Rearrangement of kappa-chain and T-cell receptor beta-chain genes in malignant lymphomas of "T-cell" phenotype

Detection of immunoglobulin gene rearrangements by molecular hybridization is considered to be a highly sensitive approach to the evaluation of clonality of B-cell-derived neoplasms. Like monoclonal surface immunoglobulin in B cells, which serves as a reliable immunophenotypic marker for clonality, rearrangement of the genes encoding immunoglobulin light chains has been accepted as a reliable genotypic marker for the presence of a clonal expansion of B lymphocytes. The authors now report 3 cases of non-Hodgkin's lymphoma that were immunologically classified as having a T-cell phenotype and in which, in addition to rearrangements of the T-cell receptor beta-chain gene, a rearrangement of an immunoglobulin light-chain gene was clearly identified by Southern blot hybridization. The results demonstrate that the data obtained by molecular hybridization should be interpreted with caution when the immunogenetic findings do not correlate with immunophenotypic expression, and that the results of molecular genetics studies should be interpreted in conjunction with morphologic and immunologic findings.     

Malignant histiocytosis X. A distinct clinicopathologic entity

Histiocytosis X (HX) is characterized morphologically by a proliferation of Langerhans' cells (LC), and most often has an indolent, chronic course. To determine whether a distinct clinicopathologic entity of malignant histiocytosis X exists, the authors examined tissues from 31 patients with HX and divided them into four categories. Group A (19 patients) was characterized morphologically by benign-appearing LC and had an indolent course. The male:female (M:F) ratio was 10:9, and the mean age was 21 years (range, 2 months to 60 years). The immunophenotype of this group was S-100+, vimentin+, LN-2+, LN-3+, lysozyme-, LCA-, Leu-M1-. Group B (three patients) had benign-appearing LC, yet had an aggressive clinical course. All patients were male, with a mean age of 47 years (range, 3 years to 72 years). Organs involved included the liver, spleen, heart, thymus, lung, kidney, and pancreas. The immunophenotype was the same as for Group A. Group C (two patients) had atypical and malignant appearing LC, yet a relatively benign clinical course. The ages were four and 65 years, with one female and one male patient. In both patients, the cells were S-100+, vimentin+, LN-2+, LN-3+, and LCA-. Group D (seven patients) was characterized by atypical and malignant-appearing LC and an aggressive clinical course. The mean age was 25 years (range, congenital to 54 years) with one female and six male patients. Organs involved were the thymus, lungs, spleen, liver, kidney, brain, heart, pancreas, stomach, and muscle. Birbeck granules were found in two patients, and the one patient on which fresh tissue was available was CD1+. The typical immunophenotype was S-100+, vimentin+, LN-2+, LN-3+, Leu-M1-, lysozyme-. The results of our study indicate that (1) a distinct clinical entity of malignant HX, characterized morphologically by malignant-appearing LC and clinically by male predominance, atypical organ involvement, and an aggressive clinical course, does exist; and (2) the morphologic appearance of the LC is an imperfect predictor of the clinical severity of HX.     

Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge

We examined the role of common genetic variation in determining the consistency and magnitude of change in plasma total cholesterol (TC) levels in response to two separate changes from a high-saturated (SFA) to a low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of free-living healthy men and women. Consistent responders were defined as those whose mean difference in the change in TC was within one SD of the mean for all participants, and the remainder were defined as variable responders. DNA was obtained from 55 individuals and genotype determined at the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T) and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent responders, the apoBSP24 allele was significantly more common than in the 17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No other polymorphism showed a significant frequency difference between groups. In the group as a whole, the correlation between the change in TC level in response to the first and second dietary change was 0.28 (p = 0.05), but those with one or more apoB SP24 alleles and those with the apoCIII genotype CC had a significantly higher correlation than those with other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02 (NS), respectively). In the group as a whole, mean response left TC 10% higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII genotypes affected the magnitude of this response. However, individuals with the LPL HindIII genotype H+ H+ had a significantly smaller change in mean TC in response to diet than those with one or more H- allele (9.3% vs. 14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the consistency of response to change in dietary fat content, while variation at the LPL gene locus affects magnitude of response.      

延边地区汉族和朝鲜族居民脂肪分布与代谢异常的关系

目的:了解延边地区朝鲜族和汉族居民的脂肪分布特征及其与血压、血脂及血糖的关系。方法:于2006-08-8/17在延边地区九龙和翁声社区随机选择40～60岁朝鲜族和汉族常住居民2378名进行内脏脂肪率和体脂肪率以及血压、血脂、血糖等生化指标的检测。调查以健康体检形式进行,①内脏脂肪和体脂肪率测定采用日本TANITA株式会社生产的BC-600型体成分计测定,并且按其判定标准确定超过标准者[内脏脂肪率≥15%(男)、≥10%(女),体脂肪率(40～59岁)≥23%(男)、≥36%(女),体脂肪率(≥60岁)≥25%(男)、≥37%(女)]。②取清晨空腹(禁食12h)静脉血,采用日立-7600-010全自动生化分析仪测量血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、空腹血糖等指标。③高血压的诊断标准:收缩压≥140mmHg(1mmHg=0.133kPa)及或舒张压≥90mmHg。④血脂异常的诊断标准:总胆固醇≥5.72mmol/L,三酰甘油≥1.7mmol/L,高密度脂蛋白胆固醇<0.90mmol/L(男)、<1.0mmol/L(女)。⑤高血糖的诊断标准:空腹血糖≥6.1mmol/L。结果:①汉族男性的内脏脂肪率和体脂肪率均值分别为(10.51±3.66)%和(22.70±4.85)%,朝鲜族男性分别为(9.16±3.81)%和(20.28±5.02)%,汉族均高于朝鲜族(P<0.01);汉族女性的内脏脂肪率和体脂肪率分别为(6.22±2.27)%和(35.31±5.65)%,朝鲜族女性分别为(5.88±2.19)%和(34.00±5.72)%,汉族均高于朝鲜族(P<0.01)。②汉族男性的内脏脂肪率和体脂肪率超标率分别为12.1%和45.8%,朝鲜族男性分别为7.8%和28.6%,汉族均高于朝鲜族(P<0.05);汉族女性的内脏脂肪率和体脂肪率超标率分别为6.7%和47.9%,朝鲜族女性分别为3.8%和37.3%,汉族均高于朝鲜族(P<0.05)。③Logistic逐步回归分析结果表明,内脏脂肪率与民族、性别、年龄、高血压、高三酰甘油血症和高血糖有密切关系;体脂肪率与民族、性别、高血压、高三酰甘油血症、低高密度脂蛋白血症和高血糖有密切的关系。结论:①延边地区汉族居民内脏脂肪率和体脂肪率平均水平及其超标率明显高于朝鲜族。②内脏脂肪率和体脂肪率均与民族、性别、年龄(体脂肪率除外)、高血压、高三酰甘油血症和高血糖相关。     

Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.     

Penetrating Missile Injuries During the Iraqi Insurgency

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.     

Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.