Diagnosis and Management of Atypical Hemolytic Uremic Syndrome In Children: Single Centre Experience

Atypical hemolytic uremic syndrome (aHUS) although rare is the commonest cause of acute renal failure (ARF) in children and has poor prognosis. We present single centre experience of aHUS. Thirty six children (29 males, 7 females) with mean age, 7.9 years presented with ARF, 2 children also had tonic–clonic type convulsions. Their hematology examination revealed hemolytic anemia with s. creatinine (SCr), 5.54 mg/dl. Acute HUS was observed in 75 %, acute on chronic HUS in 19.4 % and patchy cortical necrosis (PCN) in 5.6 % biopsies. Mean 5.4 plasma exchanges (PE) were carried out. Supportive management of anti-hypertensives and prednisone was also given. Recovery end points were establishment of urine output, improvement of SCr and hematological profile. Hematology and renal function profile improved variably in all children, 5.6 % died, relapse was observed in 80.5 % over mean 70 days; 13.9 % children are doing well over mean follow-up of 268.8 days. Thus poor prognosis was observed in 86.1 % children. Children with acute on chronic HUS and PCN did not recover. Six children who recovered had acute HUS. aHUS in Indian children occurs at an older age of around 8 years and chronic/irreversible changes on histopathology examination are harbingers of poor prognosis. PE is life-saving however further research for developing strategies to improve long-term survival is needed.     

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

Clinical Autonomic Research - In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective...     

Pharmacokinetics and pharmacodynamics of ampreloxetine,a novel,selective norepinephrine reuptake inhibitor,in symptomatic neurogenic orthostatic hypotension

Clinical Autonomic Research - Ampreloxetine is a novel, selective, long-acting norepinephrine reuptake (NET) inhibitor being investigated as a once-daily oral treatment for symptomatic neurogenic...     

Methanophosphagen: Unique cyclic pyrophosphate isolated from Methanobacterium thermoautotrophicum

A unique cyclic pyrophosphate compound has been detected at 10-12 mM intracellular concentration in Methanobacterium thermoautotrophicum by in vivo³¹P NMR. This compound has been extracted from cells and purified by anion-exchange chromatography. Studies with ¹H, ¹³C, and ³¹P NMR and fast-atom-bombardment mass spectrometry have identified it as 2,3-cyclopyrophosphoglycerate, an intramolecularly cyclized pyrophosphate of 2,3-diphosphoglycerate. Chemical degradation to 2,3-diphosphoglycerate and synthesis by dicyclohexylcarbodiimide coupling of 2,3-diphosphoglycerate are consistent with this identification. It is suggested that this compound serves as a primary phosphagen in methanogens.     

Outcome of low birth weight babies with special reference to some maternal factors

Neonatal outcome of 178 low birth weight (LBW) babies in this study was associated with 26.4% neonatal mortality. A significantly higher mortality rate was noted in presence of adverse maternal factors, birth weight less than 1.5 kg, prematurity and respiratory distress at birth. Premature rupture of membranes and leaking (greater than 12 h) were recorded in 75 cases. Significant association was observed for septicemia. Maternal postpartum weight less than 40 kg was associated with higher incidence of neonatal infections than when mother's weight was greater than 45 kg.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.