Clinical characteristics and successful treatment outcomes of children and adolescents with Kaposi sarcoma in Southwestern Tanzania.

The HIV/AIDS epidemic has driven the rise in cases of Kaposi sarcoma (KS) among children and adolescents living with HIV in countries with high Human gammaherpesvirus 8 (HHV-8) seroprevalence, such as Tanzania, where specialized oncology programs are sparse. Consequently, descriptions of successful treatment of KS in children and adolescents by general pediatricians are important. A retrospective analysis was performed of children and adolescents diagnosed with KS and treated with chemotherapy and combination antiretroviral therapy (cART) at the Baylor College of Medicine Children's Foundation Tanzania Center of Excellence - Mbeya between 2011 and 2017. Sixty-one patients were diagnosed with KS with a median age of 12.6 years (interquartile range (IQR) 9.4 - 15.5). Diagnosis was confirmed by histopathology in 36% (22/61). Among HIV positive patients (59/61), 78% (46/59) were on cART at KS diagnosis. Severe immunosuppression was present in 63% (35/56) of those with CD4 data and 44% (27/61) had SAM. Advanced-stage T1 disease was present in 64% (39/61), including 28% (17/61) with visceral/disseminated KS. Two-year estimated overall survival (OS) was 72% (95% Confidence Interval (CI): 58%-82%) and median follow up for survivors was 25.7 months (IQR 14.2-53.8). No patients were lost to follow up. Two-year OS was 63% (95% CI: 44%-77%) in patients with severe immune suppression and 60% (95% CI: 37%-76%) in patients with SAM. Among patients with visceral/disseminated KS, 53% (9/17) survived. This retrospective analysis demonstrated favorable outcomes in a complex cohort of children and adolescents with KS treated with chemotherapy by general pediatricians in Tanzania.

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease.

The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.

Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital.

Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains a principal cause of infectious mortality after bone marrow transplantation (BMT). We reviewed the medical records of 93 allogeneic and 149 autologous transplant recipients during a 20 month period, with attention to cases of proven or probable IA. No autologous transplant recipient developed IA, whereas IA was seen in 15.1% of allogeneic recipients (including two of five patients with a prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The median time to occurrence was 92 days post transplant, with no de novo cases developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk factors for the development of IA included > or = 21 days of corticosteroid therapy of >or= 1mg/kg/day and post-transplant cytomegalovirus (CMV) infection. These two risk factors were statistically linked. Our data illustrate a shift toward a later occurrence of post-transplant IA, suggesting a need for close, prolonged surveillance in the outpatient environment. The contributory role of protracted corticosteroid use is also highlighted. These data have important implications in an era of alternate donor transplants and more intense immunosuppression. Established strategies implementing newer, less toxic antifungal agents as prophylaxis in high-risk patients are needed.

Increase in brain stem cytokine mRNA levels as an early response to chemical-induced myelin edema.

This study examined the early response of pro-inflammatory and regulatory cytokines in the mouse brain following triethyltin (TET)-induced myelin injury characterized by edematous vacuolation. Following an acute intraperitoneal injection of triethyltin (TET) sulfate (3 mg/kg) to 17-day old CD1 mice, significant increases in brain stem TNF-alpha and IL-1alpha mRNA levels occurred at 6 and 24 h, respectively with elevations in TGF-beta1 and MIP-1alpha at 1 h. In the cortex, responses were limited to elevations at 6 h in TNF-alpha, TGF-beta1 and MIP-1alpha. These data suggest that a chemokine/cytokine response can occur with minimal alterations to the integrity of the myelin sheath and may contribute to the initial signaling mechanisms associated with demyelinating disorders.

Activity of calcium-sensitive phospholipid-dependent protein kinase C following nephron loss.

The localization and activity of the calcium-sensitive phospholipid-dependent protein kinase C (PKC) were examined following the loss of 50% of functioning nephron mass. Four hours following unilateral nephrectomy in rats, soluble (100,000 g supernatant) proteins in the contralateral kidney were increased by 11% compared to sham operated controls; the increase was 33% 144 hours following surgery. The specific activity of PKC did not change in the cytosol at any of the time periods examined and averaged 63.9 +/- 8.2 pmol.mg-1.min-1 in unilaterally nephrectomized animals four hours following surgery. Four hours following sham surgery total soluble PKC activity averaged 1667.0 +/- 278.4 pmol.kidney-1.min-1, whereas activity averaged 3067.7 +/- 415.4 pmol.kidney-1.min-1 in animals post-nephrectomy (N = 5, P less than 0.04). Similar data was seen 144 hours following surgery. To examine the PKC activity in plasma membranes of proximal tubular cells, brush border membranes were prepared from rat kidney cortex. Twenty-four hours following unilateral nephrectomy, activity averaged 193.8 +/- 14.9 pmol.mg-1.min-1, while activity in membranes isolated from sham operated animals averaged 76.6 +/- 8.0 pmol.mg-1.min-1 (N = 5, P less than 0.001). Similar data was evident 48 hours following surgery. A small increment in activity was seen in the basolateral membrane preparation 24 hours following unilateral nephrectomy but not at 48 hours. These data indicate that cellular PKC activity increases rapidly following reductions in renal mass, and there are selective increments in the brush border membrane of the proximal tubular cell. The localization of PKC to this membrane may have important consequences for adaptations following nephron loss.

Comparative analysis of glycosylated hemoglobins by ion-exchange column chromatography and high-performance liquid chromatography in patients with hemoglobinopathies.

Cation-exchange chromatography gives falsely decreased values for glycosylated hemoglobins (GHbs) in patients with abnormal hemoglobins (Hbs) such as S, D, G, C, E, and O. This decrease is thought to be proportional to the percentage of abnormal Hb present. In the authors' study, cation-exchange column chromatographic GHb values on 84 nondiabetic patients heterozygous for Hb S, 28 AS diabetic patients, and 23 nondiabetic patients heterozygous for Hb C were calculated to account for the percentage of abnormal Hb, and the resulting values were compared with the GHb values obtained by high-performance liquid chromatography (HPLC). There existed a good correlation between the calculated GHb and the GHb obtained by HPLC (r = 0.92 for AS and r = 0.94 for AC). In patients with elevated Hb F, chromatographic GHb values are falsely high. In such cases, correction can be made by subtracting the Hb F value from the observed GHb. In laboratories where cation exchange chromatography is used, accurate determination of GHb can be made by adjusting observed values for portion of the abnormal Hb present.

Characterization and localization of calcium/phospholipid-dependent protein kinase-C during diabetic renal growth.

The substrate specificities of calcium/phospholipid-dependent kinase-C (PKC) were examined in rat kidney cortex, and localization of the protein was studied after the induction of diabetes. The cytosolic kinase was eluted from an anion exchange resin using a linear gradient of 0-0.15 M NaCl. A sharp peak of activity was demonstrated at approximately 80 mM using histone as a substrate. The kinase demonstrated a broad pH optimum of 6.5-8.0. ATP was the preferred phosphorus donor. The Ka for ATP averaged 2.6 +/- 0.1 microM (n = 4) and was not different in diabetic animals. Lysine-rich histones, but not arginine-rich or mixed histones, were the most suitable phosphorus acceptors. Phosphatidylserine stimulated kinase activity with Ka of 4.5 +/- 0.7 microM in the presence of 20 microM diolein (n = 3). Twenty micromolar diolein in the presence of 25 microM phosphatidylserine lowered the apparent Ka for calcium from 17.2 +/- 1.4 to 3.3 +/- 1.5 microM (n = 3; P less than 0.01). Similar data were evident in diabetic animals. Diabetic renal growth was induced by the injection of streptozotocin (35 mg/kg, iv). At the end of 4 weeks, blood glucose averaged 119.6 +/- 7.4 mg/dl in vehicle-injected controls and 548.7 +/- 21.6 mg/dl in diabetic animals (n = 5; P less than 0.001). Despite reduced weight gains in diabetic animals, renal protein content was increased in this group compared to the control value. Neither cytosolic nor proximal tubule basolateral membrane PKC activity changed after the induction of diabetes; however, luminal brush border PKC activity increased from 83.8 +/- 4.6 pmol/mg.min in control animals to 107.3 +/- 55 pmol/mg.min in diabetic animals (n = 5; P less than 0.02). The increased activity in the brush border membrane may have important consequences for the growth response of the kidney in diabetes.

Platelet dysfunction and coagulopathy in intraventricular hemorrhage in the premature infant.

We investigated platelet count, bleeding time, platelet aggregation, prothrombin time, activated partial thromboplastin time, and fibrinogen level in 58 very low-birth-weight infants during the first postnatal day to determine the relationship between hemostatic disorders and intraventricular hemorrhage. Thirty-two of the 58 infants (55%) were found to have periventricular-intraventricular hemorrhage by computerized tomography or autopsy. Nine patients (16%) had subarachnoid hemorrhage only and 17 (29%) had no evidence of intracranial hemorrhage. Infants with IVH had a significantly lower mean platelet count than did infants with no SAH/IVH. However, only five patients with IVH had initial thrombocytopenia. The IVH group had a mean bleeding time which was significantly prolonged compared to that of the group without SAH/IVH. Similarly, patients with IVH had a mean platelet aggregation response which was significantly diminished in comparison to that of patients with no SAH/IVH. Infants with IVH had a significantly longer mean PT than did infants with no SAH/IVH. In addition, babies with IVH had a significantly longer mean APTT compared to that of babies without SAH/IVH. The groups did not differ significantly with respect to fibrinogen levels. Three infants with IVH had disseminated intravascular coagulation in the early neonatal period. These data suggest that disorders of platelet-capillary interaction and defects in the intrinsic and extrinsic coagulation pathways may play important roles in intraventricular hemorrhage in the premature infant.

Uttar Pradesh breaks new ground.

PIP: The new development programs in India's poorest state, Uttah Pradesh, are summarized. Family planning is among the most important components of this effort. The Chief Minister Shri Narayan Datt Tiwari, has set a target of 150,000 acceptors, 10 times the total achievement during the previous year. During March 1976 there were 50,000 sterilizations, almost 40% of the total achievement of the entire previous year. The state government is giving a 15% land rebate to small farmers who get themselves sterilized and group incentives are being offered. 1200 centers, including Primary Health Centers, are being set up where vasectomy operations will be made available. More facilities for medical termination of pregnancy are also being set up. The target is to reduce the birthrate to 30/1000 by 1980. The present rate in Uttar Pradesh is 41.8, compared with 35 for India as a whold. Reports from various sections of the state confirm increased tempo of the family planning effort.^ieng