Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance

In the present paper we review the immunophenotypic characteristics of plasma cells (PC) and the PC DNA contents from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), and its value for the differential diagnosis between both entities. The strong reactivity for CD38 and the positivity for CD138 are the two best markers for identifying PC. Myelomatous PC display an heterogeneous phenotype consistent with the fact that the neoplastic clone is able to undergo a certain degree of differentiation. In addition, PC from MM patients usually lack surface expression of B-cell associated antigens and frequently display reactivity for markers which are not restricted to the B-cell lineage. In MGUS patients, two clearly defined and distinct PC subpopulations can be identified. One of these PC subpopulations shows phenotypic characteristics identical to those of normal PC, including a very strong reactivity for the CD38 antigen, intermediate/low light scatter characteristics and positivity for CD19, in the absence of CD56, and corresponds to the residual normal bone marrow PC. The second PC subpopulation shows an immunophenotype similar to that of myelomatous PC, characterized by a slightly lower reactivity for CD38 and strong CD56 expression, on the absence of positivity for CD19, these PC corresponding to the clonal counterpart. Using a simultaneous staining for PC and DNA, around 60% of MM and 73% of MGUS patients display DNA aneuploidy, the majority of them being hyperdiploid. However, in contrast to MM patients, in MGUS patients two clearly different PC subsets can be discriminated in most cases (73%): a diploid and an aneuploid (hyperdiploid) subset, corresponding to normal and clonal PC, respectively. Upon comparing hyperdiploid with diploid patients in MM, the former display a better prognosis, in line with the higher incidence of DNA hyperdiploidy in MGUS. A clear correlation between the percentage of S-phase PC and several prognosis features of MM has been found. In spite of these findings, no significant differences in the percentage of pathological S-phase PC are detected between MM and MGUS patients. Regarding the differential diagnosis between MGUS and MM, multivariate analysis shows that the ratio between the number of clonal and normal residual PC is the best single parameter.     

Intercomparison of calibration procedures for 192Ir HDR sources in Brazil

The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country and worldwide. The main objective of this paper is to report the results from ten institutions of an intercomparison of calibration procedures for 192Ir HDR sources currently in use in Brazil. The treatment irradiator of one institution was calibrated by a reference system and used by all participants with their own measuring electrometers and ionization chambers under the same experimental conditions. Two methods were used: the calibration jig and the well-type ionization chamber. Each participant was allowed to use their own method and formalism. The results of this exercise were very positive since this was the first time in Brazil that a group of users gathered to share their experience and openly discuss the physical concepts behind the calibration procedures. The results were all within +/-3.0%, except one case where -4.6% was observed and later identified as a problem with the Nk value for x-rays. Though the magnitude of the deviations found was generally acceptable considering the diversity of formalisms currently in use, a proposal is now being prepared to be adopted as a national protocol. The identification of the institutions was left out for the sake of confidentiality.     

Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus

We investigated the effect of arachidonic acid (AA) on the release of [3H]acetylcholine ([3H]ACh) from the rat hippocampus. AA (3-30 microM) increased the basal tritium outflow and the field-electrically evoked release of [3H]ACh from hippocampal slices in a concentration-dependent manner. AA (30 microM) produced a 69+/-7% facilitation of the evoked and a 36+/-3% facilitation of basal tritium outflow. The effect of AA (30 microM) on the evoked tritium release was prevented by bovine serum albumin (BSA, 1%), which quenches AA, and was unaffected by the cyclooxygenase inhibitor, indomethacin (100 microM), and the lipooxygenase inhibitor, nordihydroguaiaretic acid (50 microM). Phospholipase A2 (PLA2, 2 U/ml), an enzyme that releases AA from the sn-2 position of phospholipids, mimicked the facilitatory effect of AA on the evoked tritium release (86+/-14% facilitation), an effect prevented by BSA (1%). The PLA2 activator, melittin (1 microM), enhanced the evoked tritium release by 98+/-11%, an effect prevented by the PLA2 inhibitor, arachidonyl trifluromethylketone (AACOCF3, 20 microM), and by BSA (1%). AA (30 microM), but not arachidic acid (30 microM), also facilitated (72+/-9%) the veratridine (10 microM)-evoked [3H]ACh release from superfused hippocampal synaptosomes, whereas PLA2 (2 U/ml) and melittin (1 microM) caused a lower facilitation (46+/-1% and 38+/-5%, respectively). The present results show that both exogenously added and endogenously produced AA increase the evoked release of [3H]ACh from rat hippocampal nerve terminals. Since muscarinic activation triggers AA production and we now observed that AA enhances ACh release, it is proposed that AA may act as a facilitatory retrograde messenger in hippocampal cholinergic muscarinic transmission as it has been proposed to act in glutamatergic transmission.     

Management of arterial hypertension in patients with acute ischemic stroke

PURPOSE: We aimed with study to assess the current clinical practice about the management of high blood pressure in patients in the acute phase of ischemic stroke. We also comment some topics of ischemic stroke treatment. METHODS: A case report of a patient admitted 8 hours after onset of ischemic stroke and with blood pressure of 186 x 110 mmHg was presented to 120 surgeons and clinician. They were asked to decide the best therapeutic option: to increase, decrease or maintenance blood pressure. RESULTS: Thirty-eight physicians (31.7%) considered decreasing blood pressure the best therapeutics, 82 (68.3%) considered maintenance and none decided to increase it (p < 0.05). There was no difference between the two specialties conduct. The physicians, with more than 10 years of graduation, had a tendency to decrease the blood pressure (p < 0.05). CONCLUSION: The maintenance of blood pressure may present a sufficient blood support to compensate brain flow. A high percentage of the physicians (31.7%) do not know about the current concepts of therapeutics considering hypertension in acute ischemic stroke. The development on special units to treat these patients ("stroke units") may eventually decrease the morbimortality rates of ischemic stroke.     

Severity of a case for outcome assessment in health care--definitions and classification of instruments

Severity of a case is one of the ingredients in management systems. Severity adjustment systems have limitations, and confusion and diversity characterize definitions of severity of a case. These facts may be a consequence of lack of conceptual knowledge. Based on a holistic theory of health, we introduce a definition of severity of a case from a patient perspective. Here severity is characterized as having two basic components: disease severity and illness severity; and five dimensions: suffering, disabilities, risk of suffering, risk of disabilities and risk of death. A classification of instruments as measures of severity dimensions is presented. This classification is based on definition and application criteria. The article's main contribution is to combine theoretical and practical knowledge about severity of a case, which may empower implementations of outcome management systems in health care.     

Chronic immobilization-induced stress increases plasma testosterone and delays testicular maturation in pubertal rats

We investigated whether chronic stress, applied from prepuberty to early puberty, interferes with the spermatogenic and androgenic testicular functions. Male pubertal rats (40 days old) were immobilized 6 h per day for 15 days. Plasma concentrations of corticosterone, prolactin and testosterone were significantly augmented following immobilization, whereas plasma luteinizing hormone decreased and follicle-stimulating hormone was not altered. Acute immobilization (5 min) increased prolactin and testosterone levels in control rats but caused a significantly higher increase in these hormones when superimposed on chronic stress. A lower extent of testicular maturation was observed in pubertal rats immobilized from prepuberty.     

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.     

Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation.

Lack of apoptosis has been linked to prolonged survival of malignant B cells expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2 protein expressed along normal human B-cell maturation and to establish the frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2 expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144 patients was found to be aberrant in 66% of the cases, usually corresponding to bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT lymphoma were the only diagnostic groups constantly showing overexpression of bcl-2. Bcl-2 overexpression was also frequently found in precursor B-acute lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma, Burkitt lymphoma and multiple myeloma.     

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.     

Blaming the victim: aspects of the Brazilian case.

This report describes the consequences and some aspects of the origin and development of victim blaming in accident analysis, and some methods for investigating such events, with particular emphasis on the situation in Brazil. In Brazil, the spread of this practice seems to have been helped by several factors. (1) The idea that occupational accidents are simple phenomena with a limited number of causal factors linked to unsafe actions and/or conditions. In the past, the theory of accident proneness had less influence than in other countries. (2) Government regulations that stipulate the hiring of health and safety officers, production of "educational" material, and "preventive" campaigns that emphasize the role of the victim's "faulty" behavior in the origin of an accident. (3) Mandatory implementation of standardized models for accident investigation directed toward searching for a single "cause." Usually one conclusion, expressed in terms of unsafe acts or conditions, is formulated so that whoever performs an unsafe act is responsible for the accident. (4) Lack of knowledge, as shown in Brazilian publications on occupational accidents and in the evolution of studies on the nature of accident phenomena and of strategies adopted for their prevention.