Does whole-cell pertussis vaccine protect black South African infants? Assessment of post-vaccination events and antibody responses to pertussis toxin, filamentous haemagglutinin and agglutinogens 2 and 3

The whole-cell pertussis vaccine currently used in South Africa has not been adequately evaluated for post-vaccination events and immunogenicity. A trial of this vaccine combined with diphtheria and tetanus toxoids (DTP) was undertaken in 115 black babies who received primary vaccination at 2, 4 and 6 months of age. Serological IgG responses to the major antigens of Bordetella pertussis, filamentous haemagglutinin (FHA), pertussis toxin (PT) and fimbriae (agglutinogens 2 and 3 (AGG 2 + 3), were evaluated by enzyme-linked immunosorbent assay in sera obtained at birth, and before vaccination at 2,4 and 6 months and at 9 months. Surprisingly, after 3 doses of DTP, responses to PT and FHA were found merely to restore levels of IgG to PT and FHA to those found in cord blood. In contrast with the positive increases in these antibodies found in other series of whole-cell vaccination, the anti-PT seroconversion rate was only 19% and the anti-FHA rate only 24%. High levels of anti-AGG 2 + 3 were produced with 67,2% seroconversion.The frequency and nature of post-vaccination events were recorded. Incidences of all reactions to the vaccine were low (7,6%): Fever (3,2%) and excessive crying (2,4%) were the most frequency occurring minor events. The rate of neurological post-vaccination events (without sequelae) during the brief follow-up period was 2 hypotonic-hyporesponsive  episodes (8,03/1 000 doses) and 1 convulsion (4,02/1000 doses).Significant pertussis antibody levels were found in maternal and cord sera with levels in the latter frequently being higher. Three cases of pertussis occurred during the study period. Only 1 of the subjects had completed primary vaccination. In view of these findings, the need for a proper efficacy and safety study of the currently used DTP vaccine is urgently indicated in South Africa

The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis.

To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity)

Rubin H. Flocks and Colloidal Gold Treatments for Prostate Cancer

In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au198) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks’ time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments

Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements

IT-101, a cyclodextrin polymer-based nanoparticle containing camptothecin, is in clinical development for the treatment of cancer. Multiorgan pharmacokinetics and accumulation in tumor tissue of IT-101 is investigated by using PET. IT-101 is modified through the attachment of a 1,4,7,10-tetraazacyclododecane-1,4,7-Tris-acetic acid ligand to bind ^(64)Cu^(2+). This modification does not affect the particle size and minimally affects the surface charge of the resulting nanoparticles. PET data from ^(64)Cu-labeled IT-101 are used to quantify the in vivo biodistribution in mice bearing Neuro2A s.c. tumors. The ^(64)Cu-labeled IT-101 displays a biphasic plasma elimination. Approximately 8% of the injected dose is rapidly cleared as a low-molecular-weight fraction through the kidneys. The remaining material circulates in plasma with a terminal half-life of 13.3 h. Steadily increasing concentrations, up to 11% injected dose per cm^3, are observed in the tumor over 24 h, higher than any other tissue at that time. A 3-compartment model is used to determine vascular permeability and nanoparticle retention in tumors, and is able to accurately represent the experimental data. The calculated tumor vascular permeability indicates that the majority of nanoparticles stay intact in circulation and do not disassemble into individual polymer strands. A key assumption to modeling the tumor dynamics is that there is a “sink” for the nanoparticles within the tumor. Histological measurements using confocal microscopy show that IT-101 localizes within tumor cells and provides the sink in the tumor for the nanoparticles

Вторая фаза исследования по проведению недельного цикла химиотерапии с использованием паклитаксела и карбоплатина у больных с метастатическим раком мочевого пузыря

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Functional abdominal complaints in pre-school children: parental reports of health-related quality of life

Purpose The aim of this study is to assess the influence of functional abdominal complaints (FAC) on health-related quality of life in a group of Dutch pre-school children. Methods Parents of children aged up to 6.0 visiting the outpatient pediatric department, Erasmus MC-Sophia, Rotterdam, The Netherlands in the period January 2005-December 2006 for functional abdominal complaints during at least 3 months were asked to complete the Infant/Toddler Quality of life Questionnaire (ITQOL), and questions of the abdominal pain index for use by parents to report pain symptoms in pre-school children. ITQOL scale scores of children with FAC were compared against with Dutch reference values. The abdominal pain index was tested for internal consistency and test-retest reliability. Correlations between ITQOL scale scores and abdominal pain index were assessed by Spearman's rank test. Results Results are based on 81 questionnaires completed by parents of children with FAC (response rate 61%). Children had a median age of 46 months (interquartile range 27-59), 48% girls. A significant impact was observed on most aspects of quality of life, particularly for physical functioning, general development, bodily pain, temperament and moods, general health perceptions and parental emotional impact. Parents of children with functional constipation tended to report lower scores than those of children with other FAC. The abdominal pain index appeared to be valid and was significantly correlated with ITQOL scales bodily pain and general health perceptions. Conclusions A substantial lower health-related quality of life is reported in pre-school children with functional abdominal complaints, with effects on physical, emotional and parental domains. The 5-question severity index of abdominal pain appeared a valid tool and may be helpful to quickly assess the severity of abdominal pain in clinical practice

Health-related quality of life in preschool children in five health conditions

Objective: To test the responsiveness of the Infant/Toddler Quality of Life Questionnaire (ITQOL) to five health conditions. In addition, to evaluate the impact of the child's age and gender on the ITQOL domain scores. Methods: Observational study of 494 Dutch preschool-aged children with five clinical conditions and 410 healthy preschool children randomly sampled from the general population. The clinical conditions included neurofibromatosis type 1, wheezing illness, bronchiolitis, functional abdominal complaints, and burns. Health-related quality of life (HRQoL) was assessed by a mailed parent-completed ITQOL. Mean ITQOL scale scores for all conditions were compared with scores obtained from the reference sample. The effect of patient's age and gender on ITQOL scores was assessed using multi-variable regression analysis. Results: In all health conditions, substantially lower scores were found for several ITQOL scales. The conditions had a variable effect on the type of ITQOL domains and a different magnitude of effect. Scores for 'physical functioning', 'bodily pain', and 'general health perceptions' showed the greatest range. Parental impact scales were equally affected by all conditions. In addition to disease type, the child's age and gender had an impact on HRQoL. Conclusions: The five health conditions (each with a distinct clinical profile) affected the ITQOL scales differently. These results indicate that the ITQOL is sensitive to specific characteristics and symptom expression of the childhood health conditions investigated. This insight into the sensitivity of the ITQOL to health conditions with different symptom expression may help in the interpretation of HRQoL results in future applications