Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: cancer and leukemia Group B study 8364.

The prognostic value of immunophenotype in adult acute lymphoblastic leukemia (ALL) has varied based on the methods used, surface markers studied, and therapy administered. From April 1991 to September 1996, samples of leukemic marrow or blood from 259 eligible and evaluable adult ALL patients entering dose-intensive Cancer and Leukemia Group B (CALGB) front-line treatment protocols were prospectively studied for immunophenotypic classification by multiparameter flow cytometry (MFC) in a central laboratory. A B-lineage (B-LIN) phenotype was expressed in 79% of cases, with one third coexpressing myeloid antigens. A T-lineage (T-LIN) phenotype was expressed in 17% of cases, with one quarter coexpressing myeloid antigens. Since the advent of more intensive CALGB therapy which incorporated cyclophosphamide and the early use of L-asparaginase into the backbone of daunorubicin, vincristine and prednisone, together with central nervous system prophylaxis for adult ALL, no significant differences in response rates, remission duration, or survival have been seen in those patients coexpressing myeloid antigens. The T-LIN phenotype was associated with younger age (P =.01), a higher male to female ratio (P =.01), higher white blood cell count (P =.001) and hemoglobin (P <.001) levels, presence of a mediastinal mass (P <. 001), and longer survival (P =.01) and disease-free survival (DFS) (P =.01) when compared to patients with a B-LIN phenotype. The 3-year probability of survival and DFS (95% confidence interval [CI]) of T-LIN adult ALL was 0.62 (0.46 to 0.76) and 0.62 (0.44 to 0. 77), respectively. Comparatively, the 3-year probability of survival and DFS (95% CI) of B-LIN adult ALL was 0.42 (0.35 to 0.50) and 0.39 (0.31 to 0.47), respectively. The number of T markers expressed in T-LIN ALL cases was shown to have prognostic significance. In particular, patients expressing six or more markers compared with patients expressing three or fewer markers had longer DFS (P =.003) and survival (P =.004). The presence of the Philadelphia chromosome was significantly associated with B-LIN ALL cases which coexpressed CD19(+), CD34(+), and CD10(+) (49%; P =.003), whereas the majority of t(4;11) cases were CD19(+), CD34(+) but CD10(-). The knowledge gained from this study of MFC of a large number of patients will permit a reduction in the number of antigens to be evaluated in future studies. Overall, this should lead to cost savings without loss of valuable information. A rational approach for future studies would be to use four-color flow cytometry (instead of the current three-color) to help further streamline the study of immunophenotype of adult ALL by MFC.     

Controversias en la obtención del injerto hepático procedente de donante vivo

Adult liver transplants from a living donor are a valid and effective alternative as a treatment in terminal liver disease. However, in the context of a donation from a brain dead donor, as in western countries (Spain), it is very high, and there are still controversial aspects that should be continuously assessed in order to ensure good results. Live donations are currently stable and represent about 5% of the total liver transplants performed in Europe. Morbidity and mortality is around 35% and 0.1%, respectively, probably reasonable figures given the characteristics of the intervention. The 1 and 5 year survival rates of the recipients of a living donor are currently 95% and 75%, which are similar to those coming from brain dead donors. However the level of biliary complications in this patient group is higher, with an incidence of around 35-40%. However, this incidence has not had any effect on the long-term results up until now.     

Contribution to the histochemical demonstration of some dehydrogenase activities in the human nervous tissue

Summary The authors have performed a histochemical investigation on the distribution of Succinic, Glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities in the human nervous tissue. Normal cortex and white matter, peritumoral and periabscessual nervous tissue and glial tumors of neurosurgical source (20 cases) have been examined. A variable degree of these enzymatic activities has been demonstrated in all the cytoplasms of neurons and normal or pathological glial cells. Considerably higher level of Glucose-6-Phosphate dehydrogenase activity has been evidenced in the oligodendrocytes.A discussion of the results in relation to prior investigations reported in the literature is given.

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Zusammenfassung Die Autoren führten histochemische Untersuchungen über die Verteilung von Succino-, Glucose-6-phosphat- und 6-Phosphogluconat-Dehydrogenase-Aktivität im Nervengewebe des Menschen durch. Untersucht wurden: normale Rinde und weiße Substanz, Nervengewebe aus der Umgebung von Tumoren und Abscessen sowie gliöse Tumoren bei 20 neurochirurgischen Fällen. Im Cytoplasma der Neurone und der normalen und pathologischen Gliazellens wurden verschiedene Intensitätsgrade dieser Enzymreaktionen beobachtet. Beträchtliche Glucose-6-Phosphat-Dehydrogenase-Aktivität konnte in den Oligodendrocyten nachgewiesen werden.Die von den Autoren gewonnenen Resultate werden im Verhältnis zu den bisher in der Literatur mitgeteilten Ergebnissen diskutiert.

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With 6 Figures in the Text     

Acute handling stress modulates methylphenidate-induced catecholamine overflow in the medial prefrontal cortex.

Although stress is an extensively investigated phenomenon, the effects of specific stressors on the pharmacologic activity of routinely administered drugs are less well characterized. We designed the present study to investigate the effect of handling stress on catecholaminergic responsivity following an acute methylphenidate (MP, Ritalin) challenge in the medial prefrontal cortex (mPFC). Norepinephrine (NE) and dopamine (DA) levels were simultaneously measured in 15-min samples of PFC dialysate using HPLC coupled with electrochemical detection. Sprague-Dawley rats were handled for 15 min, which produced an increase from basal extracellular DA and NE levels. Handling stress attenuates the DA response when administered 2 h prior to IP MP, whereas handling stress enhances the DA response when administered simultaneously with IG MP. These findings suggest that persistent alterations in mesocorticolimbic DA-ergic activity are induced by a short exposure to restraint stress as evidenced by the altered response to MP challenge.     

Lens fluorophotometry after trabeculectomy in primary open-angle glaucoma.

OBJECTIVE: To evaluate the loss of lens transparency incurred by patients undergoing trabeculectomy. DESIGN: A prospective cohort study. PARTICIPANTS AND CONTROLS: Data corresponding to 33 eyes of 33 consecutive patients with primary open-angle glaucoma (POAG) subjected to trabeculectomy (group 1) were compared with those corresponding to 12 eyes of 12 patients with POAG receiving topical antiglaucomatous treatment (group 2). INTERVENTION: Lens fluorophotometry was performed on the group 1 patients before and 12 months after surgery. In group 2, fluorophotometry was conducted at the onset of the study and at 12 months of follow-up. MAIN OUTCOME MEASURES: Starting and final lens autofluorescence and transmittance values corresponding to each subject group were compared. RESULTS: In group 1, starting and final autofluorescence was 556.3 +/- 184.3 and 691.1 +/- 179.3 Eq ng/ml, and starting and final transmittance was 0.78 +/- 0.11 and 0.67 +/- 0.14, respectively. Respective values for group 2 were 574.3 +/- 94.8 and 595.2 +/- 107.0 Eq ng/ml and 0.72 +/- 0.17 and 0.71 +/- 0.16. The mean change between final and initial autofluorescence was statistically different between groups (134.7 +/- 123.7, group 1, 20.9 +/- 25.1 Eq ng/ml, group 2; P < 0.001). Similarly, a significant difference (P < 0.001) in transmittance change was observed between the surgery and control groups (-0.11 +/- 0.072, group 1; 0.02 +/- 0.008, group 2) CONCLUSIONS: It was demonstrated by lens fluorophotometry that trabeculectomy in POAG leads to a loss in lens transparency.     

A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B.

Between 1982 and 1986, 326 evaluable patients with acute myeloid leukemia (AML) were randomized to receive cytarabine (Ara-C) at 200 mg/m2 (A200) or 100 mg/m2 (A100) for induction and maintenance therapy. Cycle 1 of induction therapy consisted of 7 days of continuous intravenous (IV) Ara-C and 3 days of i.v. daunorubicin (DNR); cycle 2, if needed, consisted of 5 days of Ara-C and 2 days of DNR. Complete responders (CR) then received monthly subcutaneous (SC) Ara-C at the respective doses (A100 or A200) with 6-thioquanine (6TG) at months 1 and 5, with vincristine (VCR) and prednisone at months 2, 4, 6, and 8, and with DNR at months 3 and 7. Complete response rates were 58% (A100) and 64% (A200) (P = .29). Median survival was 46 weeks (A100) and 38 weeks (A200) (P = .64); 5-year survival was 10% (A200) and 8% (A100). Median time to remission was 6.7 weeks (A200) and 8.1 weeks (A100) (P = .18). Median disease-free survival was 41 weeks (A200) and 44 weeks (A100) (P = .86). Deaths were attributed to therapy-related toxicities in 21% (A200) and 13% (A100) (P = .05). The 5-year survival was 15% for patients with performance status (PS) 0, 8% for PS 1 to 2, and 2% for PS 3 to 4, 18% for patients less than 40 years, 8% for ages 40 to 59, and 3% for age 60 or greater. Stratification of data by age and PS suggested that A200 may improve survival in patients less than 60 years with a good PS 0 (P = .05). This trial does not support the superiority of A200 over A100 in the treatment of AML.     

Animal welfare and colony management in cancer research

The use of animals in cancer research continues to be important for the study of tumor biology, the development and testing of new therapies, and risk assessment. The new knowledge generated from this research contributes to the health and welfare not only of human beings, but also of animals which develop cancer. However, the use of animals for cancer research is a privilege which carries with it scientific, professional, and moral obligations. The three tenets of a sound animal research program include good science, humane care, and regulatory compliance. Recognizing the complex interactions in the tumor-animal model, the investigator needs to address a wide range of issues during experimental design and implementation including animal welfare concerns, complicating factors in colony management, and compliance with laws, regulations, and policies. Therefore, both practical and philosophical considerations enjoin researchers to maintain the highest standards of animal care.     

Bcl-2 distribution in neuroepithelial tumors: an immunohistochemical study

Summary Bcl-2proto-oncogene prevents apoptosis in many conditions. First detected in lymphomas, it has been also described in non-lymphoid tissues. The immunohistochemical distribution of bcl-2 protein in 100 neuroepithelial tumors is presented. Bcl-2 was positive in some neurons of normal nervous tissue, in reactive astrocytes and variably in all neuroepitelial tumors. The reaction product was either diffuse or granular, due to bcl-2 protein localization on cytoplasmic, nuclear and mitochondrial membranes. The positivity was high in medulloblastomas and in astrocytic tumors. In the latter, the strongest staining was found in cells retaining the astrocytic aspect. Oligodendroglial cells were minimally stained.No correlation of bcl-2 staining with survival was found in each tumor type. The interpretation of the results is based on the one side on the constitutive role played by bcl-2 in the nervous tissue and its neoplastic derivatives. On the other side, in tumors bcl-2 acts by preventing tumor cells from undergoing apoptosis. Bcl-2 expression in brain tumors, therefore, receives a dual interpretation. For this reason and for the lacking of correlation with survival, bcl-2 expression cannot be regarded as a prognostic factor.