Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer cells and confers increased sensitivity to paclitaxel

Prostate cancer is the most common cancer and the second leading cause of cancer-related death in American men. To investigate the possible usefulness of tissue inhibitor of metalloproteinase-3 (TIMP-3) in prostate cancer gene therapy, we used an adenovirus expressing TIMP-3 to assess its role as an apoptosis trigger in highly metastatic prostate cancer cell lines PC-3 and DU-145. We showed that TIMP-3 alone induced apoptotic cell death which was triggered by mitochondrion-mediated caspase-3 activation. In combination treatment, we found that adenovirus-mediated expression of TIMP-3 greatly sensitised prostate cancer cells to chemotherapeutic drug paclitaxel, indicating a superadditive or synergistic effect of TIMP-3 and cytostatic treatment on prostate cancer cell death. The proper combination of adenovirus-mediated expression of TIMP-3 with conventional chemotherapeutic drug(s) could have potential benefits in treating highly metastatic prostate cancer.     

Retinal oximetry using intravitreal illumination

PURPOSE: To demonstrate spectroscopic retinal oximetry measurements on arteries and veins in swine using intravitreal illumination. Retinal arterial and venous saturations are measured for a range of inspired O2 levels after pars plana vitrectomy. METHODS: Pars plana vitrectomy and intravitreal manipulations were performed on two female American Yorkshire domestic swine. Light from a scanning monochromator was coupled into a fiberoptic intraocular illuminator inserted into the vitreous. The retinal vessels were illuminated obliquely, minimizing vessel glints. Multispectral images of the retinal vasculature were obtained as the swine's arterial blood oxygen saturation was decreased from 100% to 67% in decrements of approximately 10%. Retinal vessel spectra were used to calculate oxygen saturation in selected arteries and veins. Arterial oxygen saturations were calibrated using blood gas analysis on blood drawn from a Swan-Ganz catheter placed in the femoral artery. RESULTS: Oblique illumination of retinal vessels using an intravitreal fiberoptic illuminator provided a substantial reduction in the central vessel glint usually seen in fundus images, thus simplifying the analysis of spectral data. The vessel shadows were displaced from the vessel image simplifying the light paths in the eye. Using a full spectral analysis simplified by the light path reductions, we calculated retinal vessel saturations. The reduction of glint allowed for increased accuracy in measuring retinal vessel spectral optical density. Abnormally low retinal venous oxygen saturations were observed shortly after pars plana vitrectomy. CONCLUSIONS: Retinal oximetry using intravitreal illumination has been demonstrated. As a research tool, intravitreal illumination addresses several difficulties encountered when performing retinal oximetry with transcorneal illumination.     

Corrosive-like strictures caused by ingestion of aluminium phosphide

Aluminium phosphide ingestion is a major cause of poisoning-related mortality in tropical countries. Local oesophageal complications due to aluminium phosphide have been reported to occur rarely. We describe 3 patients who survived the intake of aluminium phosphide tablets and developed oesophageal strictures.     

Dietary intake, body image perceptions, and weight concerns of female US International Synchronized Figure Skating Teams

The objectives of the study were to determine the nutrient intakes and to examine body image perceptions and weight concerns of elite female US international synchronized skaters. One hundred and twenty-three skaters (mean age = 17.0 +/- 2.1 y; BMI = 21.32 +/- 2.13) representing six US international synchronized skating teams from the 1998 competitive season participated in the study. Nutrient intakes were determined from 3-d dietary records. Body image perceptions were assessed from responses to silhouette drawings. Skaters completed an emotional and physical self-appraisal. Weight concerns were assessed using a self-administered validated weight history questionnaire. The reported energy intake was 26 kcal/kg. The contribution of carbohydrate, fat, and protein to total energy intake was 62%, 23%, and 15% for younger (14-18 y) and 62%, 24%, and 14%, respectively, for the older (19-30 y))skaters. Significant differences (P < 0.001) were observed between perceived ideal and current body shapes. The greater the dissatisfaction with physical and emotional self, the larger the discrepancy between current versus desired body shape. Results suggest that sports nutritionists should not only assess nutrition factors but also examine psychosocial and emotional correlates related to body image and weight concerns of synchronized skaters.     

Pancreaticopleural Fistula: Report of Two Cases and Review of the Literature

Pancreaticopleural fistulas are a rare complication of pancreatitis. We report two cases from our institution and review 37 cases of pancreaticopleural fistulas identified in the literature. Endoscopic retrograde cholangiopancreatography was more sensitive compared to computed tomography in demonstrating pancreaticopleural fistulas (79% versus 43%, respectively). Medical therapy with total parenteral nutrition, octreotide, and/or chest tube placement was successful in resolving the pancreaticopleural fistula in up to 33% of cases. None of the patients who underwent pancreatic duct stent and/or nasopancreatic drain placement required surgical intervention. Endoscopic retrograde cholangiopancreatography is the initial test of choice when the diagnosis of pancreaticopleural fistula is suspected. Early endoscopic intervention with pancreatic duct stent placement is recommended given its high success rate in fistula closure. Medical therapies are useful adjuncts to endoscopic therapy, but rarely result in pancreaticopleural fistula closure alone. Surgical interventions should only be considered after failure of endoscopic and medical therapies.     

Long-Term Outcomes After Single-Balloon Enteroscopy in Patients with Obscure Gastrointestinal Bleeding

Background

Limited data exists on the long-term outcomes of patients with obscure gastrointestinal bleeding (OGIB) following single-balloon enteroscopy (SBE).

Aim

To examine the long-term outcomes of patients undergoing SBE for OGIB.

Methods

Consecutive patients undergoing SBE for OGIB at a tertiary care center between 2008 and 2010 were retrospectively identified. Clinical data and SBE findings were extracted from the medical record. Recurrence of OGIB during follow-up through 2012 was assessed by a combination of chart review and telephone interviews.

Results

One hundred and forty-seven patients were included in the study. The overall diagnostic yield of SBE was 64.6 % (95/147 patients). Findings of SBE included vascular lesions (VLs, 53.7 %), small bowel neoplasm (2.7 %), inflammatory lesions (4.8 %), and normal SBE (35.4 %). One hundred and ten patients (56.4 % female, mean age 70.6 ± 11.3 years) were followed for an average 23.9 months after initial SBE. During follow-up, OGIB recurred in 39.5 % of patients in whom a source of OGIB was identified on SBE and 55.9 % of patients with normal findings on SBE. OGIB recurred in 47.6 % of patients in whom small bowel VLs were treated endoscopically. None of the 13 patients in whom a non-VL lesion was identified as the source of bleeding on SBE experienced recurrent bleeding (p = 0.019).

Conclusions

SBE is a safe and valuable method for managing patients with OGIB. More than 50 % of patients experienced no recurrent bleeding during 2 years of follow-up after SBE. The long-term management of OGIB due to small bowel VLs remains challenging.     

Comprehensive temporal information detection from clinical text: medical events,time, and TLINK identification

Background

Temporal information detection systems have been developed by the Mayo Clinic for the 2012 i2b2 Natural Language Processing Challenge.

Objective

To construct automated systems for EVENT/TIMEX3 extraction and temporal link (TLINK) identification from clinical text.

Materials and methods

The i2b2 organizers provided 190 annotated discharge summaries as the training set and 120 discharge summaries as the test set. Our Event system used a conditional random field classifier with a variety of features including lexical information, natural language elements, and medical ontology. The TIMEX3 system employed a rule-based method using regular expression pattern match and systematic reasoning to determine normalized values. The TLINK system employed both rule-based reasoning and machine learning. All three systems were built in an Apache Unstructured Information Management Architecture framework.

Results

Our TIMEX3 system performed the best (F-measure of 0.900, value accuracy 0.731) among the challenge teams. The Event system produced an F-measure of 0.870, and the TLINK system an F-measure of 0.537.

Conclusions

Our TIMEX3 system demonstrated good capability of regular expression rules to extract and normalize time information. Event and TLINK machine learning systems required well-defined feature sets to perform well. We could also leverage expert knowledge as part of the machine learning features to further improve TLINK identification performance.