Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases

Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.

Achalasia Cardia Subtyping by High-Resolution Manometry Predicts the Therapeutic Outcome of Pneumatic Balloon Dilatation

BACKGROUND/AIMS: High-resolution manometry (HRM) with pressure topography is used to subtype achalasia cardia, which has therapeutic implications. The aim of this study was to compare the clinical characteristics, manometric variables and treatment outcomes among the achalasia subtypes based on the HRM findings. METHODS: The patients who underwent HRM at the Asian Institute of Gastroenterology, Hyderabad between January 2008 and January 2009 were enrolled. The patients with achalasia were categorized into 3 subtypes: type I - achalasia with minimum esophageal pressurization, type II - achalasia with esophageal compression and type III - achalasia with spasm. The clinical and manometric variables and treatment outcomes were compared. RESULTS: Eighty-nine out of the 900 patients who underwent HRM were diagnosed as achalasia cardia. Fifty-one patients with a minimum follow-up period of 6 months were included. Types I and II achalasia were diagnosed in 24 patients each and 3 patients were diagnosed as type III achalasia. Dysphagia and regurgitation were the main presenting symptoms in patients with types I and II achalasia. Patients with type III achalasia had high basal lower esophageal sphincter pressure and maximal esophageal pressurization when compared to types I and II. Most patients underwent pneumatic dilatation (type I, 22/24; type II, 20/24; type III, 3/3). Patients with type II had the best response to pneumatic dilatation (18/20, 90.0%) compared to types I (14/22, 63.3%) and III (1/3, 33.3%). CONCLUSIONS: The type II achalasia cardia showed the best response to pneumatic dilatation.

Urogenital fistulae: a prospective study of 50 cases at a tertiary care hospital

The misfortunate incident of formation of a ureogenital fistula remains a major challenge for surgical urologists worldwide. Such fistulae may not be a life-threatening problem, but surely the women face demoralization, social boycott and even divorce and separation. The fistula may be vaginal, recto-vaginal or a combination of the two. The World Health Organization [WHO] has estimated that in the developing nations, nearly 5 million women annually suffer severe morbidity with obstetric fistulae being the foremost on the list. The objective of our study was to enunciate the patient demography, patient profile, incidence, type of surgery, as well as the long-term outcomes encountered in the management of all types of genital fistulae at a tertiary care centre. 50 consecutive patients, attending the outpatient department with urogenital fistulae, were studied during the period of 5 years from July 2009. All female patients with complaints of urinary incontinence and fecal incontinence and dribbling, patients having a history of obstructed labor, radiotherapy, instrumental delivery, foreign body or trauma and with a history of hysterectomy [abdominal/ vaginal] and lower segment caesarean section [LSCS] were included. A thorough urological examination included a dye study using methylene blue, Renal function tests, X-ray KUB nad intravenous urography [IVU]. Cystoscopy along with examination under anaesthesia [EUA] were done to assess the actual extent of injury. All patients were subjected to appropriate surgical interventions via the same combination of surgeons. Post operatively, prophylactic antibiotics were administered to all patients and patients were managed till discharge and followed thereafter via regular outpatient visits for a period of 3 years. Age of patients ranged from 21 to 40 years. 64% patients hailed from rural areas, 76% were from the lower socio-economic strata, 40% illiterate and 69% were short Statured. Vesico vaginal fistulae [VVF] was seen in 64% cases of which 50% were due to obstructed labor, 19% cases post LSCS and 31% cases post total abdominal hysterectomy [TAH]. 68% of urogenital fistulae were between 1 to 3 cms. We obtained a 75% cure rate in UVF, 87.5% cure rate in RVF while a 93.75% cure rate was observed in patients with VVF, 765 of all patients were cured while 8% had a recurrence, probably due to the large size of fistula. Genital fistula is preventable, yet it remains a significant cause of morbidity among females of reproductive age group. Despite facilities available, certain conditions like physical, social, economic, illiteracy, and a very casual attitude towards maternal health and children birth practices limit utilization of services for women. It is important that the modern health care providers should be aware of these aspects, so that they can recognize services that are appropriate and acceptable to the people. Thus, one must agree that in cases of urogenital fistulae, "prevention is better than cure"