Percentage of Philadelphia chromosome (Ph)-negative and Ph-positive cells found after autologous transplantation for chronic myelogenous leukemia depends on percentage of diploid cells induced by conventional- dose chemotherapy before collection of autologous cells

We collected peripheral blood mononuclear cells and bone marrow cells soon after recovery from conventional-dose chemotherapy-induced myelosuppression and transplanted these cells into advanced chronic myelogenous leukemia (CML) patients after treating these patients with 120 mg/kg cyclophosphamide, 750 mg/m2 VP-16, and 1,020 cGy of total body irradiation (TBI). Of the 10 late chronic-phase patients and the eight accelerated-phase CML patients evaluable posttransplant, 90% and 87%, respectively, remain alive posttransplant, whereas none of the three blast crisis CML patients given this therapy remain alive posttransplant. We measured the percentage of Philadelphia chromosome (Ph)-negative cells in the autologous cells collected after conventional-dose chemotherapy-induced myelosuppression before autologous transplant and in the marrow of these same CML patients after autologous transplantation of these cells into recipients treated with the cyclophosphamide, VP-16, and TBI. A direct correlation (correlation coefficient = 0.91) was observed between the level of Ph+ cells in the transplanted cells and the percentage of Ph+ marrow cells after transplant in 21 patients so transplanted. The data show that the chance of generating cytogenetic remissions post-transplant depends on the percentage of diploid cells in the preparations of autologous cells used for transplant and the stage of disease of the patients at the time of collection of the autologous cells.     

Response patterns of purified myeloma cells to hematopoietic growth factors

Tumor cells were isolated from the bone marrow of seven patients with multiple myeloma and from the peripheral blood of three patients with plasma cell leukemia using Ficoll-Hypaque (FH) density sedimentation followed by immune rosette depletion of T, myeloid, monocytoid, and natural killer (NK) cells. Enrichment to greater than or equal to 93% plasma cells was confirmed with Wright's-Giemsa staining, with intracytoplasmic immunoglobulin staining, and with staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, monocytoid, and myeloma antigens in indirect immunofluorescence assays. Myeloma cells neither proliferated nor secreted Ig in response to G/M-CSF, G- CSF, M-CSF, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), or interleukin-4 (IL-4). Significant proliferation (SI greater than or equal to 3.0) was induced by interleukin-6 (IL-6) in six of ten patients (SI of 31 and 43 in two cases); and to interleukin-3 (IL-3) and interleukin-5 (IL-5), independently, in two patients each. Peak proliferation to IL-5 or IL-6 and to IL-3 occurred in cells pulsed with 3[H] thymidine at 24 and 48 hours, respectively; and proliferation to combinations of factors did not exceed that noted to IL-6 alone; Ig secretion was not documented under any culture conditions. Three myeloma-derived cell lines similarly studied demonstrated variable responses. The heterogeneity in the in vitro responses of myeloma cells and derived cell lines to exogenous growth factors enhances our understanding of abnormal plasma cell growth and may yield insight into the pathophysiology of plasma cell dyscrasias.     

Evolving Epidemiology of Japanese Encephalitis: Implications for Vaccination

Purpose of Review

We examine the present global burden of Japanese encephalitis (JE) in endemic populations, summarize published cases in travelers since 2009, examine current guidelines for vaccination for international travelers, and consider challenges in prevention of this vector-borne disease.

Recent Findings

We identified 11 JE cases in travelers that were published in peer-reviewed literature since 2009. JE incidence in endemic countries appears to be declining but the number of JE cases reported to the World Health Organization (WHO) varied from estimates derived from other published reports based on serosurveys or sentinel surveillance. Current JE vaccines appear to be safe and are not associated with delayed hypersensitivity in contrast to the older mouse brain vaccine.

Summary

Given differences between WHO-reported cases and local surveillance data, future research on true incidence is needed. Regular assessment will inform JE risk in travelers. National and international guidelines on JE vaccination varied; we suggest areas for improvement.

     

Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin

Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa are responsible for a significant proportion of episodes of nosocomial pneumonia. Since the development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of MDR pathogens, there has been renewed interest in antimicrobial agents that had previously been used but had been abandoned because of toxic side effects. This report describes three patients with nosocomial pneumonia or tracheobronchitis due to multiresistant strains of P. aeruginosa for whom aerosolized colistin proved beneficial as supplemental therapy. Aerosolized colistin merits further consideration as a therapeutic intervention for patients with pulmonary infections due to MDR P. aeruginosa.     

Metabolically healthy obesity and risk of incident type 2 diabetes: a meta‐analysis of prospective cohort studies

The risk of type 2 diabetes among obese adults who are metabolically healthy has not been established. We systematically searched Medline (1946–August 2013) and Embase (1947–August 2013) for prospective studies of type 2 diabetes incidence (defined by blood glucose levels or self‐report) among metabolically healthy obese adults (defined by body mass index [BMI] and normal cardiometabolic clustering, insulin profile or risk score) aged ≥18 years at baseline. We supplemented the analysis with an original effect estimate from the English Longitudinal Study of Ageing (ELSA), with metabolically healthy obesity defined as BMI ≥ 30 kg m^?2 and <2 of hypertension, impaired glycaemic control, systemic inflammation, adverse high‐density lipoprotein cholesterol and adverse triglycerides. Estimates from seven published studies and ELSA were pooled using random effects meta‐analyses (1,770 healthy obese participants; 98 type 2 diabetes cases). The pooled adjusted relative risk (RR) for incident type 2 diabetes was 4.03 (95% confidence interval = 2.66–6.09) in healthy obese adults and 8.93 (6.86–11.62) in unhealthy obese compared with healthy normal‐weight adults. Although there was between‐study heterogeneity in the size of effects (I² = 49.8%; P = 0.03), RR for healthy obesity exceeded one in every study, indicating a consistently increased risk across study populations. Metabolically healthy obese adults show a substantially increased risk of developing type 2 diabetes compared with metabolically healthy normal‐weight adults. Prospective evidence does not indicate that healthy obesity is a harmless condition.     

A comparison of infant and toddler feeding practices of mothers with and without histories of eating disorders

This preliminary study surveyed the feeding practices of mothers with eating disorder histories through evaluation of mothers' reported feeding styles, child diet composition and restrictive special approaches to feeding. For this non‐randomised cohort study, 25 mothers with eating disorder histories and 25 mothers with no history of an eating disorder with children ages 6–36 months were selected such that the groups were similar based on child age group and child sex. Mothers were compared on self‐reported feeding style using the Infant Feeding Styles Questionnaire and on child diet composition and special feeding approaches using a modified version of the Toddler Diet Questionnaire from the Women, Infants, and Children program. Mothers with eating disorder histories scored lower on the restrictive feeding style subscale than controls. No significant differences were detected between groups in child diet including the percentage of mothers who breastfed, duration of breastfeeding, age at solid food introduction, daily number of meals or snacks or daily frequency of consumption of fruits, vegetables or protein foods. Mothers with eating disorder histories were more likely to report taking a restrictive special approach to feeding such as limiting processed foods or feeding organic foods only. Although mothers with eating disorder histories may not differ greatly from control mothers in terms of child diet composition (smaller effects may not have been detected due to limited sample size), they may be more likely to take restrictive special approaches to feeding which mirror dietary rules common in individuals with eating disorders.     

Geographic variation in the relationship between human Lyme disease incidence and density of infected host-seeking Ixodes scapularis nymphs in the Eastern United States

Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.     

Colonic bowel wall thickening: Is there a need for endoscopic evaluation?

Purpose  

Clinical relevance of colonic bowel wall thickening seen on abdominal CT scans is unknown. Recommendations for further diagnostic procedures are lacking. The aim of this retrospective study was to evaluate detecting of bowel wall thickening on CT scan and findings that were seen in case of endoscopical evaluation.