Humoral immune response to active root resorption with a murine model

A depression in autoantibody titers to tooth root antigens has been shown to coincide with active root resorption in the dog. Since a murine model would facilitate immunologic studies of root resorption because of the availability of syngeneic and immunodeficient strains, the objectives of this study were to develop a quantitative mouse model for root resorption and to determine if a similar drop in tooth root autoantibodies coincides with active root resorption in this species. Uniform areas of necrosis were created in the periodontal ligaments of lower incisors of 36 male Swiss albino mice by inserting a cryoprobe through a skin incision (-80 degrees C; 5 minutes). Contralateral incisors served as controls. At 0, 3, 5, 7, 10, 14, and 21 days; six mice were killed, and blood and incisors were collected. Relative surface areas of root resorption were quantified with micrographs taken at a standardized position, tilt, and magnification with a scanning electron microscope. Serum autoantibody titers were determined with an enzyme-linked immune sorbent assay with antigen prepared from a 5 mol/L guanidine-HCl-EDTA (pH 5.0) extract of incisor roots that were harvested from syngeneic mice. ANOVA and the paired Student t test were used to compare data at the various time points. No root resorption was evident on control teeth. Localized lesions on treated teeth were found to be of significant size between 7 and 14 days (p less than 0.05), but most of these erupted into the mouth by 21 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Loss of heterozygosity of APC and MCC genes in oral squamous cell carcinomas in Taiwan

Loss of heterozygosity (LOH) at adenomatous polyposis coii (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC. Homozygous deletion of MCC was detected in one patient. Of the 37 patients. 29 were informative at APC or MCC or both: LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location. TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play role in the pathogenesis of human oral SCCs in Taiwan.     

Hyperthermia treatment planning for cervical cancer patients based on electrical conductivity tissue properties acquired in vivo with EPT at 3 T MRI

Introduction The reliability of hyperthermia treatment planning (HTP) is strongly dependent on the accuracy of the electric properties of each tissue. The values currently used are mostly based on ex vivo measurements. In this study, in vivo conductivity of human muscle, bladder content and cervical tumours, acquired with magnetic resonance-based electric properties tomography (MR-EPT), are exploited to investigate the effect on HTP for cervical cancer patients. Methods Temperature-based optimisation of five different patients was performed using literature-based conductivity values yielding certain antenna settings, which are then used to compute the temperature distribution of the patient models with EPT-based conductivity values. Furthermore, the effects of altered bladder and muscle conductivity were studied separately. Finally, the temperature-based optimisation was performed with patient models based on EPT conductivity values. Results The tumour temperatures for all EPT-based dielectric patient models were lower compared to the optimal tumour temperatures based on literature values. The largest deviation was observed for patient 1 with ΔT90 = ?1.37?°C. A negative impact was also observed when the treatment was optimised based on the EPT values. For four patients ΔT90 was less than 0.6?°C; for one patient it was 1.5?°C. Conclusions Electric conductivity values acquired by EPT are higher than commonly used from literature. This difference has a substantial impact on cervical tumour temperatures achieved during hyperthermia. A higher conductivity in the bladder and in the muscle tissue surrounding the tumour leads to higher power dissipation in the bladder and muscle, and therefore to lower tumour temperatures.     

The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study

Background

It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology.

Methods

The health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test.

Results

For women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years.

Conclusion

For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines.

     

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis

AimsAt diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease.Materials and methodsThis retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors.ResultsForty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS.ConclusionsDefinitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.     

Stability of soluble adhesion molecules, selectins, and C-reactive protein at various temperatures: implications for epidemiological and large-scale clinical studies

BACKGROUND: We assessed the impact of sample storage conditions on soluble vascular cell adhesion molecules (sVCAM), soluble intracellular adhesion molecules (sICAM-1), soluble (s)E-selectin, C-reactive protein (CRP), and sP-selectin. METHODS: Markers were measured by ELISA in venous blood from 10 healthy volunteers on aliquots stored as plasma or whole blood at 4, 21, or 30 degrees C for 1-5 days and after 1-5 freeze-thaw cycles. We compared results on these samples to results for samples processed immediately and stored at -80 degrees C. Statistical models assessed time-related effects and effects of postprocessing conditions. RESULTS: Using an upper limit of 10% variation from baseline with P >0.05, we found that stability duration in plasma was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 1 day at 30 degrees C. Stability duration in whole blood was 5 days for sVCAM-1 and sICAM-1 and at least 2 days for sE-selectin at 4, 21, and 30 degrees C and 5 days for CRP at 4 and 21 degrees C and 2 days at 30 degrees C. sP-selectin was not stable in plasma or whole blood. sICAM-1, sVCAM-1, CRP, and sE-selectin were stable after 5 freeze-thaw cycles. CONCLUSIONS: sVCAM-1, sICAM-1, and CRP are stable in plasma or whole blood at 4 and 21 degrees C for at least 3 days and sE-selectin for 2 days. sP-selectin is not stable and therefore requires immediate assay.     

Multivariate Analysis of Health-related Quality of Life in Donors After Live Kidney Donation

Background

Live-kidney donation has a low mortality rate. Evidence suggests that live-kidney donors experience a quality of life (QoL) comparable to or even superior to that of the general population. There is limited information on factors associated with a decrease in QoL in particular for baseline factors, which would improve information to the donor, donor selection, and convalescence.

Bile Acid Synthesis in Man: Metabolism of 7α-Hydroxycholesterol-14C and 26-Hydroxycholesterol-3H

The pathways of bile acid synthesis in man were evaluated by studying the metabolism of 7alpha-hydroxycholesterol-4-(14)C and 26-hydroxycholesterol-16, 22-(3)H administered parenterally to individuals requiring external biliary drainage. Techniques for the identification of metabolites were thin-layer chromatography, column chromatography, gas-liquid chromatography with stream splitting, and crystallization to constant specific activity. It was found that both compounds were rapidly metabolized to bile acids and excreted in bile. Of the total radioactivity recovered in bile as bile acids, 87% of the 26-hydroxycholesterol-(3)H and 90% of the 7alpha-hydroxycholesterol-(14)C was found to be metabolized to both chenodeoxycholate and cholate. Compared to 7alpha-hydroxycholesterol, a greater proportion of 26-hydroxycholesterol was found to be metabolized to chenodeoxycholate.These findings indicate that both 7alpha-hydroxycholesterol and 26-hydroxycholesterol can be intermediates in the metabolism of cholesterol to bile acids in man. The observation that conversion to cholate takes place less readily after C-26 hydroxylation is consistent with previous findings in other species.