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Biomedical subjects

M Quinn

Publications and source records attributed to M Quinn.

At least 55 records · Page 3Linked to original sources
PubMed2001

Socioeconomic inequalities in cancer survival in England and Wales.

BACKGROUND: Cancer survival often has been reported as lower for the poor than the rich, but, to the authors' knowledge, systematic national estimates of deprivation gradients in survival over long periods of time have not been available. METHODS: The authors estimated national population-based survival rates for almost 3 million people who were diagnosed with 1 of 58 types of cancers (47 in adults, 11 in children) in England and Wales during the 20-year period 1971-1990 and followed through December 31, 1995. Cancer patients were assigned by their address at diagnosis to 1 of 5 categories (quintiles of the national distribution) of material deprivation by using a standard index derived from census data on unemployment, car ownership, household overcrowding, and social class that was available for all 109,000 census tracts in Great Britain. The authors used relative survival rates: the ratio of observed survival among the cancer patients to the survival that would have been expected if they had had the same background mortality as the general population. Background mortality differed widely among socioeconomic categories, and the authors constructed life tables from raw national mortality data by gender, single year of age, calendar period of death, and socioeconomic category to adjust for it. The authors used variance-weighted least squares regression to estimate both time trends in age standardized survival and socioeconomic gradients in survival. The number of avoidable deaths was estimated from the observed mortality excess compared with the expected mortality in each group of patients. RESULTS: Survival rose steadily for most cancers over 25 years to 1995 in England and Wales, but inequalities in survival between patients living in rich and poor areas were geographically widespread and persistent over this period of time. These patterns existed for 44 of 47 adult cancers examined but not for 11 childhood cancers. These inequalities in survival represented more than 2500 deaths that would have been avoided each year if all cancer patients had had the same chance of surviving up to 5 years after diagnosis as patients in the most affluent group. CONCLUSIONS: The largest national cancer survival study has provided strong evidence of systematic disadvantage in outcome among patients who lived in poorer districts compared with those who lived in wealthier districts.

Adolescent↗
PubMed2001

Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study.

OBJECTIVE: In view of the significant activity of topotecan in ovarian cancer with dose-limiting toxicity (DLT) of myelosuppression, we evaluated the addition of topotecan to carboplatin and paclitaxel with peripheral blood progenitor cell (PBPC) support. METHODS: Patients with previously untreated stage IIIC or IV ovarian cancer with macroscopic residual disease following primary debulking surgery were eligible. Patients received two cycles of carboplatin AUC = 5 and 175 mg/m(2) of paclitaxel with collection of PBPCs after the second cycle. Patients subsequently received three cycles of high-dose therapy (HDT) with topotecan on a daily x5 schedule, paclitaxel (250 mg/m(2) over 24 h), and carboplatin (AUC = 12-16). RESULTS: Nineteen patients with a median age of 49 years (range 21-63) were enrolled and topotecan was escalated in 6 patient cohorts up to a dose of 4.5 mg/m(2)/day. Fifty-two of the planned 57 treatment cycles were delivered with no treatment-related deaths. Neutrophil and platelet recovery was rapid and the interval between HDT was 28 days. Febrile neutropenia occurred following 57% of all HDT cycles. DLTs of mucositis and diarrhea were observed at topotecan (4.5 mg/m(2)/day), paclitaxel (250 mg/m(2)) and carboplatin (AUC = 12). The protocol was subsequently modified to administer topotecan (2.5 mg/m(2)/day) with carboplatin (AUC = 16); however, 2 patients developed grade 4 diarrhea (1 with grade 3 mucositis and 1 with grade 4 mucositis). The clinical CR rate was 73% (14/19) with an overall clinical response rate of 95% (18/19). Of the 14 patients with a CCR, 13 of these underwent a second-look laparotomy with 8 (61%) achieving a pathological CR. With a median follow-up of 28 months (range 11-40 months), the median PFS is 36 months and OS has not been reached. CONCLUSION: When combined with carboplatin (AUC = 12) and paclitaxel (250 mg/m(2)), the recommended topotecan dose is 3.5 mg/m(2)/day for 5 days. This outpatient HDT regimen combines three of the most active drugs in ovarian cancer with acceptable toxicity and promising activity.

Adult↗
PubMed2001

Characteristics of ovarian and uterine cancers in a cohort of in vitro fertilization patients.

OBJECTIVE: The aim of this study was to describe the features of cancers of the uterus, ovary, and other uterine adnexae in a large cohort of in vitro fertilization (IVF) patients and to thereby assist gynecologic oncologists in counseling patients with a history of infertility. METHODS: Record-linkage to population-based cancer registries was used to determine the incidence of invasive cancer in a cohort of 29,700 IVF patients. Pathology reports were made available by the cancer registries and reviewed blind to IVF treatment status. Patient information was abstracted from IVF clinic records. RESULTS: Twelve cancers of the uterus and 13 cancers of the ovary and other uterine adnexae were identified and pathology reports were reviewed for all but 1. Patients ranged in age at diagnosis from 28 to 48 years. Five cancers were diagnosed within 8 months of referral for IVF or IVF treatment; the others were diagnosed between 1 and 12 years later. The ovarian cancers were of the following histologic types: serous (4), mucinous (1), seromucinous (1), endometrioid (3), clear cell (2), and unknown type (1). A choriocarcinoma of the fallopian tube was diagnosed in a woman with a history of tubal infertility. Cancers of the uterus included endometrial adenocarcinomas (8), stromal sarcomas (2), and leiomyosarcomas (2). Ovarian cancer was diagnosed in a woman with Bloom's syndrome, a rare autosomal recessive disorder associated with increased cancer risk. CONCLUSION: Cancer cases in this large, well-defined cohort of IVF patients show a broad range of patient and tumor characteristics. We found an increased incidence of uterine sarcoma in women with a history of infertility. Increased ascertainment of preexisting cancers in the course of infertility investigations and management is to be expected.

Adult↗
PubMed2001

Pharmacokinetics and pharmacodynamic effects of 5-fluorouracil given as a one-hour intravenous infusion.

PURPOSE: Clinical toxicity associated with 5-fluorouracil (5-FU) is related to the area under the plasma concentration-time curve (AUC). Recently, short-term infusions of 5-FU given over 30 or 60 min have been substituted for conventional "bolus" 5-FU given over 3-5 min in randomized clinical trials, but there are only limited pharmacokinetic data for these altered infusion durations. We therefore wished to determine the pharmacokinetics and toxicity associated with 5-FU given as a 1-h intravenous (i.v.) infusion. METHODS: A group of 22 adults with advanced gastrointestinal tract cancers and no prior systemic chemotherapy for advanced disease received interferon alpha-2a (5 MU/m2 s.c., days 1-7), leucovorin (500 mg/m2 i.v. over 30 min, days 2-6) and 5-FU (370 mg/m2 i.v. over 1 h, days 2-6). The doses of 5-FU and interferon-alpha were adjusted according to individual tolerance. The pharmacokinetics and clinical toxicity were retrospectively compared with patients receiving the same regimen under the same treatment guidelines except that 5-FU was given over 5 min. RESULTS: The regimen was well tolerated, and 41% of the patients tolerated 5-FU dose escalations to 425-560 mg/m2 per day. Grade 3 or worse diarrhea and fatigue ultimately occurred in 14% of the patients each. Granulocytopenia, mucositis, and diarrhea appeared to be appreciably milder in the present trial compared with our prior phase II experience in colorectal cancer. The peak 5-FU plasma levels and AUC with 370 mg/m2 5-FU given over 1 h were 7.3-fold and 2.4-fold lower than previously measured in 31 patients who received 5-FU over 5 min. CONCLUSION: Increasing the length of 5-FU infusion to 1 h seemed to substantially reduce the clinical toxicity with this modulated 5-FU regimen, likely due to markedly lower peak 5-FU plasma levels and AUC. Changes in the duration of a short infusion of 5-FU clearly affects the clinical toxicity, but raises the concern of a potentially adverse impact on its antitumor activity. These results suggest the importance of including precise guidelines concerning the time over which 5-FU is given in clinical trials. Having a specified duration of 5-FU infusion is also important if 5-FU dose escalation is considered.

Adult↗
PubMed2001

Evidence for prebudding arrest of ER export in animal cell mitosis and its role in generating Golgi partitioning intermediates.

During mitosis the interconnected Golgi complex of animal cells breaks down to produce both finely dispersed elements and discrete vesiculotubular structures. The endoplasmic reticulum (ER) plays a controversial role in generating these partitioning intermediates and here we highlight the importance of mitotic ER export arrest in this process. We show that experimental inhibition of ER export (by microinjecting dominant negative Sar1 mutant proteins) is sufficient to induce and maintain transformation of Golgi cisternae to vesiculotubular remnants during interphase and telophase, respectively. We also show that buds on the ER, ER exit sites and COPII vesicles are markedly depleted in mitotic cells and COPII components Sec23p, Sec24p, Sec13p and Sec31p redistribute into the cytosol, indicating ER export is inhibited at an early stage. Finally, we find a markedly uneven distribution of Golgi residents over residual exit sites of metaphase cells, consistent with tubulovesicular Golgi remnants arising by fragmentation rather than redistribution via the ER. Together, these results suggest selective recycling of Golgi residents, combined with prebudding cessation of ER export, induces transformation of Golgi cisternae to vesiculotubular remnants in mitotic cells. The vesiculotubular Golgi remnants, containing populations of slow or nonrecycling Golgi components, arise by fragmentation of a depleted Golgi ribbon independently from the ER.

COP-Coated Vesicles↗
PubMed2001

Effect of Carmeda BioActive Surface coating versus Trillium Biopassive Surface coating of the oxygenator on circulating platelet count drop during cardiopulmonary bypass.

An investigation was conducted to evaluate the effect that surface coating of the hollow-fiber membrane oxygenator had on circulating platelet count drop during cardiopulmonary bypass (CPB). Sixty patients undergoing non-emergency myocardial revascularization for coronary artery disease were randomly divided into two groups. Group one (n = 32) received the Carmeda-coated Maxima-Plus PRF oxygenator while the patients in Group two (n=28) received the Trillium-coated Affinity oxygenator during CPB. The net platelet count drops for the pump specimen (15-20 min after the initiation of bypass) for the Carmeda and the Trillium groups were 3.6 +/- 15.8% and 6.2 +/- 10.2%, respectively. The net platelet count drop for the warming specimen for the Carmeda and the Trillium groups were 2.9 +/- 19.4% and 0.5 +/- 11.0%, respectively. There were no statistically significant differences between the groups. The authors conclude that using either the Carmeda-coated Maxima-Plus PRF oxygenator or the Trillium-coated Affinity oxygenator afford similar benefits in regards to preserving circulating platelet counts during bypass.

Aged↗
PubMed2001

The precautionary principle in environmental science.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.

Decision Making↗
PubMed2001

Good Practice Guidelines for occupational health research funded by the private sector.

The role of the private sector in funding academic research is increasing and the well-developed guidelines for government-sponsored research do not apply to the academic-industry arena. Good Practice Guidelines for privately funded occupational health research are necessary. Industry sponsors and academic researchers belong to differing systems with differing goals and means to achieve and evaluate them. As a result, problems are inherent in the relationship. Guidelines would benefit industry by providing criteria against which industry-funded research could be judged and evaluated. Guidelines would help university researchers assure that their work is examined and criticized on its merits. Such protection would foster quality research over the long term. Here, we consider the issues involved and explore questions that came out of a workshop convened under the auspices of the Centers for Disease Control and Prevention. When private funding is involved, university scientists have a professional responsibility to ensure that the integrity of researchers, subjects, and the research process is well protected. A body of experience allows us to create Good Practice Guidelines beneficial to all parties.

Journal Article↗
PubMed2001

Impaired microvascular vasodilatory function in 3-month-old infants of low birth weight.

OBJECTIVE: Low birth weight has been linked to an increased risk of type 2 diabetes and cardiovascular disease in adult life. The fetal insulin hypothesis proposed that a genetic predisposition to insulin resistance may also influence vascular development. Therefore, impaired vascular function may be an intrinsic abnormality in low-birth weight infants that antedates clinical features of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: Two groups of 3-month-old term infants were included in the study: 17 infants of lowest quartile birth weight (LQBW) and 21 infants of highest quartile birth weight (HQBW). Three aspects of skin microvascular function were examined; response to local heating, response to acetylcholine iontophoresis, and capillary density. RESULTS: Median (interquartile ranges) birth weights of the LQBW and HQBW infants were 3,140 g (2,738-3,254) and 3,920 g (3,750-4,020), respectively. Skin maximal hyperemic response to local heating was 2.14 V (1.68-2.30) in the LQBW group vs. 2.44 V (1.96-2.90) in the HQBW group (P = 0.020), and the endothelium-dependent vasodilatory response was 1.03 V (0.62-1.32) in the LQBW group vs. 0.78 V (0.45-1.32) in the HQBW group (P = 0.297). Capillary density in the LQBW and HQBW groups were 46.3 mm(-2) (40.1-53.7) and 44.1 mm(-2) (41.7-56.0), respectively (P = 0.736). CONCLUSIONS: Skin maximal hyperemic response was lower in LQBW infants, although no reduction in capillary density or defect in endothelium-dependent vasodilatation was observed. Such a lower maximal hyperemic response in early life in LQBW subjects who are at risk for type 2 diabetes and cardiovascular disease supports the hypothesis that impaired microvascular function is an early antecedent to diabetes in later life.

Acetylcholine↗
PubMed2000

Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes.

OBJECTIVES: The study was done to determine the role of partial agonist activity in the lack of effectiveness of the oral GPIIb/IIIa antagonist orbofiban. BACKGROUND: Orbofiban, an oral GPIIb/IIIa antagonist, was found to increase the mortality of patients with acute coronary syndromes (ACS) in the OPUS-TIMI-16 trial, despite the fact that it is a very potent anti-platelet agent and that IV agents have proven very effective. METHODS: Patients (n = 520) with ACS were randomized to orbofiban 30 mg, 40 mg or 50 mg twice daily or 50 mg once daily or placebo. Platelet activity was assessed in 175 patients by examining GPIIb/IIIa receptor conformation, expression of CD63 antigen, and platelet aggregation. RESULTS: Plasma concentrations of orbofiban at the highest dose (74 +/- 6 ng/ml peak, 61 +/- 5 ng/ml trough) exceeded the IC50 for platelet aggregation to adenosine diphosphate (ADP) (29 +/- 6 ng/ml) and thrombin-activating peptide (61 +/- 18 ng/ml). Orbofiban induced a conformational change in GPIIb/IIIa detected as the displacement of the monoclonal antibody mAb2; such conformational changes have been linked to partial agonist activity. Consistent with this, platelet expression of CD63 ex vivo was significantly increased at five time points during the study. In vitro, orbofiban increased platelet aggregation to a submaximal concentration of epinephrine (67 +/- 19% vs. 27 +/- 9%, n = 5) and increased thromboxane formation when the platelet GPIIb/IIIa were clustered using monoclonal antibodies to the receptor. CONCLUSIONS: Orbofiban is both an antagonist and a partial agonist of platelet GPIIb/IIIa. At low concentrations of the drug, this partial agonist activity may enhance platelet aggregation. Along with suboptimal plasma drug levels, these findings may help explain the lack of efficacy seen with orbofiban in patients with ACS.

Acute Disease↗
PubMed2000

Adenocarcinoma in situ of the uterine cervix: an experience with 100 cases.

OBJECTIVE: The aim of this study was to ascertain whether cold knife conization alone for cervical adenocarcinoma in situ is safe. METHODS: One hundred consecutive patients with a histologically proven adenocarcinoma in situ (AIS) of the cervix were studied from 1970 to 1992. RESULTS: Ninety-two women presented with abnormal smears, and of these 56% contained abnormal glandular cells. Sixty-seven (74%) of 90 women who underwent colposcopy had an abnormal examination, but a glandular abnormality was suspected in only 19 (28%). In all, 80 cold knife conizations were performed. In 7, no abnormality was found following punch biopsy. The margins were free of disease in 55 (75%). The most commonly involved margin in the remainder was the apical. Conization was followed by hysterectomy in 20 women: in 8 of these the cone margins were free and residual disease was found in 2 of the extirpated uteri: as these were extramural cases, inadequate sampling could not be excluded. Of the 12 women where hysterectomy followed conization with diseased margins, 9 had residual disease in the hysterectomy specimen. The definitive therapy was cold knife conization in 56 patients, hysterectomy in 38, and electrocoagulation diathermy in 6. Follow-up of the 53 patients treated by conization alone ranging from 1 to 16 years, with a mean of 8 years (3 have been lost to follow-up) revealed no recurrence of AIS or adenocarcinoma to date. CONCLUSION: It is concluded that cold knife conization is a safe therapeutic modality, provided that the cone biopsy has been adequately sampled and the margins are free.

Adenocarcinoma↗