Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Accuracy of Preoperative Templating in Total Hip Arthroplasty With Special Focus on Stem Morphology: A Randomized Comparison Between Common Digital and Three-Dimensional Planning Using Biplanar Radiographs

BackgroundAccurate preoperative planning is a key component of successful total hip arthroplasty (THA). The purpose of the present study was to compare the accuracy and reliability of three-dimensional (hipEOS) and common digital two-dimensional (TraumaCad) templating with special focus on stem morphology.Methods51 patients undergoing THA were randomized to two groups. Preoperative planning was performed on 23 patients with hipEOS (3D) and on 28 patients with TraumaCad (2D) planning software. Planning results were compared with the implanted component size. Inter- and intraobserver reliability as well as planning accuracy of both planning methods with special focus on straight and short stem design were recorded.ResultsIntraobserver reliability of both planning methods was good for component planning (ICC_2,1: 0.835-0.967). Interobserver ICC_2,1 for stem and cup planning were higher for 3D templating (3D ICC_2,1: 0.906-0.918 vs. 2D ICC_2,1: 0.835-0.843). Total stem and cup size predictions were within 2 sizes for 3D and within 3 sizes for 2D planning. Comparing short stem planning accuracy of both planning methods, absolute difference between implanted and planned component size was significantly lower in 3D planning (P = .029). There was no significant difference in straight stem (P = .935) and cup (P = .954) planning accuracy.ConclusionOur findings suggest that 3D templating with hipEOS software has a good overall reliability and may have a better planning accuracy of short stem prostheses than digital templating with TraumaCad software. Assuming that the number of implanted short stem prostheses will further increase in coming years, a more precise planning with 3D technique can contribute to improve surgery outcome.     

A large primary malignant melanoma of the female urethra

We present a case of large, primary malignant melanoma of the female urethra with poor prognosis in this case report. Malignant melanoma is one of the rare tumors of the female urethra and accounts for 0.2% of all malignant melanoma cases. Large (5.6 cm in diameter), primary malignant melanoma of the female urethra is exceedingly rare.     

Effects of unilateral testicular torsion on the blood flow of contralateral testis--an experimental study on dogs

The effects of unilateral testicular torsion on the blood flow of the contralateral testis were investigated. Fourteen adult male dogs were recruited. Seven dogs underwent unilateral testicular torsion of 4 h duration, and the other seven dogs had a control operation. Testicular blood flow was determined by colour Doppler ultrasonography before and after the testicular torsion. Bilateral orchidectomy was performed at the end of the study and histopathological changes were evaluated. Values of peak systolic velocity, end diastolic velocity, and resistive index were not statistically significant between ipsilateral and contralateral testes in the study group (p > 0.05). On comparison with the control group, blood flow in the contralateral testes showed no statistically significant difference (p > 0.05). Oedema and congestion were seen on ipsilateral testes in the study group. No histopathological changes were noted on the contralateral testes. Minimal oedema and congestion secondary to manipulation were found in the control operation testes. We conclude that unilateral testicular torsion does not decrease contralateral testicular blood flow as shown by colour Doppler ultrasonography.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance

Objective

The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN).

Methods

The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation.

Results

The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively.

Conclusion

Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.     

Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.     

Higher Incidence of Cholelithiasis in Chronic Renal Failure Patients with Secondary Hyperparathyroidism Undergoing Peritoneal Dialysis

Background. In this study, we endeavored to determine whether the incidence of cholelithiasis (CL) was increased in chronic renal failure (CRF) patients with secondary hyperparathyroidism on a peritoneal dialysis (PD) program. We also evaluated the factors that might have some influence on the development of CL. Methods. A total of 59 CRF patients undergoing PD were included in the study. We studied the following groups to determine whether parathyroid hormone (PTH) levels were increased in CRF-PD patients: twenty patients with secondary hyperparathyroidism (group 1) and 39 patients with normal PTH levels (group 2). PTH levels were maintained at three times the upper limit of normal. Biochemical parameters were obtained for each CRF-PD patient. All patients underwent abdominal ultrasonography to screen for the presence of cholelithiasis. For statistical analysis, χ², t test, and logistic regression analysis were used; p < 0.05 was considered as significant. Results. We found an almost ten times higher incidence (25% vs. 2.6%) of CL in group 1 patients with statistical significance (p = 0.007). When the incidence of CL according to sex, creatinine, and PTH levels were considered, female gender, creatinine, and PTH levels were higher in group 1, which was also significant statistically. No significant relationship was detected between gallbladder stone formation and the other analyzed biochemical parameters. Conclusions. We found that the incidence of CL in CRF-PD patients with secondary hyperparathyroidism was higher than CRF-PD patients with normal PTH levels. It was also detected that female gender, high creatinine levels, and elevated PTH levels might influence the development of CL in CRF-PD patients.