Diagnosis of Alzheimer's disease in the predementia phase: possibilities and benefits

THE PREDEMENTIA PHASE: Alzheimer's disease is a progressive condition. The state of dementia defined by international criteria only appears after brain lesions have become important. Dementia is defined by the presence of multiple cognitive deficits and restricted independence. Prior to this, the patient experiences isolated memory impairment, either alone or associated with behavior changes which have little effect on his/her independence (predementia phase). The goal of diagnosis at this time is to reduce psychic suffering for the patient and family as well as the social cost of the disease by retarding the onset of dementia. DIAGNOSIS IN THE PREDEMENTIA PHASE: Diagnosis is based on i) evidence of an alteration of the internal temporal regions leading to memory deficit due to impaired memorization processes. There is an elective impairment of recent memory rapidly leading to difficulties perceived by the family and which diminish performance in complex activities of daily living. Recall processes lose their efficacy. ii) Tomoscintigraphic evidence of a perfusion defect or structural imaging evidence of atrophy of the hippocampal regions. iii) Presence of associated psychoaffective changes (apathy). When these three elements are found, the diagnosis of Alzheimer's disease is highly probable and should be made. If all three are not present, it would be advisable to diagnose what is termed "mild cognitive impairment", defined as a group of subjects with a high risk of progressing to dementia in a few years. PATIENT CARE AT THIS PHASE: Neuroprotective drugs may be prescribed in association with psychological and cognitive support within the framework of regular follow-up.     

Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.

PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.     

Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients.

PURPOSE: To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.     

Controversies over the surgical placebo: legal issues and the ethical debate

The debate on controlled surgery trials has had some rather "sensational" repercussions, enlivening the placebo issue. In France, there is a consensus on the ethical conditions necessary for proper protection of individual persons. This consensus has taken on a legal form with the promulgation of the Huriet law. For this reason, all studies and research protocols in medicine and surgery are examined by ethics committees (CCPPRB) who assess the inclusion conditions within the framework of biomedical research and in compliance with the concept that individual participants must be give proper protection. These committees are faced with increasingly complex situations, particularly concerning the pertinence of information give to the participant and the modalities of consent. In France, standard measures were established after a parliamentary debate issuing from a wider public debate. The issue has become a social transaction between biomedical research professionals and the society in general. The international debate over the surgery placebo is an interesting illustration of how mediation institutions, working along the principles of ethical committees, play a key role in social awareness of the ethical issues involved before an innovating practice is initiated. But how legitimate are sensational pieces published in the media, which as is clearly demonstrated with the debate over the surgical placebo, are almost always individual points of view? Shouldn't the debate take into account the contributions of ethical committees which integrate representatives of the social community as well as the importance of a legal framework for individual protection as proposed by the French law? Shouldn't personal points of view be counterbalanced by regularly expressed ethical committee opinions formed after appropriate ethics-oriented discussion going beyond the simple question of "should we do it", a question often dismissed by extreme theoretical arguments that leave unanswered the practical question of "how should we do it"?     

基质金属蛋白酶-2、E-钙黏附素和DNA含量与胃癌侵袭、转移的相关性研究

目的 :探讨基质金属蛋白酶 - 2 (MMP- 2 )、E-钙黏附素 (E- cadherin)在胃癌组织中的表达和癌细胞核 DNA含量与胃癌侵袭、转移的相关性。方法 :对 83例胃癌组织、2 5例正常胃组织进行了上述 3个指标的检测。结果 :正常胃黏膜中 MMP- 2呈阴性表达 ,E- cadherin呈强阳性表达。胃癌组织中 MMP- 2表达呈阳性 ,阳性率为 78.3% (6 5 / 83) ,MMP- 2表达强度与胃癌分化程度、淋巴结转移、浸润深度、弥漫性生长、 TNM分期显著相关 (P<0 .0 5 ) ;而 E- cadherin的阳性率明显减低为16 .9% (14 / 83) ,E- cadherin表达减低与胃癌细胞分化差、浸润深度、弥漫性生长、淋巴结转移密切相关 (P<0 .0 5 )。 DNA指数在胃癌组织和正常胃组织分别为 1.4 7± 0 .2 3和 0 .97± 0 .15 (P<0 .0 1) ;DNA指数与胃癌的分化程度、浸润深度、生长方式、淋巴结转移有相关性 (P<0 .0 1)。结论 :MMP- 2、E- cadherin表达和 DNA含量与胃癌浸润转移密切相关 ,三者在癌组织中水平的变化属胃癌细胞重要的恶性生物学特征 ,其检测有助于对胃癌患者的转移及预后作出判断     

Family history of autoimmune thyroid disease and childhood acute leukemia.

The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.     

Immunogene Therapy of Recurrent Glioblastoma Multiforme with a Liposomally Encapsulated Replication-Incompetent Semliki Forest Virus Vector Carrying the Human Interleukin-12 gene – a phase I/II Clinical Protocol

Journal of Neuro-Oncology -