Chloramphenicol-dependent antibody: a case report

BACKGROUND: Chloramphenicol-dependent antibodies are a rare cause of interference in pretransfusion serologic testing. Their presence can be confirmed by the testing of red cells in both the presence and absence of chloramphenicol. CASE REPORT: A 29-year-old, group A, Rh-positive man with no history of chloramphenicol exposure was found to have a chloramphenicol-dependent panagglutinin in his serum. The antibody was IgM with a titer of 8. It showed no blood group specificity when tested with common and rare red cell phenotypes, and it failed to react with platelets and granulocytes. Confirmation attempts using a chloramphenicol sodium succinate solution as the cell-suspending medium led to negative results. The antibody reacted serologically only in the presence of chloramphenicol, which arises from the succinate derivative by the action of blood esterases. CONCLUSION: This case is an additional example of a chloramphenicol-dependent antibody. It demonstrates how the laboratory investigation of drug-related phenomena is dependent on testing the drug from that reacts in vivo.     

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study

Objectives

Dyslipidaemia is common in perinatally HIV‐infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs.

Methods

We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and TC:HDL‐C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)‐ or darunavir/ritonavir (DRV/r)‐based antiretroviral therapy (ART) from an older PI‐based ART and those remaining on an older PI. Generalized estimating equation models were fitted to assess the association of a switch to ATV/r‐ or DRV/r‐based ART with the rate of change in lipids, adjusted for potential confounders.

Results

From 2007 to 2014, 47 PHIV children/adolescents switched to ATV/r or DRV/r, while 120 remained on an older PI [primarily lopinavir/r (72%) and nelfinavir (24%)]. Baseline age ranged from 7 to 21 years. After adjustment for age, Tanner stage, race/ethnicity, and HIV RNA level, a switch to ATV/r or DRV/r was associated with a more rapid annual rate of decline in the ratio of TC:HDL‐C. (β = ?0.12; P = 0.039) than remaining on an older PI. On average, TC declined by 4.57 mg/dL/year (P = 0.057) more in the switch group. A switch to ATV/r or DRV/r was not associated with the rate of HDL‐C, LDL‐C, or TG change.

Conclusions

A switch to ATV/r or DRV/r may result in more rapid reduction in TC and the TC:HDL‐C ratio in PHIV youth, potentially impacting long‐term cardiovascular disease risk.

     

Clinical features and predictors of diphtheritic cardiomyopathy in Vietnamese children

BACKGROUND: Despite the availability of antitoxin and antibiotics, the mortality rate for diphtheria remains high, mostly because of cardiac complications. METHODS: During 1 year, 154 Vietnamese children with diphtheria admitted to a referral hospital were studied prospectively with clinical examination, including a simple pseudomembrane score, 12-lead and 24-hour electrocardiography, measurement of serum cardiac enzyme levels, and estimation of troponin T levels. RESULTS: Thirteen children had diphtheritic cardiomyopathy on admission, and 19 developed it subsequently. Twelve children (8%) died. The combination of pseudomembrane score of >2 and bull neck predicted the development of diphtheritic cardiomyopathy, with a positive predictive value of 83% and a negative predictive value of 93%. Administration of 24-hour electrocardiography on admission improved the ability to predict diphtheritic cardiomyopathy by 57%. Fatal outcome was best predicted by the combination of myocarditis on admission and a pseudomembrane score of >2. Of the cardiac enzyme levels measured, an elevated aspartate aminotransferase level was the best predictor. The presence of troponin T identified additional children with subclinical cardiac damage. CONCLUSIONS: The development of diphtheritic cardiomyopathy can be predicted by means of simple measures.     

Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem-cell disorder in which the glycolipid-anchored membrane proteins, including the cell-surface complement inhibitors, CD55 and CD59, are partially or completely deleted from the plasma membranes of mature blood cells. To gain insight into the pathogenesis of thrombosis that is frequently observed in this disorder, the procoagulant responses of PNH platelets exposed to the human terminal complement proteins C5b-9 were investigated. C5b-9 complexes were assembled on gel-filtered platelets by incubation with purified C5b6, C7, C9, and limiting amounts of C8. Platelet microparticle formation and exposure of plasma membrane- binding sites for coagulation factor Va were then analyzed by flow cytometry. PNH platelets exhibiting undetectable levels of surface CD59 antigen showed an approximately 10-fold increase in sensitivity to C5b- 9-stimulated expression of membrane-binding sites for factor Va when compared with platelets from normal controls. Expression of catalytic surface for the prothrombinase complex (VaXa) paralleled the exposure of factor Va-binding sites; the rate of prothrombin conversion by C5b-9- treated PNH platelets exceeded that of C5b-9-treated normal controls by approximately 10-fold at the maximal input of C8 tested (500 ng/mL). These data indicate that PNH platelets deficient in plasma membrane CD59 antigen are exquisitely sensitive to C5b-9-induced expression of prothrombinase activity, and suggest that the tendency toward thrombosis in these patients may be due, at least in part, to the deletion of this complement inhibitor from the platelet plasma membrane.     

去糖基化突变体肾素元的分子特点

应用野生体和去糖基化突变体肾素元ｃＤＮＡ，转染ＧＨ４细胞，经３５Ｓ代谢标记表达产物，免疫沉淀，ＳＤＳ／ＰＡＧＥ电泳检测观察去糖基后肾素元结构与功能的变化．发现去糖基化后的肾素元突变体，除半衰期缩短外，其分子粘度明显增高，转染细胞清除作为代谢标记去糖基化肾素元的时间延长。说明肾素元的糖基化的对其分子不仅在自稳中起重要作用，同时在成熟中可能也有重要生物学意义。     

Treatment of patients over 50 years of age with acute myelogenous leukemia with a combination of rubidazone and cytosine arabinoside, vincristine, and prednisone (ROAP)

We administered a combination of rubidazone, cytosine arabinoside, vincristine, and prednisone (ROAP) to 91 patients with acute myelogenous leukemia who were 50 yr of age or older. These patients had been identified in previous studies to be a group with a relatively poor prognosis. One-third of the patients had an antecedent hematologic disorder prior to treatment. Forty patients (48%) obtained a complete hematologic and clinical remission. A history of an antecedent hematologic disorder, male sex, and absence of Auer rods were adverse factors for achieving remission in this older population. More than half of the patients achieved remission in one course. The major cause of failure to obtain a remission was death due to infection, 40% of which were caused by fungi. Resistance to chemotherapy, although uncommon, was noted more frequently in patients with an antecedent hematologic disorder. Univariate and multivariate prognostic factor analysis was used to compare these patients with a historical control group treated with a program in which adriamycin was used instead of rubidazone (AdOAP). No significant difference in remission rate was detected. Cyclocytidine was used as a maintenance agent in this study, and while the median remission duration was only 37 wk, 30% of patients are expected to be in remission for 2 yr. Chemotherapy programs combining an anthracycline with cytosine arabinoside, given to older patients in similar fasion to younger patients will achieve remissions in one-half of a group of older patients. These remissions are of comparable quality to those of younger patients. Mathematical models derived from analysis of prognostic factors are of use in identifying patients likely to fail these programs who are in need of innovative approaches to treatment.     

Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.     

The parallel wire technique for septal defect closure

Percutaneous closure of sedundum atrial septal defects (ASD) has been shown to be safe and effective. Usually crossing the defect is relatively straightforward. Occasionally, with fenestrated ASDs, trying to cross the defect(s) may be challenging. We report the use of a “paralle wire” (0.018 or 0.014 inch wire) technique to maintain access and be able to recross the same defect easily in case of misplacement until just before the device was secured and released. This technique could be used also as a “body wire” for large ASDs with deficient rims to reduce the incidence of device prolapse, and for patent foramen ovale and ventricular septal defect closures. This is a simple and easily reproducible method with the equipment readily available in virtually all catheterization laboratories. © 2008 Wiley‐Liss, Inc.     

Prevention of mother‐to‐child transmission of HIV in Denmark, 1994–2008

Objectives

The aim of this study was to describe trends in the management of pregnancies in HIV‐infected women and their outcomes over a 14‐year period in Denmark on a national basis.

Methods

The study was a retrospective cohort study of all HIV‐infected women in Denmark giving birth to one or more children between 1 June 1994 and 30 June 2008.

Results

We identified 210 HIV‐infected women with 255 pregnancies, ranging from 7 per year in 1995 to 39 per year in 2006. Thirty per cent of the women were Caucasian and 51% were Black African. Knowledge of HIV status before pregnancy increased from 8% (four of 49) in 1994–1999 to 80% (164 of 206) in 2000–2008. Only 29% (53 of 183) of the women chose to consult an infectious disease specialist when planning pregnancy, while 14% (27 of 199) received assistance with fertility. The proportion of women on antiretroviral therapy (ART) increased from 76% (37 of 49) in 1994–1999 to 98% (201 of 206) in 2000–2008. Vaginal deliveries ranged from 0 in 2003 to 35% of pregnancies in 2007. Mother‐to‐child transmission (MTCT) of HIV decreased from 10.4% in 1994–1999 to 0.5% in 2000–2008. All women giving birth to an HIV‐positive child were diagnosed with HIV during or after delivery and did not receive prophylactic ART.

Conclusions

The annual number of HIV pregnancies increased fivefold during this 14‐year period and substantial changes in pregnancy management were seen. No woman treated according to the national guidelines, i.e. ART before week 22, intravenous zidovudine (ZDV) during labour, neonatal ZDV for 4 to 6 weeks and no breastfeeding, transmitted HIV to her child.