Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation

After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers.     

Abnormal accessory mitral leaflet simulating left ventricular outflow tract tumor

This is a case report of an uncommon form of subaortic stenosis caused by an abnormal accessory mitral leaflet simulating a left ventricular outflow tract tumor. A 5-year-old boy with a systolic heart murmur underwent cardiac catheterization which demonstrated a subaortic stenosis with a 90 mmHg peak systolic pressure gradient. Angiography showed a tumor-like structure in the left ventricular outflow tract. At operation this mass was found to be an abnormal bulky accessory mitral leaflet. Resection of this deformed leaflet was carried out successfully.     

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.     

Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive

The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen

Using the CD40 system, in vitro proliferation of hairy cell leukemia (HCL) was examined in 43 patients. In this culture system, cells were stimulated by interleukin-4 (IL-4) and anti-CD40 monoclonal antibodies (MoAbs) that were added in soluble form or were cross-linked via their Fc part using Fc gamma RII-transfected mouse fibroblast cells. Proliferation was induced and confirmed by 3H-thymidine incorporation in 14 cases and by the presence of metaphases in 42 cases. 3H-thymidine incorporation showed a heterogeneous pattern: cross-linking of anti- CD40 gave the highest proliferation in 8 cases; in 11 cases, stimulation with anti-CD40 MoAbs alone, without cross-linking also resulted in proliferation; the addition of IL-4 further enhanced 3H- thymidine incorporation in 5 cases, but suppressed this phenomenon in 5 other cases. The CD40 system proved to be very effective in obtaining cytogenetic data. With a success rate of 42 of 43 patients tested, we found clonal abnormalities in 8 cases (19%) and nonclonal abnormalities with involvement of one or two abnormal metaphases in another 7 cases. The chromosomes most frequently involved in the abnormal karyotypes, both structurally and numerically, were chromosomes 5, 7, and 14. By fluorescence-activated cell-sorting analysis of the cultured cells, and by immunophenotypic analysis of metaphase spreads, T-cell growth could be excluded and the HCL-lineage confirmed. Stimulation via the CD40 antigen is an excellent tool for growing hairy cell leukemia cells.     

包膜活性炭吸附血液灌流清除人血浆中毒鼠强的实验

目的:观察包膜活性炭对血浆中毒鼠强的清除率及吸附规律。方法:实验于2004-05/2006-04在军事医学科学院毒物药物研究所国家重点实验室完成。采用包膜活性炭灌流器对毒鼠强血浆样进行血液灌流吸附,在灌流的1,2,3h分别取样,经乙酸乙酯萃取后,用气相色谱氮磷检测器法(GC/NPD)测定其含量并计算清除率。结果:活性炭对毒鼠强的吸附作用在血液灌流1h最高,灌流2h后毒鼠强质量浓度无明显变化。400,200μg/L毒鼠强血液灌流1h清除率分别为(57.83±1.85)%,(48.18±1.81)%。结论:用包膜活性炭吸附剂进行血浆的灌流吸附,能清除大部分毒物,迅速降低血浆中毒鼠强的质量浓度。     

Surgical therapy of life-threatening tachycardic cardiac arrhythmias in children

Surgical techniques for tachyarrhythmias refractory to medical treatment are used with increasing frequency. Among 211 patients undergoing antiarrhythmic surgery 10 children (2 to 14 years old) were operated by electrophysiologically directed procedures. 7 patients suffered from WPW syndrome, 2 from focal atrial tachycardias and 1 from recurrent ventricular tachycardia following the repair of Fallot's tetralogy. In all cases preoperative electrophysiologic study and intraoperative mapping preceded operative ablation. Surgical treatment consisted of interruption of the bundle of Kent (3 right-sided, 2 left-sided, 3 septal), ablation of the atrial focus (1 right-sided, 1 left-sided) and right ventricular outflow tract incision. In 7 operations cryo-techniques were added. 2 children with WPW syndrome had two interventions because of tachycardia recurrences due to multiple accessory pathways. In 1 case a VVI-pacemaker was implanted postoperatively due to complete atrioventricular block. Another 2 children with prolonged postoperative bradycardia received a pacemaker prophylactically. Only the child with previous tetralogy of Fallot is still under antiarrhythmic medication while all other children are free of tachycardiac episodes. Our data confirm the efficacy of surgical treatment of tachyarrhythmias in children thereby abolishing the need for life-long antiarrhythmic medication.     

Recurrent ventricular tachycardia in asymptomatic young children with an apparently normal heart

Abstract Ventricular tachycardia without underlying heart disease is rare in infancy and childhood. Four young children (median age 8 months at initial presentation) with frequently recurrent episodes of asymptomatic and self-limiting ventricular tachycardia are reported. By noninvasive investigation no apparent heart disease has been found in all patients. Initially three of the four children had been treated with an anti-arrhythmic drug. Treatment was soon stopped in two patients for lack of symptoms and for lack of efficacy of therapy; one patient remained on beta-blocker therapy. One child did not receive anti-arrhythmic therapy. After a mean follow up of 32 months all patients continued to be asymptomatic despite frequently recurrent episodes of self-limiting ventricular tachycardia.Conclusion Ventricular tachycardia in asymptomatic children with an otherwise normal heart carries a good prognosis. Invasive investigation (cardiac catheterization with electrophysiological study and right ventricular biopsy) can be with-hold, as long as there are no symptoms. For lack of efficiency of antiarrhythmic drugs in suppressing ventricular tachycardia in asymptomatic children with apparently normal hearts, these patients may be left without therapy but have to be followed closely.     

Cavernous hemangioma and disseminated intravascular coagulation (Kasabach-Merritt syndrome) in a newborn infant with a large ventricular septal defect

In a 3170 g newborn with a large cavernous hemangioma at the left thigh, heart failure was evident. Echo- and angiographically a large perimembranous ventricular septal defect was found. An important a-v shunt within the hemangioma could be excluded by hemodynamic investigation and selective arteriographic examination of the vascular tumor. Thrombocytopenia present from the first day of life was only temporarily overcome by corticosteroid therapy but nevertheless consumption coagulopathy (Kasabach-Merritt-Syndrome) developed and additional therapy with heparin was necessary in order to normalize the coagulation factors. However, no regression in size of the tumor occurred over the first 8 weeks of life and a total exstirpation of the hemangioma was performed. Postoperatively no further cortison or heparin therapy was necessary. Despite vigorous medical treatment the congestive heart failure persisted. After surgical closure of the ventricular septal defect at the age of three months the infant thrived and could be discharged without pathological symptoms.