Stroke mortality in urban and rural Tanzania. Adult Morbidity and Mortality Project.

BACKGROUND: Most data for stroke mortality in sub-Saharan Africa are hospital based. We aimed to establish the contribution of cerebrovascular disease to all-cause mortality and cerebrovascular disease mortality rates in adults aged 15 years or more in one urban and two rural areas of Tanzania. METHODS: Regular censuses of the three surveillance populations consisting of 307,820 people (125,932 aged below 15 years and 181,888 aged 15 or more) were undertaken with prospective monitoring of all deaths arising in these populations between June 1, 1992 and May 31, 1995. Verbal autopsies were completed with relatives or carers of the deceased to assess, when possible, the cause of death. FINDINGS: During the 3-year observation period 11,975 deaths were recorded in the three surveillance areas, of which 7629 (64%) were in adults aged 15 years or more (4088 [54%] of these in men and 3541 [46%] in women). In the adults, 421 (5.5%) of the deaths were attributed to cerebrovascular disease, 225 (53%) of these in men and 196 (47%) in women. The yearly age-adjusted rates per 100,000 in the 15-64 year age group for the three project areas (urban, fairly prosperous rural, and poor rural, respectively) were 65 (95% CI 39-90), 44 (31-56), and 35 (22-48) for men, and 88 (48-128), 33 (22-43), and 27 (16-38) for women, as compared with the England and Wales (1993) rates of 10.8 (10.0-11.6) for men and 8.6 (7.9-9.3) for women. INTERPRETATION: We postulate that the high rates in Tanzania were due to untreated hypertension. Our study assessed mortality over a single time period and therefore it is not possible to comment on trends with time. However, ageing of the population is likely to lead to a very large increase in mortality from stroke in the future.

Validation of the Kiswahili version of the SF-36 Health Survey in a representative sample of an urban population in Tanzania.

The objective of this study was to assess the validity of a Kiswahili translation of the SF-36 Health Survey (SF-36) among an urban population in Tanzania, using the method of known-groups validation. People were randomly selected from a demographic surveillance system in Dar es Salaam. The representative sample consisted of 3,802 adults (15 years and older). Health status differences were hypothesized among groups, who differed in sex, age, socioeconomic status and self-reported morbidity. Mean SF-36 scale scores were calculated and compared using t-test and ANOVA. Women had significantly lower mean SF-36 scale scores (indicating worse health status) than men on all scales and scores were lower for older people than younger on all domains, as hypothesized. On five of the eight SF-36 scales, means were higher for people of higher socioeconomic status compared to those of lower socioeconomic status. People who reported an illness within the previous 2 weeks scored significantly lower on all scales compared to those who were healthy, as did people who said they had a disability or a chronic condition.

Outlook for survivors of childhood in sub-Saharan Africa: adult mortality in Tanzania. Adult Morbidity and Mortality Project.

OBJECTIVE: To measure age and sex specific mortality in adults (15-59 years) in one urban and two rural areas of Tanzania. DESIGN: Reporting of all deaths occurring between 1 June 1992 and 31 May 1995. SETTING: Eight branches in Dar es Salaam (Tanzania's largest city), 59 villages in Morogoro rural district (a poor rural area), and 47 villages in Hai district (a more prosperous rural area). SUBJECTS: 40,304 adults in Dar es Salaam, 69,964 in Hai, 50,465 in Morogoro rural. MAIN OUTCOME MEASURES: Mortality and probability of death between 15 and 59 years of age (45Q15). RESULTS: During the three year observation period a total of 4929 deaths were recorded in adults aged 15-59 years in all areas. Crude mortalities ranged from 6.1/1000/year for women in Hai to 15.9/1000/year for men in Morogoro rural. Age specific mortalities were up to 43 times higher than rates in England and Wales. Rates were higher in men at all ages in the two rural areas except in the age group 25 to 29 years in Hai and 20 to 34 years in Morogoro rural. In Dar es Salaam rates in men were higher only in the 40 to 59 year age group. The probability of death before age 60 of a 15 year old man (45Q15) was 47% in Dar es Salaam, 37% in Hai, and 58% in Morogoro; for women these figures were 45%, 26%, and 48%, respectively. (The average 45Q15s for men and women in established market economies are 15% and 7%, respectively.) CONCLUSION: Survivors of childhood in Tanzania continue to show high rates of mortality throughout adult life. As the health of adults is essential for the wellbeing of young and old there is an urgent need to develop policies that deal with the causes of adult mortality.

Survival of T- and B-Phenotype Diffuse Aggressive Non-Hodgkin's Lymphomas.

Survival of immunophenotyped non-Hodgkin's lymphomas (NHLs) diagnosed as diffuse mixed, diffuse large and large cell immunoblastic by the working formulation was evaluated based on phenotypic categories. These subtypes were grouped as diffuse aggressive NHLs due to their similarities, and categorized into T- and B-phenotype NHLs. There were 45 (57.7%) cases of T-NHL and 33 (42.3%) B-NHL. Major clinical factors such as sex, age, stage, B-symptoms and site of disease, as well as performance status (PS), LDH, primary site and number of extra-nodal sites involved showed equal distributions between T- and B-NHLs. Combination chemotherapeutic regimens based on doxorubicin were used in 84% of these cases. Complete remission was achieved in 73.6% of T-NHL and 74.1% of B-NHL. Median survival for the T- and B-NHL was the same over 30 months. Projected survival at 5 years was also similar, T-NHL (35%) and B-NHL (38%). Unilaterally, survival was adversely affected in stage III/IV of T-NHL and for age over 65 years for B-NHL. Survival was unfavorable for the B-NHL without B-symptoms when compared to T-NHLs. Multivariately, only sex, B-symptoms and PS significantly (P < 0.05) affected the survival of T-NHL. Although the overall results indicate that the response and survival of T- and B-NHL are similar, the differences observed on the effect of sex, age, stage, B-symptoms and PS on survival of T- and B-NHLs imply that, their influence on T-NHLs was different from that for B-NHLs. Therefore we suggest that separate prognostic models are needed for the T- and B-phenotype NHLs.

Immunophenotype, histopathology and clinical stage: their predictive value in the prognosis of non-Hodgkin's lymphomas.

The relationship between immunophenotype, histopathology and clinical stage in influencing prognosis was evaluated in 99 cases of non-Hodgkin's lymphoma (NHL). All cases were histopathologically classified according to the system of the international conference on working formulation (WF), immunologically analysed by flow cytometry with a panel of monoclonal antibodies and clinically staged by the Ann Arbor scheme. Eighty eight percent of T- and 87.7% of B-phenotype NHLs respectively received combination chemotherapies with or without radiotherapy. Early stages I and II showed higher response rates (86% for T- and B-NHL) compared to the advanced ones III and IV (58% for T-NHL and 65% for the B-NHLs), p less than 0.05. Higher overall survival rates were observed in low and intermediate grade NHLs, p less than 0.05. The early stages further showed relatively higher survival rates in T- than in B-phenotype of intermediate grade NHL. Low grade NHL had the highest survival rates in both early and advanced stages, whereas the survival rate was the lowest in high grade NHL irrespective of the clinical stages. Immunophenotype, pathological grade and clinical stage jointly displayed varied predictive values in the prognosis of NHL. Since the present prognostic models are based on histological and staging criteria only, the results suggest that, phenotype should be included in the classification systems or prognostic models for the NHLs, thus facilitating the establishment of effective lineage specific therapies.

FAB L3 type of B-cell acute lymphoblastic leukemia (B-ALL) without chromosome abnormalities.

Acute lymphocytic leukemias (ALLs) are morphologically classified into L1, L2, and L3. The former two types are phenotypically constituted of quite heterogeneous ALLs. In the present study, phenotypes of cells from five L3 type ALL were analysed in FACS-IV using a panel of monoclonal antibodies (MAbs). The leukemic cells of all these patients coexpressed la (HLA-DR), CD19, CD20, CD21, CD24, CD38, and surface immunoglobulins, whereas a negative reaction with MAbs CD1, CD2, CD3, CD4, CD7, CD8, and Ti (WT31), Ti gamma A, delta TCS 1, and anti TCR-gamma/delta was observed. Neither myeloid-monocyte-erythroid nor megakaryocyte related cell surface antigens were detected in these cases with L3 type ALL. Chromosomal analysis of the ALL cells from two cases revealed a normoploid karyotype with specific translocation t(8;14)(q24;q32), whereas it was normal (46XY or 46XX) for the remaining three cases. Expression of myc oncogene was high in the former group, but low in the later one. Basing from our findings, we conclude that L3 type ALL is heterogeneous with respect to immunophenotypes, cytogenetics and oncogene analysis.

Distribution of cell surface glycoprotein CD9 (P24) antigen on megakaryocyte lineage leukemias and cell lines.

We herein describe CD9 (p24) antigen as existing on the cell surface of megakaryocyte lineage leukemias as well as megakaryocytic leukemia cell line, MEG-01 and HEL, by means of fluorescence-activated cell sorter (FACS IV) with a panel of monoclonal antibodies (Mabs). We found CD9 antigen expression on the cell surface of megakaryoblastic leukemias as well as MEG-01 and HEL cells. Furthermore, CD9 antigen expression increased while culturing these cells with phorbol esters, and was also found in the cytoplasm by means of indirect immunofluorescence test. These findings clearly showed that CD9 antigen exists on the cell surface of megakaryocytic cells which are capable of synthesizing the CD9.

Discordance between phenotype and function of Japanese adult T cell leukemia cells.

Phenotypes of cells from 12 patients with ATL were analysed by means of a fluorescence-activated cell sorter by utilizing a panel of monoclonal antibodies. A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD2, CD3, CD4, CD5, Ti (WT31), CD25, CD38, CD45, and CD29, but did not express the antigens against CD1, CD13, CD14, CD33, CD36, CD10, CD19, CD20, CD21, CD24, CD41, CD42, CD45RA, CD56, and CD57. The expression of antigen for TQ-1 or Leu8 was variable. Surface immunoglobulins were not detected. Phenotypes of cultured cells established by utilizing recombinant interleukin II were similar to those of the uncultured peripheral blood lymphoid cells except for the lack of expression of CD8. By means of two-color fluorescence, the ATL cells possessing CD4 in peripheral blood and culture coexpressed CD29, but did not express CD45RA. The suppression of PWM-induced B-cell immunoglobulin synthesis by normal T and B cells was found in five cases in the presence of ATL cells. The ATL cells demonstrated helper T-cell phenotypes (CD4+, CD29+) with suppressor function, paradoxically. We conclude that the phenotype of the ATL cells was CD4+, CD29+, and CD45RA- but that the function of these cells was of suppressor T-cells. Our results inevitably suggest the possible existence of suppressor T-cells with CD4+, CD29+ phenotype in persons without evidence of any underlying hematologic disorder.

Different expression of CD36 antigen molecule on the surface of megakaryocyte lineage leukemias and megakaryocyte leukemia cell lines MEG-01 and HEL.

Peripheral blood leukemic cells from four patients with peroxidase negative acute leukemia, which expressed neither myeloid nor lymphoid cell surface antigens, were analyzed by using monoclonal antibodies (MoAb) capable of recognizing megakaryocyte-platelet-related antigens. Leukemic cells from one case reacted with 5F1 MoAb, whereas cells from all the tested cases reacted with OKM5 MoAb, which belongs to the same CD group as 5F1 (CD36). Also, culture cells from megakaryoblastic leukemia cell line, MEG-01, and human erythroleukemia cell line, HEL, showed a different pattern of expression for the CD36 antigen molecule detected by 5F1 and OKM5 MoAb, individually. Furthermore, we have demonstrated that the epitopes recognized by 5F1 and OKM5 MoAb appear on the same CD36 molecule on the surface of HEL cells by means of the two-color analysis using FACS-IV. On the basis of our experiments, we conclude that, CD36 molecule, a receptor for TSP, is synthesized and expressed in at least two ways, inside the cells and on the surface of megakaryocyte lineage leukemias and megakaryocytic leukemia cell lines MEG-01 and HEL. This is strongly suggestive that thrombospondin (TSP)-mediated adhesion represents an alternative pathway for cytoadherence, and that CD36 expression on various kinds of cells may lack some essential modifications or components necessary for the TSP receptor activity.

Varied expressions of receptors on the human megakaryoblastic cell line MEG-01 by monoclonal antibodies.

We herein describe the regulation of specific receptors on the megakaryoblastic cell line MEG-01 by means of fluorescence-activated cell sorting (FACS IV) with a panel of monoclonal antibodies (MAbs). MEG-01 cells expressed GpIIb/IIIa (CD41a) and OKM5 (CD36) antigens on their cell surface, whereas they showed only a little expression of GPIb (CD42b), suggesting that these are megakaryoblastic cells. The up regulation of von Willebrand factor receptor (GPIb) and thrombospondin receptor (GPIV) and the down regulation of fibrinogen receptor (GPIIb/IIIa) and C3bi receptor (CD11b) were found by incubation with MAbs AN51 (CD42b), OKM5 (CD36), J15 (CD41a), and OKM1 (CD11b), respectively. This phenomenon was enhanced in the Ca2+ containing medium, except for the experiment with OKM5 (CD36) MAb. We thus suggest that several kinds of receptors on the surface of MEG-01 cells are dexterously regulated through stimulation from outside the cell.

Blastic transformation in essential thrombocythemia. In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages.

A 57-year-old man with essential thrombocythemia (ET) developed myelofibrosis, that progressed to a blastic transformation state. The characteristics of the blastic cells were serially studied both morphologically and phenotypically as well as in cell culture. The blastic cells that were first detected in peripheral blood had features of myeloid stem cells with slight differentiation toward megakaryocytic lineage. However, later in the course, most of the blastic cells were immature. During culture in the presence of human plasma-derived serum (PDS), some blastic cells obtained at the initial stage differentiated, mainly to both granulocytes and macrophages morphologically, but later tended to differentiate into both megakaryocytes and macrophages. Finally the blasts appeared to have lost their ability to differentiate morphologically. However, the blasts formed mixed colonies consisting of erythroblasts, granulocytes, macrophages, and immature blasts when cultured in methylcellulose with PHA-leukocyte conditioned medium. In addition, the blastic cells in suspension culture strongly expressed phenotypic features which are characteristic of erythroblasts, in the presence of both PDS and 12-0-tetradecanoylphorbol 13-acetate (TPA), whereas they expressed features of megakaryoblasts in the presence of PDS alone. These results suggest that essential thrombocythemia is of myeloid stem cell origin. This is the first case in the literature in which a clonal evolution in ET has been followed closely, essential events were identified serially, and the blastic cells, which appeared as a result of the progression of ET, were found to have the capability to differentiate toward the three myeloid lineages.

[Multiple myeloma following chronic neutrophilia terminated with acute monocytic leukemia (AML, M 5 b)].

A case of a 70 years old female who developed multiple myeloma during a course of neutrophilia, and later on terminated with acute monocytic leukemia (AML, M 5 b) following Melphalan therapy for five years is reported. This patient was first found to have neutrophilia in 1966, After six years, she developed monoclonal gammopathy, (IgG1 kappa type) which coexisted with the neutrophilia. She was put on Melphalan regimen for 5 years which was discontinued due to anemia, leukocytopenia and the reduction of serum IgG. By routine bone marrow examination, she was diagnosed as AMoL (AML, M 5 b) in July 1984. Thereafter, a combination chemotherapy of BH-AC, 6-MP and prednisolone was started and complete remission for the AMoL was achieved after 2 months. Sixteen months later, she relapsed and a similar combination chemotherapy for reinduction regimen was administered. However, the AMoL was resistant and after 7 months, she died of pneumonia and multiple organ failure. The association of neutrophilia with multiple myeloma, the occurrence of AMoL after prolonged Melphalan therapy for the multiple myeloma and the strategy of therapy for secondary leukemia is discussed.