Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

<p>Abstract</p> <p>Background</p> <p>High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors.</p> <p>Methods</p> <p>Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 10⁵U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BED_tumor= 30.6 Gy).</p> <p>Results</p> <p>In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals.</p> <p>Conclusion</p> <p>The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.</p

Disparities in dialysis treatment and outcomes for Dutch and Belgian children with immigrant parents

BACKGROUND: In Belgium and the Netherlands, up to 40% of the children on dialysis are children with immigrant parents of non-Western European origin (non-Western). Concerns exist regarding whether these non-Western patients receive the same quality of care as children with parents of Western European origin (Western). We compared initial dialysis, post-initial treatment, and outcomes between non-Western and Western patients on dialysis. METHODS: All children <19 years old on chronic dialysis in the Netherlands and Belgium between September 2007 and May 2011 were included in the study. Non-Western patients were defined as children of whom one or both parents were born in non-Western countries. RESULTS: Seventy-nine of the 179 included patients (44%) were non-Western children. Compared to Western patients, non-Western patients more often were treated with hemodialysis (HD) instead of peritoneal dialysis (PD) as first dialysis mode (52 vs. 37%, p = 0.046). Before renal transplantation, non-Western patients were on dialysis for a median (range) of 30 (5-99) months, vs. 15 (0-66) months in Western patients (p = 0.007). Renal osteodystrophy was diagnosed in 34% of non-Western vs. 18% of Western patients (p = 0.028). The incidence rate ratio [95% confidence interval] for acute peritonitis was 2.44 [1.43-4.17] (p = 0.032) for non-Western compared to Western patients. CONCLUSIONS: There are important disparities between children on chronic dialysis with parents from Western European origin and those from non-Western European origin in the choice of modality, duration, and outcomes of dialysis therapy

Long-term disease burden and survivorship issues after surgery and radiotherapy of intracranial meningioma patients

BACKGROUND Many intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention. OBJECTIVE To assess the long-term (≥5 yr) disease burden of meningioma patients. METHODS In this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported. RESULTS At a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (–2.11, 95% CI: –3.52 to –0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls. CONCLUSION In the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning

Increased Monocyte Turnover from Bone Marrow Correlates with Severity of SIV Encephalitis and CD163 Levels in Plasma

Cells of the myeloid lineage are significant targets for human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in monkeys. Monocytes play critical roles in innate and adaptive immunity during inflammation. We hypothesize that specific subsets of monocytes expand with AIDS and drive central nervous system (CNS) disease. Additionally, there may be expansion of cells from the bone marrow through blood with subsequent macrophage accumulation in tissues driving pathogenesis. To identify monocytes that recently emigrated from bone marrow, we used 5-bromo-2′-deoxyuridine (BrdU) labeling in a longitudinal study of SIV-infected CD8+ T lymphocyte depleted macaques. Monocyte expansion and kinetics in blood was assessed and newly migrated monocyte/macrophages were identified within the CNS. Five animals developed rapid AIDS with differing severity of SIVE. The percentages of BrdU+ monocytes in these animals increased dramatically, early after infection, peaking at necropsy where the percentage of BrdU+ monocytes correlated with the severity of SIVE. Early analysis revealed changes in the percentages of BrdU+ monocytes between slow and rapid progressors as early as 8 days and consistently by 27 days post infection. Soluble CD163 (sCD163) in plasma correlated with the percentage of BrdU+ monocytes in blood, demonstrating a relationship between monocyte activation and expansion with disease. BrdU+ monocytes/macrophages were found within perivascular spaces and SIVE lesions. The majority (80–90%) of the BrdU+ cells were Mac387+ that were not productively infected. There was a minor population of CD68+BrdU+ cells (<10%), very few of which were infected (<1% of total BrdU+ cells). Our results suggest that an increased rate of monocyte recruitment from bone marrow into the blood correlates with rapid progression to AIDS, and the magnitude of BrdU+ monocytes correlates with the severity of SIVE

The human resource for health situation in Zambia: deficit and maldistribution

<p>Abstract</p> <p>Introduction</p> <p>Current health policy directions in Zambia are formulated in the National Health Strategic Plan. The Plan focuses on national health priorities, which include the human resources (HR) crisis. In this paper we describe the way the HRH establishment is distributed in the different provinces of Zambia, with a view to assess the dimension of shortages and of imbalances in the distribution of health workers by province and by level of care.</p> <p>Population and methods</p> <p>We used secondary data from the "March 2008 payroll data base", which lists all the public servants on the payroll of the Ministry of Health and of the National Health Service facilities. We computed rates and ratios and compared them.</p> <p>Results</p> <p>The highest relative concentration of all categories of workers was observed in Northern, Eastern, Lusaka, Western and Luapula provinces (in decreasing order of number of health workers).</p> <p>The ratio of clinical officers (mid-level clinical practitioners) to general medical officer (doctors with university training) varied from 3.77 in the Lusaka to 19.33 in the Northwestern provinces. For registered nurses (3 to 4 years of mid-level training), the ratio went from 3.54 in the Western to 15.00 in Eastern provinces and for enrolled nurses (two years of basic training) from 4.91 in the Luapula to 36.18 in the Southern provinces.</p> <p>This unequal distribution was reflected in the ratio of population per cadre. The provincial distribution of personnel showed a skewed staff distribution in favour of urbanized provinces, e.g. in Lusaka's doctor: population ratio was 1: 6,247 compared to Northern Province's ratio of 1: 65,763.</p> <p>In the whole country, the data set showed only 109 staff in health posts: 1 clinical officer, 3 environmental health technologists, 2 registered nurses, 12 enrolled midwives, 32 enrolled nurses, and 59 other.</p> <p>The vacancy rates for level 3 facilities(central hospitals, national level) varied from 5% in Lusaka to 38% in Copperbelt Province; for level 2 facilities (provincial level hospitals), from 30% for Western to 70% for Copperbelt Province; for level 1 facilities (district level hospitals), from 54% for the Southern to 80% for the Western provinces; for rural health centres, vacancies varied from 15% to 63% (for Lusaka and Luapula provinces respectively); for urban health centres the observed vacancy rates varied from 13% for the Lusaka to 96% for the Western provinces. We observed significant shortages in most staff categories, except for support staff, which had a significant surplus.</p> <p>Discussion and Conclusions</p> <p>This case study documents how a peaceful, politically stable African country with a longstanding tradition of strategic management of the health sector and with a track record of innovative approaches dealt with its HRH problems, but still remains with a major absolute and relative shortage of health workers. The case of Zambia reinforces the idea that training more staff is necessary to address the human resources crisis, but it is not sufficient and has to be completed with measures to mitigate attrition and to increase productivity.</p

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Independent Validation of an Existing Model Enables Prediction of Hearing Loss after Childhood Bacterial Meningitis

Objective: This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice. Study design: 116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values. Results: Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort. Conclusions: Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing