Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.     

Outcome of Transurethral Plasmakinetic Vaporization for Benign Prostatic Hyperplasia

Purpose

To assess the outcome of transurethral plasmakinetic vaporization (PKVP) in the management of benign prostatic hyperplasia (BPH).

Patients and methods

From August 2010 to May 2012, 60 patients with obstructive LUTS due to BPH were included in the study. All patients were evaluated by International Prostate Symptom Score (IPSS), general examination, digital rectal examination, PSA, routine laboratory examinations, pelvi-abdominal ultrasound, trans-rectal ultrasound, and uroflowmetry. Patients with Qmax of <10 mL/sec., an IPSS of >8 and a prostate volume of >40 mL underwent transurethral PKVP.

Results

Mean age of the patients was 66.8±4.5 years. The mean times of the operation, post-operative bladder irrigation, and post-operative catheterization were 63.8±13.9 minutes, 15.2±5.7 hours, and 23.9±5.2 hours, respectively. At 3 months of follow-up, there were significant reductions in the mean IPSS from 23.4±3.5 to 9.2±3.7 (P=0.4), mean PSA from 3.03±2.2 ng/mL to 1.2±1.04 ng/mL (P value=0.02), mean post voiding residual urine from 149.8±59.5 mL to 46.9±24.1 mL (P value <0.01), and mean prostate volume from 72.8±10.3 mL to 22.7±6.1 mL (P value <0.01). Also, there was a statistically significant increase in the mean Q max. from 8.7±2.4 mL/s to 19.5±3.5 mL/s (P value <0.01).

Conclusion

PKVP is an effective and safe treatment option in the management of symptomatic BPH.     

Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors

In continuation of our previous work on the design and synthesis of topoisomerase II (Topo II) inhibitors and DNA intercalators, a new series of quinoxaline derivatives were designed and synthesized. The synthesized compounds were evaluated for their cytotoxic activities against a panel of three cancer cell lines (Hep G‐2, Hep‐2, and Caco‐2). Compounds 18b, 19b, 23, 25b , and 26 showed strong potencies against all tested cell lines with IC₅₀ values ranging from 0.26 ± 0.1 to 2.91 ± 0.1 µM, comparable with those of doxorubicin (IC₅₀ values ranging from 0.65 ± 0.1 to 0.81 ± 0.1 µM). The most active compounds were further evaluated for their Topo II inhibitory activities and DNA intercalating affinities. Compounds 19b and 19c exhibited high activities against Topo II (IC₅₀ = 0.97 ± 0.1 and 1.10 ± 0.1 µM, respectively) and bound the DNA at concentrations of 43.51 ± 2.0 and 49.11 ± 1.8 µM, respectively, whereas compound 28b exhibited a significant affinity to bind the DNA with an IC₅₀ value of 37.06 ± 1.8 µM. Moreover, apoptosis and cell‐cycle tests of the most promising compound 19b were carried out. It was found that 19b can significantly induce apoptosis in Hep G‐2 cells. It has revealed cell‐cycle arrest at the G2/M phase. Moreover, compound 19b downregulated the Bcl‐2 levels, indicating its potential to enhance apoptosis. Furthermore, molecular docking studies were carried out against the DNA–Topo II complex to examine the binding patterns of the synthesized compounds.     

Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

Aims The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. Methods and results All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). Conclusion We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.     

Three-dimensional evaluation of soft tissue changes in the orofacial region after tooth-borne and bone-borne surgically assisted rapid maxillary expansion

Objectives

This study seeks to three-dimensionally assess soft tissue changes in the orofacial region following tooth-borne and bone-borne surgically assisted rapid maxillary expansion (SARME).

Materials and methods

This prospective cohort study included 40 skeletally mature patients with transverse maxillary hypoplasia. A tooth-borne distractor (Hyrax) was used for expansion in 25 patients. In the remaining 15, a bone-borne distractor (transpalatal distractor, TPD) was used. Cone beam computed tomography (CBCT) scans were acquired before treatment (T0) and 22 months later (T1). 3D models were constructed from CBCT data and superimposed using voxel-based matching. Distance maps between the superimposed 3D models were computed to evaluate the degree of skeletal and soft tissue changes in the maxillary region.

Results

Distance maps showed negative distances (mean ?1.25 (±1.5) mm) in the middle of the upper lip, indicating posterior repositioning of this area. The cheek region showed positive changes (mean 1.66 (±1.1) mm), reflecting the underlying increase in maxillary width. There was no significant difference between the two groups in all measured distances (p?>?0.05). Retro-positioning of the upper lip accompanied skeletal remodeling in the anterior alveolar region at a mean ratio of 88 %, while the cheek region followed 32 % of the alveolar expansion.

Conclusion

Soft tissue changes following SARME include posterior repositioning of the upper lip and increased projection of the cheek area. These changes were comparable between bone-borne and tooth-borne appliances.

Clinical relevance

This study provides clinicians with more information over the expected orofacial soft tissue changes following SARME     

Core–shell nanoparticles used in drug delivery-microfluidics: a review

Developments in the fields of lab-on-a-chip and microfluidic technology have benefited nanomaterial production processes due to fluid miniaturization. The ability to acquire, manage, create, and modify structures on a nanoscale is of great interest in scientific and technological fields. Recently, more attention has been paid to the production of core–shell nanomaterials because of their use in various fields, such as drug delivery. Heterostructured nanomaterials have more reliable performance than the individual core or shell materials. Nanoparticle synthesis is a complex process; therefore, various techniques exist for the production of different types of nanoparticles. Among these techniques, microfluidic methods are unique and reliable routes, which can be used to produce nanoparticles for drug delivery applications.

Developments in the fields of lab-on-a-chip and microfluidic technology have benefited nanomaterial production processes due to fluid miniaturization.