Problems in treatment of sterility in developing countries--experiences with sterility consultation in Gondar/Ethiopia

101 women were treated because of sterility in the Gondar College of Medical Sciences, Gondar/Ethiopia, in the years 1987/88. The results revealed some typical difficulties in diagnosis and treatment of sterility in developing countries, arising from limited technological facilities and special characteristics of the group of treated patients. In 61 women a final diagnosis could be made. The main cause of sterility was complete tubal occlusion in 65.6% of the cases due to a high incidence of pelvic inflammatory diseases in the investigated patients. Ovarian causes accounted for only 18%. The importance of the male factor was not evaluable due to a traditionally conservative attitude of most men against sterility investigations. Chromolaparoscopy in combination with endometrial biopsy in the second half of the cycle were well suitable for clearing most of female causes of sterility.     

New therapies for immune thrombocytopenic purpura

PURPOSE OF REVIEW: The treatment landscape of immune thrombocytopenic purpura has the potential for dramatic change in the near future as promising new agents and adaptations of older therapies enter clinical study. An update on the status of current research in immune thrombocytopenic purpura and a preview of agents in development are provided here. RECENT FINDINGS: The recent literature shows a multitude of strategies employed in the treatment of immune thrombocytopenic purpura. These therapies under active investigation include the use of the B-cell-depleting monoclonal antibody rituximab, higher doses of dexamethasone and anti-D immunoglobulin, and thrombopoiesis-stimulating agents that are in early clinical development. SUMMARY: Clinical investigation of novel therapies in immune thrombocytopenic purpura is undergoing a revolution that has the potential to change the standard of care. While older therapies are experiencing a rebirth by being given a new spin, newer agents such as thrombopoietins are showing significant promise.     

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis

Purpose

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients.

Methods

We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000–2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors.

Results

Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14–4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74–3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29–1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90–11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68–5.29).

Conclusions

comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

     

Evaluating indoor residual spray for reducing malaria infection prevalence in Eritrea: results from a community randomized control trial

This paper examines the relationship between indoor residual spray (IRS) and malaria parasite infection in Gash Barka Zone, Eritrea, an area with near universal coverage of insecticide treated bednets (ITN) and already low malaria parasite prevalence. A community randomized control trial was conducted in 2009. Malaria parasite infection prevalence was 0.5% [95% confidence interval (CI): 0.37-0.78%], with no significant difference detected between treatment and control areas. ITN possession remains high, with over 70% of households reporting ITN ownership [95% CI: 68.4-72.9]. ITN use among individuals within ITN-owning households was just under half [46.7% (95% CI: 45.4-48.0)]. Slight differences in ITN possession and use were detected between treatment and control areas. There was no significant difference in malaria parasite infection prevalence among individuals in households with ≥1 ITN compared to those in households without ITNs, nor among individuals reporting ITN use. Among individuals in ITN-owning households, sleeping under an ITN offered no statistically significant protection from malaria parasite infection. Community participation in environmental and larval habitat management activities was low: 17.9% (95% CI: 16.0-19.7). It is likely that IRS, larval habitat management and ITN distribution alone may be insufficient to interrupt transmission without corresponding high ITN use, sustained IRS application in areas where infections are clustered, and promptly seeking laboratory diagnosis and treatment of all fevers. Eritrea is ready for elimination, irrespective of inconclusive impact evaluation results.     

Splenic Morphological Changes Are Accompanied by Altered Baseline Immunity in a Mouse Model of Sickle-Cell Disease

Although functional asplenia from infarctions may be a major contributor to increased infectious mortality in sickle-cell disease (SCD), this relationship has not been fully defined. We used the transgenic Berkeley SCD mouse to define blood and splenic immunophenotypic differences in this model compared with C57BL/6 and hemizygous controls. In the serum of SCD mice, we found increased IgG2a and suppressed IgM, IgG2b, and IgA levels. Serum IL-6 levels in SCD mice were elevated, whereas IL-1α, CXCL10, and CCL5 levels were decreased. The blood of SCD mice had higher white blood cell counts, with an increased percentage of lymphocytes and decreases in other leukocytes. Immunophenotyping of lymphocytes revealed higher percentages of CD8⁺ and T-regulatory cells and lower percentages of B cells. SCD mouse spleens exhibited histological disorganization, with reduction of defined lymphoid follicles and expansion of red pulp, a greater than fourfold increase in splenic mononuclear cells, marked expansion of the nucleated red blood cell fraction, and B-cell and CD8⁺ T-cell lymphopenia. Within the splenic B-cell population, there was a significant decrease in B-1a B cells, with a corresponding decrease in IgA secreting plasma cells in the gut. Confocal microscopy of spleens demonstrated complete disruption of the normal lymphofollicular structure in the white pulp of SCD mice without distinct B, T, and marginal zones. Our findings suggest that altered SCD splenic morphological characteristics result in an impaired systemic immune response.Millions worldwide live with sickle-cell disease (SCD), the most common inherited blood disorder that is caused by a single point mutation in the β-globin gene, resulting in the production of abnormal red blood cell (RBC) hemoglobin. In the deoxygenated state, hemoglobin polymerizes to form relatively stiff filaments, forcing RBCs to assume an irregular sickled shape. These sickled RBCs are thought to occlude small blood vessels, resulting in what is termed a vaso-occlusive crisis. Such episodes are recurrent, spontaneous complications of SCD in which microvascular infarction leads to extreme pain and widespread organ dysfunction. These problems often lead to several other complications of the disease, such as anemia and stroke; consequently, most patients with SCD live to between the ages of 40 and 50 years.¹ Surprisingly, the most common cause of death in those with SCD is infection, not stroke or organ failure. The life expectancy of patients with SCD has increased in recent decades because of early interventions, such as universal newborn screening for the disease, the use of prophylactic penicillin, and the administration of vaccines to prevent infections.One critical immunological organ that is affected early in individuals with SCD is the spleen. It is a complex, but highly organized, structure composed of white pulp, red pulp, and the marginal zone. The red pulp is critical for blood filtration, iron recycling from erythrophagocytosis, extramedullary hematopoiesis, and the production of antibodies from resident plasmablasts that migrate out of the splenic follicles after antigen-specific differentiation. The white pulp is organized as lymphoid sheaths with B- and T-cell compartments. Clonal expansion of activated B cells occurs in the B-cell follicles, leading to isotype switching and somatic hypermutation, whereas T cells form T-cell zones, where they interact with dendritic cells and passing B cells. The marginal zone serves as a transitory boundary between the red and white pulp and contains unique sets of macrophages and B cells that appear to be important for mounting responses against T-cell–independent antigens, such as the capsular polysaccharide of invasive bacterial species.² Intrasplenic shunting results in reduced blood flow through the spleen in pediatric patients with SCD, rendering them functionally asplenic. Repeated infarction of the spleen throughout childhood causes severe fibrosis and calcification and eventually results in autosplenectomy and, presumably, impaired immunity. Loss of the spleen has a dramatic negative effect on natural IgM-producing B-1a B-cell numbers on splenectomy in mice³ and may also have a similar effect in homologous cells in humans.⁴ B-1a B cells are imperative for protection against invasive encapsulated bacteria, such as Streptococcus pneumoniae,⁵ and they are essential for maintaining high levels of secretory IgA in the gut.⁶ Much of the morbidity and mortality associated with SCD can be attributed to diseases caused by encapsulated bacteria, such as S. pneumoniae,⁷ making the study of the role of the SCD spleen in infectious disease pathogenesis imperative to the improvement of patient health.SCD is a human disease that is not found in other species, making the generation of an animal model to study the disease in detail a difficult endeavor. However, several different transgenic mice have been developed, including a mouse with fully humanized hemoglobin.⁸ The murine globin genes have been knocked out of these mice, whereas transgenes express human hemoglobin. These mice recapitulate several aspects of disease observed in humans, including sickled erythrocytes and histological damage to multiple organ systems. These mice also demonstrate a pro-inflammatory state when administered a low-dose lipopolysaccharide challenge that produces an exaggerated inflammatory response, with elevated levels of tumor necrosis factor-α, IL-1β, and soluble vascular cell adhesion molecule-1 in the serum and bronchoalveolar lavage fluid.⁹ Unfortunately, there is a paucity of data about the immune system of these SCD mice at baseline, which is important because this disease in humans has many secondary, and even life-threatening, infectious complications.¹⁰We hypothesized that altered splenic histopathological architecture from repeated vaso-occlusive infarctions leads to impaired systemic immunity. To our knowledge, detailed immunophenotyping and imaging of SCD mouse spleens have not been published. Therefore, the purpose of this study was to assess the basic immune status of the SCD transgenic mouse. In doing so, we have identified blood, gut, and splenic immunophenotypic differences that might lead to further mechanistic explanations for how the spleen is involved in increased morbidity and mortality from infection in SCD.     

Roll back malaria--an African success story in Eritrea.

BACKGROUND: High morbidity and mortality from malaria in Africa prompted the Abuja Declaration by African Heads of State in 2000. The goal set in the declaration for 2010 was to reduce malaria mortality by 50%. Countries were therefore expected to ensure that 60% of people suffering from malaria had access to treatment, that 60% of those at risk received intermittent prophylaxis, and that 60% of people in high-risk groups were using insecticide-treated nets (ITNs) by 2005. In 1999 Eritrea introduced malaria policies, strategies and multi-level interventions targeting households, communities and health facilities. OBJECTIVES: To assess Eritrea's progress towards meeting the Abuja Declaration goal, targets and key determinants. METHODS: A retrospective study was undertaken using data from the Health Management Information System (HMIS) and reports of annual reviews. Correlation and regression analysis were used to assess associations between selected variables. RESULTS: The incidence rate for malaria decreased from 6000/100000 in 1998 to 1100/100000 in 2003, representing > 80% decline in morbidity. The cumulative number of ITNs distributed increased from 50000 in 1998 to 685000 in 2003. The ITN impregnation rate increased from 15% to > 70% during the same period. Indoor residual spraying increased from 7444 kg to 41157 kg of insecticide in 2004 resulting in the protected population increasing from 117017 to 244315 respectively. The number of health workers recruited and trained rose from 936 to 4118. There was a strong correlation between the malaria incidence rate, distribution of ITNs (R2 = 0.76) and the total number of health workers trained (R2 = 0.72). The association was consistent in regression analysis (beta = -0.05, p = 0.03 for ITNs, and beta = -0.249, p = 0.05 for trained health workers). CONCLUSION: Within 5 years Eritrea met the Abuja Declaration objectives through multiple vector-control methods, case management and surveillance.     

Bortezomib in combination with rituximab, dexamethasone, ifosfamide, cisplatin and etoposide chemoimmunotherapy in patients with relapsed and primary refractory diffuse large B-cell lymphoma

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population.     

Should all patients with indolent lymphoma be treated with rituximab maintenance therapy? An overview of the data

Indolent non-Hodgkin's lymphoma remains a generally incurable malignancy. Administration of the anti-CD20 monoclonal antibody rituximab as a single agent or in combination with chemotherapy has become widely employed in this patient population. Although the addition of maintenance treatment after 1 course of single-agent rituximab prolongs time to progression in patients with indolent non-Hodgkin's lymphoma, a similar "duration of rituximab benefit" is observed when rituximab is administered at the time of relapse. Progression-free survival is clearly improved when rituximab is administered with chemotherapy whether it is given concomitantly, in a maintenance fashion, or both. In fact, the available data show a trend toward survival benefit with these strategies in some settings. Further follow-up will elucidate the effect of maintenance rituximab on long-term outcomes. For now, these initial data suggest that patients with indolent lymphoma might derive significant benefit from these novel therapeutic strategies.