Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis.

BACKGROUND: The neural consequences of early-life exposure to methylphenidate (MPH; Ritalin) are of great interest given the widespread, and sometimes inappropriate, use in children. Here we examine the impact of juvenile MPH exposure on adult hippocampal neurogenesis. METHODS: Rats received MPH (2.0 mg/kg, intraperitoneal, twice daily) or saline (SAL) during preadolescence (postnatal days 20-35). Hippocampal cell proliferation (Experiment 1), neurogenesis (Experiment 2), and stress-induced changes in cell proliferation (Experiment 3) were assessed at several developmental stages including adulthood. RESULTS: Juvenile exposure to MPH did not alter proliferation at any developmental time point relative to control rats; however, exposure to MPH significantly decreased the long-term survival of newborn cells in adult rats, particularly in the temporal hippocampus. Although MPH-treated rats had higher levels of corticosterone after restraint stress, they did not show the expected greater decrease in hippocampal cell proliferation relative to control animals. CONCLUSIONS: Early-life exposure to MPH inhibits the survival of adult-generated neurons in the temporal hippocampus and may reduce progenitor sensitivity to corticosterone-induced decreases in proliferation. These findings suggest that decreased adult neurogenesis is an enduring consequence of early-life exposure to MPH and are discussed for their relevance to humans.     

The effects of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia

A small subset of leukemic cells from most patients with acute myeloblastic leukemia (AML) have properties of stem cells and can be assayed by colony formation in agar or methylcellulose. Colony formation generally requires the addition of exogenous growth factors, but the exact factors required are incompletely defined. The AML colony- promoting activities of two recombinant human colony-stimulating factors (GM-CSF and G-CSF) were investigated by using blasts from 48 patients with AML. In nine cases, no colonies formed with either CSF. In seven cases colonies formed only in response to G-CSF and in 11 cases only in response to GM-CSF. In 21 cases colonies formed in response to either GM-CSF or G-CSF, and in 12 of these cases there was an additive effect between the two CSFs in determining maximum colony size. For cases responding to both GM- and G-CSF, the total number of colonies formed in response to the combination of both CSFs was almost always less than additive compared with the number of colonies formed in response to the individual CSFs. Further, the AML-CFU responding to either GM-CSF or G-CSF could not be distinguished by surface markers or by the cytochemical staining pattern of the colonies. These results suggest that there is considerable overlap between the GM-CSF- and G- CSF-responsive AML-CFU subpopulations in most cases. For five of seven cases, the combination of GM-CSF and G-CSF could replace a leukocyte feeder layer in providing maximum growth stimulation. These results indicate that GM-CSF and G-CSF are active growth factors for AML cells and are frequently additive in promoting maximum colony size.     

促红细胞生成素对实验性肾性贫血的作用

促红细胞生成素(erythropoietin,EPO)是由肾细胞分泌的一种糖蛋白激素。从人胚肾细胞中诱导,经生物化学方法分离、提纯得到此品。本试验用5/6肾切除的方法造成大鼠慢性肾衰性(CRF)贫血,研究不同剂量EPO对CRF贫血的作用。结果表明EPO有显著的促进红细胞生成,改善CRF贫血状态,使其接近或达到正常水平,最佳剂量为1000 U/kg,并可预防实验性贫血,对正常鼠未见明显作用。     

Phylogenetic analysis of human G9P[8] rotavirus strains circulating in Jiangsu,China between 2010 and 2016

Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children’s Hospital between 2010 and 2016 (named JS2010‐JS2016) were analyzed through whole‐genome sequencing. All evaluated strains showed the Wa‐like constellation G9‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9‐III and G9‐VI. With the exception of strain JS2012 (P[8]‐4), the VP4 sequences of all strains belonged to the P[8]‐3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis.     

Topology of Kell blood group protein and the expression of multiple antigens by transfected cells

Kell is one of the major blood group systems in human red blood cells (RBCs). The Kell antigens are carried on a 731 amino acid glycoprotein that is thought to span the erythrocyte membrane once. Rabbit antibodies to three synthetic peptides, derived from different parts of the Kell protein, were used to determine the topology of Kell protein on the RBC. Antibodies to a C-terminal peptide and to a peptide derived from amino acid residues 410 to 439 reacted with RBCs treated with 0.2 mol/L dithiothreitol. An antibody to the N-terminal peptide reacted with inside-out RBC vesicles but not with right-side-out vesicles nor with intact RBCs, showing that Kell is a type II membrane protein and that the extracellular portion of the protein is folded by disulfide bonds. By transfection, Kell protein was expressed on the cell surface of surrogate cells, and the transfected cells expressed similar antigenic properties as native RBCs. Kell protein was expressed in COS- 1 and K562 cells and in Sf9 cells infected by the Baculovirus system. Transfected K562 cells expressed several high-incidence antigens but not the low-incidence antigen K1.     

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.