Invasive pneumococcal infection in children, 1981-92: A hospital-based study

Objective: To document the pattern and sequelae of invasive pneumococcal infection in hospitalized children.
Methodology Retrospective review of Streptococcus pneumoniae (Sp) isolates from normally sterile sites from 1981 to 1992 at three paediatric centres in Sydney for demographic data, spectrum of disease, predisposing conditions, mortality, and sequelae from meningitis.
Results: Four hundred and thirty-one episodes in 417 patients were identified. Foci of infection were: meningitis, 34%; pneumonia, 29%; bacteraemia without apparent focus, 30%; and other foci, 7%. Sixty-one per cent of all cases and 64% of cases with meningitis were less than 2 years old. Predisposing conditions were present in 37%, were significantly more common in patients over age 2 years and were more common with foci other than meningitis. Overall mortality was 6.6% whereas the mortality for those with meningitis was 8%. Neurological sequelae were identified in 34% of previously normal children, and severe hearing loss occurred in 11.5%.
Conclusions The high morbidity and mortality from invasive pneumococcal infection in children justifies further evaluation of preventive strategies.     

Comparisons of sectioned micro-TLD dose measurements with predicted dose from 131I-labeled antibody.

The dose distribution from radioimmunotherapy is very heterogeneous because of variability in antigen expression, antibody penetration, and tumor architecture. Many models of dose distribution have been constructed but it has been very difficult to confirm these predictions with actual measured doses. The purpose of this study was to determine what degree of resolution could be obtained using mini-thermoluminescent dosimeter(s) (TLD) in a micrometastasis model. TLDs were inserted into 1-mm-diam multicell tumor spheroids that had been treated with 131I-labeled antibody. The spheroids were then sectioned at 30-microns intervals and the TLD sections (measuring 0.14 x 0.1 x 0.03 mm) were removed and read. Calibration of the TLDs was done with whole TLDs using external beam radiation and an 131I-containing gel, and with TLD sections using external beam radiation. Predicted doses were determined by measuring the activity in individual spheroids and the time the TLDs were in the spheroids and incorporating these numbers into a model that assumed either surface binding of 131I or some degree of penetration. There was a correlation between the measured TLD dose and the predicted absorbed dose when comparing the low- to high-dose regions. However, there was considerable variation within any particular dose range, probably due to heterogeneity in TLD grain size.(ABSTRACT TRUNCATED AT 250 WORDS)     

The filaggrin null genotypes R501X and 2282del4 seem not to be associated with psoriasis: results from general population study and meta‐analysis

Background Psoriasis vulgaris could be associated with the filaggrin null genotype since certain known susceptibility loci for psoriasis are shared with susceptibility loci for atopic dermatitis. Furthermore, filaggrin expression is lowered in psoriatic skin lesions but normally expressed in uninvolved skin. So far five relatively small patient‐based case‐control studies have rejected a possible association between psoriasis and the two most prevalent filaggrin null mutations, 2282del4 and R501X. Objectives To reinvestigate a possible association between psoriasis and filaggrin null mutation status by using cross‐sectional general population questionnaire data. Also, to perform a meta‐analysis including published studies that investigated the relation between filaggrin gene mutations R501X and 2282del4, respectively, and psoriasis vulgaris. Methods Between June 2006 and May 2008, a cross‐sectional study was performed in the general population in Copenhagen. A random sample of 7931 subjects aged 18–69 years was invited to participate in a general health examination including a questionnaire and 3471 (43.7%) participated. A total of 3335 (96.1%) individuals were filaggrin genotyped for the 2282del4 and R501X mutations. A meta‐analysis was undertaken to investigate the relation between filaggrin gene mutations and psoriasis vulgaris. Results The prevalence of self‐reported psoriasis was 6.7% among the 3240 respondents. The prevalence of the R501X and 2282del4 filaggrin null genotypes was 9.3% in subjects who reported psoriasis and 8.0% in subjects who did not report psoriasis (OR = 1.28; 95% CI = 0.74–1.89; P = 0.78). The meta‐analysis found no association between the filaggrin null genotypes R501X and 2282del4 and psoriasis (OR = 1.04; 95% CI = 0.81–1.35). Conclusions Psoriasis was not associated with the R501X and 2282del4 filaggrin null genotypes in a general population study and in a meta‐analysis on published studies.     

Bone marrow abnormalities in the non-obese diabetic mouse

Several lines of evidence point to abnormalities of the phenotype,cytokine responses, and function of cells of the myeiold lineagein non-obese diabetic (NOD) mice. In this study we have characterizedthe phenotype and myeloid progenitor function of NOD bone marrow.Two hematopoletic differentiation antigens, Ly-6C and AA4.1,are expressed abnormally on NOD bone marrow cells. While multillneageerythromyeloid progenitor cells (day 12 CFU-S) are normal innumber in NOD mice, more differentiated myeloid progenitorsare deficient in their in vitro responses to IL-3, granulocyte/macrophagecolony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposingldd-5 gene of NOD mice maps close to the IL-1 receptor, we testedNOD bone marrow cells for a defect in synergy between IL-1 andIL-3; no defect was found. The defects in myelopoiesis describedhere may predispose the NOD mouse to autoimmunlty by impairingmacrophage maturation.     

Set-up variation of patients treated with radiotherapy to the prostate measured with an electronic portal imaging device

The set-up variation of 11 patients treated supine with radical radiotherapy for carcinoma of the prostate was measured with an electronic portal imaging device to determine the adequacy of set-up techniques and current margins, as well as the need for immobilization. During the treatments 172 images of the anterior fields and 159 images of the left-lateral fields were taken and the errors in treatment placement were measured by template matching. The variation in the superior-inferior direction was small, 1.4-1.6 mm (1 SD), while the medio-lateral variation was 2.8 mm (1 SD). The anterior-posterior variation was largest, 4.6 mm (1 SD) with an offset of 3.3 mm anterior. This anterior offset and large anterior-posterior variation suggests that set-up techniques were not optimal for this direction. The 1 cm margin used was adequate for set-up variation except in a small number of cases, which was mainly due to the anterior trend. Random (treatment-to-treatment) variations were small (1.1-2.3 mm; 1 SD), indicating that immobilization would result in only modest improvement in reproducibility for these supine patients.     

Iodine-125-NRLU-10 kinetic studies and bismuth-212-NRLU-10 toxicity in LS174T multicell spheroids

Alpha emitter-labeled antibodies (Abs) are of considerable interest in cancer therapy. Alpha particles are densely ionizing and therefore have a high radiobiologic effectiveness, and the cell killing produced is influenced very little by dose rate or hypoxic conditions. LS174T human colon adenocarcinoma spheroids were used in this study to evaluate the efficacy of alpha emitter-labeled Abs in a three-dimensional model. NRLU-10, an IgG2b Ab to a pancarcinoma antigen, and its Fab fragment were used. Initial kinetic studies using 125I-NRLU-10 revealed that a large number of binding sites/cell and high Ab affinity led to slow Ab penetration. This effect could be overcome by increasing the Ab concentration ten-fold for Fab but not for intact Ab. Bismuth-212-NRLU-10 therapy was very effective in killing single cells (over 3 log reduction in surviving fraction) but was ineffective in spheroids (less than 1 log reduction). This was likely due to inadequate penetration into the spheroids before the 212Bi decayed. The use of higher Ab concentrations, tumors with fewer antigenic sites/cell for the Ab being used, lower affinity Abs, alpha emitters with longer half-lives, and pretargeting with bifunctional Ab are all potential ways of increasing the efficacy of alpha emitter-labeled Abs for cancer therapy.