Inhalation delivery of a novel diindolylmethane derivative for the treatment of lung cancer

The purpose of this study was to determine the anticancer efficacy of 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC?H?) by inhalation delivery alone and in combination with i.v. docetaxel in a murine model for lung cancer. An aqueous DIM-C-pPhC?H? formulation was characterized for its aerodynamic properties. Tumor-bearing athymic nude mice were exposed to nebulized DIM-C-pPhC?H?, docetaxel, or combination (DIM-C-pPhC?H? plus docetaxel) using a nose-only exposure technique. The aerodynamic properties included mass median aerodynamic diameter of 1.8 ± 0.3 μm and geometric SD of 2.31 ± 0.02. Lung weight reduction in mice treated with the drug combination was 64% compared with 40% and 47% in mice treated with DIM-C-pPhC?H? aerosol and docetaxel alone, respectively. Combination treatment decreased expression of Akt, cyclin D1, survivin, Mcl-1, NF-κB, IκBα, phospho-IκBα, and vascular endothelial growth factor (VEGF) and increased expression of c-Jun NH?-terminal kinase 2 and Bad compared with tumors collected from single-agent treatment and control groups. DNA fragmentation was also enhanced in mice treated with the drug combination compared with docetaxel or DIM-C-pPhC?H? alone. Combination treatment decreased expressions of VEGF and CD31 compared with single-agent treated and control groups. These results suggest that DIM-C-pPhC?H? aerosol enhanced the anticancer activity of docetaxel in a lung cancer model by activating multiple signaling pathways. The study provides evidence that DIM-C-pPhC?H? can be used alone or in combination with other drugs for the treatment of lung cancer using the inhalation delivery approach.     

Influence of hospital volume and outcomes of adult structural heart procedures

Hospital volume is regarded amongst many in the medical community as an important quality metric. This is especially true in more complicated and less commonly performed procedures such as structural heart disease interventions. Seminal work on hospital volume relationships was done by Luft et al more than 4 decades ago, when they demonstrated that hospitals performing > 200 surgical procedures a year had 25%-41% lower mortality than those performing fewer procedures. Numerous volume-outcome studies have since been done for varied surgical procedures. An old adage "practice makes perfect" indicating superior operator and institutional experience at higher volume hospitals is believed to primarily contribute to the volume outcome relationship. Compelling evidence from a slew of recent publications has also highlighted the role of hospital volume in predicting superior post-procedural outcomes following structural heart disease interventions. These included transcatheter aortic valve repair, transcatheter mitral valve repair, septal ablation and septal myectomy for hypertrophic obstructive cardiomyopathy, left atrial appendage closure and atrial septal defect/patent foramen ovale closure. This is especially important since these structural heart interventions are relatively complex with evolving technology and a steep learning curve. The benefit was demonstrated both in lower mortality and complications as well as better economics in terms of lower length of stay and hospitalization costs seen at high volume centers. We present an overview of the available literature that underscores the importance of hospital volume in complex structural heart disease interventions.     

A questionnaire-based analysis of parental perspectives on pediatric cochlear implant (CI) re/habilitation services: a pilot study from a developing CI service in India

Objective: To study parental perspectives on re/habilitation services offered for pediatric cochlear implant (CI) users at a non-profit organization in India.

Methodology: A non-standardized questionnaire comprising 46 items was created to understand perspectives of parents of pediatric CI users. Questions were designed to examine re/habilitation services from the angles of service delivery, parental stress levels, reasons for delay in obtaining services, sources of emotional support, concerns, and fears during each stage starting from diagnosis of hearing loss to CI surgery, re/habilitation services and parents’ views of their children post-CI. The questionnaire was posed to 30 parents and responses were recorded and coded.

Results and discussion: Qualitative and quantitative analyses based on parents’ responses identified several factors that significantly influenced parental perspectives during each stage. The major factors delaying the decision to go for CI included a fear of surgery, lack of funds for CI and the subsequent re/habilitation process, and limited knowledge. Key concerns were the child’s academic performance and social acceptance. Familial support played an important role during each stage. A significant reduction in the parental stress levels was observed following CI surgery. Parents indicated that local support for therapy, financial assistance and better guidance at each stage would substantially help in lowering stress levels.

Conclusions: The parental perspectives analyzed in this study can be utilized towards improving the quality of service delivery in terms of parental satisfaction and outcomes post-CI. Efforts should be taken to improve parental awareness, funding options, and access to re/habilitation services and social networks connecting similar parents.     

Intake of saffron reduces γ-radiation-induced genotoxicity and oxidative stress in mice

Saffron (SAF), the dried stigmas of Crocus sativus, is commonly used for flavoring and coloring food. Studies on bioactivity of SAF have demonstrated its in vivo antioxidant activity. The aim of our study was to assess the impact of SAF intake on γ-radiation (RAD) induced (a) chromosomal damage, (b) oxidative stress in liver and brain, and (c) histopathological effects in the intestinal cells and male germ cells in mice. Freeze-dried aqueous extract of SAF was used for the experiments. Our preliminary cell-free DNA nicking assay using pBR322 DNA revealed protective effects of freeze-dried SAF extract against hydroxyl radical induced DNA damage. For the in vivo investigations, freeze-dried SAF extract in distilled water was administered by gavage (40?mg/kg b.w.) to male Swiss albino mice for six consecutive days. On the sixth day, the animals were exposed to RAD (1 or 2?Gy) and sacrificed 24?h later to collect bone marrow cells for assessing chromosomal damage by measuring micronucleated polychromatic erythrocytes (MnPCEs). Liver and brain samples from animals exposed to 2?Gy RAD were used for evaluating lipid peroxidation and activity of antioxidant enzymes. The testis and intestine were used for histopathological analysis. Our results demonstrated significant protective effects of SAF against RAD-induced genotoxic damage. SAF pretreatment reduced the level of lipid peroxidation with concomitant increase in glutathione content and activity of glutathione S-transferase, glutathione peroxidase, and catalase. The histopathological analysis showed minimal impact of SAF on RAD-induced damage in the intestinal cells and male germ cells.     

Prevalence of primary angle-closure disease in retinitis pigmentosa

Purpose:To determine the prevalence of primary angle-closure disease (PACD) in patients with retinitis pigmentosa (RP).Methods: This was a retrospective review of the electronic medical records of all RP patients over the age of 10 years attending the Genetics Eye Clinic of a tertiary-care hospital during a 7-year period. Information regarding age, gender, vision, refraction, lens, intraocular pressure (IOP), type of RP, and inheritance pattern using pedigree charts for all patients were obtained. Patients with a shallow anterior chamber, high IOP, or glaucomatous optic discs were referred to the glaucoma department where they underwent additional IOP measurements, a gonioscopy, and disc evaluation by a glaucoma specialist. The prevalence of PACD was determined.Results: A total of 618 RP patients were examined during the study period, of which 95.1% had typical RP. The prevalence of primary angle-closure suspects was 2.9%, primary angle closure was 0.65%, and primary angle-closure glaucoma (PACG) was 2.27%. In contrast, the prevalence of primary open-angle glaucoma was 1.29%. The prevalence of PACG in those older than 40 years was 3.8% (95% confidence interval: 1.6–6.0).Conclusion: The prevalence of PACG in RP patients over 40 years was higher than that found in the general population of a similar age (3.8% vs. 0.8%). In our cohort of RP patients, 5.9% had PACD. Hence, gonioscopy is warranted in all RP patients to identify this condition and treat it appropriately.     

Oral Misoprostol Solution for Induction of Labour

Objective

To determine the effects of oral misoprostol solution for induction of labour.

Study Design

This is a prospective observational study.

Setting

This study was conducted in Government Medical College, Aurangabad.

Method

Patients undergoing induction of labour after 36 weeks of pregnancy were allocated by randomization to induction of labour with oral misoprostol solution administered 2 h apart. Delivery within 24 h after induction with oral misoprostol solution was the primary outcome on which the sample size was based. The data were analysed by Statistical Software for Social Sciences software.

Result

Two hundred patients were randomly selected for induction with oral misoprostol solution. There were no significant differences in substantive outcomes. Vaginal delivery within 24 h was achieved in 80.5 % of patients. The caesarean section rate was 19.5 %. Uterine hyperactivity occurred in 4 % of patients. The response to induction of labour in women with unfavourable cervices (modified Bishop’s score <2) was somewhat slower with misoprostol, induction to delivery interval was more, oxytocin requirement was more, and vaginal delivery rate was less.

Conclusion

This new approach to oral misoprostol solution administration was successful in achieving vaginal delivery rate in 24 h in 80.5 % of patients; rate of LSCS was less 19.5 %.