Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

Previous Violent Events and Mental Health Outcomes in Guatemala

Objectives. We analyzed a probability sample of Guatemalans to determine if a relationship exists between previous violent events and development of mental health outcomes in various sociodemographic groups, as well as during and after the Guatemalan Civil War.Methods. We used regression modeling, an interaction test, and complex survey design adjustments to estimate prevalences and test potential relationships between previous violent events and mental health.Results. Many (20.6%) participants experienced at least 1 previous serious violent event. Witnessing someone severely injured or killed was the most common event. Depression was experienced by 4.2% of participants, with 6.5% experiencing anxiety, 6.4% an alcohol-related disorder, and 1.9% posttraumatic stress disorder (PTSD). Persons who experienced violence during the war had 4.3 times the adjusted odds of alcohol-related disorders (P < .05) and 4.0 times the adjusted odds of PTSD (P < .05) compared with the postwar period. Women, indigenous Maya, and urban dwellers had greater odds of experiencing postviolence mental health outcomes.Conclusions. Violence that began during the civil war and continues today has had a significant effect on the mental health of Guatemalans. However, mental health outcomes resulting from violent events decreased in the postwar period, suggesting a nation in recovery.For 36 years Guatemala experienced a violent civil war in which over 200 000 civilians were killed, 440 villages destroyed, and more than 1 million Guatemalans displaced, both internally and into southern Mexico.1–3 Those killed included indigenous persons, laborers, academics, religious leaders, and others who were clearly noncombatants.3,4 In 1996, peace accords were signed between a number of rurally based guerrilla forces and Guatemala’s national army.Nearly three quarters of the people in the world’s poorest societies have recently been through a civil war or are still in one. The average civil war lasts approximately 5 years and can be embedded in a societal context that fuels the longevity of the conflict itself by marking it as culturally “normal.”5–7 Because of cultural normalization and numerous other factors, both within and outside of Guatemala, the Guatemalan Civil War far exceeded the length of the average national civil war and might have long-standing implications for the safety and health of Guatemalans today.Civil wars produce a legacy of postconflict violence and disease,7–12 and Guatemala is no exception. Today, the northern triangle of Central America, which includes Guatemala, Honduras, and El Salvador, is described as the most violent area of the world outside of active theaters of war.3,13 Less than a decade after the civil war peace accords were signed in Guatemala, persistent violence reportedly resulted in the second highest rates of fear from armed crime in the world and the proliferation of more private security personnel than members of the regular army.3,14 Approximately at the same time, some 1500 Guatemalan Civil War refugees living in Mexico reported alarmingly high levels of depression, anxiety, and posttraumatic stress disorder (PTSD).15 The World Health Organization (WHO) also reported elevated alcohol use disorders in Guatemala in the years following the civil war.16 These indicators occurred alongside reports that 40% of the country continued to have no mental health services, leaving many Guatemalans, repatriated refugees, and affected citizens, who remained throughout the civil war without a key aspect of care on the road to national recovery.17In dealing with the effects of civil conflicts, such as recurring violence, PTSD, depression, anxiety, alcohol abuse, and other mental health issues, postconflict societies like Guatemala face difficult decisions between enacting extraordinary military spending3,5 or provisions of enhanced social and public health services.7,18 However, policymakers in Guatemala (and internationally) have limited population-level and epidemiologic evidence19 with which to make such decisions. With this in mind, we completed the first national probability sample of the mental health of Guatemalans still living in Guatemala. We analyzed these survey data to obtain nationally representative estimates of the prevalence of select mental health problems in Guatemala,9,11,15 and to determine if a relationship existed between previous violent events and the development of subsequent mental health outcomes. We compared different sociodemographic groups,20–25 as well as the periods before and after the signing of the 1996 civil war peace accords.     

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.     

Validation of computed tomography image integration into the EnSite NavX mapping system to perform catheter ablation of atrial fibrillation

Introduction: The complex anatomy of the left atrium (LA) makes location of ablation catheters difficult using fluoroscopy alone, and therefore 3D mapping systems are now routinely used. We describe the integration of a CT image into the EnSite NavX System with Fusion and its validation in patients undergoing atrial fibrillation (AF) or left atrial tachycardia (AT) catheter ablation. Methods and Results: Twenty‐three patients (61 ± 9.2 years, 16 male) with paroxysmal (14) and persistent (8) AF and persistent (1) AT underwent ablation using CT image integration into the EnSite NavX mapping system with the EnSite Fusion Dynamic Registration software module. In all cases, segmentation of the CT data was accomplished using the EnSite Verismo segmentation tool, although repeat segmentation attempts were required in seven cases. The CT was registered with the NavX‐created geometry using an average of 24 user‐defined fiducial pairs (range 9 to 48). The average distance from NavX‐measured lesion positions to the CT surface was 3.2 ± 0.9 mm (median 2.4 mm). A large, automated, retrospective test using registrations with random subsets of each patient's fiducial pairs showed this average distance decreasing as the number of fiducial pairs increased, although the improvement ceased to be significant beyond 15 pairs. In confirmation, those studies which had used 16 or more pairs had a smaller average lesion‐to‐surface distance (2.9 ± 0.7 mm) than those using 15 or fewer (4.3 ± 0.8 mm, P < 0.02). Finally, for the 13 patients who underwent left atrial circumferential ablation (LACA), there was no significant difference between the circumference computed using NavX‐measured positions and CT surface positions for either the left pulmonary veins (178 ± 64 vs. 177 ± 60 mm; P = 0.81) or the right pulmonary veins (218 ± 86 vs. 207 ± 81 mm; P = 0.08). Conclusion: CT image integration into the EnSite NavX Fusion system was successful in all patients undergoing catheter ablation. A learning curve exists for the Verismo segmentation tool; but once the 3D model was created, the registration process was easily accomplished, with a registration error that is comparable with registration errors using other mapping systems with CT image integration. All patients went on to have subsequent successful ablation procedures. Where LACA was performed (13 patients), only four patients required segmental ostial lesions to achieve electrical isolation.     

Blood rheology and cardiovascular risk factors in type 1 diabetes: relationship with microalbuminuria.

Whole blood and plasma viscosity, erythrocyte aggregation and deformability, plasma fibrinogen, lipids, lipoproteins, apolipoproteins, and measures of blood glucose control were compared between 21 Type 1 diabetic patients with microalbuminuria (overnight albumin excretion rate 30-200 micrograms min-1) and 21 patients with albumin excretion below this range matched for age, sex, and duration of diabetes. Patients with microalbuminuria had significantly higher glycosylated haemoglobin (9.4 +/- 1.6 (+/- SD) vs 7.9 +/- 1.8% (normal range 5.0 to 7.6%)), total-cholesterol (5.6 +/- 1.1 vs 4.6 +/- 1.3 mmol l-1), apolipoprotein B (0.82 +/- 0.21 vs 0.66 +/- 0.14 g l-1), and apolipoprotein B:A1 ratio (0.58 +/- 0.18 vs 0.50 +/- 0.15) than those without microalbuminuria (all p less than 0.05). HDL-cholesterol was also raised (1.71 +/- 0.46 vs 1.43 +/- 0.37 mmol l-1, p less than 0.05). Lipoprotein(a) concentration was possibly higher in the microalbuminuric group (median (95% Cl) 105 (82-140) vs 72 (52-114) mg l-1, p = 0.06). No differences were seen in any of the rheological measurements. These results confirm the presence of potentially atherogenic lipoprotein changes in Type 1 diabetic patients with microalbuminuria, but suggest that altered blood rheology does not predate the development of nephropathy.     

Pseudoaneurysm of the Left Ventricle

Abstract: A case study is reported of a patient with rheumatoid arthritis who developed a pseudoaneurysm of the left ventricle after inferior myocardial infarction. The clinical diagnosis was confirmed by radionuclide cardiac blood pool imaging and by contrast ventricu-lography; the aneurysm was successfully excised.     

Isocaloric substitution of plant sterol-enriched fat spread for carbohydrate-rich foods in a low-fat, fibre-rich diet decreases plasma low-density lipoprotein cholesterol and increases high-density lipoprotein concentrations

BACKGROUND AND AIM: The aim of the study was to determine the effects on plasma cholesterol of replacing a plant sterol-enriched fat spread with carbohydrate-rich foods relative to a diet high in saturated fat. METHODS AND RESULTS: Twenty-nine men and women, from the general community, with mean age (SD) 48 (14)y, body mass index 29.0 (6.2)kg/m(2), and plasma total cholesterol concentration 6.48 (0.97)mmol/L completed the randomised, crossover dietary intervention. There were three diets: New Zealand diet (NZ diet) high in total (34%kJ) and saturated (15%kJ) fat, a cholesterol-lowering fibre-rich diet reduced in total (30%kJ) and saturated fat (8%kJ) but including a plant sterol spread (PS diet), and the same cholesterol-lowering diet with the plant sterol spread isocalorically replaced with carbohydrate (CHO diet); total fat, 26%kJ; saturated fat 7%kJ. All foods were provided and each diet was followed for four weeks. Mean (SD) plasma low-density lipoprotein cholesterol concentration declined from 4.68 (0.91)mmol/L on the high saturated fat diet to 4.12 (0.83)mmol/L (P<0.001) on the carbohydrate diet and 3.76 (0.84)mmol/L (P<0.001) on the plant sterol diet. The 20% decrease on the plant sterol diet was significantly greater (P<0.001) than the 12% decrease on the carbohydrate diet. Relative to the NZ diet, mean (95% CI) plasma high-density lipoprotein cholesterol concentration changed by -0.11 (-0.16, -0.06)mmol/L on the CHO diet but was not different at the end of the PS diet, -0.03 (-0.09, 0.02). CONCLUSION: Including a plant sterol-enriched fat spread in a cholesterol-lowering diet produces a more favourable plasma lipid profile than the same diet made lower in total and saturated fat by replacing the spread with carbohydrate-rich foods.