Biomedical subjects
J Boyd
Publications and source records attributed to J Boyd.
Electronic health summaries--building on the foundation of Scottish Record Linkage system.
Developing electronic patient records is currently a priority for Health Services, so that the clinician treating the patient has all the relevant information available on the desktop. However, as with paper records, there is the danger of information overload, with key information being missed. It is now recognized that electronic health summaries of patient events will be needed. This paper describes the Scottish Record Linkage system, which has been routinely used over the last 10 years to build event histories for patients in the NHS in Scotland. Probability matching has been used to identify records belonging to an individual since a unique patient identification number has not been in general use. We present examples of use of this rich information resource, either for clinical decision making, evidence based medicine, or population needs assessment, and investigate how the system may be developed in a data-warehousing environment to populate electronic health summaries for the five million residents of Scotland.
Analysis of fibroblast growth factor receptor 3 S249C mutation in cervical carcinoma.
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Evidence of improving prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995.
BACKGROUND: Contemporary survival in unselected patients with heart failure and the population impact of newer therapies have not been widely studied. Therefore, we have documented case-fatality rates (CFRs) over a recent 10-year period. METHODS AND RESULTS: In Scotland, all hospitalizations and deaths are captured on a single database. We have studied case fatality in all patients admitted with a principal diagnosis of heart failure from 1986 to 1995. A total of 66 547 patients (47% male) were studied. Median age was 72 years in men and 78 years in women. Crude CFRs at 30 days and at 1, 5, and 10 years were 19.9%, 44.5%, 76.5%, and 87.6%, respectively. Median survival was 1.47 years in men and 1.39 years in women (2.47 and 2. 36 years, respectively, in those surviving 30 days). Age had a powerful effect on survival, and sex, comorbidity, and deprivation had modest effects. One-year CF was 24.2% in those aged <55 years and 58.1% in those aged >84 years. After adjustment, 30-day CFRs fell between 1986 and 1995, by 26% (95% CI 15 to 35, P<0.0001) in men and 17% (95% CI 6 to 26, P<0.0001) in women. Longer term CFRs fell by 18% (95% CI 13 to 24, P<0.0001) in men and 15% (95% CI 10 to 20, P<0.0001) in women. Median survival increased from 1.23 to 1. 64 years. CONCLUSIONS: Heart failure CF is much higher in the general population than in clinical trials, especially in the elderly. Although survival has increased significantly over the last decade, there is still much room for improvement.
Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.
BACKGROUND: The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. METHODS: Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age-matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. RESULTS: Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB-2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. CONCLUSIONS: Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare.
Ten year audit of secondary prevention in coronary bypass patients.
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Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.
CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.
"I don't like Mondays"-day of the week of coronary heart disease deaths in Scotland: study of routinely collected data.
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Carcinosarcoma of the ovary in a patient with a germline BRCA2 mutation: evidence for monoclonal origin.
BACKGROUND: Themajority of hereditary breast and ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. While the occurrence of breast carcinoma and epithelial ovarian carcinoma in association with BRCA mutations is firmly established, the etiologic role of these genes in the development of other tumor types is less well documented. Carcinosarcoma of the ovary is an uncommon tumor consisting of both malignant epithelial and malignant mesenchymal components. OBJECTIVE: Here we report a patient with an ovarian carcinosarcoma who was found to harbor a germline mutation in BRCA2. We sought to link the BRCA2 mutation to the pathogenesis of this tumor as well as to determine whether both histologic components arose from the same progenitor cell. METHODS: Microdissection and molecular genetic analyses of the carcinomatous and sarcomatous components of this tumor were performed. RESULTS: Clonal loss of the wild-type BRCA2 allele as well as the same somatic mutation of the TP53 gene was evident in both histologic components. CONCLUSIONS: These data indicate that hereditary ovarian carcinosarcoma may result from a mutation in BRCA2 and that both histologic elements of this tumor arose from the same progenitor cell.
Punctuated recovery of sediments and benthic infauna: a 19-year study of tailings deposition in a British Columbia fjord.
Sediment organic and metal chemistry, benthic infauna and tissue contaminants surveys have been conducted over 19 years before and following tailings deposition from a metal (Mo, Pb, Zn) mine in Alice Arm, a British Columbia fjord. We found changes in benthic fauna and habitat after tailings disposal to be predictable in terms of sediment chemistry and faunal recolonization. What was not predictable was the timing and extent of slope failure or resuspension following abandonment. These events can have essentially the same or greater effect than the initial tailings disposal and produce long-term unpredictability particular to cases of submarine disposal on slopes. The present study focused on the submarine deposition of 4 x 10(6) tonnes of tailings during an 18-months period ending October 1982. When the mine closed, gross defaunation had occurred at three stations in the tailings path, and two others showed recent defaunation and recolonization. A year later, a large tailings slump near the outfall transported tailings to the deep basin; fauna were impoverished both in the slump region and through most of the deep basin. Declining metal concentrations in surface sediments was accompanied by considerable recovery of fauna 3 years after the mine closed. Nevertheless, fauna at the three stations defaunated at the time of mine closure could still be statistically distinguished from all other stations due to high abundances of small opportunistic polychaetes and bivalves. A resuspension in tailings between 1988 and 1990 coincided with a moderate decline in abundance of all macrofauna taxa. From 1989 to 1995 recovery toward natural sediment conditions was evident as increasing organic content together with the highest faunal biomass values found during the study. Small polychaetes were the first recolonizers in defaunated areas, whereas small bivalves were more tolerant of moderate tailings deposition. By 1989 and 1995 small colonizers had declined and amphipods and larger echinoderms had increased. Dominant species patterns and exceptionally high biomass values in 1995 show that the largest fauna did not recover until much later than smaller taxa. One genus of bivalve (Yoldia spp.) accumulated metals in a pattern similar to the sediment chemistry, indicating that the metals from the most recent mine had entered the benthic food chain. It is not possible to tell from this study whether biota were affected by toxicity from metals. However, many of the observed biotic effects could be caused by physical disruption from tailings.
[Does primary melanoma of the bladder exist?].
Primary melanoma of the urinary bladder is a rare neoplasm to which very strict diagnostic criteria apply. Although reports of previous cases exist, these criteria have yet to be met. We report a case of a young lady from whom a malignant melanoma of the bladder was resected. This was presumed to be primary as detailed investigation failed to find any other site from which metastases could have originated. We discuss the diagnostic criteria of this entity and stress the difficulty in conclusively demonstrating that, despite some of these criteria being met, a lesion such as this is primary in origin. This case could be the longest surviving patient with primary melanoma of the bladder, however we will never be able to prove that spontaneous regression of an undiagnosed extravesical primary malignant melanoma did not occur.
Trends in case-fatality in 117 718 patients admitted with acute myocardial infarction in Scotland.
OBJECTIVES: To analyse short- and long-term case-fatality trends following admission to hospital with a first acute myocardial infarction, in men and women between 1986 and 1995, after adjusting for risk factors known to influence survival. DESIGN: A Scottish-wide retrospective cohort study. SETTING: The Linked Scottish Morbidity Record Database was analysed. This contains accurate data on all hospital admissions since 1981, for the Scottish population of 5.1 million. It is linked to the Registrar General's death certificate data. SUBJECTS: All 117 718 patients admitted to Scottish hospitals with a principal diagnosis of first acute myocardial infarction (ICD-9 code 410) between 1986 and 1995. MAIN OUTCOME MEASURES: The outcome was death, both in and out of hospital, from any cause, at 30 days, 1 year, 5 and 10 years. RESULTS: Overall case-fatality following hospital admission with acute myocardial infarction was 22. 2%, 31.4%, 51.1% and 64.0% at 1 month, 1 year, 5 and 10 years, respectively. Multivariate analyses identified statistically significant independent prognostic factors. Thirty day mortality increased twofold for each decade of increasing age, and increased with any prior admission to hospital. When comparing the most deprived category to that of the most affluent, men had a 10% increased mortality (P<0.01), whilst women had an increased mortality of 4% (not significant). After adjustment for age, sex, deprivation and prior admission to hospital, case-fatality rates fell significantly between 1986 and 1995. Short-term case-fatality fell by 46% in men (27% in women) and long-term by 34% in men (30% in women) (both P<0.001). CONCLUSIONS: Population-based case-fatality rates in Scotland have fallen dramatically since 1986, particularly in men. The increasing survival in patients admitted to hospital suggests that the trial-based efficacy of modern therapies is now translating into population-based effectiveness. However, an individual's life expectancy still halves after a diagnosis of acute myocardial infarction. Of the variables that we could examine, age was the most powerful predictor of prognosis.
First trimester ultrasound with nuchal translucency measurement for Down syndrome risk estimation using software developed by the Fetal Medicine Foundation, United Kingdom--the first 2000 examinations in Newcastle, New South Wales, Australia.
In September 1997 screening for Down syndrome using first trimester ultrasound to measure nuchal translucency, with risk estimation by the software program developed in the United Kingdom by the Fetal Medicine Foundation, was introduced in Newcastle, New South Wales. In the first 2,000 such risk estimations 134 women (6.7 %) were screen positive (with a risk of greater than 1 in 300 at that gestation for Trisomy 21). In the first 1,000 of these 2,000 fetuses delivered thus far there were 8 cases of Trisomy 21, 2 of Trisomy 18 and 1 of 47 XXX. Nine of these 11 were screen positive, the only false negative results being for 2 cases of Trisomy 21. The detection rate for Trisomy 21 was 6 out of 8 (75%) and for every case of Trisomy 21 (Down Syndrome) detected by this process, 11.3 invasive tests would have been needed to make that diagnosis in a screen positive woman.
[Is there a physician on board?].
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Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations.
BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer who have inherited mutations in these genes have a different outcome after breast conservation therapy than women with "sporadic" cancer is unresolved. Consequently, we compared the outcomes after breast conservation therapy in Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA). METHODS: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast cancers. We reviewed their clinical records, retrieved their archival tissue samples, and tested those samples for the founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All Pvalues are two-sided. RESULTS: We detected mutations in BRCA genes in 28 of 305 women. Women with BRCA mutations were more likely to be diagnosed with cancer before the age of 50 years (P<.001) and to have lymph node involvement (P =.04). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative risk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03). Women with mutations were more likely to develop contralateral breast cancer (RR = 3.50; 95% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in women with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor stage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis. CONCLUSIONS: Women with BRCA founder mutations are at increased risk for breast cancer-related events after breast conservation. However, mutation status is not an independent predictor of survival and should not influence decisions regarding adjuvant therapy. The increased contralateral breast cancer risk in women heterozygous for BRCA mutations mandates careful surveillance.
Re: Association between nonrandom X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer.
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p53 and genetic susceptibility to cervical cancer.
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Natural and anthropogenic inputs of hydrocarbons to the Strait of Georgia.
Sediment cores from the Fraser estuary, Vancouver Harbour and Strait of Georgia, suspended sediment samples from the Fraser River and sediment grabs from Vancouver Harbour have been analyzed for alkanes and parent and alkyl PAHs (polycyclic aromatic hydrocarbons). Principal components analysis (PCA) clearly distinguishes mixed sources by separating parent PAHs according to molecular size, and separating alkyl substituted PAHs from higher plant PAHs. We find the Fraser River to be the predominant source for natural and anthropogenic hydrocarbons to the Strait of Georgia. The natural hydrocarbon burden from the Fraser River is augmented principally by petroleum hydrocarbons and combustion PAHs from Vancouver. Contaminated sediments from Vancouver Harbour very likely have also been transported to a major ocean disposal site off the Fraser estuary. Petroleum alkanes, which dominate Fraser River suspended sediment samples, are lost by processes such as dissolution or microbial degradation during transport and sedimentation, while PAHs from the river are delivered essentially unchanged to sediments in the strait. Hydrocarbon composition undergoes little change with depth at a reference location in the Strait of Georgia, indicating that PAH inputs have changed very little since the early part of this century. In Vancouver Harbour the low rate of sediment accumulation coupled with surface mixing has led to the retention of contaminant PAHs within the surface mixed layer, while the rapid delivery of sediments from the Fraser River has buried contaminant PAHs from historical ocean disposal in the Strait of Georgia.