Hyperfractionated high-dose rate brachytherapy in the treatment of oral tongue cancer

Background

Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results.

Aim

The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily.

Patients and methods

Twenty patients with squamous cell tongue cancer were treated in the years 2001–2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8–118) since brachytherapy.

Results

The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases.

Conclusion

It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.     

Estimation of the cutoff value of vitamin D: the Dong-gu study

Background

Vitamin D plays an essential role in bone health and growth, but the optimal serum 25-hydroxyvitamin D (25(OH)D) concentration is not known. This study was performed to investigate the optimal 25(OH)D concentration in regard to parathyroid hormone (PTH) concentration in the Korean general population aged 50 years or older.

Findings

The study population consisted of 8,857 subjects (3,545 men and 5,312 women) who participated in the baseline survey of the Dong-gu study, conducted in Korea between 2007 and 2010. Serum 25(OH)D and PTH concentrations were measured by chemiluminescent microparticle immunoassay. The optimal 25(OH)D concentration was estimated by using nonlinear regression model. Our data show that PTH concentration reached a theoretical plateau at 38.2 pg/ml and corresponding 25(OH)D concentration was 21.1 ng/ml in men and PTH concentration at 42.9 pg/ml and 25(OH)D concentration at 13.8 ng/ml in women.

Conclusions

These results indicate that, for Korean general population aged 50 years or older, the optimal 25(OH)D concentration is 21.1 ng/ml in men and 13.8 ng/ml in women.     

Genetic Variants in Meiotic Program Initiation Pathway Genes Are Associated with Spermatogenic Impairment in a Han Chinese Population

Background

The meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.

Objective

To elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.

Design, Setting, and Participants

In this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×10⁶/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×10⁶/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.

Measurements

Eight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.

Results and Limitations

The genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29–4.94) and 2.92 (1.41–6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.

Conclusions

Our results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population.     

Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis

Introduction

Although it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.

Methods

We analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717). We conducted a single-marker association test and a gene-based analysis of rare variants. For meta-analysis or enrichment tests, we also used ethnically matched independent samples of Korean genome-wide association studies (GWAS) (n = 4,799) or immunochip data (n = 4,722).

Results

After stringent quality control, we analyzed 10,588 variants of 398 genes from 1,934 Korean RA case controls. We identified 13 nonsynonymous variants with nominal association in single-variant association tests. In a meta-analysis, we did not find any novel variant with genome-wide significance for RA risk. Using a gene-based approach, we identified 17 genes with nominal burden signals. Among them, VSTM1 showed the greatest association with RA (P = 7.80 × 10⁻⁴). In the enrichment test using Korean GWAS, although the significant signal appeared to be driven by total genic variants, we found no evidence for enriched association of coding variants only with RA.

Conclusions

We were unable to identify rare coding variants with large effect to explain the missing heritability for RA in the current targeted resequencing study. Our study raises skepticism about exon sequencing of targeted genes for complex diseases like RA.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0447-7) contains supplementary material, which is available to authorized users.     

Vacuum-assisted core-needle biopsy as a diagnostic and therapeutic method in lesions radiologically suspicious of breast fibroadenoma

Background

Treatment of breast fibroadenoma remains a subject of clinical discussion. Recommended methods include clinical observation or surgical excision of the lesion. The procedure involves hospitalisation and anaesthesia, leaving a scar on the breast.

Aim

The aim of this study was to present the Centre''s experience in removing lesions radiologically suspicious of fibroadenoma by means of an ultrasound-guided vacuum-assisted core-needle biopsy as an alternative to a classical surgery.

Materials and methods

Between March 2007 and April 2010, 196 ultrasound-guided vacuum-assisted biopsies were performed in the Mammotome Biopsy Laboratory of the 1st Surgical Oncology and General Surgery Department at the Greater Poland Cancer Centre in Poznań. The procedure was delivered to female patients aged 17–91 years (mean 40.8, median 39). Qualified for removal were ultrasound identified lesions described as fibroadenomas.

Results

The average size of excised lesions according to pre-biopsy ultrasound image was 13.53 ± 8.92 mm (median 11 mm, range 4–60 mm). In 184 cases (93.9%), benign lesions were found in the final histopathologic examination. Pre-cancer lesions were found in 10 cases, and invasive lesions in two cases. Overall, after follow-up ultrasound examination, four patients were qualified for subsequent surgical resection of lesions that had been left behind.

Conclusion

Vacuum core-needle biopsy is an effective tool enabling removal of breast fibroadenomas. It combines features of a lesion resection and histopathologic material collection providing an access with minimum invasiveness.     

A powerful tool for genome analysis in maize: development and evaluation of the high density 600 k SNP genotyping array

Background

High density genotyping data are indispensable for genomic analyses of complex traits in animal and crop species. Maize is one of the most important crop plants worldwide, however a high density SNP genotyping array for analysis of its large and highly dynamic genome was not available so far.

Results

We developed a high density maize SNP array composed of 616,201 variants (SNPs and small indels). Initially, 57 M variants were discovered by sequencing 30 representative temperate maize lines and then stringently filtered for sequence quality scores and predicted conversion performance on the array resulting in the selection of 1.2 M polymorphic variants assayed on two screening arrays. To identify high-confidence variants, 285 DNA samples from a broad genetic diversity panel of worldwide maize lines including the samples used for sequencing, important founder lines for European maize breeding, hybrids, and proprietary samples with European, US, semi-tropical, and tropical origin were used for experimental validation. We selected 616 k variants according to their performance during validation, support of genotype calls through sequencing data, and physical distribution for further analysis and for the design of the commercially available Affymetrix® Axiom® Maize Genotyping Array. This array is composed of 609,442 SNPs and 6,759 indels. Among these are 116,224 variants in coding regions and 45,655 SNPs of the Illumina® MaizeSNP50 BeadChip for study comparison. In a subset of 45,974 variants, apart from the target SNP additional off-target variants are detected, which show only a minor bias towards intermediate allele frequencies. We performed principal coordinate and admixture analyses to determine the ability of the array to detect and resolve population structure and investigated the extent of LD within a worldwide validation panel.

Conclusions

The high density Affymetrix® Axiom® Maize Genotyping Array is optimized for European and American temperate maize and was developed based on a diverse sample panel by applying stringent quality filter criteria to ensure its suitability for a broad range of applications. With 600 k variants it is the largest currently publically available genotyping array in crop species.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-823) contains supplementary material, which is available to authorized users.     

The COL5A1 genotype is associated with range of motion

[Purpose]

The aim of our study was to investigate the association between COL5A1 genotype and Range of Motion as measured by the passive straight leg raise (SLR) and whole body join laxity (WBJL) in Asian population.

[Methods]

One hundred and seventy seven participants including Korean and Japanese college students (male = 109, female = 68) participated in the study. Each subject performed the passive straight leg raise and whole body join laxity test. Genotyping for the COL5A1 (rs 12722) polymorphism was performed using the TaqMan approach. The COL5A1 genotype exhibited a Hardy-Weinberg equilibrium distribution in our population.

[Results]

The physical parameters including height, weight, and BMI were higher in < 90° group than > 90° group. The SLR exhibited significant difference among the COL5A1 group. However, the WBJL did not differ significantly among the COL5A1 genotype, but significant difference was seen in CC genotype when compared to CT (2.99 ± 1.72) or TT (2.70 ± 1.52) genotype.

[Conclusion]

We concluded that COL5A1 gene polymorphism is associated with increased SLR ROM in Asian population.     

A Low Selenium Level Is Associated with Lung and Laryngeal Cancers

Purpose

It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls.

Methods

We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype.

Results

Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers.

Conclusion

A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.     

Radio-chemotherapy in anal cancer: Institutional experience at a large radiation oncology center in Chile

Aim

In this article the aim is to provide a concise narrative review and inform the institutional experience at a referral center in Chile with the use of radio-chemotherapy in anal cancer.

Background

Cancer of the anus and anal canal is mainly a loco-regional disease. For years the standard of care has been concomitant radio-chemotherapy, which permits organ preservation and better local control than alternative surgical procedures.

Materials and methods

A retrospective analysis of 44 patients treated between 2002 and 2010 was performed. Local recurrence, distant recurrence and overall survival were analyzed with the Kaplan–Meier method. Relevant groups where compared with the log-rank test and univariate analysis were done with the Cox proportional hazards model.

Results

Median follow-up of the cohort was 56 months, with a minimum follow-up of at least 24 months. There was a significant difference between clinical stages in disease free survival (log-rank trend p < 0.001), and a significant difference in overall survival (OS) when comparing clinical stages that were grouped in stage I–IIIa and IIIB (log-rank p = 0.001). On univariate analysis, age older than 60, having received full treatment and dose above 45 Gy were all significantly related to OS (p < 0.05). An overall survival of 45% and disease free survival of 45% at 5 years were found in our series.

Conclusions

Our findings show that results at the Instituto de Radiomedicina in Chile are comparable to published literature. Dismal results in stage IIIb cases indicate much work remains in therapies to achieve loco-regional control in locally advanced cases.     

Evaluation of Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2) as a positional candidate gene for variation in estimated Glomerular Filtration Rate (eGFR) in Mexican American participants of San Antonio Family Heart Study

Background

The estimated glomerular filtration rate (eGFR) is a well-known measure of kidney function and is commonly used for the diagnosis and management of patients with chronic kidney disease. The inter-individual variation in eGFR has significant genetic component. However, the identification of underlying genetic susceptibility variants has been challenging. In an attempt to identify and characterize susceptibility genetic variant(s) we previously identified the strongest evidence for linkage of eGFR occurring on chromosome 9q21 in the Mexican American participants of San Antonio Family Heart Study (SAFHS). The objective of the present study was to examine whether the common genetic variants in Neurotrophic Tyrosine Receptor Kinase 2 (NTRK2), a positional candidate gene on 9q21, contribute to variation in eGFR.

Results

Twelve tagging single nucleotide polymorphisms (SNPs) across the NTRK2 gene region were selected (r2 ≥ 0.80, minor allele frequency of ≥ 0.05) from the Hapmap database. SNPs were genotyped by TaqMan assay in the 848 Mexican American subjects participated in the SAFHS. Association analysis between the genotypes and eGFR (estimated by the Modification of Diet in Renal Disease equation) were performed by measured genotype approach as implemented in the program SOLAR. Of the 12 common genetic variants examined, the rs1036915 (located in 3′UTR) and rs1187274 (located in intron-14), present in perfect linkage disequilibrium, exhibited an association (P = 0.017) with eGFR after accounting for the effects of age, sex, diabetes, diabetes duration, systolic blood pressure and blood pressure medication. The carriers of minor allele of rs1036915 (G; 38%) had increased eGFR (104 ± 25 ml/min/1.73 m²) in comparison to the carriers of major allele A (98 ± 25 ml/min/1.73 m²).

Conclusion

Together, our results suggest for the first time that the genetic variants in NTRK2 may regulate eGFR.     

Estimation of body size and growth patterns in Korean boys

Background

Anthropometric surveys devised by each country attempt to fulfill the requirements of the manufacturers, designers, and human welfare device production, providing them with data and tools and allowing them to face both the internal and export markets. To this end, national anthropometric data collections and comparisons including three-dimensional information, together with comparison of these data among countries, are conducted at both the domestic and global levels.

Methods

The anthropometric data of the Korean population measured in 2013 (Korean Agency for Technology and Standard (KATS) 2013 data) and the data collected from 2010 (KATS 2010 data) that was conducted on 710 males between the ages of 13 and 18 years were analyzed in this section to obtain information on Korean boy’s physical features and growth.

Results

The mean height increased about 5 cm from 13 to 14 years which shows the early fast maturing somatotype. Also, the mean height of boys aged from 15 to 16 increased about 1 to 2 cm. For the results of body proportion rate index against height, they show 0.93, 0.81, 0.38, 0.99, and 0.26 times the height in eye height, shoulder height, fingertip height, and span and maximum shoulder breadth, respectively, in 16-year-old boys. For the body mass index, the weight is increased from the age of 16 years.

Conclusions

There are several studies that cover growth features of the entire range from birth to maturity, and they have reported the comparison of the growth patterns among Europeans. Even though such researches have been made, as for the industry, the human modeling tools based on the anthropometric data and morphological features that cover all the countries should be developed for well-fit garments and other human-oriented design process.     

Volumetric modulated arc therapy for prostate cancer patients with hip prosthesis

Aim

To study the use of RapidArc techniques in the treatment of prostate cancer patients with hip prosthesis.

Background

An important aspect of treatment planning is to achieve dose homogeneity inside the planning target volume (PTV). Especially for those patients presenting with hip prosthesis, it becomes a challenging task to achieve dose uniformity inside the PTV.

Materials and methods

Five prostate patients presenting with hip prosthesis who had undergone radical radiotherapy were selected for this study. Depending on the composition of prosthesis, a predefined set of Hounsfield values were assigned to each study set. RapidArc plans were generated on an Eclipse treatment planning system. Two arcs that include clockwise and counter-clockwise arcs were used in all these cases. To avoid beams passing through the prosthesis, a simple structure was defined around it with 1 cm margin and a strict dose constraint applied to the block during VMAT optimization.

Results

The mean D2/D98 ratio of PTV for all the patients was 1.06 ± 0.01. The mean percentage rectum volume receiving 50 Gy, 60 Gy, 70 Gy and 75 Gy for all the patients were 33.1 ± 5.9, 21.7 ± 5.5, 13.8 ± 4.4 and 9.5 ± 3.0, respectively.

Conclusions

This study shows that using a double arc RapidArc technique is a simple and effective treatment method of treating prostate cancer in patients presenting with a hip prosthesis. The definition of a beam avoidance structure encompassing the prosthesis and applying strict dose constraints to it reduces the beam contribution to the prosthesis     

Role of radiation therapy in the multidisciplinary management of Ewing's Sarcoma of bone in pediatric patients: An effective treatment for local control

Background

Radiotherapy (RT) plays an important role in the multidisciplinary management of Ewing''s Sarcoma (ES), especially in unresectable cases.

Aim

Assessment of efficacy of RT in terms of local control in pediatric patients with primary ES of bone.

Materials and methods

Thirty-six patients younger than 17 years old with ES treated with combined RT and chemotherapy with (N = 14) or without (N = 22) prior surgery from 1981 to 2008 were retrospectively reviewed. Since 1995, they were all treated according to the Spanish Society of Pediatric Oncology protocol (55.5% cases). Those patients received vincristine, ifosfamide, doxorubicin and etoposide. The TNM classification was as follows: 17 T1, 18 T2 and 1 T3; 36 N0; 29 M0, 5 M1a and 2 M1b. Analysis was stratified by treatment: definitive RT or pre/postoperative RT.

Results

The 36 patients (21 male; 15 female) had a median age of 10 years (range 2–17 years). Median follow-up of living patients was 105 months. The 2-year local control (LC) rate for all patients was 88%. Five-year LC rates for patients treated with definitive and pre/postoperative RT were 91% and 86%, respectively. Two-year overall survival and disease-free survival rates for all patients were 68% and 66%, respectively. Low phosphatase alkaline levels and local and distant recurrences were significantly predictive of worse prognosis (P = 0.021, P = 0.011, P = 0.007, respectively).

Conclusion

Radiotherapy with and without surgery is a highly effective local treatment option in the multidisciplinary management of ES in pediatric patients.     

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology,Rheumatoid Arthritis cohort study

Introduction

Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients.

Methods

DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years).

Results

Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P = 8.1 × 10^-5). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval) = 2.52 (1.05-6.05), P = 0.039).

Conclusions

A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.     

A genome-wide association study of limb bone length using a Large White?×?Minzhu intercross population

Background

In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length.

Methods

A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values.

Results

A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively.

Conclusions

Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-014-0056-6) contains supplementary material, which is available to authorized users.     

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications

Background

Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry.

Aim

The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application.

Material and methods

A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with ⁶⁰Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters.

Results

The results showed the dose sensitivity of ΔN_CT (H) = 0.282 ± 0.018 (H Gy⁻¹) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kV_p and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data.

Conclusion

According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.     

Mannose Binding Lectin and Susceptibility to Rheumatoid Arthritis in Brazilian Patients and Their Relatives

Introduction

Rheumatoid arthritis (RA) is a commonly occurring systemic inflammatory auto immune disease and is believed to be associated with genetic factors. The innate immune complement protein Mannose binding lectin (MBL) and their MBL2 genetic variants are associated with different infectious and autoimmune diseases.

Methods

In a Brazilian cohort, we aim to associate the functional role of circulating MBL serum levels and MBL2 variants in clinically classified patients (n = 196) with rheumatoid arthritis including their relatives (n = 200) and ethnicity matched healthy controls (n = 200). MBL serum levels were measured by ELISA and functional MBL2 variants were genotyped by direct sequencing.

Results

The exon1+54 MBL2*B variant was significantly associated with an increased risk and the reconstructed haplotype MBL2*LYPB was associated with RA susceptibility. Circulating serum MBL levels were observed significantly lower in RA patients compared to their relatives and controls. No significant contribution of MBL levels were observed with respect to functional class, age at disease onset, disease duration and/or other clinical parameters such as nodules, secondary Sjögren syndrome, anti-CCP and rheumatoid factor. Differential distribution of serum MBL levels with functional MBL2 variants was observed in respective RA patients and their relatives.

Conclusions

Our results suggest MBL levels as a possible marker for RA susceptibility in a Brazilian population.     

Unintended irradiation of internal mammary chain – Is that enough?

Aim

To evaluate the unintentional coverage of the internal mammary chain (IMC) with tangential fields irradiation to the breast, and its relation with the type of surgery employed.

Background

The dose distribution in regions adjacent to the treatment targets (mammary gland or chest wall), with incidental irradiation of the IMC, could translate into clinical benefit, due to the proximity of these regions.

Materials and methods

One hundred and twelve consecutive conformal radiotherapy plans were correlating the average dose to the IMC with the type of surgery employed, the extent of disease and the irradiation techniques.

Results

The mean doses to IMC after modified radical mastectomy (MRM), modified radical mastectomy with immediate reconstruction (MRM + R), and breast conservative surgery (BCS) were 30.34 Gy, 30.26 Gy, and 18.67 Gy, respectively. Significant differences were identified between patients who underwent MRM or MRM + R over BCS (p = 0.01 and 0.003, respectively), but not between MRM and MRM + R (p = 0.88). Mean doses to IMC were greater in patients with T3–T4 tumors when compared with more initial stages (≤T2) (p = 0.0096). The lymph node involvement also correlated with higher average doses to IMC (node positive: 26.1 Gy × node negative: 17.8 Gy, p = 0.0017).

Conclusions

The moderate dose level to the IMC in the unintentional irradiation scenario seems to be insufficient to treat the subclinical disease, although it could have an impact in patients undergoing mastectomy.     

Pattern of Pseudoexfoliation Deposits on the Lens and Their Clinical Correlation- Clinical Study and Review of Literature

Purpose

To study the clinical correlates of pattern of deposits over the lens in patients with pseudoexfoliation syndrome (PXF) or pseudoexfoliation glaucoma.

Methods

This retrospective observational study screened 346 patients with PXF seen in glaucoma clinic of a tertiary hospital from 2011–2013. Details like pattern of deposits, location on the lens surface and pupillary abnormalities in slit lamp photographs and their correlation with clinical and demographic variables, were analysed.

Results

A total of 84 eyes of 42 patients with bilateral PXF were included for the study. Glaucoma was seen in 30 eyes with baseline IOP of 24+3.8 mm Hg. Comparing the type of deposits, namely classical (n = 39 eyes), radial pigmentary (RP) form (n = 39 eyes) and combined classical and radial pigmentary (CR) forms (n = 6 eyes) of deposits, pupillary ruff atrophy was common in all forms while poor dilatation was rare in the RP type (n = 5 vs n = 25 in classical forms, p<0.001). Mean deviation (MD) was worse in the classical and CR form as compared to RP type with the latter presenting much earlier, 43±3.2 years vs 48±4.1 years in CR and 56±5.7 years in classical form, p<0.001. The baseline IOP in the RP group (18±2.3 mm Hg) was significantly lower than the other two forms (CR 20±3.2 mm Hg, classical 28±2.3 mm Hg), p<0.001, with only 2 eyes on anti-glaucoma drugs at presentation.

Conclusion

Pattern of exfoliation deposits may indicate the stage and severity of the disease process in evolution with the RP representing an earlier/less severe form of pseudoexfoliation syndrome.