation (SNL) or streptozotocin (STZ)-induced diabetes. The activation profile was defined by comparing the responses of resident macrophages against microglia in the spinal cord as they share a common origin. After SNL, the Iba-1 (+) macrophages in L5 DRG reached their activation peak 5 days later, clustered as satellite cells around large A-neurons, expressed the MHC-II marker, but did not show p-p38 and p-ERK1/2 activation and did not secrete IL-18. After STZ-induced diabetes, the Iba-1 (+) macrophages reached their activation peak 1 week later in L4 and L5 DRG, remained scattered between neurons, expressed the MHC-II marker only in L5 DRG, did not show p-p38 and p-ERK1/2 activation and did not secrete any of the investigated cytokines/chemokines. These responses suggest that depending on the type of lesion DRG Iba-1 (+) resident macrophages have different activation mechanisms, which are dissimilar to those in microglia.