Odontogenic foci--possible etiology of urticaria?]

Recent studies have shown that chronic odontogenic infections could pose a risk for myocardial infarction, cerebral ischemia, and arteriosclerosis. However, the correlation between urticaria and dental infections has rarely been examined so far. Therefore, we performed a case-control study using a standardized questionnaire and examination. We investigated 66 patients suffering from an acute or chronic urticaria and 65 age- and sex-matched healthy patients as a control group. Dental status was determined by a so-called total dental index (TDI) which primarily reflects caries, periodontitis, periapical lesions, and nonvital and missing teeth. All 66 patients were referred from the department of dermatology. After their treatment in hospital, all patients received a questionnaire with questions on intensity and localization of the urticaria. The TDI of the urticaria patients was slightly better ( n=66; 2.6+/-1.98) than that of the control group ( n=65, TDI=3.3+/-1.86). Subsequently, it was determined if the urticaria had receded after dental treatment. In conclusion, chronic dental infections do not seem to correlate with an increased risk for urticaria.     

Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial.

BACKGROUND AND PURPOSE: The late morbidity of a randomized study was analyzed after a follow up of 2 years. The difference in intestinal morbidity was analyzed as a function of the treatment arm and dose volume parameters. The correlation with acute toxicity and (pre-existing) bowel complaints was investigated. PATIENTS AND METHODS: 266 T1-4N0M0 prostate cancer patients were randomized for conventional (open fields) and 3D conformal radiotherapy using beams eye view blocked fields with the same dose (66 Gy) and gross target volume-planning target volume margin (15 mm). Apart from the RTOG toxicity scoring system a patient self-assessment questionnaire was used to obtain detailed information on morbidity. RESULTS: At 2 years there is only a trend for less rectal toxicity (grade >/=1) in favor of the conformal radiotherapy (grade 1, 47 versus 40% and grade 2, 10 versus 7% for conventional and conformal radiotherapy, respectively (P=0.1). A significant relation was found between late rectal toxicity (grade >/=1) and the volume of the anus and rectum exposed to >/=90% tumor dose (TD). A highly significant relationship is observed between acute rectum and anal toxicity and late rectal toxicity. The patient self-assessment questionnaire analysis revealed that patients are most bothered by compliance related symptoms like urgency, soiling and fecal loss. In a multivariate analysis, all other variables loose significance, when anal volume exposed to >/=90% TD and pre-treatment defaecation frequency are accounted for. Late anal toxicity is low and related only to acute anal toxicity. Late bladder toxicity is related solely to pre-treatment frequency and overall urological symptoms. The incidence of grade 2 toxicity increases with a factor 2.5-4 when (stool or urine) frequency is unfavorable at the start of treatment. CONCLUSIONS: Conformal radiotherapy at the dose level of 66 Gy does not significantly decrease the incidence of rectal, anal and bladder toxicity compared to conventional radiotherapy. There is a significant relationship between acute and late toxicity and the anal volume exposed to 90% TD. Intestinal (and urological) symptoms at start have a major impact on late toxicity.     

Significance of plasma transforming growth factor-β levels in radiotherapy for non–small-cell lung cancer

PURPOSE: In dose-escalation studies of radiotherapy (RT) for non-small-cell lung cancer (NSCLC), radiation pneumonitis (RP) is the most important dose-limiting complication. Transforming growth factor-beta1 (TGF-beta1) has been reported to be associated with the incidence of RP. It has been proposed that serial measurements of plasma TGF-beta1 can be valuable to estimate the risk of RP and to decide whether additional dose-escalation can be safely applied. The aim of this study was to evaluate prospectively the time course of TGF-beta1 levels in patients irradiated for NSCLC in relation to the development of RP and dose-volume parameters. METHODS AND MATERIALS: Plasma samples were obtained in 68 patients irradiated for medically inoperable or locally advanced NSCLC (dose range, 60.8-94.5 Gy) before and 4, 6, and 18 weeks after the start of RT. Plasma TGF-beta1 levels were determined using a bioassay on the basis of TGF-beta1-induced plasminogen activator inhibitor-1 expression in mink lung cells. All patients underwent chest computed tomography scans before RT that were repeated at 18 weeks after RT. The computed tomography data were used to calculate the mean lung dose (MLD) and to score the radiation-induced radiologic changes. RP was defined on the basis of the presence of either radiographic changes or clinical symptoms. Symptomatic RP was scored according to the Common Toxicity Criteria (Grade 1 or worse) and the Southwestern Oncology Group criteria (Grade 2 or worse). Multivariate analyses were performed to investigate which factors (pre- or posttreatment TGF-beta1 level, MLD) were associated with the incidence of RP. To improve our understanding of the time course of TGF-beta1 levels, we performed a multivariate analysis to investigate which factors (pre-RT TGF-beta1 level, MLD, RP) were independently associated with the posttreatment TGF-beta1 levels. RESULTS: The pre-RT TGF-beta1 levels were increased in patients with NSCLC (median 21 ng/mL, range, 5-103 ng/mL) compared with healthy individuals (range, 4-12 ng/mL). On average, the TGF-beta1 levels normalized toward the end of treatment and remained stable until 18 weeks after RT. In 29 patients, however, TGF-beta1 was increased at the end of RT with respect to the pre-RT value. The multivariate analyses revealed that the MLD was the only variable that correlated significantly with the risk of both radiographic RP (p = 0.05) and symptomatic RP, independent of the scoring system used (p = 0.05 and 0.03 for Southwestern Oncology Group and Common Toxicity Criteria systems, respectively). The TGF-beta1 level at the end of RT was significantly associated with the MLD (p <0.001) and pre-RT TGF-beta1 level (p = 0.001). CONCLUSION: The MLD correlated significantly with the incidence of both radiographic and symptomatic RP. The results of our study did not confirm the reports that increased levels of TGF-beta1 at the end of RT are an independent additional risk factor for developing symptomatic RP. However, the TGF-beta1 level at the end of a RT was significantly associated with the MLD and the pre-RT level.     

Incorporating an improved dose-calculation algorithm in conformal radiotherapy of lung cancer: re-evaluation of dose in normal lung tissue.

BACKGROUND AND PURPOSE: The low density of lung tissue causes a reduced attenuation of photons and an increased range of secondary electrons, which is inaccurately predicted by the algorithms incorporated in some commonly available treatment planning systems (TPSs). This study evaluates the differences in dose in normal lung tissue computed using a simple and a more correct algorithm. We also studied the consequences of these differences on the dose-effect relations for radiation-induced lung injury. MATERIALS AND METHODS: The treatment plans of 68 lung cancer patients initially produced in a TPS using a calculation model that incorporates the equivalent-path length (EPL) inhomogeneity-correction algorithm, were recalculated in a TPS with the convolution-superposition (CS) algorithm. The higher accuracy of the CS algorithm is well-established. Dose distributions in lung were compared using isodoses, dose-volume histograms (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy (V20). Published dose-effect relations for local perfusion changes and radiation pneumonitis were re-evaluated. RESULTS: Evaluation of isodoses showed a consistent overestimation of the dose at the lung/tumor boundary by the EPL algorithm of about 10%. This overprediction of dose was also reflected in a consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/-1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both parameters, a strong correlation was found between the EPL and CS algorithms yielding a straightforward conversion procedure. Re-evaluation of the dose-effect relations showed that lung complications occur at a 12-14% lower dose. The values of the TD(50) parameter for local perfusion reduction and radiation pneumonitis changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively. CONCLUSIONS: A simple tissue inhomogeneity-correction algorithm like the EPL overestimates the dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20) computed using both algorithms are strongly correlated making an easy conversion feasible. Dose-effect relations should be refitted when more accurate dose data is available.     

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PURPOSE: To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. PATIENTS AND METHODS: The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). RESULTS: Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. CONCLUSION: Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.     

Peri-implant bone formation around cylindrical and conical implant systems]

BACKGROUND: The treatment of patients with early or immediately loaded dental implants has renewed interest in the behavior of osseointegration at the implant surface. Whereas it is generally accepted that peri-implant tissue formation and mineralization are dependent on the local mechanical environment in the interface zone, controversies exist concerning the impact of implant design on peri-implant bone formation. The aim of the present study was the in vivo evaluation of peri-implant bone formation by two different implant systems: cylindrical (ITI) versus conical (ILI). MATERIAL AND METHOD: A total of 60 implants (30 ITI and 30 ILI) were placed in the cranial and caudal part of the tibia of eight G?ttinger minipigs. Half of the minipigs were sacrificed at 7 days and 28 days of osseointegration. Implant-containing bone specimens were prepared for histological and ultrastructural investigations. RESULTS: Histological and scanning electron-microscopic investigations showed a direct contact of bone-like minerals over the whole implant surface from day 7 of implant/bone interaction. Whereas the ILI implant showed direct contact up to the top of the crestal bone, ITI implants demonstrated a crestally located narrow gap without ossification over the whole experimental period. CONCLUSION: Our investigations support the hypothesis of an implant design-inherent emergence and maintenance of crestal bone.     

Insights in particulate matter‐induced allergic airway inflammation: Focus on the epithelium

Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM‐induced respiratory responses. We describe the available literature on the topic including in vitro studies, findings in humans (ie observations in human cohorts, human controlled exposure and ex vivo studies) and in vivo animal studies. In brief, it has been shown that exposure to PM modulates the airway epithelium and promotes the production of several cytokines, including IL‐1, IL‐6, IL‐8, IL‐25, IL‐33, TNF‐α, TSLP and GM‐CSF. Further, we propose that PM‐induced type 2‐promoting cytokines are important mediators in the acute and aggravating effects of PM on airway inflammation. Targeting these cytokines could therefore be a new approach in the treatment of asthma.     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

Objective

To investigate the proxy‐reported health‐related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).

Methods

In this multinational, multicenter, cross‐sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.

Results

A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean ± SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 ± 10.6 versus 54.6 ± 4.0, P < 0.0001; psychosocial: 47.6 ± 8.7 versus 51.9 ± 7.5, P < 0.0001), with the physical well‐being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10‐cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.

Conclusion

We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well‐being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.     

Proviral HIV-DNA predicts viral rebound and viral setpoint after structured treatment interruptions

In HIV-1-infected patients with long-term undetectable viraemia on highly active antiretroviral treatment (HAART), we found that pre-HAART plasma viraemia and the baseline proviral DNA level were significantly associated with the viraemia setpoint during scheduled treatment interruptions. In long-term treated patients, pre-HAART viraemia may not be available, and in these circumstances proviral DNA, measured at the time of scheduled treatment interruption, can help to identify patients likely to reach a low viraemia setpoint after treatment interruption.