Failure of bacillus calmette guerin (bcg) therapy for the treatment of bladder cancer: al-azhar experience

Objective: To determine the failure rate of intravesical Bacillus Calmette Guerin (BCG) instillation following complete transurethral resection of superficial transitional cell carcinoma (TCC) of the urinary bladder at the Urology Department, Al-Azhar University, Cairo, Egypt. Patients and Methods: A prospective analysis of 160 patients with superficial TCC of the urinary bladder treated by transurethral resection of the bladder tumor (TURT) and adjuvant intravesical BCG instillation was performed at the Urology Department, Al-Azhar University, Cairo, between 2002 and 2008. The mean follow-up was 37 ± 4 (range 3 to 64) months. Results: After the initiation of BCG treatment 12 patients (7.5%) were lost to follow-up, 6 (3.8%) stopped BCG due to side-effects and were subsequently treated with intravesical chemotherapy, while another 5 (3.1%) died during BCG therapy due to tumor-unrelated causes. The overall survival rate at 3 years was 90.4%. At a mean follow-up period of 37 ± 4 months, 70.4% of the patients showed no tumor recurrence and 82% no tumor progression. BCG failure was significantly observed in cases with stage T1, or grade-3 tumors or in cases associated with carcinoma in situ. Conclusion: TURT with adjuvant intravesical BCG therapy is considered the first treatment option in high and intermediate risk patients with superficial TCC. Failure of BCG treatment is mainly observed in stage T1 or grade-3 tumors. Different treatment modalities can be used after a second tumor recurrence or progression according to the tumor aggressiveness and the patient’s preference.Keywords : Superficial bladder cancer, Bacillus Calmette Guerin (BCG), tumor recurrence, progressio

Double-nippled ureteroneocystostomy: a novel surgical technique in the management of the obstructed dilated ureter

Objective: To present the outcome of double-nippled ureteroneocystostomy as a novel technique in the treatment of the dilated obstructed distal ureter. Patients and Methods: The technique was performed in 55 patients with lower ureteric stricture. The lowest segment of the dilated obstructed ureter is transected and passed through the bladder dome for ureterovesical implantation. The distal 3 cm is folded twice like a sleeve to fashion a double-nippled valve. Evaluation of the appearance and function of the ureter and ipsilateral renal function was done by laboratory, imaging and endoscopic studies at 3, 6 and 12 months following surgery, then annually. Results: Functional and morphological improvement was observed in 80% of the cases. Imaging and endoscopic verification of the valve stability and ipsilateral renal unit status, integrity and patency were confirmed in all patients but two (3.6%) who developed grade 2 vesico-ureteric reflux. Conclusion: Double-nippled ureteroneocystostomy is a safe and efficient surgical modality for the management of the dilated ureter due to bilharzial stricture

The Euro-Med Free Trade Area: An Empirical Assessment of the main Trade Agreements' Effects

This paper provides an assessment of the effects of the main trade agreements implemented in the Euro-Mediterranean region. The empirical analysis in this paper is based on a gravity model for a panel of 14 countries (7 South Mediterranean, 4 EU member states in addition to USA and Japan) for the time span 1991 till 2012. The trade agreements of interest are the Pan-Arab Free Trade Agreement (PAFTA), the Agadir Agreement and the Association Agreements (AAs) signed between the EU and the South Mediterranean countries (SMCs) and are considered the main building blocks for the Euro-Med Free Trade Area. Results show a positive and significant effect of both the PAFTA and the Agadir Agreement on the exports of their signatories. Differently, signing the AAs seems to have no significant impact on the exports of the countries on average as well as the exports of the majority of the SMCs in specific. However, there is a positive and significant impact of the AAs on the exports of the EU member states. When analyzing the behavior of the single countries, emerges a positive impact of PAFTA on the exports of Egypt and Morocco, a negative impact on Tunisia and insignificant impact on Algeria and Jordan. The Agadir Agreement benefited both Egypt and Morocco, leaving no significant effects on both Tunisia and Jordan. Finally, signing the AAs had a positive impact on Egypt, Morocco and Turkey, a negative impact on Algeria and Jordan, and insignificant impact on the exports of both Israel and Tunisia. These results imply the success of the intra-regional integration efforts, unlike the outcome of the inter-regional AAs. The current design of the AAs seems to have asymmetric outcome on its signatories. The persistence of this problem can hinder the path towards a mutually beneficial and fully fledged Euro-Med Free Trade Area

Characterization of Respiratory Phenotype in Very Long-chain Acyl-CoA Dehydrogenase Deficient Mice.

Rationale: Very Long-chain Acyl-CoA dehydrogenase (VLCAD) deficiency the most common inherited long-chain fatty acid disorder. The VLCAD enzyme catalyzes the first step of mitochondrial fatty acid oxidation and loss of the enzyme results in energy deficiency as well as accumulation of long chain fatty acids. Recently, a related enzyme, Long-chain Acyl-CoA dehydrogensase (LCAD), which unlike VLCAD is not highly expressed in metabolic tissues like liver, heart and skeletal muscle, was found to be expressed in the lung and surfactant and lung dysfunction were observed in LCAD deficient mice. Respiratory distress syndrome has been described in other fatty acid oxidation disorders. VLCAD is expressed in lung, and likely plays an important role in lung compliance. Methods: VLCAD deficient mice and litter-mate controls were fasted for 18 hours, then exercised on a treadmill for 2 hours. Breathing was immediately assessed using whole body plethysmography in unanaesthetized spontaneously breathing mice. After a stable baseline was achieved, mice were given a “respiratory” challenge with 7% hypercapnia. In a subgroup of animals, pulmonary mechanics were assessed using Flexivent (Scireq). Results: Following exercise, VLCAD deficient mice had a decreased tidal volume and minute ventilation compared to their wild type controls. However, post-exercise VLCAD deficient mice were able to stabilize to similar levels as wild-type during baseline. The VLCAD deficient mice had a decreased response to a respiratory challenge with 7% hypercapnia. Early preliminary results suggest that VLCAD deficient animals have lower airway resistance. Conclusions: Respiratory insufficiency was demonstrated in a fasted and exercise challenged VLCAD deficient mice

Gene Therapy 2017: Progress and Future Directions

Introduction: Gene therapy has changed dramatically in the 28 years since the first human gene transfer experiment in 1989. Alipogene tiparvovec, GlyberaR®, a recombinant adeno-associated virus (rAAV) product for lipoprotein lipase deficiency, and Strimvelis®, a lentivirus vector for severe combined immune deficiency are approved in Europe. An rAAV2 product for a congenital form of blindness is currently under review in the United States, likely to be followed by numerous other gene therapies

Airway smooth muscle pathology in Pompe Disease

Pompe disease is a rare autosomal recessive disease which results from a deficiency of acid α-glucosidase (GAA) - an enzyme that degrades lysosomal glycogen. Patients with Pompe disease develop intra-lysosomal accumulation of glycogen in multiple tissues including skeletal muscle, CNS and smooth muscle. Pulmonary dysfunction is a hallmark of Pompe disease and has classically been attributed to muscle weakness and CNS neuropathology. However, the potential role of respiratory smooth muscles in the respiratory pathology is unknown. Therefore we postulated that GAA deficiency results in airway smooth muscle glycogen accumulation that leads to airway smooth muscle dysfunction. Using the Pompe mouse model, the Gaa-/- mouse, we examined the airway smooth muscle structure and function. We used in vivo forced oscillometry measurements (N=7WT, N=7 Gaa-/-) to examine pulmonary physiology and administered methacholine challenges to assess in vivo airway resistance. Also, we used ex-vivo contraction testing (N=6WT, N=5 Gaa-/-) to determine bronchi contractility. In response to the highest dose methacholine challenge (100mg/ml), there was a significant decrease in conducting airway resistance in Gaa-/- versus WT mice (p=0.007). Also, ex vivo bronchi contraction testing demonstrated a significantly weaker response to potassium chloride (p=0.008) and methacholine (2-way ANOVA p=0.005) in Pompe mice compared to WT mice, suggesting impaired smooth muscle contraction. Furtherly, we performed PAS staining on fresh-frozen tissue to examine the degree of glycogen accumulation as a result of GAA deficiency. PAS staining revealed robust glycogen accumulation in the trachea and bronchi of Pompe mice and a disruption of the airway smooth muscle architecture. In conclusion, GAA deficiency results in glycogen accumulation and a disruption of the architecture in the airway smooth muscles of Gaa-/- mice. Furthermore, both in vivo and ex vivo tests reveal that Gaa-/- murine airways have impaired function as evidenced by decreased contractility and a decreased response to methacholine

Commercial PV Property Characterization: An Analysis of Solar Deployment Trends in Commercial Real Estate

The commercial rooftop solar energy market remains an under-developed sector. The market is estimated to contain 150 gigawatts of potential in the U.S. but it faces significant barriers to deployment to meet that potential, with an estimated 1.4 GW developed through 2017. This analysis focuses on of over 30,000 solar systems installed through 2017 and the properties on which they are located. The sample represents greater than 60% of the installed market at that time. The properties covered 20 states and almost 30 different types including industrial, warehouse, school/university, office, retail, and municipal/government and were compared to more than 2.4 million non-solar properties in the same geographies. The analysis finds overall commercial rooftop PV penetrations have only surpassed 1% recently across all property types with education properties (schools and universities) leading at over 6% penetration and with NJ and CA seeing the highest overall penetrations close to 2.5%. Also revealed were characteristics of those buildings, owners, and tenants and how solar penetrations change as those characteristics change. The research found clearly higher penetrations on owner-occupied larger (>9000 ft2) buildings with fewer tenants indicating, potentially, areas for future customer acquisition for PV developers. Also investigated were differences of solar system characteristics on commercial buildings such as system installed prices, size, and percentages of third-party owned (TPO) systems. The research found a steady and substantial drop in installed prices over time, a drop in the percentage of TPO systems being installed, and a relatively steady trend of system size. This latter finding indicates that smaller systems remain difficult to develop

Design Indicators of Criteria of Different Activities in Public Places During Covid-19 Pandemic

Health pandemics are one of the greatest threats to human life. The more spacious and interdependent the city becomes, the faster the spread of epidemics is unless the State takes public health measures. Green places and public places contribute to improving the health of the population during the pandemics. Therefore, Poland has banned cars in parks to help people to get out and walk of their homes during the quarantine. However, as spatial spacing measures continue, cities may allocate more public places to, people only to practice their various activities. This paper aims to observe ideas introduced about how to change our relationship with public places, through a review some proposals by multiple parties concerned with the issue of urbanization under the Corona pandemic. Such proposals focus on identifying design guides for activities in public places within; the city, Such as providing the places with sanitary facilities that help with the ongoing sterilization process, as well as technical facilities that help monitor the status quo to alert and act accordingly. In addition to the various urban solutions that we will review in the context of the study in terms of achieving the principle of social convergence and spatial divergence. The study follows the theoretical and analytical approach in monitoring the changes that occurred on urban places as a result of Corona virus, analyzing models for the study that clarified the changes of activities in urban places, and reaching a set of indicators for designing urban places during the pandemic