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Biomedical subjects

Catherine Hill

Publications and source records attributed to Catherine Hill.

At least 19 recordsLinked to original sources
PubMed2006

Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer.

PURPOSE: To determine the risk factors for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast cancer. PATIENTS AND METHODS: We conducted a case-control study among women treated for breast cancer between 1985 and 2001 in French general hospitals, cancer centers, or clinics. We included 182 AML and MDS patients and 534 matched controls. Breast cancer characteristics, type of treatment, and family history of cancer were compared in both groups. RESULTS: The risk of AML/MDS was increased after topoisomerase-II inhibitor-based chemotherapy (P < 10-16) and was higher for mitoxantrone-based chemotherapy than for anthracycline-based chemotherapy (relative risk [RR] = 15.6; 95% CI, 7.1 to 34.2; and RR = 2.7; 95% CI, 1.7 to 4.5, respectively). After adjustment for other treatment components, the risk of AML/MDS in patients who received radiotherapy was multiplied by 3.9 (95% CI, 1.4 to 10.8) but was not increased by alkylating agents. Patients receiving granulocyte colony-stimulating factor (G-CSF) support had an increased risk of AML/MDS (RR = 6.3; 95% CI, 1.9 to 21), even when controlling for chemotherapy doses. Similar results were obtained when AML and MDS were considered separately. CONCLUSION: This large case-control study demonstrates that the risk of AML/MDS is much higher with mitoxantrone-based chemotherapy than with anthracyclines-based chemotherapy in a population of women recently treated for breast cancer. The risk of AML/MDS associated with mitoxantrone must be kept in mind when using this drug to treat diseases other than breast cancer (eg, prostate cancer or multiple sclerosis). In addition, our study suggests the need to monitor the long-term effects of G-CSF therapy.

Acute Disease↗
PubMed2006

A mitochondrial stratigraphy for island southeast Asia.

Island Southeast Asia (ISEA) was first colonized by modern humans at least 45,000 years ago, but the extent to which the modern inhabitants trace their ancestry to the first settlers is a matter of debate. It is widely held, in both archaeology and linguistics, that they are largely descended from a second wave of dispersal, proto-Austronesian-speaking agriculturalists who originated in China and spread to Taiwan approximately 5,500 years ago. From there, they are thought to have dispersed into ISEA approximately 4,000 years ago, assimilating the indigenous populations. Here, we demonstrate that mitochondrial DNA diversity in the region is extremely high and includes a large number of indigenous clades. Only a fraction of these date back to the time of first settlement, and the majority appear to mark dispersals in the late-Pleistocene or early-Holocene epoch most likely triggered by postglacial flooding. There are much closer genetic links to Taiwan than to the mainland, but most of these probably predated the mid-Holocene "Out of Taiwan" event as traditionally envisioned. Only approximately 20% at most of modern mitochondrial DNAs in ISEA could be linked to such an event, suggesting that, if an agriculturalist migration did take place, it was demographically minor, at least with regard to the involvement of women.

Asia, Southeastern↗
PubMed2006

Management of an incidentally discovered pulmonary nodule.

The incidental finding of a pulmonary nodule on computed tomography (CT) is becoming an increasingly frequent event. The discovery of such a nodule should evoke the possibility of a small bronchogenic carcinoma, for which excision is indicated without delay. However, invasive diagnostic procedures should be avoided in the case of a benign lesion. The objectives of this review article are: (1) to analyze the CT criteria defining benign nodules, nodules of high suspicion of malignancy and indeterminate nodules, (2) to analyze the diagnostic performances and limitations of complementary investigations requested to characterize indeterminate lung nodules, (3) to review the criteria permitting to assess the probability of malignancy of indeterminate nodules and (4) to report on the new guidelines provided by the Fleischner Society for the management of small indeterminate pulmonary nodules, according to their prior probability of malignancy.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2006

Phylogeography and ethnogenesis of aboriginal Southeast Asians.

Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula approximately 4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia.

Asia, Southeastern↗
PubMed2006

Estimates of the cancer burden in Europe from radioactive fallout from the Chernobyl accident.

The Chernobyl accident, which occurred April 26, 1986, resulted in a large release of radionuclides, which were deposited over a very wide area, particularly in Europe. Although an increased risk of thyroid cancer in exposed children has been clearly demonstrated in the most contaminated regions, the impact of the accident on the risk of other cancers as well as elsewhere in Europe is less clear. The objective of the present study was to evaluate the human cancer burden in Europe as a whole from radioactive fallout from the accident. Average country- and region-specific whole-body and thyroid doses from Chernobyl were estimated using new dosimetric models and radiological data. Numbers of cancer cases and deaths possibly attributable to radiation from Chernobyl were estimated, applying state-of-the-art risk models derived from studies of other irradiated populations. Simultaneously, trends in cancer incidence and mortality were examined over time and by dose level. The risk projections suggest that by now Chernobyl may have caused about 1,000 cases of thyroid cancer and 4,000 cases of other cancers in Europe, representing about 0.01% of all incident cancers since the accident. Models predict that by 2065 about 16,000 (95% UI 3,400-72,000) cases of thyroid cancer and 25,000 (95% UI 11,000-59,000) cases of other cancers may be expected due to radiation from the accident, whereas several hundred million cancer cases are expected from other causes. Although these estimates are subject to considerable uncertainty, they provide an indication of the order of magnitude of the possible impact of the Chernobyl accident. It is unlikely that the cancer burden from the largest radiological accident to date could be detected by monitoring national cancer statistics. Indeed, results of analyses of time trends in cancer incidence and mortality in Europe do not, at present, indicate any increase in cancer rates -- other than of thyroid cancer in the most contaminated regions -- that can be clearly attributed to radiation from the Chernobyl accident.

Adolescent↗
PubMed2006

Does the CONSORT checklist improve the quality of reports of randomised controlled trials? A systematic review.

OBJECTIVE: To determine whether the adoption of the CONSORT checklist is associated with improvement in the quality of reporting of randomised controlled trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, Cochrane CENTRAL, and reference lists of included studies and of experts were searched to identify eligible studies published between 1996 and 2005. STUDY SELECTION: Studies were eligible if they (a) compared CONSORT-adopting and non-adopting journals after the publication of CONSORT, (b) compared CONSORT adopters before and after publication of CONSORT, or (c) a combination of (a) and (b). Outcomes examined included reports for any of the 22 items on the CONSORT checklist or overall trial quality. DATA SYNTHESIS: 1128 studies were retrieved, of which 248 were considered possibly relevant. Eight studies were included in the review. CONSORT adopters had significantly better reporting of the method of sequence generation (risk ratio [RR], 1.67; 95% CI, 1.19-2.33), allocation concealment (RR, 1.66; 95% CI, 1.37-2.00) and overall number of CONSORT items than non-adopters (standardised mean difference, 0.83; 95% CI, 0.46-1.19). CONSORT adoption had less effect on reporting of participant flow (RR, 1.14; 95% CI, 0.89-1.46) and blinding of participants (RR, 1.09; 95% CI, 0.84-1.43) or data analysts (RR, 5.44; 95% CI, 0.73-36.87). In studies examining CONSORT-adopting journals before and after the publication of CONSORT, description of the method of sequence generation (RR, 2.78; 95% CI, 1.78-4.33), participant flow (RR, 8.06; 95% CI, 4.10-15.83), and total CONSORT items (standardised mean difference, 3.67 items; 95% CI, 2.09-5.25) were improved after adoption of CONSORT by the journal. CONCLUSIONS: Journal adoption of CONSORT is associated with improved reporting of RCTs.

Editorial Policies↗
PubMed2006

Assessment of lung disease in children with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison with Shwachman score, Chrispin-Norman score and spirometry.

This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years), with different severity of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a 21-second breath-hold and scored according to previously defined criteria. Spearman's non-parametric correlations test was performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted (r=-0.41; p=0.047) and FVC% predicted (r=-0.42; p=0.04), while there were trends of correlations between Shwachman score and MRI score (r=-0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring lung disease and assessing therapy in this patient population.

Adolescent↗
PubMed2006

Hyperpolarized 3helium magnetic resonance ventilation imaging of the lung in cystic fibrosis: comparison with high resolution CT and spirometry.

The purpose of this study was to compare hyperpolarized 3helium magnetic resonance imaging (3He MRI) of the lungs in adults with cystic fibrosis (CF) with high-resolution computed tomography (HRCT) and spirometry. Eight patients with stable CF prospectively underwent 3He MRI, HRCT, and spirometry within 1 week. Three-dimensional (3D) gradient-echo sequence was used during an 18-s breath-hold following inhalation of hyperpolarized 3He. Each lung was divided into six zones; 3He MRI was scored as percentage ventilation per lung zone. HRCT was scored using a modified Bhalla scoring system. Univariate (Spearman rank) and multivariate correlations were performed between 3He MRI, HRCT, and spirometry. Results are expressed as mean+/-SD (range). Spirometry is expressed as percent predicted. There were four men and four women, mean age = 31.9+/-9 (20-46). Mean forced expiratory volume in 1 s (FEV)1 = 52%+/-29 (27-93). Mean 3He MRI score = 74%+/-25 (55-100). Mean HRCT score = 48.8+/-24 (13.5-83). The correlation between 3He MRI and HRCT was strong (R = +/-0.89, p < 0.001). Bronchiectasis was the only independent predictor of 3He MRI; 3He MRI correlated better with FEV1 and forced vital capacity (FVC) (R = 0.86 and 0.93, p < 0.01, respectively) than HRCT (R = +/-0.72 and +/-0.81, p < 0.05, respectively). This study showed that 3He MRI correlates strongly with structural HRCT abnormalities and is a stronger correlate of spirometry than HRCT in CF.

Adult↗
PubMed2006

[The frequency of cancer in France in year 2002, and trends since 1968].

The estimated number of cancers diagnosed in 2002 is 150,000 in the male population and 120,000 in the female population and there were close to 88,000 cancer deaths among men and 59,000 cancer deaths among women in France. The most frequent cancer sites in the male population are prostate, lung, colon, intestine and head & neck (mouth, pharynx, larynx). In the female population, breast cancer is by far the most frequent cancer, followed by colorectal cancer. Between 1968 and 2002, cancer mortality decreased by 5% for men and by 19% for women. Cancer mortality reached a maximum in 1987 in the male population and in the last 15 years the decrease is larger among men than among women.

Adult↗
PubMed2005

Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes.

A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated "relict" populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia approximately 65,000 years ago was rapid, most likely taking only a few thousand years.

Africa↗
PubMed2005

Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies.

Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.

Amino Acids↗
PubMed2005

Mortality of workers exposed to ionizing radiation at the French National Electricity Company.

BACKGROUND: Exposure to ionizing radiation increases the risk of cancer in humans. Nuclear workers receive low doses over a relatively long period of time. METHODS: A mortality study of a cohort of workers exposed to ionizing radiation at Electricité de France (EDF) was conducted. The cohort consisted of 22,395 individuals monitored for radiation exposure between 1961 and 1994, and followed-up for an average of 11.7 years. RESULTS: Our study demonstrates a clear healthy worker effect (HWE) since mortality is less than half what is expected from National mortality statistics. The HWE is greater among workers who have spent most of their career in the nuclear sector. The analysis by cancer site shows no excess compared with the general population. No significant trend was observed according to level of exposure to ionizing radiation. CONCLUSIONS: The mortality of workers exposed to ionizing radiation at the French National Electricity company is very low compared to the French national mortality.

Adolescent↗
PubMed2005

Quantitative analysis of regional airways obstruction using dynamic hyperpolarized 3He MRI-preliminary results in children with cystic fibrosis.

PURPOSE: To investigate regional airways obstruction in patients with cystic fibrosis (CF) with quantitative analysis of dynamic hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: Dynamic radial projection MRI of HP (3)He gas was used to study respiratory dynamics in a group of eight children with CF. Signal kinetics in a total of seven regions of interest (ROIs; three in each lung, and one in the trachea) were compared with the results of spirometric pulmonary function tests (PFTs). The tracheal signal intensity was used as a form of "input function" to normalize for input flow effects. RESULTS: A pattern of low flow rate in the upper lobes was observed. When the flow measurements from the peripheral ROIs were averaged to obtain an index of flow in the peripheral lung, a good correlation was found (P = 3.74 x 10(-5)) with the forced expired volume in one second (FEV1). CONCLUSION: These results suggest that a quantitative measurement of localized airways obstruction in the early stages of CF may be obtained from dynamic (3)He MRI by using the slope of the signal rise as a measure of air flow into the peripheral lung. This study also demonstrates that children can cooperate well with the (3)He MRI technique.

Adolescent↗
PubMed2005

Results of two randomized trials evaluating adjuvant anthracycline-based chemotherapy in 1146 patients with early breast cancer.

Two randomized trials evaluated the effect of 6 courses of anthracycline-based chemotherapy in early breast cancer. A total of 1146 patients were included: 311 high-risk node-negative premenopausal patients and 835 high-risk node-negative or node-positive postmenopausal patients. Patients were randomized after surgery to receive either no chemotherapy (control group) or 6 courses of anthracycline-based chemotherapy (CT group). Postmenopausal patients received adjuvant tamoxifen for at least two years. Radiotherapy was delivered after completion of chemotherapy in the CT group. The 10-year disease-free survival (DFS) rates were 60% in the control group and 65% in the CT group (log-rank test, p = 0.01). The 10-year distant metastasis rates were 28% and 23% (p = 0.02), and the 10-year local recurrence rates were 12% and 10%, respectively (p = 0.24). Chemotherapy was significantly less effective in post-menopausal patients with estrogen receptor-positive tumors. Adjuvant anthracycline-based chemotherapy yielded a significant benefit for DFS by lowering the risk of distant metastases. After up to 10 years of follow-up, deferring radiotherapy after chemotherapy did not compromise local control.

Adult↗
PubMed2005

[The frequency of cancer in France in year 2000, and trends since 1950].

In 2000, there were 87,000 cancer deaths among men and 57,000 cancer deaths among women in France. Cancer mortality is decreasing since 1987 in the male population and since the mid 1960s in the female population. The decrease is larger among men than among women. The estimated number of cancers diagnosed in 2000 is 160,000 in the male population and 120,000 in the female population. The most frequent cancer sites in the male population are prostate, lung, colon, intestine and mouth, pharynx plus larynx. In the female population, breast cancer is by far the most frequent cancer, followed by colorectal cancer. Between 1980 and 2000, cancer incidence increased by 30%, whereas cancer mortality decreased by 10%, these results are observed for each sex.

Age Distribution↗
PubMed2004

Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide.

A series of mono- and bidentate phosphites was prepared with (S)-5,5',6,6'-tetramethyl-3,3'-di-tert-butyl-1,1'-biphenyl-2,2'-dioxy [(S)-BIPHEN] as a chiral auxiliary and screened in the asymmetric hydroformylation of allyl cyanide. These hydroformylation results were compared with those of two existing chiral ligands, Chiraphite and BINAPHOS, whose utility in asymmetric hydroformylation has been previously demonstrated. Bisphosphite 11 with a 2,2'-biphenol bridge was found to be the best overall ligand for asymmetric hydroformylation of allyl cyanide with up to 80% ee and regioselectivities (branch-to-linear ratio, b/l) of 20 with turnover frequency of 625 [h(-)(1)] at 35 degrees C. BINAPHOS gave enantioselectivities up to 77% ee when the reaction was conducted in either acetone or neat but with poor regioselectivity (b/l 2.8) and activities 7 times lower than that of 11. The product of allyl cyanide hydroformylation using (R,R)-11 was subsequently transformed into (R)-2-methyl-4-aminobutanol, a useful chiral building block. Single-crystal X-ray structures of (S,S)-11 and its rhodium complex 19 were determined.

Journal Article↗