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.     

Hematopoietic stem cell transplantation in autoimmune diseases: the Ahmedabad experience

INTRODUCTION: Autoimmune disease represents a (AD) breakdown of natural tolerance against autoreactive antigens leading to a high mortality and morbidity. The reaction is usually polyclonal; T- and B-cell components of the hematopoietic system are responsible for disease progression. Allogeneic/autologous hematopoietic stem cell transplantation (HSCT) are the current modalities for treating drug-resistant AD. PATIENTS AND METHODS: We present a single-center retrospective evaluation of allogeneic HSCT with nonmyeloablative, low-intensity conditioning in nine patients (five males, four females) with pemphigus vulgaris (PV) and 27 patients with systemic lupus erythematosus (SLE; 3 males, 24 females). The mean follow-up period was 4.24 years for PV and 4.9 years for SLE. Cytokine-mobilized HSC from unmatched related donors, with mean dose of 21.3 x 10(8) nucleated cells/kg body weight (BW; mean CD34(+) count, 6 x 10(6)/kg BW) was administered in to the thymus as well as the portal and peripheral circulations of recipients. Cyclosporine (4 +/- 1 mg/kg BW per day) and prednisolone (10 mg/kg BW per day) were administered for 6 months to protect mixed chimerism. A subset of patients with cross-gender donors were analyzed for peripheral blood chimerism at 1 month post-HSCT and every 3 months thereafter. RESULTS: Sustained clinical remission with peripheral lymphohematopoietic chimerism of 0.7 +/- 0.3% was observed in PV, whereas SLE relapsed after mean of 7.35 months of disease-free interval associated with fall in chimerism from 5 +/- 3% to < or =0.08 +/- 0.03%. CONCLUSION: HSCT was effective to achieve early clinical remission of PV; and in SLE relapsed after a 7.35-month disease-free interval accompanied by a fall in mixed lymphohematopoietic chimerism.     

Influence of total cholesterol levels on long-term mortality in coronary heart disease: a reappraisal

To examine the prognostic significance of total cholesterol levels at baseline in subjects with stable coronary heart disease, 605 patients with stable coronary heart disease were enrolled; 45 of these did not meet inclusion criteria, 41 were lost to follow-up and 40 opted for coronary bypass surgery. Data of the remaining 479 (389 males, 90 females) were analysed. There were 102 males in group I (cholesterol < 200 mg/dL), 187 in group II (cholesterol 200-239 mg/dL), and 100 in group III (cholesterol > or = 240 mg/dL) and 49 females in group I and 41 in group II. The groups were evenly matched for age and numbers with stable angina or survivors of myocardial infarction. Proportion of smokers, hypertensives, diabetics or obese was also similar (p > 0.05). Mean follow-up in years in men was 6.82 +/- 3.15 in group I, 6.37 +/- 3.11 in group II and 6.81 +/- 2.84 in group III while in women it was 6.95 +/- 2.84 in group I and 7.03 +/- 2.58 years in group II and was not different in various groups (p > 0.05). The overall cardiovascular mortality in various groups in men was 20.6 percent in group I, 28.9 percent in group II and 23.0 percent in group III and in women it was 14.3 percent in group I and 22.0 percent in group II. The crude mortality rate was 2.51 percent per year in males and 1.77 percent per year in females. Actuarial survival at end of seven years in males was 0.76 +/- 0.05 in group I, 0.67 +/- 0.04 in group II, and 0.67 +/- 0.05 in group III and in females it was 0.85 +/- 0.05 in group I and 0.73 +/- 0.09 in group II. The cumulative hazard rates per 1000 person- year follow-up in group I, II and III in males were, at age less than 50 years: 5.4 +/- 5, 19.8 +/- 7, 17.4 +/- 8; at 50-59 years: 23.8 +/- 11, 38.5 +/- 9, 39.8 +/- 13; and at 60 years and over: 76.9 +/- 20, 112.6 +/- 20, 108.2 +/- 28, respectively (p < 0.001 on comparison of group I with groups II and III). In females the trends were not significant. Total cholesterol levels at baseline predict long-term cardiovascular mortality in men with stable coronary heart disease.     

Prognostic value of profound ST segment depression during treadmill stress test in coronary heart disease: nine years follow-up study.

To define the prognostic significance of profound ST segment depression (greater than or equal to 3mm) during exercise test, 106 patients of definite coronary heart disease enrolled in a prospective study were followed for up to 9 years. Group A (56 patients) had profound (greater than or equal to 3mm) ST segment depression (3.56 +/- 0.74mm) and Group B (50 patients) had less than 3mm ST segment depression (1.23 +/- 0.35mm, P less than 0.01) during treadmill testing. Group A patients tolerated exercise for a lesser duration in comparison to group B patients (7.22 +/- 3.35 vs. 10.18 + 4.07 minutes, p less than 0.01). At the end of the study, 21 (37.5%) group A patients either died or underwent coronary artery bypass surgery as compared to 8 (16.0%) group B patients (p = 0.02). The difference in the incidence of cardiac deaths between the two groups was not statistically significant (19.6% in group A and 14.0% in group B). However, sudden deaths were significantly more common in group A as compared to group B patients (10 of 11 (90.9%) vs 4 of 7 (57.1%), p = 0.02). These data suggest that profound ST segment depression (greater than 3mm) during treadmill stress test indicates an adverse long term prognosis with the risk in particular, of sudden cardiac death.     

Avulsion of the upper lateral cartilage: Etiology,diagnosis, surgical anatomy and management

Relatively little has been published about upper lateral cartilage abnormalities, trauma, and management in rhinoplastic literature. In this paper we would like to present a relatively common problem seen either by trauma or as a result of rhinoplasty. The upper lateral cartilages are a pair of triangular cartilages, one on each side of the dorsum, which comprise the upper cartilaginous vault with the septum and can be avulsed due to direct trauma. This results in loss of their attachments and resultant healing in a new angulated position. The middle third of the nose, being relatively mobile, is less susceptible to trauma than the upper third which is rigid and comprised of bone, and that frequently is the reason for less incidence of avulsion of the upper lateral cartilages compared to fractured nasal bones. The surgical treatment of the structures adjacent to the upper lateral cartilage during the process of rhinoplasty severs many attachments of these cartilages and frequently causes them to be free floating. This may not be recognized and not treated. Lack of appropriate realignment in the normal anatomical position may heal the cartilage in a distorted angulated position. Irrespective of etiology, when distortions of the upper lateral cartilage occur, they may cause significant concavity and “hollowed out” appearance on the side of the avulsion which functionally may impede the nasal airway by encroachment and/or “flutter valve” effect. During inspiration this unsupported upper lateral cartilage may interfere with anatomy, physiology and efficiency of the internal nasal valve function. Avulsion of the upper lateral cartilage is a definite entity and should be recognized and treated appropriately to realign the lateral cartilage in its normal anatomical position for a functional as well as a good cosmetic result.