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Biomedical subjects

T Dodd

Publications and source records attributed to T Dodd.

14 recordsLinked to original sources

Cyclo-oxygenase-2 expression in esophageal adenocarcinoma as a determinant of clinical outcome following esophagectomy.

The aim of this study was to determine if cyclo-oxygenase-2 (COX-2) expression in adenocarcinoma of the esophagus affects survival outcome in patients undergoing esophagectomy. Ten patients surviving more than 3 years following an esophagectomy for adenocarcinoma of the esophagus were identified from an esophagectomy database maintained by the University of Adelaide Department of Surgery. An additional group of 10 patients, who underwent esophagectomy for adenocarcinoma, but who died within 12 months of surgery due to recurrent disease, were also identified. Pieces of the original formalin fixed carcinoma tissue embedded in paraffin blocks from all of these patients were obtained, and slices of the tumor specimens underwent immunohistochemical staining with COX-2 protein. The extent of staining was then graded by a single 'blinded' pathologist: grade 0, no staining; grade 1 +, limited staining; and grade 2 +, strong staining. Kaplan-Meier survival curves were then constructed and used to determine correlations between survival and COX-2 staining, tumor T-stage, local lymph node metastases, and tumor vascular invasion. Ninety-five percent (19/20) of patients stained positively for COX-2. Patients with grade 2 + staining had a significantly poorer survival outcome compared to grade 1 + patients (P = 0.03). There were also trends towards shorter survival with worsening T-stage, lymph node metastasis and vascular invasion. COX-2 protein appears to be expressed by most esophageal adenocarcinomas. An increased level of expression of COX-2 was associated with a poorer survival outcome in this study. COX-2 protein expression association could be a better prognostic indicator for esophageal adenocarcinoma than traditional histopathological staging.

Adenocarcinoma↗

Mitomycin C as an adjunct in the treatment of localised ocular surface squamous neoplasia.

AIM: To report the outcome of topical mitomycin C (MMC) used as adjunctive treatment following primary excision of ocular surface squamous neoplasia (OSSN). METHOD: Prospective, non-comparative interventional case series of 27 primary OSSN lesions from 26 patients treated in a single ocular oncology centre over a 4 year period. RESULT: 27 cases of OSSN received a treatment regimen of surgical excision, followed by topical MMC. Mean follow up of 27 (SD 12) months (range 12-50, median 25 months) revealed zero recurrences. CONCLUSION: MMC treatment following surgical excision decreases the recurrence rate of primary ocular surface neoplasia and should be considered as adjunctive therapy in primary treatment.

Aged↗

Cyclizine.

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Antiemetics↗

Excision of laparoscopic port sites increases the likelihood of wound metastases in an experimental model.

BACKGROUND: Case reports of patients developing tumor metastases at port sites following laparoscopic surgery have prompted the development of preventive strategies to address this potential problem, including local excision of the port sites. While it has been suggested that this strategy could be used clinically, its efficacy has not been established. METHODS: Twenty four immune-competent Dark Agouti rats underwent laparoscopy and standardized intraperitoneal laceration of an implanted abdominal flank tumor, using an established laparoscopic cancer model. Rats were randomized to either control (n = 12) or wound excision (n = 12) groups. Both groups underwent laparoscopy using carbon dioxide (CO2) insufflation and two mini-laparoscopy ports. In the wound excision group, one of the port site wounds was excised following desufflation of the abdominal cavity. One week later, the port site wounds were excised for histological examination. RESULTS: Wound involvement with tumor was significantly more common following wound excision than with untreated control wounds (nine of 12 vs two of 12, p = 0.002). In the wound excision group, tumor metastases arose preferentially in the excised port site wound. CONCLUSION: This study suggests that excision of laparoscopy port site wounds following laparoscopic surgery for cancer does not prevent the subsequent development of port site tumors. Furthermore, the excision of port sites may actually increase the risk of tumor metastases arising in port sites, suggesting that the clinical application of this strategy should be avoided pending further evaluation.

Abdominal Neoplasms↗

Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy.

BACKGROUND: We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. METHODS: The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. RESULTS: In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. CONCLUSION: Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.

Abdomen↗

Efficacy of cytotoxic agents for the prevention of laparoscopic port-site metastases.

BACKGROUND: Recent experimental studies support initial clinical impressions that laparoscopic surgery for malignant neoplasms may be associated with an increased incidence of metastases to port sites. This study investigated in an experimental model the influence of cytotoxic agents (administered intraperitoneally or intramuscularly) on the development of port-site metastases following laparoscopic surgery. METHODS: Seven days after the implantation of an adenocarcinoma in the left abdominal flank, 72 Dark Agouti rats underwent laparoscopy with carbon dioxide insufflation, instillation of an intraperitoneal agent, and intraperitoneal tumor laceration within the following study groups (12 rats in each group): (1) control (no intraperitoneal instillation); (2) intraperitoneal instillation of isotonic sodium chloride solution (0.9%); (3) intraperitoneal instillation of povodine-iodine (1:10 dilution of povidine-iodine and isotonic sodium chloride solution); (4) intraperitoneal instillation of methotrexate (0.125 mg of methotrexate in 3 mL of isotonic sodium chloride solution); and (5) intraperitoneal instillation of aqueous chlorhexidine acetate. Twelve additional rats underwent laparoscopic tumor laceration following intramuscular injection of 0.125 mg of methotrexate (no intraperitoneal agent). Rats were killed 7 days after the procedure, and the wounds were examined histologically by a blinded histopathologist for the presence of tumor metastases. RESULTS: No tumor was found in any port site following the intraperitoneal administration of povidine-iodine (P=.04). In contrast, port-site metastases developed in the control group (5 [41.7%] of 12), the isotonic sodium chloride solution group (4 [33.3%] of 12), the chlorhexdine group (4 [33.3%] of 12), the intraperitoneal methotrexate group (2 [16.7%] of 12), and the parenteral methotrexate group (5 [41.7%] of 12). CONCLUSIONS: The results of this study suggest that the development of metastases to port sites following laparoscopic surgery may be prevented by the intraperitoneal instillation of diluted povodine-iodine. Other agents failed to influence the incidence of port-site metastases. Further studies are needed to determine if these findings can be applied to humans.

Animals↗

186Re-labeled antibodies to p185HER2 as HER2-targeted radioimmunopharmaceutical agents: comparison of physical and biological characteristics with 125I and 131I-labeled counterparts.

Overexpression of the HER2/neu protooncogene has been shown to correlate with poor clinical prognosis. A murine monoclonal antibody (4D5) directed against the extracellular domain (ECD) of p185HER2 has been shown to inhibit in vitro and in vivo growth of carcinomas overexpressing HER2 and has been humanized (rhuMAb HER2). The objective of the study was the identification of an agent which might be useful for in vitro studies, tumor imaging and/or radioimmunotherapy by linking beta-emitting radionuclides to these HER2-targeted antibodies. Murine 4D5 and humanized rhuMAb HER2 were radiolabeled with 125I, 131I or 186Re. Physical characteristics (TCA precipitability, SDS-PAGE, size exclusion chromatography), binding affinities to the HER2 ECD (in an ELISA and on SK-BR-3 cells) and antiproliferative activities of the radiolabeled antibodies were determined. Although 131I-4D5 and 131I-rhuMAb HER2 usually retained > 85% ECD binding, they exhibited increased aggregation and fragment content, drastically reduced antiproliferative activities and poor stability upon storage at 4 degrees C. For these antibody preparations, conservation of binding did not necessarily correlate with preservation of bioactivity indicating the importance of bioactivity determinations in radiolabeled antibody studies. Conversely, 4D5 and rhuMAb HER2 labeled with 125I or 186Re maintained physical properties, ECD binding, antiproliferative activities and were stable upon storage at 4 degrees C for at least 8 days. The superior retention of physical and biological characteristics of 186Re-labeled 4D5 and rhuMAb HER2 compared with their 131I-labeled counterparts suggests the potential for their use as radioimaging and radioimmunotherapeutic agents in the treatment of HER2 overexpressing tumors.

Animals↗

Prospective audit of costs and outcome of aminoglycoside treatment and of therapy for gram-negative bacteraemia.

The aims of this study were to audit the monitoring of aminoglycoside treatment to develop a method for measurement of the cost and outcome of treatment, and to assess the accuracy of a previously published sepsis score to predict cost and outcome. Measurements of costs and outcomes were also made for all patients (n = 85) with Gram-negative bacteraemia. Of these, 40 received an aminoglycoside and an additional 215 patients received aminoglycosides for other indications (total aminoglycoside patients 255; total patients 300). There were no interpretable assays for 82 (32%) of the aminoglycoside patients and only 33/173 (19%) patients assayed had first peak serum concentrations within the recommended range of 8-10 mg/L. Median costs of aminoglycoside treatment were 599 pounds in neutropenic patients, 471 pounds in ICU patients and 185 pounds in other patients. In the bacteraemic patients, median costs of aminoglycoside regimens (278 pounds) were higher than for non-aminoglycoside regimens (97 pounds). Death in hospital was twice as common in bacteraemic patients (20% versus 10%) and there was a stepwise increase in rate of mortality with sepsis scores. Treatment costs were markedly higher in patients who failed to respond to initial treatment, the mean difference in cost was 418 pounds per patient (95% CI 89 pounds - 747). Sepsis scores only explained 2.6% of the variance in treatment costs, and 22 patients with zero sepsis scores received prolonged courses of i.v. antibiotic treatment at an average cost of 209 pounds per patient. In conclusion, aminoglycoside regimens rarely conformed to accepted standards of care and treatment failure was associated with markedly increased treatment costs. Three readily measurable indicators of adverse outcome were identified (death in hospital, change of i.v. treatment and readmission within 2 weeks of discharge) and all were related to initial severity of illness as measured by sepsis score. The sepsis score may prove useful for assessment of individual risk but would benefit from further analysis to validate and possibly reduce the number of items in the score.

Adolescent↗

Antigenic variation of Borrelia hermsii.

At least 24 different serotypes were detected in populations of Borrelia hermsii that originated from a single organism. These serotypes were identified by staining with specific fluoresceinated antisera prepared against cloned populations of living organisms of each type. In the order of decreasing frequency, the 10 types more often encountered were 7, which was clearly dominant, and 2, 17, 24, 13, 2, 1, 21, 11, and 12. Each of the 24 types were shown to change to 7 or more other serotypes. Spirochetemia in mice was persistent, and relapses occurred when the concentration of organisms was sufficient for detection by visual means. After mice were inoculated with a single organism, peak spirochetemia usually occurred on day 4, after which clearance of organisms occurred, and an apparently pure population was replaced by a mixed population consisting of as many as seven variants. These types persisted for 2-3 d before being replaced by other types. Conversions occurred constantly and were independent of relapses. The rate of conversion in mice treated with cyclophosphamide to delay antibody production was comparable to that of controls. Spontaneous conversion was clearly demonstrated in tubes of fortified Kelly's medium inoculated with a single organism of type 7 or 21. 11 different variants appeared in eight cultures of type 21 by the time growth had reached 4 X 10(6)-10(7) organisms/ml. The rate of spontaneous change was estimated to be or approximately 10(-4)-10(-3) per cell per generation.

Antigens, Bacterial↗