Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost

PURPOSE: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. METHODS AND MATERIALS: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. RESULTS: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. CONCLUSION: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women.     

Assessing the introduction of universal varicella vaccination in the Netherlands

Although varicella is seen as a benign disease in the Netherlands, about 40,000 visits to a general practitioner (GP) are made, over 200 hospital admission occur, and 2.3 persons die on average each year. Most of this burden of disease can be prevented by universal varicella childhood vaccination. Ten years after the introduction of the single-shot, single-component varicella childhood vaccination in the USA, a major reduction in hospitalization, mortality, and burden of disease has been reported. Using our recently vaccine evaluation model for the introduction of a new vaccine in our national immunization program, we have analyzed the feasibility of universal varicella vaccination by replacing the measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV) vaccine. After structuring and reviewing the available data, two major points of uncertainty remain: (1) the influence of universal childhood vaccination on the incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch situation. Despite these uncertainties it is clear that universal childhood vaccination will prevent most of the varicella related GP-visits, hospitalizations, and deaths.     

A CX3CR1 genotype associated with retinal vasculitis in patients in the United Kingdom

PURPOSE: To investigate whether polymorphisms in the gene encoding the chemokine receptor CX3CR1, which has been linked to changes in functional ligand-binding activity, are associated with retinal vasculitis (RV) in a cohort of patients in the United Kingdom. METHODS: DNA was prepared from whole blood of 126 patients with RV and 95 healthy individuals by a standard salting-out procedure. Two polymorphisms, V249I and T280M, were analyzed by multiplex polymerase chain reaction-sequence-specific primers (PCR-SSPs). RESULTS: There was no significant difference between the prevalence of V249 or I249 variants in patients with RV or in control subjects. By contrast, the 280M variant was significantly raised in patients compared with control subjects (P=0.01), the IV/MT haplotype was also more prevalent in patients with RV than in control subjects (P=0.006), and the I249/M280 haplotype was associated with retinal vasculitis (P=0.01). The 280M variant was significantly associated with the nonischemic form of RV compared with healthy control subjects (P=0.009). CONCLUSIONS: Polymorphisms related to a functional decrease in ligand binding activity of CX3CR1 are associated with disease in U.K. patients with retinal vasculitis. CX3CR1 and its ligand CX3CL1 have been implicated in leukocyte adhesion and neuronal protection. Changes in the activity of this interaction may have a role in the pathogenesis of RV.     

Theoretical model and Rasch analysis to develop a revised Foot Function Index

BACKGROUND: The Foot Function Index (FFI) is a widely used self-reported measure of health-related foot function. Several areas have been identified for potential improvement, and this study responds to such criticisms. The objectives of this study were to: (1) develop a theoretical model of foot functioning, (2) develop a revised FFI (FFI-R), and (3) field-test the FFI-R. METHODS: A literature review was conducted to develop the theoretical model. The FFI-R items were developed from the original 23 FFI items, and more items were added as a result of the literature review. A focus group discussion with clinicians and pilot interviews with patients resulted in a final draft of the FFI-R. This draft consisted of four subscales and comprised 68 items with a six-point response scale. The FFI-R was field tested on 92 patients in the podiatry clinic of a Veterans Administration Hospital in the Midwest. Psychometric analyses were conducted with modern item response theory (IRT) methods. RESULTS: A theoretical model of foot functioning was developed. The FFI-R response scale was revised from six to five categories since confusion was found between categories 4 and 5. Rasch analyses indicated a person reliability of 0.96 and item reliability of 0.93. The subscale reliability of pain and stiffness, psychosocial, and disability were all >0.80; the exception was assistive devices (>0.50). Construct validity of FFI-R was supported based on the correlation of 50-ft walk time with an FFI-R total of 0.306, p = 0.018, N = 59. Rasch analyses indicated several items with poor fit statistics and a short form with 34 items was developed. CONCLUSION: The FFI was revised, and new items were added to compose the FFI-R. The chief theoretical change was adding a psychosocial scale. Both long and short forms had very good psychometric properties.     

Subsequent dental research output of South African division of the IADR Colgate Prize entrants

This study recorded the research output of all participants for the IADR (South African Division; SA) Colgate Prize for 1967-2004 to establish whether, in their later careers, prize winners had a greater research output than runners-up. Using a list of all entrants, each individual was classified as winner or runner-up and by gender, race, and research field of presentation. The publication output for each individual was obtained from PubMed. A Poisson regression set at P < 0.05 compared publication numbers between winners and runners-up. There were two groups of entrants: 101 participated once, and twenty-two participated twice or thrice. Winners had significantly more publications than runners-up, more so for the multiple entrants (winners 27.5+/-22.4; runners-up 16.5+/-25.5) than single entrants (winners 16.0+/-40.8; runners-up 12.0+/-27.7). The number of individuals participating in the Colgate Prize has declined, but representivity for race and gender is improving. This is the first study to establish that SA IADR Colgate Prize participants fulfil the long-term IADR ideal of research promotion among young investigators.     

Health problems of persons with spinal cord injury living in the Netherlands

Purpose. To investigate the prevalence of health problems among persons with spinal cord injury (SCI) living in the Netherlands, to identify the problems experienced as most important, and to analyse the experienced impact of these most important problems on daily activities and social life.

Method. Postal survey among all members of the Dutch Association of Patients with SCI. The questionnaire focused on 26 health problems: 13 secondary impairments, 8 problems of daily living and 5 psychosocial problems.

Results. The respondents (response rate 45.5%, 454 persons) experienced an average of 8 health problems. The most frequently occurring problems regarded bladder and bowel regulation, spasms, pain, oedema and sexuality. Except for oedema, these problems were also most often cited as the most important. The most disabling condition for both daily and social activities was pain. Few significant relationships were found between the prevalence of health problems and the level, completeness and duration of the injury or gender.

Conclusion. Persons with SCI living in the community experience many health problems and limitations in daily activities and social life due to these problems. The occurrence of these problems does not diminish with increasing time after injury. This strongly emphasises the need for follow-up care.     

Dysregulation of Rho GTPases in the αPix/Arhgef6 mouse model of X-linked intellectual disability is paralleled by impaired structural and synaptic plasticity and cognitive deficits

Mutations in the ARHGEF6 gene, encoding the guanine nucleotide exchange factor αPIX/Cool-2 for the Rho GTPases Rac1 and Cdc42, cause X-linked intellectual disability (ID) in humans. We show here that αPix/Arhgef6 is primarily expressed in neuropil regions of the hippocampus. To study the role of αPix/Arhgef6 in neuronal development and plasticity and gain insight into the pathogenic mechanisms underlying ID, we generated αPix/Arhgef6-deficient mice. Gross brain structure in these mice appeared to be normal; however, analysis of Golgi-Cox-stained pyramidal neurons revealed an increase in both dendritic length and spine density in the hippocampus, accompanied by an overall loss in spine synapses. Early-phase long-term potentiation was reduced and long-term depression was increased in the CA1 hippocampal area of αPix/Arhgef6-deficient animals. Knockout animals exhibited impaired spatial and complex learning and less behavioral control in mildly stressful situations, suggesting that this model mimics the human ID phenotype. The structural and electrophysiological alterations in the hippocampus were accompanied by a significant reduction in active Rac1 and Cdc42, but not RhoA. In conclusion, we suggest that imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in αPix/Arhgef6 knockout mice.