利妥昔单抗治疗老年人脾边缘区淋巴瘤二例并文献复习

目的 探讨老年人脾边缘区淋巴瘸(SMZL)的诊断、治疗方法.方法 报道2例年龄＞70岁伴有巨脾的SMZL,并对其临床表现、诊断及治疗进行文献复习.结果 SMZL多见于老年患者,常表现为脾大,具有与脾功能亢进相似的症状和体征.骨髓流式细胞术结合细胞形态学检查有助于诊断.可行利妥昔单抗单药治疗,疗效较好.结论 流式细胞术对SMZL的诊断及治疗均有重要的指导作用.     

利妥昔单抗联合氟达拉滨、环磷酰胺治疗慢性淋巴细胞白血病17例

目的 评价利妥昔单抗联合氟达拉滨、环磷酰胺（FCR方案）治疗慢性淋巴细胞白血病(CLL)患者的疗效和安全性。方法选取年龄＜70岁且CD20阳性的初治或既往仅用苯丁酸氮芥治疗的CLL患者,应用FCR方案治疗,利妥昔单抗375 mg/m2,第1天,静脉滴注;氟达拉滨25 mg/m2,第2天至第4天,静脉滴注;环磷酰胺250 mg/m2,第2天至第4天,静脉滴注。28d为1个疗程,治疗4～6个疗程,治疗结束后评价疗效。结果共入组17例患者,总有效率为94.12％(16/17),完全缓解率为35.29％(6/17)。Ⅲ-Ⅳ级不良反应主要为中性粒细胞减少,白细胞减少。结论FCR方案治疗CLL疗效确切,患者耐受良好,可以作为初治患者的一线治疗方案。     

应用番泻叶对老年便秘的护理干预

目的:比较对老年便秘患者使用番泻叶进行缓泻,能实现在24小时内排出大便并无明显不良反应的最小有效剂量.方法:对90例老年便秘患者随机分组,每组30例,Ⅰ组为番泻叶1g,Ⅱ组为番泻叶2g,Ⅲ组为番泻叶3g.每个患者观察3次服药效果.当患者符合服药条件时,按要求服用该组剂量的番泻叶,3次服药后12小时内均能排出大便并无不良反应的为有效.结果:Ⅱ组的缓泻剂量是最小有效剂量.结论:推荐使用2g番泻叶用于缓泻治疗老年人的便秘,其疗效确切,不良反应小.     

Combined therapy for primary central nervous system lymphoma in immunocompetent patients

A retrospective series of 13 immunocompetent patients with histological diagnosis of primary central nervous system lymphoma (PCNSL) is presented. The series was divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7 patients treated with chemotherapy and radiotherapy. Clinicopathological patterns were similar for the two groups. In Group A, 4 patients achieved complete remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died within 21 months of diagnosis. 4 Group B patients received chemotherapy followed by radiotherapy, and three who received a methotrexate-containing regimen are alive and disease-free at 34, 42 and 45 months, while the fourth died after 11 months. The other 3 subjects in this group were treated with radiotherapy followed by chemotherapy, and died within 15 months of diagnosis. Although radiotherapy is the standard treatment, chemotherapy has potentially an important role in the management of PCNSL. The sequence of combined treatment could be crucial to improvement of outcome.     

Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS

OBJECTIVE: To evaluate high-dose intravenous methotrexate in primary central nervous system (CNS) lymphoma in HIV-infected patients. DESIGN: An uncontrolled pilot trial. SETTING: An infectious diseases department in Paris, France. PATIENTS: All consecutive AIDS patients with primary CNS lymphoma attending the same unit from August 1994 to March 1996. INTERVENTIONS: Methotrexate was intravenously administered at a dose of 3 g/m2 every 14 days with leucovorin rescue. A maximum of six cycles was planned. Steroids were given to all patients and haematological growth factors were administered as required. MAIN OUTCOME MEASURES: Rate of response, time to response and survival. RESULTS: Fifteen patients (10 with histological documentation) were recruited. The median time since clinical onset was 27 days (range, 7-69 days), median Karnofsky score was 51 (range, 30-70), and mean CD4+ cell count was 30 +/- 19 x 10(6)/l (range, 7-69 x 10(6)/l). Complete responses, defined as clinical improvement and disappearance of contrast-enhancing brain abnormalities on computed tomography or magnetic resonance imaging, were obtained in seven out of 15 patients (three out of 10 patients with histological diagnosis and four out of five patients without histological confirmation). The Karnofsky score of these seven patients improved to 80 +/- 10 (range, 70-100). The mean time taken to respond was 62 +/- 20 days (range, 45-90 days). One patient relapsed at 6 months. Six patients failed to respond, and two died of severe sepsis on days 15 and 45. The median survival time was 290 days (range, 11-570 days): 73 days (range, 11-570 days) in the 10 patients with histological diagnosis, and 347 days (range, 286-409 days) in the five patients without histological confirmation. Side-effects occurred in 10 patients, with gastrointestinal disorders in five, mucositis and skin rash in two, and fever in three patients; however, these events were mild and did not require cycle postponement or dose changes. No cognitive dysfunction occurred. CONCLUSION: Methotrexate appears to be an attractive alternative to radiation therapy for primary CNS lymphoma and is associated with a far greater improvement in quality of life relative to historical series of radiation therapy.     

Successful treatment with high dose chemotherapy following peripheral blood stem cell transplantation for relapsed Burkitt''s lymphoma with central nervous system involvement

BACKGROUND: The family of uncoupling proteins is thought to play an important role in the regulation of energy metabolism by uncoupling the respiratory chain reactions from ATP synthesis. The recently discovered uncoupling protein 2 (UCP2) is upregulated in genetically obese rodent models and during long term high fat feeding. AIM: We have examined the UCP2 mRNA levels in liver, heart and white adipose tissue (WAT) of obese ventromedial hypothalamus (VMH)-lesioned rats, during the dynamic and the early stage of the static phase of obesity, before the appearance of most of the metabolic perturbations associated with long term established obesity. RESULTS: The amount of UCP2 mRNA was not increased in any tissue of VMH-lesioned rats relative to control animals during the dynamic phase nor during the early static phase of obesity. CONCLUSION: These results indicate that in the rat, obesity does not necessarily lead to an increase in UCP2 expression and suggest that the up-regulation of UCP2 described in other models may be secondary to metabolic perturbations, rather than to a direct adaptative response to the increased adipose tissue content of the organism.     

AIDS primary central nervous system lymphoma: molecular analysis of the expressed VH genes and possible implications for lymphomagenesis

AIDS-associated primary central nervous system lymphomas are late events that have an extremely poor prognosis. Despite different hypotheses, the brain localization of these B cell lymphomas remains an enigma. To better define the cell origin of the lymphomas and the possible role of the B cell receptor (BCR) in the brain localization and/or in the oncogenic transformation, we analyzed the V region genes of the Ig heavy chain expressed by lymphoma cells in five randomly selected patients. After amplifying the rearranged VHDJH DNA by PCR, cloning, and sequencing of the amplified products, we observed that: 1) of the five lymphomas analyzed, four were clearly monoclonal; 2) there was no preferential use of one peculiar VH family or one peculiar segment of gene; 3) the mutation analysis showed that an Ag-driven process occurred in at least two cases, probably before the oncogenic event; and 4) there was no intraclonal variability, suggesting that the hypermutation mechanism is no longer efficient in these lymphoma B cells. Taken together, our results suggest that distinct Ags could be recognized by the BCR of the lymphoma cells in different patients and that, if the Ags are responsible for the brain localization of these B cells bearing mutated BCR, other factors must be involved in B cell transformations in primary central nervous system lymphoma.     

Malignant non-Hodgkin lymphoma of the central nervous system with ocular site. Value of vitrectomy for diagnosis

Diagnosis of intraocular lymphoma is difficult and should be considered in middle-aged or older patients with a chronic uveitis. Many explorations (lumbar punctures, brain imaging and vitrectomies) may be needed before correct diagnosis is made. We report the case of a 50-year-old woman with an intraocular lymphoma for whom the diagnosis was confirmed by a vitrectomy.     

Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD)

Recently, Khayat et al. reported that high-dose recombinant interleukin-2 (rIL-2) i.v. may induce tumour regressions in metastatic melanoma patients through an association with cisplatin (CDDP) and alpha-interferon (alpha-IFN). Treatment-related toxicities are, however, important. Previous studies have demonstrated that rIL-2 toxicity may be reduced through a subcutaneous injection. In order to evaluate the effectiveness of low subcutaneous rIL-2 doses in a chemoimmuno-hormonotherapeutic combination, 36 metastatic melanoma patients were treated with CDDP, rIL-2, alpha-IFN and tamoxifen (TAM). The overall response rate was 47.2%: five patients had complete response (14%), 12 partial response (33%) and 13 stable disease (36%). Median response duration was 6.4 months (range: 2-29+). Median overall survival was 10 months (range: 3-36+). The CDDP/rIL-2/alpha-IFN/TAM regimen was effective both on soft tissue and visceral metastases. Toxicity was low and patient management did not require an intensive care unit. A statistically significant increase in both percentage and absolute values of lymphocytes, eosinophils, CD3+/CD4+, CD25+, CD16/56+ and HLA-DR+ cells was found in all patients after two treatment courses. This study shows that lower doses of subcutaneous rIL-2, as well as CDDP and alpha-IFN, associated with TAM, may have similar anticancer efficacy with respect to Khayat's schedule but lower toxicity.     

Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol

BACKGROUND: Anecdotal reports have suggested that systemic chemotherapy with agents that better cross the blood-brain barrier may result in long term disease remission in some patients with central nervous system (CNS) lymphoma. This treatment strategy has the advantage of sparing patients the late neurologic complications from brain irradiation. METHODS: Eligible patients were required to 1) have tissue-proven and measurable non-acquired immunodeficiency syndrome (AIDS)- related primary or metastatic CNS lymphoma; 2) have normal hemogram, renal function, and hepatic function; 3) be age < or = 75 years; and 4) have provided informed consent. Patients with lymphoblastic lymphoma or patients who previously had been exposed to nitrosoureas, etoposide, or high dose methotrexate were not eligible. The systemic chemotherapy (BOMES regimen) included carmustine, 65 mg/m2/day, intravenously (i.v.) on Days 1-2; vincristine, 2 mg/day, i.v. on Days 1 and 8; methotrexate, 1.5 g/m2, i.v. on day 15 followed by leucovorin rescue; etoposide, 50 mg/m2/day, i.v. on Days 1-5; and methylprednisolone, 200 mg/day, i.v. on Days 1-7; repeated every 4 weeks (BOMES regimen). Four doses of intrathecal methotrexate were given to patients who had involvement in the cerebrospinal fluid. RESULTS: Between March 1991 and March 1997 a total of 19 patients were enrolled on the study. There were 13 men and 6 women, with a median age of 57 years. Fourteen patients had primary CNS lymphoma and 5 patients had concurrent extra-CNS lymphoma. Nine patients previously had been treated by radiotherapy (four patients), chemotherapy (three patients), or both (two patients). There were 11 complete remissions (CR) (57.9%) and 5 partial remissions (26.3%), with a total remission rate of 84.2%. One patient had had progressive brain lymphoma during systemic chemotherapy with the conventional cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, but achieved CR soon after the regimen was changed to BOMES. The median time to progression of the responders was 6 months. At last follow-up, 4 patients were alive without lymphoma at 10, 47, 64, and 66 months, respectively. There were two treatment-related deaths due to sepsis. Another two patients died of fulminant hepatitis that most likely was chemotherapy-related reactivation of chronic B viral hepatitis. CONCLUSIONS: The authors believe systemic chemotherapy alone may result in long term disease remission in some select patients with non-AIDS-related CNS lymphoma. Further investigation for better protocols is mandatory.     

吉西他滨联合卡铂作为诱导方案治疗老年不可手术的非小细胞肺癌

Objective:The purpose of this study was to evaluate the efficacy and safety of gemcitabine (GEM) and carboplatin (CBP) used as induction regimen in the treatment of elderly patients with locally advanced unresectable non-small cell lung cancer (NSCLC). Methods: Seventy-eight cases of elderly patients have been cytologically and pathologically confirmed with locally advanced unresectable NSCLC, the age of the patients ranged from 65 to 75 years. The patients were treated with the combined regimen of gemcitabine and cisplatin. GEM 1000 mg/m2 intravenously injected by drip on the 1st, 8th day and the dosage of CBP was AUC 4 that was used on the 1st day, 21 days apart to each cycle, most patients received 2 cycles. Treatment response was evaluated according to the criteria of RECIST (Response Evaluation Criteria in Solid Tumor), the side effect of the regimen was judged based on WHO criteria. Results: Seventy-eight patients were evaluated and received a total of 156 cycles chemotherapy. There were no complete regression that could be observed, but 32 cases had partial regression (PR), 37 cases with no change (NC) and 9 cases with progression disease (PD). The overall response rate was 41.0%. The main side effects were hematological toxicity. Conclusion: The GC regimen could be used as induction treatment for elderly patients with locally advanced unresectable NSCLC, and the regimen could be well tolerated and is safe in terms of side effects.     

Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy

The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization that not all patterns of demyelination can be modeled by autoimmune-triggered mechanisms. To evaluate the contribution of local tumor necrosis factor (TNF) ligand/receptor signaling pathways to MS immunopathogenesis we have analyzed disease pathology in central nervous system-expressing TNF transgenic mice, with or without p55 or p75TNF receptors, using combined in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and cell identification techniques. We demonstrate that local production of TNF by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology. These results demonstrate that aberrant local TNF/p55TNF receptor signaling in the central nervous system can have a potentially major role in the aetiopathogenesis of MS demyelination, particularly in MS subtypes in which oligodendrocyte death is a primary pathological feature, and provide new models for studying the basic mechanisms underlying oligodendrocyte and myelin loss.