Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial

Indian Journal of Pediatrics - To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean...     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.     

Sequential radiation changes in cytology of vaginal smears in carcinoma of cervix uteri during radiotherapy

The study deals with acute/immediate radiation changes in 2020 sequential vaginal smears in 101 patients of carcinoma of the cervix uteri, 97 were of squamous cell carcinoma and 4 of adenocarcinoma. The smears were collected after 12-14 days, 15-24 days and 25 days to 6 weeks following radiotherapy. The pretreatment vaginal smears were collected and examined for percentage of cancer cells. Subsequent smears were studied for radiation changes in benign and malignant cells, such as cell size, vacuolation of cytoplasm, multinucleation and nuclear changes, etc. A gradual and linear decline in cancer cells was observed until the end of therapy; 41.6% of patients had less than 10% cancer cells within 12-14 days of therapy, 63.4% of patients between 15 and 24 days and 74.6% after 25 days to 6 weeks following radiation. Eighty three percent of the patients attained zero level at the end of therapy.     

Pseudomyxoma peritonei usually originates from the appendix: a review of the evidence

Pseudomyxoma peritonei (PMP) is a rare condition, said to be more common in females during the fourth or fifth decade of life with an incidence believed to be in the region of one per million per year. Although PMP has been reported as originating from many intra-abdominal organs, in the majority of cases an ovarian or appendix cystadenoma or cystadenocarcinoma has been implicated as the primary site. Our experience suggests that most cases arise from the appendix. We have reviewed the clinical and scientific evidence. In the four largest reported series of 393 patients, 181 (46%) were males. Immunohistochemistry techniques in women with both appendical and ovarian tumours favour an appendiceal primary in most cases. The distinction between "benign" adenomucinosis and mucinous adenocarcinoma is important in both treatment and prognosis. Experience suggests that there may well be a spectrum of disease and possibly an "adenoma carcinoma sequence".     

Isolation and characterization of degradation impurities in docetaxel drug substance and its formulation

The degradation of docetaxel drug substance and its injection formulation has been investigated. The majority of impurities were observed in a base degradation study and all five degradation products were characterized. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, these were characterized as 10-deacetyl baccatin III, 7-epi-10-deacetyl baccatin III, 7-epi-10-oxo-10-deacetyl baccatin III, 7-epi docetaxel and 7-epi-10-oxo-docetaxel, respectively. The last two impurities were also detected in the stability study of docetaxel formulation. Out of these degradation impurities two substances have been previously identified while the other three previously unreported.     

Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Physician‐related facilitators and barriers to patient involvement in treatment decision making in early stage breast cancer: perspectives of physicians and patients

Objective To identify patients’ and physicians’ perceptions of physician‐related verbal and nonverbal facilitators and barriers to patient involvement in treatment decision making (TDM) occurring during clinical encounters for women with early stage breast cancer (ESBC). Methods Eligible women were offered treatment options including surgery and adjuvant therapy. Eligible physicians provided care for women with ESBC in either a teaching hospital or an academic cancer centre. In Phase 1, women were interviewed 1–2 weeks after their initial consultation. In Phase 2, women and their physicians were interviewed separately while watching their own consultation on a digital video disk. All interviews were audiotaped, transcribed and analysed. Results Forty women with ESBC and six physicians participated. Patients and physicians identified thirteen categories of physician facilitators of women’s involvement. Of these, seven categories were frequently identified by women: conveyed a rationale for patient involvement in TDM; explained the risk of cancer recurrence; explained treatment options; enhanced patient understanding of information; gave time for TDM; offered a treatment recommendation; and made women feel comfortable. Physicians described similar information‐giving facilitators but less often mentioned other facilitators. Few physician barriers to women’s involvement in TDM were identified. Conclusions Women with ESBC and cancer physicians shared some views of how physicians involve patients in TDM, although there were important differences. Physicians may underestimate the importance that women’s place on understanding the rationale for their involvement in TDM and on feeling comfortable during the consultation.     

Role of immunotherapy in bacillus Calmette–Guérin-unresponsive non–muscle invasive bladder cancer

Intravesical instillation of live attenuated bacillus Calmette–Guérin (BCG) is the gold standard for patients with intermediate- and high-risk non–muscle-invasive bladder cancer (NMIBC). BCG-failures include a heterogenous population of patients who share a designation of disease recurrence or progression following BCG and include patients with complete unresponsiveness to BCG, patients who respond initially but develop relapse and, in some cases, patients who are intolerant to BCG due to side effects. Given the efficacy and relatively rapid approval of several monoclonal antibodies against PD-L1 or PD-1 for advanced and metastatic bladder cancer, the role of these checkpoint inhibitors in BCG-relapsing disease at various disease stages is under consideration. Data supporting a role for immune checkpoint inhibitors is largely theoretical with limited supportive data from animal models and from clinical evidence of increased PD-L1 expression in BCG-unresponsive tumors. Current trials in BCG-unresponsive disease are underway and expected to provide insight regarding these concepts.     

Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer

BACKGROUND: S100A6 and S100A2 are members of the S100 family of calcium binding proteins, which are down regulated in prostate cancer, however the molecular mechanism(s) underlying their loss of expression is unknown. METHODS: The promoter and exon 1 region of the S100A6 and S100A2 genes was sequenced in bisulfite modified DNA from non-malignant, benign prostatic hyperplasia (BPH), malignant and metastatic prostate tissues and in cell lines. Immunohistochemistry was performed to correlate S100A2 expression with methylation status. RESULTS: S100A6 methylation was absent or occurred at isolated sites in 14/14 cases of non-malignant epithelium and 5/5 cases of BPH tissues, whereas methylation was seen in 14/27 (52%) cases of prostatic cancer (P<0.0001), 2/2 cases of metastatic cancer and in the CWR22 prostatic cancer xenograft. Critical CpG sites within the S100A2 promoter were methylated in LNCaP, LNCaP-LN3, and CWR22 cells but not in Du145, PC3 or BPH45 cells. In tissues, S100A2 methylation was seen in 32/34 (94%) cases of adenocarcinoma and 5/5 cases of metastatic cancer. However, S100A2 methylation was also seen in 9/12 (75%) cases of non-malignant tissues and in 5/5 cases of BPH. Immunostaining, showed absent S100A2 expression all 41 cases of prostatic cancer, whereas staining was seen in the basal cells of non-malignant epithelium. CONCLUSIONS: Loss of S100A6 and S100A2 proteins is frequent in human prostatic cancer. A major mechanism underlying the loss of S100A6 expression appears to involve promoter hyper-methylation. However, mechanisms other than methylation of the known promoter are involved in silencing S100A2 in the prostate.