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Yi-Zarn Wang

Publications and source records attributed to Yi-Zarn Wang.

7 recordsLinked to original sources

Development of 125I-methylene blue for sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy is an established alternative to complete lymph node dissection in some patients. We have developed a novel, radiolabeled methylene blue dye that may be a useful alternative to the traditional two-step procedure involving 99mTc-labeled colloid and unlabeled blue dye. We hypothesize that 125I-labeled methylene blue will be rapidly absorbed into the lymphatics and transported to the drainage basin containing the sentinel nodes. MATERIALS AND METHODS: Rabbits footpads were injected with 1 mCi of 125I-labeled methylene blue admixed with unlabeled dye. A hand-held gamma detection device allowed tracking of radiolabeled dye to nodes in the popliteal and inguinal regions. At pre-established time points animals were sacrificed, and the nodal basin dissected. Nodal radioactivity as well as uptake of blue dye was recorded. RESULTS: The spread of the radiolabeled methylene blue compound from the footpad to the popliteal lymph nodes occurred in 5-10 min. CONCLUSION: The radiolabeled dye rapidly progresses through lymphatics to the draining nodes. Use of radiolabeled methylene blue may be an attractive alternative to current two-step sentinel node techniques, as it may be less painful, and may reduce the cost associated with the time-delay between the injection of the radioactive compound and surgery.

Animals↗

Gamma-guided diagnostic peritoneal lavage for detection of bowel perforation.

HYPOTHESIS: Bowel perforation can be diagnosed by detection of orally administered technetium Tc 99m sulfur colloid ((99m)Tc SC) in diagnostic peritoneal lavage (DPL) fluid using a handheld gamma-detection probe. DESIGN: A canine intestinal-injury model was used to test the hypothesis. The (99m)Tc SC (55.5 MBq) was administered in 500 mL of saline via a nasogastric tube. A DPL with 500 mL of saline was performed at 60, 90, and 120 minutes after administration of (99m)Tc SC. The radioactivity in the DPL effluent was measured using a handheld gamma probe. A DPL effluent count that was 3 SDs above the background count was considered a positive test result. Twenty animals with perforation and 5 without perforation (negative control) were studied. RESULTS: There were no false-positive gamma-DPL test results. Sensitivity improved by time up to 90 minutes. The lowest positive count in the DPL effluent measured by the gamma probe corresponded to 0.2% of the administered activity. No radioactivity was detected in blood and urine samples or liver and spleen specimens. The sensitivity, specificity, accuracy, positive predictive values, and negative predictive values at 90 minutes were 95%, 100%, 96%, 100%, and 83%, respectively. CONCLUSIONS: gamma-Guided DPL is a highly sensitive and 100% specific test in the detection of small-bowel perforation. Clinical studies are warranted to determine the patient-specific factors affecting diagnostic accuracy.

Animals↗

Effect of human Angiostatin protein on human angiogenesis in vitro.

Angiostatin, a 38-kD fragment of plasminogen, inhibits angiogenesis in both animal tumor models and in vitro endothelial cell models. However, human Angiostatin has not been tested in vitro against an intact human tissue target to determine its ability to inhibit the initiation or subsequent promotion of the human angiogenic response. We hypothesized that high doses of human Angiostatin would inhibit the development of an angiogenic response in an intact human vessel target, and would suppress the subsequent growth of blood vessels following the initiation of an angiogenic response. To test these hypotheses, full-thickness human placental vein disks were cultured for 15 days in an in vitro fibrin-thrombin clot assay. This assay system had been used to evaluate the efficacy of a wide variety of compounds. Vessels were obtained from three placentas. Treatments included a control medium plus fetal bovine serum (FBS), heparin-steroid (300 micro g/ml heparin and 350 micro g/ml hydrocortisone; a treatment known to inhibit angiogenesis) and Angiostatin at doses from 1 x 10(-4) to 1 x 10(-9) M. In the control groups, 81% of vessels initiated an angiogenic response compared to 53% of the vessels treated with heparin-steroid. Angiostatin (10(-4)-10(-9) M) decreased the initiation of an angiogenic response, but this was not statistically significant. Of the disks that initiated an angiogenic response, the mean ( +/- standard error of the mean (SEM)) semi-quantitative visual angiogenic index (AI) of the control vessels was 9 +/- 1.7 on day 15. In comparison, the mean AI of heparin-steroid treated vessels was 3.7 +/- 0.4. Angiostatin at doses of 10(-4)-10(-9) M also failed to inhibit blood vessel growth after initiation of the angiogenic response. Based on these observations, we cannot demonstrate significant activity of human Angiostatin (10(-4)-10(-9) M) against the initiation or promotion of a human angiogenic response in this in vitro model of angiogenesis using an intact human vessel target.

Angiogenesis Inhibitors↗

Development of a novel in vitro human tissue-based angiogenesis assay to evaluate the effect of antiangiogenic drugs.

OBJECTIVE: To describe a novel in vitro human tissue-based angiogenic model that can predict an individual tumor's response to antiangiogenic drugs. SUMMARY BACKGROUND DATA: A number of in vitro and in vivo angiogenesis assays exist, but they do not provide potentially useful information for the treatment of an individual patient. Clonogenic assays have been used to evaluate the response of an individual's tumor to antineoplastic agents, but these tumor fragments are cultured in an environment that does not lead to neovessel growth. The authors have previously demonstrated that human vein disks or human tumor xenograft fragments incorporated into a 0.3% fibrin-thrombin clot will develop angiogenic vessel growth from the cut edge of the vessel disk or xenograft fragment. METHODS: Fresh human tumor or normal tissue disks (2 x 1 mm) from fresh surgical specimens were incorporated into fibrin-thrombin clots overlain with nutrient medium containing either 20% fetal bovine serum alone or in combination with Epothilone B, a tubulin inhibitor with antiangiogenic properties. Tissue disks were visually assessed over time to determine the percentage of wells that developed an angiogenic response. Neovessel growth, density, and length were graded at intervals using a semiquantitative visual neovessel growth-rating scheme (angiogenic index, 0-16 scale) devised in the authors' laboratory. RESULTS: Epothilone B treatment at doses of 10-6 mol/L and 10-8 mol/L decreased the number of wells that developed an invasive angiogenic response and limited the development of vessels that invaded the matrix. At these doses, Epothilone B also caused regression of vessels in wells that had been allowed to develop an angiogenic response. Treatment of tumors or normal tissues with Epothilone B at doses less than 10-8 mol/L was ineffective. CONCLUSIONS: Epothilone B may be an effective antiangiogenic agent in a variety of tumor types. The authors speculate that this in vitro model might provide useful information to the clinician on the effect of specific antiangiogenic agents on individual tumors. This may be particularly useful in patients with tumors that, as a group, are unresponsive to treatment with antineoplastic agents.

Angiogenesis Inhibitors↗

Effect of human recombinant Endostatin protein on human angiogenesis.

Tumor growth and metastasis are dependent on the development of new blood vessels. Inhibitors of new vessel growth have been widely investigated as anti-tumor agents. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII inhibits endothelial cell proliferation, induces endothelial cell apoptosis, and can both inhibit and reverse tumor growth in mice. However, human recombinant endostatin has had limited testing against human tissue targets. To investigate the effect of human endostatin on a human vessel target over a broad range of concentrations (10(-l2)-10(-4) M), human placental vein disks were grown for a period of 2 weeks in a 0.3% fibrin clot overlayed with growth medium. Disks from five individual placentas were tested. For each placenta utilized, a control (medium and 20% fetal bovine serum [FBS]) group and a group treated with heparin (300 microg/ml) and hydrocortisone 21-phosphate (350 microg/ml) (heparin-steroid) at a dose known to inhibit angiogenesis were included. Endostatin was tested at concentrations of 10(-12)-10(-4) M in medium containing 20% FBS. The rate of initiation and the angiogenic growth index (on a visually graded semi-quantitative scale of 0-16) were determined for all experimental conditions. Endostatin inhibited angiogenesis in our model only in high concentrations. At 10(-5) M, endostatin did not alter the percent of wells that initiated an angiogenic response, but significantly inhibited subsequent vessel growth. At 10(-4) M, endostatin was able to inhibit both initiation and subsequent new vessel growth. Human endostatin can inhibit the initiation of a human angiogenic response and inhibit the subsequent proliferation of human neovessels when used at high doses in a continuous exposure model.

Angiogenesis Inhibitors↗

Stoma complications: a multivariate analysis.

Construction of a gastrointestinal stoma is a frequently performed surgical procedure. We sought to analyze a large cohort to document the frequency and types of ostomy complications and the risk factors associated with them. The charts of patients undergoing a procedure which resulted in ostomy during a 3-year period were reviewed. Demographics, indication, ostomy type/location, perioperative risk factors, and complications were recorded. Case-control methodology was used to determine crude odds ratios and multiple logistic regression was used to calculate adjusted odds ratios. A P value of less than 0.05 was considered significant. An ostomy was constructed in 204 patients and records were available for 164. Forty-one patients (25.0%) had ostomy complications. Sixteen of these complications (39.0%) occurred within one month of the procedure. Complications included prolapse in nine (22%), necrosis in nine (22%), stenosis in seven (17%), irritation in seven (17%), infection in six (15%), bleeding in two (5%), and retraction in two (5%). Gender, cancer, trauma, diverticulitis, emergency surgery, ileostomy, and ostomy location/type were not associated with a stoma complication. Significant predictors of ostomy malfunction are presented as odds ratios (ORs) with 95 per cent confidence intervals (CIs) and include inflammatory bowel disease (OR = 4.49; 95% CI = 1.16-17.36) and obesity (OR = 2.66; 95% CI = 1.15-6.16). The care of an enterostomal nurse was found to prevent complications (OR = 0.15; 95% CI = 0.03-0.69). We conclude that ostomies have a high risk of complication, which is not related to stoma location or type. Obesity and inflammatory bowel disease predispose to complications. Enterostomal nursing may be instrumental in preventing complications.

Adolescent↗