Use of D11S2179 and D11S1343 as markers for prenatal diagnosis of ataxia telangiectasia in Iranian patients

Ataxia telangiectasia (AT) is an autosomal recessive disorder with an estimated prevalence of 1/40,000 to 1/100,000 in reported populations. There is a 25% possibility for having an affected child when parents are carriers for the ATM gene mutation. There is no cure available for this disease and prenatal testing is strongly recommended for prevention of this disease. Although the preferred method is the direct mutation analysis of the ATM gene, the large size of the ATM gene with 63 exons and the large number of possible mutations in patients considerably limit efficiency of mutation analysis as a diagnostic choice. Indirect method is a better tool when parents are not carriers of founder mutation and pass different mutations to their children. Indirect molecular diagnosis using ATM-related molecular markers facilitates prenatal diagnosis of AT children. In this study, four molecular markers: D11S2179, D11S1787, D11S535, D11S1343 are genotyped in 19 unrelated families from different regions of Iran. Those markers are amplified using extracted sequence primers from the Gene Bank with their described PCR conditions. Amplified products were separated using denaturing PAGE gels, and data were analyzed to detect their pattern of inheritance in each family. In all families, segregation of alleles was according to Mendelian inheritance, and affected chromosomes were distinguishable from unaffected ones. All carriers and affected patients were diagnosed accurately. Thus, this method is effectively useful in prenatal diagnosis of AT.     

Low molecular weight heparin improves peritoneal ultrafiltration and blocks complement and coagulation.

OBJECTIVES: Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. DESIGN: Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. RESULTS: Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. CONCLUSIONS: The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.     

Development of a physical shoulder simulator for the training of basic arthroscopic skills

Background

Orthopaedic training programs are incorporating arthroscopic simulations into their residency curricula. There is a need for a physical shoulder simulator that accommodates lateral decubitus and beach chair positions, has realistic anatomy, allows for an objective measure of performance and provides feedback to trainees.

Methods

A physical shoulder simulator was developed for training basic arthroscopic skills. Sensors were embedded in the simulator to provide a means to assess performance. Subjects of varying skill level were invited to use the simulator and their performance was objectively assessed.

Results

Novice subjects improved their performance after practice with the simulator. A survey completed by experts recognized the simulator as a valuable tool for training basic arthroscopic skills.

Conclusions

The physical shoulder simulator helps train novices in basic arthroscopic skills and provides objective measures of performance. By using the physical shoulder simulator, residents could improve their basic arthroscopic skills, resulting in improved patient safety.     

Coping strategy in infertile couples undergoing assisted reproduction treatment

Objective

The purpose of the study was to determine whether infertility is associated with coping processes and is there a difference between infertile women and men in the use of coping strategies?

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study

BACKGROUND:

A study was undertaken to use the 2‐tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3‐tier system and determine the progression‐free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158.

METHODS:

The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2‐tier system. The association of tumor grade with PFS and OS was assessed.

RESULTS:

Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2‐tier system, patients with low‐grade versus high‐grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high‐grade versus low‐grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17‐5.04; P = .02).

CONCLUSIONS:

Women with high‐grade versus low‐grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2‐tier grading system provides a simple yet precise framework for predicting clinical outcomes. Cancer 2012;118: 3087–94. © 2011 American Cancer Society.     

Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma

B-cell lymphomas express tumor-specific immunoglobulin, the variable regions of which [idiotype (Id)] can serve as a target for active immunotherapy.Promising results have been obtained in clinical studies of Id vaccination using Id proteins.However, Id protein is laborious and time-consuming to produce. DNA vaccination is an attractive alternative for delivering Id vaccines, because Id DNA can be rapidly isolated by PCR techniques. DNA coding for lymphoma Id can provide protective immunity in murine models. In the present study, we performed a Phase I/II clinical trial to study the safety and immunogenicity of naked DNA Id vaccines in 12 patients with follicular B-cell lymphoma. The DNA encoded a chimeric immunoglobulin molecule containing variable heavy and light chain immunoglobulin sequences derived from each patient's tumor, linked to the IgG2a and kappa mouse immunoglobulin (MsIg) heavy- and light-chain constant regions chains, respectively. Patients in remission after chemotherapy received three monthly i.m. injections of the DNA in three dose escalation cohorts of four patients each (200, 600, and 1800 micro g). After vaccination, 7 of 12 patients mounted either humoral (n = 4) or T-cell-proliferative (n = 4) responses to the MsIg component of the vaccine. In one patient, a T-cell response specific to autologous Id was also measured. Anti-Id antibodies were not detectable in any patient. A second series of vaccinations was then administered using a needle-free injection device (Biojector) to deliver 1800 micro g both i.m. and intradermally (i.d.); 9 of 12 patients had humoral (n = 6) and/or T-cell (n = 4) responses to MsIg. Six of 12 patients exhibited humoral and/or T-cell anti-Id responses; yet, these were cross-reactive with Id proteins from other patient's tumors. Subsequently, a third series of vaccinations was carried out using 500 micro g of human granulocyte-macrophage colony-stimulating factor DNA mixed with 1800 micro g of Id DNA. The proportion of patients responding to MsIg remained essentially unchanged (8 of 12), although humoral or T-cell responses were boosted in some cases. Throughout the study, no significant side effects or toxicities were observed. Despite the modest level of antitumor immune responses in this study, DNA vaccine technology retains potential advantages in developing anti-Id immunotherapies. Additional studies are warranted to optimize vaccine dose, routes of administration, vector designs, and prime-boost strategies. These results will help guide the design of such future DNA vaccine trials.     

The Effects of UVB and Vitamin D on Decreasing Risk of Colorectal Cancer Incidence and Mortality: A Review of the Epidemiology,Clinical Trials,and Mechanisms

The solar ultraviolet B–vitamin D-cancer hypothesis was first suggested in 1980 based on a geographical ecological study. Since then, several ecological and observational studies, as well as researches of mechanisms have supported the hypothesis. Also, the association between vitamin D condition and cancer risk has been assessed in a number of epidemiologic studies, while data from interventional studies remain scant. In regard of cancer locations, the body of evidence is most substantial for colorectal cancer, for which support comes from studies of 25(OH)D, vitamin D intake, and region of residence in a sunny weather. Collectively evidence demonstrates that vitamin D has a potent and beneficial effect at antagonizing and blocking several mitogenic mechanisms related to tumorigenesis. Taken together with the epidemiological studies and limited clinical trials, individuals may need to consider elevating 25(OH)D levels via sun exposure and/or vitamin D supplementation to decrease risk of colorectal cancer, in addition to standard care, treat cancer.     

Personalized 3D printed model of kidney and tumor anatomy: a useful tool for patient education

Purpose

To assess the impact of 3D printed models of renal tumor on patient’s understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education.

Methods

A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients’ satisfaction with their specific 3D printed model was also assessed through a visual scale.

Results

After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % (p = 0.018), kidney anatomy by 50 % (p = 0.026), tumor characteristics by 39.3 % (p = 0.068) and the planned surgical procedure by 44.6 % (p = 0.026).

Conclusion

Presented herein is the initial clinical experience with 3D printing to facilitate patient’s pre-surgical understanding of their kidney tumor and surgery.