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R O'Toole

Publications and source records attributed to R O'Toole.

At least 19 recordsLinked to original sources
PubMed2000

Role of motility in adherence to and invasion of a fish cell line by Vibrio anguillarum.

To understand further the role of the flagellum of Vibrio anguillarum in virulence, invasive and adhesive properties of isogenic motility mutants were analyzed by using a chinook salmon embryo cell line. Adhesion was unaffected but invasion of the cell line was significantly decreased in nonmotile or partially motile mutants, and the chemotactic mutant was hyperinvasive. These results suggest that active motility aids invasion by V. anguillarum, both in vivo and in vitro.

Animals↗
PubMed1999

Teachers' recognition and reporting of child abuse: a factorial survey.

OBJECTIVE: The major aim of this study was to determine the effect of characteristics of the case, the teacher, and the organizational setting on recognition and reporting of child abuse. METHOD: A factorial survey design was employed in which a probability sample of teachers (N = 480) responded to vignettes in which case characteristics were systematically manipulated. RESULTS: Analysis using OLS regression showed that case characteristics alone accounted for 50.30% of the variance in recognition and 51.08% of the variance in reporting: the strongest effects were from type and seriousness of abuse, positive behavior of the victim and positive psychology of the perpetrator. The inclusion of variables describing the teachers and the school explained only a very small additional proportion of the variance in teacher's responses. CONCLUSIONS: Teachers responses to child abuse are relatively unbiased by either the extraneous characteristics of the perpetrator or victim, the responding teacher, or the school setting. The findings do not appear to support the problem of "overreporting." There is evidence for "underreporting," particularly in less serious cases involving physical and emotional abuse. Teachers are undeterred by the many problems and fears that may accompany a report of child abuse to Child Protective Services. Teachers use discretion in reporting abuse they recognize.

Adolescent↗
PubMed1999

The chemotactic response of Vibrio anguillarum to fish intestinal mucus is mediated by a combination of multiple mucus components.

Chemotactic motility has previously been shown to be essential for the virulence of Vibrio anguillarum in waterborne infections of fish. To investigate the mechanisms by which chemotaxis may function during infection, mucus was isolated from the intestinal and skin epithelial surfaces of rainbow trout. Chemotaxis assays revealed that V. anguillarum swims towards both types of mucus, with a higher chemotactic response being observed for intestinal mucus. Work was performed to examine the basis, in terms of mucus composition, of this chemotactic response. Intestinal mucus was analyzed by using chromatographic and mass spectrometric techniques, and the compounds identified were tested in a chemotaxis assay to determine the attractants present. A number of mucus-associated components, in particular, amino acids and carbohydrates, acted as chemoattractants for V. anguillarum. Importantly, only upon combination of these attractants into a single mixture were levels of chemotactic activity similar to those of intestinal mucus generated. A comparative analysis of skin mucus revealed its free amino acid and carbohydrate content to be considerably lower than that of the more chemotactically active intestinal mucus. To study whether host specificity exists in relation to vibrio chemotaxis towards mucus, comparisons with a human Vibrio pathogen were made. A cheR mutant of a Vibrio cholerae El Tor strain was constructed, and it was found that V. cholerae and V. anguillarum exhibit a chemotactic response to mucus from several animal sources in addition to that from the human jejunum and fish epithelium, respectively.

Animals↗
PubMed1996

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Adult↗
PubMed1996

Chemotactic motility is required for invasion of the host by the fish pathogen Vibrio anguillarum.

The role of the flagellum and motility in the virulence of the marine fish pathogen Vibrio anguillarum was examined. Non-motile mutants were generated by transposon mutagenesis. Infectivity studies revealed that disruption of the flagellum and subsequent loss of motility correlated with an approximate 500-fold decrease in virulence when fish were inoculated by immersion in bacteria-containing water. However, the flagellar filament and motility were not required for pathogenicity following intraperitoneal injection of fish. The transposon-insertion site for six mutants was determined by cloning and sequencing of the Vibrio DNA flanking the transposon. V. anguillarum genes whose products showed strong homology to proteins with an established role in flagellum biosynthesis were identified. One of the aflagellate mutants had a transposon insertion in the rpoN gene of V. anguillarum. This rpoN mutant failed to grow at low concentrations of available iron and was avirulent by both the immersion and intraperitoneal modes of inoculation. A chemotaxis gene, cheR, was located upstream of one transposon insertion and an in-frame deletion was constructed in the coding region of this gene. The resulting non-chemotactic mutant exhibited wild-type pathogenicity when injected intra-peritoneally into fish but showed a decrease in virulence similar to that seen for the non-motile aflagellate mutants following immersion infection. Hence, chemotactic motility is a required function of the flagellum for the virulence of V. anguillarum.

Amino Acid Sequence↗
PubMed1996

Nurses' diagnostic work on possible physical child abuse.

The concept of diagnostic work (A. Strauss, S. Fagerhaugh, B. Suczek, & C. Wiener, 1985) is used to explore nurses' responses to potential child abuse. A total of 1,036 nurses (response rate of 67%) completed a mailed questionnaire that included open-ended qualitative-type questions about a hypothetical situation involving possible child abuse. We report their judgments regarding information presented in the hypothetical situation and additional information they requested to make the diagnosis. Nurses focused primarily on the child's injuries and behavior and wanted more information about the abuse event. Diagnostic work was then analyzed by specialty group: community health, school health, emergency, and pediatric nursing. Nurses' specialization influenced the choice of information that was determined to be decisive and the additional information desired to make a diagnosis.

Adult↗
PubMed1996

Flagellin A is essential for the virulence of Vibrio anguillarum.

A flagellin gene from the fish pathogen Vibrio anguillarum was cloned, sequenced, and mutagenized. The DNA sequence suggests that the flaA gene encodes a 40.1-kDa protein and is a single transcriptional unit. A polar mutation and four in-frame deletion mutations (180 bp deleted from the 5' end of the gene, 153 bp deleted from the 3' end of the gene, a double deletion of both the 180- and 153-bp deletions, and 942 bp deleted from the entire gene) were made. Compared with the wild type, all mutants were partially motile, and a shortening of the flagellum was seen by electron microscopy. Wild-type phenotypes were regained when the mutations were transcomplemented with the flaA gene. Protein analysis indicated that the flaA gene corresponds to a 40-kDa protein and that the flagellum consists of three additional flagellin proteins with molecular masses of 41, 42, and 45 kDa. N-terminal sequence analysis confirmed that the additional proteins were flagellins with N termini that are 82 to 88% identical to the N terminus of FlaA. Virulence studies showed that the N terminal deletion, the double deletion, and the 942-bp deletion increased the 50% lethal dose between 70- and 700-fold via immersion infection, whereas infection via intraperitoneal injection showed no loss in virulence. In contrast, the polar mutant and the carboxy-terminal deletion mutant showed approximately a 10(4)-fold increase in the 50% lethal dose by both immersion and intraperitoneal infection. In summary, FlaA is needed for crossing the fish integument and may play a role in virulence after invasion of the host.

Amino Acid Sequence↗
PubMed1994

Phase II trial of amonafide in patients with advanced metastatic or recurrent endometrial adenocarcinoma. A Southwest Oncology Group study.

Amonafide, a benzisoquinoline-1,3-dione was administered to 38 patients with recurrent or metastatic, bidimensionally measurable endometrial cancer. There were 34 patients with no prior cytotoxic chemotherapy, performance status of 0-2, and normal bone marrow, renal, and hepatic function were eligible for response and toxicity evaluation. Amonafide, 300 mg/m2, was administered intravenously over 1 hour daily for 5 consecutive days. Courses were repeated every 21 days. The major grade 3 or 4 toxicities were hematologic with granulocytopenia in 18 patients (53%), thrombocytopenia in 6 patients (18%), and anemia in 8 patients (24%). Infectious complications occurred in 3 patients (9%). Other side effects included cardiac dysrhythmias, hypotension, pain and phlebitis at the site of injection, nausea, vomiting, and flu-like symptoms. The overall objective response rate was 6% (95% confidence interval of 1-20%); 2 patients had a complete response (6%), 9 patients had stable disease (26%) and 21 patients had progressive disease (62%). Two patients had insufficient follow-up for response determination and are assumed to be nonresponders. The median survival of the eligible patients was 8 months. With the toxicity observed and the low response rate, amonafide at this dose and schedule has no efficacy in the treatment of endometrial cancer.

Adenine↗
PubMed1993

Analysis of patient age as an independent prognostic factor for survival in a phase III study of cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in stages III (suboptimal) and IV ovarian cancer. A Southwest Oncology Group study.

BACKGROUND: The purpose of this study was to evaluate the effect of age (i.e., less than 65 years or 65 years of age and older) on survival in a recently completed phase III Southwest Oncology Group study in ovarian cancer patients. METHODS: Multivariate and univariate regression analyses were used to identify independent prognostic factors of survival in 342 patients with previously untreated Stage III (suboptimal) or Stage IV ovarian cancer who participated in a randomized, phase III study of intravenous (I.V.) carboplatin 300 mg/m2 plus I.V. cyclophosphamide 600 mg/m2 versus I.V. cisplatin 100 mg/m2 plus I.V. cyclophosphamide 600 mg/m2 every 4 weeks for six courses. RESULTS: Multivariate regression analysis showed the following variables to be independent prognostic factors of survival: age (P = 0.04); performance status (P = 0.004); disease stage (P = 0.03); and race (P = 0.05). Patients under 65 years of age survived significantly longer than those 65 years or older, especially patients with a performance status of 2. Patients with a baseline performance status of 0-1 survived longer than patients with a performance status of 2, and Stage III patients longer than those with Stage IV disease. An unexpected finding was that white patients survived significantly longer than black patients, regardless of age, performance status, or stage of disease. Carboplatin-cyclophosphamide-treated patients experienced similar survival and significantly less nausea and emesis, renal toxicity, hearing loss, tinnitus, neuromuscular toxicities, and alopecia. CONCLUSIONS: Ovarian cancer patients with advanced disease who are 65 years of age or older and/or with a performance status of 2 have significantly decreased survival compared to their younger and/or less debilitated counterparts. Carboplatin-cyclophosphamide is the recommended treatment (rather than cisplatin-cyclophosphamide), especially for older or debilitated patients because it is associated with less toxicity and similar survival.

Adult↗
PubMed1993

Results of a Southwest Oncology Group phase III trial of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide in advanced ovarian cancer.

Cisplatin combined with cyclophosphamide has been considered a very active treatment for advanced ovarian cancer. Unfortunately, cisplatin is associated with dose-limiting neurotoxicity, as well as possible neuropathy, ototoxicity, and occasional renal dysfunction. Carboplatin, a cisplatin analogue, is active against advanced ovarian cancer, with a presumed lower incidence of emesis, ototoxicity, neuropathy, and renal dysfunction. The Southwest Oncology Group initiated a phase III randomized trial, in which 342 patients with stage III (suboptimal disease) and stage IV ovarian cancer were randomly assigned to treatment with six courses of intravenous cisplatin 100 mg/m2 plus cyclophosphamide 600 mg/m2 or carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. The median survival for the cisplatin arm was 17.4 months; for the carboplatin arm, median survival was 20.0 months. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the p = 0.02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. There was less thrombocytopenia in the cisplatin arm (p < 0.001); however, there was less nausea and emesis (p < 0.001 for courses one to five), renal toxicity (p < 0.001), anemia (p < 0.001), hearing loss (p < 0.001), and neuromuscular toxicity (p < 0.001) in the carboplatin arm. Carboplatin/cyclophosphamide proved to have a significantly better therapeutic index than cisplatin/cyclophosphamide in these patients with advanced ovarian cancer.

Adult↗
PubMed1992

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE: To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS: Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS: The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION: Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

Adult↗
PubMed1991

Physicians' recognition of and response to child abuse: Northern Ireland and the U.S.A.

There is a long history of professional and public concern with the problems of recognizing and reporting child abuse. The research reported here compares recognition of and response to potential abuse by physicians in Northern Ireland and the United States. An experimental study using vignettes in the USA and hospital data, showed that physicians' judgments were moderately affected by ethnic status (black-white) and socioeconomic status of the family, in addition to level of injury to the child. We conducted a comparative study to test whether the social cleavage based on religion (Protestant-Catholic in North Ireland), would affect the recognition of and response to child abuse by medical practitioners in North Ireland. While there was a slight tendency for responses to be affected by socioeconomic status and religion, the results were not statistically significant, as was true for the level of injury to the child. We also compared "diagnostic behavior," signs used to diagnose abuse and causal notions concerning abuse. Medical practitioners in the two countries differ with respect to (1) the amount and type of information desired about a case, and (2) the factors believed to "cause" abuse, but are in general agreement about the "signs" of abuse.

Child↗
PubMed1990

Carboplatin therapy in advanced endometrial cancer.

A phase II study of the effectiveness and toxicity of carboplatin in the treatment of metastatic or locally advanced endometrial cancer was carried out by the Southwest Oncology Group. Thirty-two patients were registered in the study and 23 were fully evaluable for response and toxicity. Carboplatin was administered in a dose of 400 mg/m2 at 28-day intervals without concomitant hydration if blood counts had recovered sufficiently. There were seven responses (two complete and five partial responses) among the 23 evaluable patients, for an overall response rate of 30%. Four (two of two complete responders and two of five partial responders) of the seven responding patients remain alive at 839+ to 987+ days from the start of therapy. The two complete responders and one of the partial responders had small-volume disease, which may have contributed to their prolonged survival. Myelosuppression was the most prominent toxicity encountered. Seventeen of 27 patients evaluable for toxicity developed platelet counts of less than 75 X 10(3)/muL during therapy, but no hemorrhagic complications were encountered. Leukopenia was less prominent, with only nine of 27 patients developing white blood cell counts of less than 3.0 X 10(3)/microL. No important nephrotoxicity or neurotoxicity was observed. Emesis occurred in ten of 27 patients but was not dose-limiting. No unexpected toxicities were encountered. Carboplatin appears to be an active agent in the treatment of endometrial carcinoma.

Aged↗
PubMed1986

Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study.

We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis.

Adult↗