Biomedical subjects

Paul Harnett

Publications and source records attributed to Paul Harnett.

5 recordsLinked to original sources

PubMed2006

Predictors of failure by medical practitioners to report suspected child abuse in Queensland, Australia.

OBJECTIVE: The goal of this investigation was to examine the level of notification of child abuse and neglect and the perceived deterrents to reporting by medical practitioners, who are mandated to report their suspicions but might choose not to do so. DESIGN: A random sample of medical practitioners was surveyed. About three hundred medical practitioners were approached through the local Division of General Practice. 91 registered medical practitioners in Queensland, Australia, took part in the study. RESULTS: A quarter of medical practitioners admitted failing to report suspicions, though they were mostly cognisant of their responsibility to report suspected cases of abuse and neglect. Only the belief that the suspected abuse was a single incident and unlikely to happen again predicted non-reporting (chi(2) [1, N = 89] = 7.60, p < 0.01). No gender, age or parent status differences were found between reporters and non-reporters. CONCLUSIONS: Although the rate of non-reporting shows improvement from previous research, it is still at an unacceptable level. The failure to report appears to result not from judgement about the presence or absence of indicators of child abuse and neglect but a threshold that moves individuals to act on their suspicions. Professional development should focus on some of the fallacies which often influence medical practitioners' decisions.

Adult↗

PubMed2005

Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer.

Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 amplification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.

Biomarkers, Tumor↗

PubMed2004

A phase II trial of capecitabine in heavily pre-treated platinum-resistant ovarian cancer.

OBJECTIVE: To determine the activity of capecitabine in women with platinum-resistant ovarian cancer. METHODS: In this multi-centre phase II trial, 35 patients with platinum-resistant ovarian, primary peritoneal or fallopian tube carcinomas were treated with capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. Platinum resistance was defined as progression within 4 months of completing the last platinum and all patients had previously received a taxane. Response was assessed by both RECIST criteria for patients with measurable disease and CA125 criteria. Responders were defined as patients with measurable disease who achieved a CR or PR according to RECIST criteria, patients without measurable disease who met the CA125 criteria for response and patients with stable measurable disease who met the CA125 criteria for response. RESULTS: Patients had received a median of four prior chemotherapy regimens (range 1-9). The median number of cycles of capecitabine administered was 3 (range 1-10). The response rate using the combined RECIST and CA125 criteria was 9% (95% CI 2-25%). In patients evaluable using RECIST criteria, the response rate was 5% (95% CI 0-25%). In patients evaluable for CA125 response, the response rate was 7% (95% CI 1-22%). The median progression-free survival was 2.3 months, and the median survival was 7.1 months. Treatment was generally well tolerated with most frequent grade 3 toxicities being hand-foot syndrome (17%) and diarrhea (9%). CONCLUSION: Capecitabine is well tolerated but has limited activity in patients with heavily pre-treated platinum-resistant ovarian cancer.

Adult↗

PubMed2004

Carboplatin desensitization.

BACKGROUND: IgE-mediated carboplatin hypersensitivity reactions occur in up to 30% of patients receiving this agent for chemotherapy of solid tumors, thus limiting therapeutic options. OBJECTIVE: To describe our experience with intravenous carboplatin desensitization regimens, which culminated in a standardized, successful protocol for safe administration. METHODS: Eight consecutive patients with ovarian cancer who had experienced severe anaphylactic reactions to carboplatin were referred to our hospital. Intradermal skin testing was performed by raising a 3-mm bleb by injection of undiluted carboplatin at 10 mg/mL, and the wheal size was read at 20 minutes. The outcomes of the various desensitization regimens were documented prospectively, and the experience gained was used to develop a standardized protocol for administration. RESULTS: All patients had positive intradermal skin test results. The first 3 patients were treated with short (90 minutes to 6 hours) desensitization protocols, and all protocols failed on the first or second infusions. These 3 and a subsequent 5 patients were given intravenous carboplatin according to a protocol of gradual dose escalation over a 4-log dose range given during a 4-day period, with subsequent 3-weekly infusions given more rapidly by omitting the most dilute log dose on each occasion. All patients tolerated the longer infusion protocol without event, and all but 1 patient experienced appropriate tumor marker response. CONCLUSIONS: Short carboplatin desensitization protocols (less than 6 hours) have an unacceptable failure rate in patients with carboplatin allergy, but longer infusion times (days) are well tolerated without recurrence of the allergic reaction and with good tumor response. In cases where carboplatin is the optimal therapeutic agent, clinicians should not be deterred by an anaphylactic reaction to it or by failure of shorter desensitization regimens.

Aged↗

PubMed2003

Incidence of microsatellite instability in synchronous tumors of the ovary and endometrium.

PURPOSE: Families with hereditary nonpolyposis colorectal cancer (HNPCC) have an increased lifetime risk of endometrial (40%) and ovarian (10%) carcinomas. Endometrial and ovarian carcinomas from members of these families frequently display a mutator phenotype as manifest by high levels of microsatellite instability (MSI-H). Microsatellite instability (MSI) occurs in 17-32% of sporadic endometrial carcinomas and 3-17% of sporadic ovarian carcinomas. We hypothesized that there might be a higher rate of MSI in tumors from women with synchronous primary carcinomas of the ovary and endometrium. EXPERIMENTAL DESIGN: We identified 52 cases of synchronous tumors of the ovary and endometrium from the databases of four gynecological oncology units. Archival material and clinical data were available on 45 of these patients. We examined DNA extracted from ovarian and endometrial tumor tissue for MSI using DNA extracted from normal tissue of that patient as a germ-line DNA control. MSI was assessed using a panel of five standard microsatellite markers: D2S123, D5S346, D17S250, BAT25, and BAT26. MSI-H was defined by more than two markers being positive. Low-level MSI (MSI-L) was defined as one or two markers positive and microsatellite stable (MSS) was defined as no markers positive. RESULTS: The 45 patients had a median age at diagnosis of 53 years. Of a total of 134 samples analyzed, only three samples (3.3%) were MSI-H. No patient had high levels of MSI in both ovarian and endometrial tumors. One ovarian carcinoma had five of five markers positive with the corresponding endometrial carcinoma being MSI-L. Two endometrial carcinomas were MSI-H, and the corresponding ovarian carcinomas were MSI-L and MSS, respectively. Seven ovarian tumors and seven endometrial tumors were MSI-L. The majority of patients had early-stage ovarian carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage I, 44.4%; stage II, 26.7%; and stage III, 26.6%]. Eighty-two % of the endometrial primaries were FIGO stage I. Progression-free survival was significantly better for patients with synchronous primaries than those presenting with ovarian carcinoma alone [adjusted hazards ratio, 1.94; P = 0.023; 95% confidence interval, 1.096-3.44]. CONCLUSION: Synchronous primary carcinomas of the ovary and endometrium are unlikely to be part of the HNPCC syndrome unless the family history is in keeping with the modified Amsterdam criteria.

Colorectal Neoplasms, Hereditary Nonpolyposis↗