Immunologic characterization of a helper T-cell lymphoma

The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide "help" for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.     

High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty- two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty- three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno- occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high- dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.     

Tracking of lipids in schoolchildren: a four-year follow-up,population-based study in Sousse (Tunisia)

Objective

Dyslipidaemia, which is now seen as one of the most important cardiovascular risk factors, is becoming more common in the younger population. The aim of this study was to assess the efficacy of tracking serum lipid levels over a four-year period in an urban population of schoolchildren.

Methods

The study began in 1999 with a cohort of 789 schoolchildren. Four years later this group was resurveyed and a further 452 adolescent were recruited to the study.

Results

The percentages of boys who were initially in the extreme quartile for total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and triglycerides were 42.5, 54.8 and 40.4%, respectively. Similarly, the percentages of girls in the extreme quartile were 62.7, 53.8 and 38.2%. Four years later, both the boys and girls were still in the extreme quartile for these parameters. Therefore, the best predictor of follow-up level for each of the serum lipoprotein cholesterol fractions was the corresponding baseline level. Interestingly, the next best predictor in most of the groups was change in body mass index (ΔBMI) and smoking status.

Conclusion

Prevention of coronary heart diseases in adults must begin early on in childhood, and should be driven by health education towards achieving a healthy lifestyle.     

氯离子通道和药物靶标

氯离子通道的生物功能非常广泛,如参与上皮细胞内液体分泌、细胞容积调控等。氯离子通道突变可引起多种疾病,如囊性纤维化、黄斑部退化、肌强直等。氯离子通道调节剂的应用也非常广泛,其中γ氨基丁酸A（GABA_A）受体氯离子通道调节剂已在临床上使用,其他小分子调节剂正在临床前研究或临床试验阶段。本文主要讨论靶向氯离子通道药物的应用前景。     

Age-related changes of vergence under natural viewing conditions

Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing conditions. Transient vergence showed an age-related increase in latency and decreases in peak velocity and acceleration in the binocular stimulus condition but not in accommodative vergence. Sustained vergence showed no age-related effect in the binocular condition, but there was an age-related decrease in accommodative vergence steady-state velocity and an increase in latency. Age-related changes of the transient and sustained components were very similar to those reported for saccades and smooth pursuit; they thus might support a distinction between a sustained and transient vergence system. Furthermore, such age-related effects have to be taken into account when assessing eye movement disorders in neurodegenerative and cerebrovascular diseases.     

Fractionated radioimmunotherapy with 90Y‐clivatuzumab tetraxetan and low‐dose gemcitabine is active in advanced pancreatic cancer

BACKGROUND:

It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single‐dose yttrium‐90‐labeled hPAM4 (⁹⁰Y‐hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low‐dose gemcitabine in this disease.

METHODS:

Thirty‐eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m² weekly for 4 weeks with ⁹⁰Y‐hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2‐4). In the first part of the study, 19 patients received escalating weekly ⁹⁰Y doses of 6.5 mCi/m², 9.0 mCi/m², 12.0 mCi/m², and 15.0 mCi/m². In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m² or 12.0 mCi/m².

RESULTS:

Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single‐dose radioimmunotherapy. The maximum tolerated dose of ⁹⁰Y‐hPAM4 was 12.0 mCi/m² weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m² weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography‐based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses.

CONCLUSIONS:

Fractionated radioimmunotherapy with ⁹⁰Y‐hPAM4 and low‐dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma. Cancer 2012. © 2012 American Cancer Society.