Phenotypic and Genotypic Lineage Switch of a Lymphoma with Shared Chromosome Translocation and T-Cell Receptor γ Gene Rearrangement

A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) γ gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR δ/α gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR δ/α gene complex was studied. The result showed that two rearrangements of TCR α gene detected with J_α probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.     

Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment

Objective: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. Methods: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. Results: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. Conclusion: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment – particularly for high dose regimens (> 22 mg per 24 hours). Received: 7 May 1996 / Accepted in revised form: 21 August 1996     

MANAGEMENT OF SEMINOMA OF THE TESTIS: RECOMMENDATIONS BASED ON TREATMENT RESULTS

Background : The results of management of seminoma of the testis at the Department of Radiation Oncology St Vincent's Hospital, Sydney were evaluated retrospectively to: (i) establish that outcomes were in keeping with published results from centres in Australia and overseas; (ii) assess the impact of chemotherapy on management; and (iii) to determine ‘best practice’ management protocols based on our results and a review of the relevant literature. Methods : (i) Assessment of treatment results for stage I and II seminoma of the testis treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's Hospital between 1979 and 1993; (ii) literature review of published data from Australian and overseas centres on the management of seminoma of the testis, and in particular the use of surveillance or chemotherapy either alone, at time of relapse or combined with radiotherapy; and (iii) development of recommendations for use as management protocols in our department. Results : Our data and a review of the literature suggest that post-orchidectomy radiotherapy with chemotherapy for relapse in stage I and IIA disease results in long-term cure rates approaching 100%. Treatment with chemotherapy either routinely or selectively or using a surveillance policy is unlikely to show any improvement in outcome and may be less cost-effective and/or produce increased morbidity and the risk of secondary leukaemia. For stage IIB disease (5–10 cm) the use of initial combination chemotherapy with or without subsequent radiotherapy did not appear to give better outcomes than initial radical radiotherapy alone, reserving chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease (> 10cm). the use of initial chemotherapy plus consolidation radiotherapy appeared to be an appropriate treatment. Conclusions : Management protocols for seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation Oncology currently are (i) stage I, IA and IIB (5–10 cm): post-orchidectomy radiotherapy alone with chemotherapy or further radiotherapy for relapse; and (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed by radiotherapy to sites of initial disease involvement.     

DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

The features of enamel hypoplasia in a small group of patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are described. Using a recently developed method, the authors evaluated quantitatively the amount of defect in each tooth by measuring the width of the hypoplastic lesions and dividing the value by the crown height. They then assessed the degree of damage in each tooth type (from central incisors to second premolars) and patient. Canines were the most severely affected among maxillary and mandibular teeth, but all tooth types were involved. Analysing both the differences between patients and their age at the beginning of the defect, the authors observe that hypoparathyroidism is not responsible for the onset of enamel hypoplasia in APECED, although it may contribute to the damage.     

滇缅边境打洛镇6年的疟疾防治措施与效果

方法:1983—1985年在滇缅边境打洛镇采取DDT加DDVP全面滞留喷洒灭蚊,1986—1988年改用溴氰菊酯浸泡蚊帐灭蚊,并均辅以现症病人根治、重点人群保护和流动人口预防服药等综合性防治措施。结果:防治后全镇1983—1988年的年带虫发病率依次降为10.1‰、5.8‰、5.5‰、4.8‰、14.4‰和10.1‰。各年均明显较全面防治前1982年的29.0‰低。有效控制了疟疾流行。     

中国三囊库蠓亚属的种类分布及分类研究(双翅目:蠓科)

本文报告了我国三囊库蠓亚属Culicoides(Trithecoides)已知24种。亚属的鉴别特征,主要特征测量值以及雌虫和雄虫分种检索表。     

Pre- and postoperative nutritional care in liver transplantation in children

Orthotopic liver transplantation (OLT) is now a definitive treatment option for most cases of endstage liver disease (ESLD) in children. Efforts now focus on active supportive treatment to maintain, if not improve, the patient's clinical status before OLT and to ensure normal patterns of growth and development after OLT. Malnutrition adversely affects the outcome of OLT and is probably the single area in pre-operative management where the largest potential improvement can be made. Our studies indicate significant abnormalities of protein energy metabolism and body composition in children referred for OLT. We have shown that the use of enteral formulae, enriched with branched-chain amino acids, have significant advantages. Other adjunctive therapy, such as growth hormone, is the subject of current investigation. Following transplantation, catch-up weight and growth does occur with the advent of normal liver functioning, but patients at continuing risk for undernutrition, such as those with rejection and/or chronic infection, need to be targeted for specific nutritional therapy.