Selective pancreatic toxicity of palmitoylpentachlorophenol

Palmitoylpentachlorophenol (PPCP), which is a lipid conjugate of a xenobiotic compound, has been found in human fat. To study the toxicity associated with PPCP, rats were given 100 mg/kg PPCP and sacrificed at 4, 8 and 12 days. The target organ identified was the exocrine pancreas; no other major organs examined showed any gross or histopathological abnormality. At 4 and 8 days after treatment, focal, spotty vacuolation, and loss of pancreatic acini was observed. Acute inflammatory infiltrate was also observed in parenchyma at all time points and the loss of acinar tissue was resolved through fibrous tissue formation by 12 days. The present study indicates that PPCP has a specific target organ toxicity.     

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.     

Evaluation of the effect of extra-amniotic normal saline infusion alone or in combination with dexamethasone for the induction of labor

AIM: To compare the effect of extra-amniotic normal saline solution infusion on its own, and in combination with dexamethasone on the ripening of the cervix and induction of labor. METHODS: A double-blind randomized clinical trial study was performed at Akbar Abadi Teaching Hospital in Tehran, Iran, between March 2002 and March 2003 on 84 pregnant women at a gestational age of 40 weeks or more, and with a Bishop score 相似文献   

Effect of language switching on arithmetic: a bilingual FMRI study

The role of language in performing numerical computations has been a topic of special interest in cognition. The "Triple Code Model" proposes the existence of a language-dependent verbal code involved in retrieving arithmetic facts related to addition and multiplication, and a language-independent analog magnitude code subserving tasks such as number comparison and estimation. Neuroimaging studies have shown dissociation between dependence of arithmetic computations involving exact and approximate processing on language-related circuits. However, a direct manipulation of language using different arithmetic tasks is necessary to assess the role of language in forming arithmetic representations and in solving problems in different languages. In the present study, 20 English-Chinese bilinguals were trained in two unfamiliar arithmetic tasks in one language and scanned using fMRI on the same problems in both languages (English and Chinese). For the exact "base-7 addition" task, language switching effects were found in the left inferior frontal gyrus (LIFG) and left inferior parietal lobule extending to the angular gyrus. In the approximate "percentage estimation" task, language switching effects were found predominantly in the bilateral posterior intraparietal sulcus and LIFG, slightly dorsal to the LIFG activation seen for the base-7 addition task. These results considerably strengthen the notion that exact processing relies on verbal and language-related networks, whereas approximate processing engages parietal circuits typically involved in magnitude-related processing.     

Study of short-pulse laser propagation in biological tissue by means of the boundary element method

Propagation of short pulses of light through biological tissues can be studied by numerically solving the diffusion equation. The boundary integral method was used to convert the differential equation to integral form and the result was solved using the boundary element method. The effects of different optical parameters of the tissue, i.e. scattering, absorption coefficients and anisotropic factor, on temporal evolution of the diffusely reflected pulse were studied. The results were compared with those obtained using the finite difference time domain method and the boundary integral method was found to be more precise and faster than the last method. The method can be used to investigate reflected pulses in the study of cell morphology and tumours in different types of tissue.     

The role of caspases in methotrexate-induced gastrointestinal toxicity.

BACKGROUND: Enterocolitis is the major toxicity of methotrexate-based cancer chemotherapy, which limits its clinical applications. Methotrexate induces gut mucosal apoptosis in vivo; however, little is known about the molecular mechanism involved. The effectors of apoptosis include the caspase family of proteases, which are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were (1) to establish an in vitro model of methotrexate-induced gut apoptosis and (2) to determine the role of caspases in methotrexate-induced apoptosis in intestinal epithelial cells. METHODS: Rat intestinal epithelial cells (RIE-1) were treated with methotrexate in the absence or presence of ZVAD-fluoromethyl ketone, a general caspase inhibitor. Apoptosis was quantified by means of deoxyribonucleic acid (DNA) fragmentation assays and Hoechst nuclear staining. Caspase activation was measured with the use of fluorogenic substrates. RESULTS: Methotrexate induced apoptosis and decreased cell number in RIE-1 cells. DNA fragmentation was preceded by the sequential activation of caspases 9, 2, and 3, whereas caspases 1 and 8 remained inactive. ZVAD-fluoromethyl ketone inhibited methotrexate-induced caspase activation, DNA fragmentation, and nuclear condensation. CONCLUSIONS: These results indicate that methotrexate activates specific caspases and induces apoptosis in RIE-1 cells. Furthermore, caspases may play an important role in methotrexate-induced apoptosis in RIE-1 cells and may be potential therapeutic targets to attenuate methotrexate-induced enterocolitis.     

National survey on orthotopic neobladder

Objective A national survey was conducted among the urologists in India to find the preference for urinary diversion after radical cystectomy for muscle invasive carcinoma of the urinary bladder, percentage of neobladder reconstruction, segment of the bowel used, complication rate, need for self-intermittent catherisation on follow up and the survival. Material and methods A detailed questionnaire was mailed to all members of the urological society of India (USI) to find out their preference for urinary diversion following radical cystectomy for muscle invasive carcinoma urinary bladder. For the neobladder reconstruction, they were asked for the type of bowel segment used, complication rate, reoperation rate, need for intermittent clean catheterisation on follow up and 5-year survival. Results A total of 24 institutions responded to the mailed questionnaire. Of all institutions 12 (50%) did not prefer the orthotopic neobladder (ONB) reconstruction. Among the institutions carrying out neobladder reconstruction, majority perform ileal conduit in more than 50% of the cases. Ileum (66.66%) or ileocaecal (16.66%) segment was the choice of bowel segment for most of the urologists. Only three institutions used sigmoid colon. The complications encountered were wound infection (5–25%), burst abdomen (5%), urinary fistulas (3–25%), faecal fistulas (2–5%), bladder neck stenosis (5–15%) and ureterointestinal anastomosis stenosis (5–25%). The reoperation rate was 5–15% with a perioperative mortality of 0.5–3%. Around 10–100% (average 50%) of the patients require intermittent clean catherisation. Only seven institutions could provide 5-year survival rate data. Of these three institutions reported more than 50% and four institutes less than 50% 5-year survival. Conclusion Ileal conduit still remains the urinary diversion of choice following radical cystectomy for muscle invasive carcinoma of the bladder among most of the urologists in India. Orthotopic neobladder reconstruction is practiced only in selected centres. Wound infection, urinary leak and obstruction at ureterointestinal anastomosis are the main complications. Clean intermittent cathaterisation is required at an average of 50% of the patients to ensure complete emptying of the neobladder.     

Radical cystectomy in septuagenarian patients with bladder cancer

Introduction: Clinical results of radical cystectomy performed on elderly bladder cancer patients over 70 years old were assessed to determine whether age is one of the critical points for the application of this type of surgery. Materials: From January 1992 to December 2002, 41 radical cystectomy performed in septuagenarian population were compared with 197 performed in patients less than 70 years of age. Results: The early and late complication rate for septuagenarians was 29.7% and 12%, compared with 26.9% and 9.6% for patients younger than 70 years respectively. The overall mortality rate for septuagenarians was 4.9%, compared with 8.6% for patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 5-year overall survival rate for septuagenarians was 53% compared with 59% for patients younger than 70 years. Conclusions: When indicated after adequate preoperative assessment and optimization of the patient, radical cystectomy is a safe procedure in the septuagenarians and patient should not be denied surgery dependent on chronologic age.