Membrane phenotype and response to deoxycoformycin in mature T cell malignancies

The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sézary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sézary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin.     

Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab.

Adenoviruses are emerging as a major cause of infectious complications after allogeneic transplantation. We evaluated the incidence and outcome of symptomatic adenovirus infection or adenovirus disease after alemtuzumab-based reduced-intensity conditioning in 86 consecutive patients. The overall probability of adenovirus disease was 18.4% (11/86 patients). Five patients died of progressive adenovirus disease, and this was the most important infectious cause of mortality in this cohort. The probability of nonrelapse mortality was 49% in patients with adenovirus disease compared with 25.5% in those without (P=.007). The severity of lymphocytopenia and continuation of immunosuppressive therapy were the most important risk factors for progressive adenovirus disease and death. In contrast, patients who were not receiving immunosuppressive therapy or had had it reduced or withdrawn cleared the virus. We also detected a correlation between the lack of preemptive anti-cytomegalovirus (CMV) therapy for CMV reactivation and the risk of progressive adenovirus disease (P=.05). Our findings highlight the emergence of adenovirus as an important posttransplantation pathogen even after reduced-intensity conditioning and demonstrate the effect of the severity of lymphocytopenia, anti-CMV prophylaxis, and immunosuppressive therapy on the outcome of adenovirus disease.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.     

Comparison of the sensitivity of normal and leukaemic myeloid progenitors to in-vitro incubation with cytotoxic drugs: a study of pharmacological purging

The sensitivity of myeloid leukaemic colony forming cells (AML-CFC), to five cytotoxic drugs has been compared in two culture systems with the sensitivity of normal myeloid progenitor cells (GM-CFC). No increased sensitivity was found for AML-CFC to any of the chemotherapeutic agents studied. AML-CFC were significantly less sensitive than normal GM-CFC to mafosfamide at the doses commonly used to purge bone marrow autografts. It is suggested that AML cells probably display similar sensitivity to cytotoxic agents as normal myelopoietic cells at a similar stage of differentiation. Hence complete elimination of the leukemic clone by pharmacological purging may be incompatible with bone marrow re-engraftment. We conclude that purging AML autografts with any of the agents examined has little scientific basis.     

β-阻滞剂塞利洛尔的合成

报道了β－阻滞剂塞利洛尔的简便制备方法，即以对乙氧基苯胺为原料，经酰胺化，傅克反应，以环氧氯丙烷取代，最后用叔丁胺直接与环氧基反应开环等４步反应制得。比文献五步反应缩短了一步，产物经元素分析、红外光谱、核磁共振谱、质谱等分析确定结构。     

正常人口服磷酸川芎嗪的药代动力学研究

本文建立了用高效液相色谱法测定人体内川芎嗪血药浓度的方法,以C18化学键合硅胶(10μgm)为固定相,以甲醇—水(58:42)为流动相,280 nm俭测,安眠酮为内标,进行定量测定,得出俭测限为3.5 ng(S/N=4),最低检测血清浓度为17.4 ng/ml,川芎嗪血药浓度在0.029～5.82μg/ml范围内,线性关系良好,方法回收率为99.84%。方法重现性好,专一性强,内源性物质、代谢产物及同时服用的药物均不干扰。用本法测定了健康人口服川芎嗪的药代动力学参数。     

Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation

PURPOSEFibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to determine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation.METHODSAn institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All catheters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagulation and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined.RESULTSPatients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median catheter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respectively. Time to fibrin sheath formation was not significantly associated with hematocrit (P  = .16), platelet count (0.12), PT (P  = .51), or INR (P  = .74).CONCLUSIONAnticoagulation has no significant benefit in delaying sheath formation in patients with tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter placement were also not associated with catheter dwell time.

Main points

• Tunneled dialysis catheter dwell time was not significantly longer with anticoagulation, antiplatelet or statin therapy.
• There is no association between baseline coagulation profile and clinically significant fibrin sheath formation.

Tunneled dialysis catheters are frequently the initial access for patients requiring dialysis.^1,2 According to the United States Renal Data System, 80% of end-stage renal disease patients require a catheter when starting dialysis. At 90 days after the start of dialysis, 68.5% of patients are still reliant on catheters.³Fibrin sheaths are a significant cause of catheter dysfunction. Increased catheter infection risk and persistent bacteremia are also associated with fibrin sheaths.⁴ Studies have demonstrated fibrin sheaths can develop within 24 hours of catheter placement and may affect up to 47% of catheters.^5,6 When thrombolytic treatment fails, patients have to undergo additional procedures to exchange the catheter, disrupt the sheath, or strip the sheath, which contribute to patient morbidity.^7-10Prevention of fibrin sheath formation would be expected to have a beneficial impact on satisfactory dialysis maintenance. Placing patients on anticoagulation is a potential strategy that may decrease the risk for catheter dysfunction secondary to fibrin sheaths.¹¹ The aim of this study is to determine whether anticoagulation, antiplatelet medication, or other factors may influence the rate of fibrin sheath development in patients with tunneled dialysis catheters.     

Escherichia coli tetracycline efflux determinants in relation to tetracycline residues in chicken

ObjectiveTo screen for Escherichia coli (E. coli) resistant to tetracycline, followed by identification of tet efflux genes by polymerase chain reaction (PCR). In addition, detection of tetracycline residues in chicken livers and kidneys were conducted using high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS).MethodsStrains of E. coli were isolated from samples of chicken colon and screened for tetracycline resistance. Tetracycline genes conferring resistance (Tc^r) were detected by polymerase chain reaction (PCR). Most of the isolates were resistant to tetracycline (97.9%).ResultsPCR analysis indicated that Tc^r E. coli R-plasmids contained tet(A), tet(B) and a combination of both efflux genes. None of the isolates contained other efflux tet genes tet (C, D, E and Y). High performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS), a sensitive technique, was used to detect residues of chlortetracycline (CTC), oxytetracycline (OTC), doxycycline (DC) in chicken livers and kidneys. The samples containing tetracycline residues were at 0.13-0.65 pg/μL levels.ConclusionsTetracycline and other antibiotics are commonly used in the poultry and meat production industry for prevention of microbial infections. Multiple antibiotic resistant bacteria in Oman have increased to alarming levels, threatening public health, domestic and may have adverse effect on environment.