Biomedical subjects

D Fleming

Publications and source records attributed to D Fleming.

At least 19 recordsLinked to original sources

PubMed2005

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York.

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

Adult↗

PubMed2003

Harmonisation of national influenza surveillance morbidity data from EISS: a simple index.

The European Influenza Surveillance Scheme is a collaboration with 18 member countries (2001/02) which monitors the activity and impact of influenza by collecting morbidity and virological data in primary care facilities throughout the winter season each year. Despite being in principle similar in the surveillance concept, the indicators used and observations made are very different. Different healthcare systems and organisational needs (eg a certificate of illness for the employer) influence the consultation behaviour. Furthermore, and partly as a result of differences in the healthcare systems, the definitions used for the numerator and denominator when calculating morbidity rates are different. Thus comparative interpretation of participating countries' morbidity data is extremely difficult. Reporting 'harmonisation' by using equivalent numerators and denominators is one option but is difficult to achieve in the short term. Moreover, several additional issues would need to be considered, for example, the need for continuity of surveillance and whether such steps would indeed result in direct comparability etc. A simple index was tested, through which the impact of influenza morbidity in any one year is compared with what is considered a 'usual' epidemic in that country. The index in principle describes numerically the extent to which the influenza-attributable excess morbidity in the current epidemic in each country is within, exceeds, or is less than a range typical for an influenza epidemic. In this pilot study, the usefulness of such an index is explored with the example of eight countries for the seasons 1999/2000 and 2000/01. A fine tuning of the methods has not yet been performed.

Belgium↗

PubMed2003

Influenza and adult hospital admissions for respiratory conditions in England 1989-2001.

Influenza is recognised as a major cause of excess hospital admissions during winter months. This study sets out to quantify admissions related to influenza during the last twelve winters and to examine the importance of age. Total admission data for respiratory disorders in adults for England during the years 1989 to 2001 have been used. Weekly admission data were examined in five-year age bands. Influenza epidemics were identified from clinical incidence data in the community. Baseline admission levels were determined by averaging weekly incidence data from weeks in which there was no clinical evidence of influenza activity. Excess admissions were estimated from the difference between observed and baseline admissions after adjusting the baseline in each group and year for the secular trend. Estimates for all adults were consolidated from the five-year age bands. Bed occupancy was estimated by applying data on average bed stay to excess admissions in age- and year-specific groups. We estimated 2.7% of all respiratory admissions were related to influenza. Excess admissions were strongly age related. Of the 16,227 annual average excess, 52% occurred in persons over 75 years. The excess admissions account for an average 145,544 bed days annually, two thirds (69%) in persons over 75 years. Annual excess bed occupancy was highest in 1999/2000 (39,512) though 30,000 excess admissions per year is not unusual. Hospital admissions due to influenza remain a major problem for health service delivery particularly in elderly populations. Though robust programmes of vaccination are needed, vaccination by itself will not eliminate the impact of influenza on hospital admissions in winter.

Adolescent↗

PubMed2002

The clinical diagnosis of influenza.

Effective management of influenza depends on early recognition of influenza in the community and on rapid diagnosis. Early recognition is achieved by integrated clinical and laboratory based surveillance programmes in representative populations. The recent introduction of 'near patient tests' for influenza provide increased opportunities for surveillance but diagnosis remains largely clinically based. The combination of cough and fever in conditons of known local influenza virus circulation provide a useful indicator of diagnosis to guide management.

Humans↗

PubMed2001

cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma.

The histological diagnosis of hepatocellular carcinoma (HCC) can be complicated by difficulty in differentiation from cholangiocarcinoma and metastatic carcinoma. Immunohistochemical stains currently in use are suboptimal in terms of specificity and sensitivity. Using cDNA array analysis for differential gene expression, we demonstrated a significant increase in mRNA expression level of CD10/CALLA, a type 2 cell-surface metalloproteinase, in HCC, which was subsequently confirmed by reverse transcriptase-polymerase chain reaction and Western blotting analysis. To test the possibility of using CD10/CALLA as a diagnostic marker for HCC, various intrahepatic tumors were studied immunohistochemically using a monoclonal antibody for CD10. A characteristic canalicular-staining pattern was observed in normal hepatocytes and at the apical surface of bile duct epithelial cells. The canalicular expression of CD10 was identified in 9 of 15 HCCs examined (60%), whereas 10 cholangiocarcinomas and 8 of 9 metastatic carcinomas lacked this staining. In three of the six HCCs negative for CD10, the surrounding nonneoplastic liver tissue was also negative, suggesting fixation-associated loss of immunoreactivity. Six HCCs had stronger CD10 staining in tumor cells when compared to the surrounding nonneoplastic tissue. Three cases of benign bile duct adenomas also expressed CD10 at the luminal aspect. One of the MCs showed a diffuse, cytoplasmic staining for CD10, a pattern readily distinguishable from that of HCC. A panel of other immunohistochemical markers were also studied for comparison, including polyclonal anti-carcinoembryonic antigen, cytokeratin (CK) 7, CK20, and alpha-fetoprotein. Our results demonstrate that cDNA arrays can be effectively used to identify new diagnostic markers, and that CD10 is a reliable marker for identifying HCC, particularly when used in conjunction with a panel of immunohistochemical markers (polyclonal anti-carcinoembryonic antigen, CK7, CK20, and alpha-fetoprotein) and in the distinction from cholangiocarcinoma.

Adenoma↗

PubMed2001

Docetaxel-carboplatin as first line chemotherapy for epithelial ovarian cancer.

A prospective, non-randomized, multicentre, open, dose-finding study of a carboplatin-docetaxel (C-D) combination as first-line chemotherapy in FIGO stage Ic-IV epithelial ovarian cancer. C-D was given 3-weekly for 6 planned cycles, with a 3-day prophylactic dexamethasone regimen (8 mg b.i.d.). 139 eligible patients (Pts) (median age 56 years, range 28-85) were given a total of 750 cycles of chemotherapy in 5 cohorts: Co1, 32 pts, 169 cycles (C at AUC 5 + D 60 mg/m(2)); Co2, 22 pts, 122 cycles (5 + 75), Co3, 29 pts, 156 cycles (6 + 75), Co4, 27 pts, 146 cycles (7 + 75), Co5, 30 pts, 157 cycles (6 + 85). 110 patients (79%) completed 6 cycles; 17 (12%) stopped due to toxicity. 104 patients (75%) had CTC grade IV neutropenia, and 5 patients (4%) had this associated with fever. There were 2 probable treatment-related deaths. Only 8 patients (6%) experienced grade II-III neurotoxicity (all sensory; no motor > grade I). The maximum tolerated dose was reached in cohorts 4 and 5, and the dose limiting toxicities were myelosuppression and diarrhoea. The overall response rate for the study was 66% (49/74); CA125 response was 75% (70/93). Median progression-free survival was 16.6 months (95% CI 13.3-19.1). Recommended doses are carboplatin AUC 5 (via(51)Cr EDTA) or AUC 6 (if calculated) plus docetaxel 75 mg/m(2). A randomized trial comparing this regimen with carboplatin-paclitaxel has just completed recruitment.

Adenocarcinoma↗

PubMed2001

Resistance to glucocorticoid feedback in obesity.

Increased hypothalamo-pituitary-adrenal axis drive has been reported in obese subjects but with paradoxically low or normal levels of plasma cortisol. Our current study was designed to investigate whether glucocorticoid feedback was altered in obesity, both under basal and stressed conditions. Plasma ACTH and cortisol concentrations in male control or obese subjects (age range 20-50 yr) were measured at frequent intervals over 24 h during infusion of saline or hydrocortisone at two physiological doses (7.5 and 15 mg/d) designed to occupy predominantly mineralocorticoid rather than glucocorticoid receptors. The same subjects then underwent insulin-induced hypoglycemia either in the morning or the evening. Obese subjects had significantly higher basal ACTH and lower cortisol concentrations throughout the 24 h infusion period, compared with controls (P < 0.05, two-way ANOVA followed by Newman-Keuls posthoc analysis). Basal plasma ACTH was decreased in obese groups given low- or high-dose hydrocortisone during the day (P < 0.05) but not during the night, unlike controls who responded to hydrocortisone both during the day and at night (P < 0.05). Obese subjects also showed resistance to steroid-induced inhibition of the ACTH response to hypoglycemia, compared with controls (P < 0.05). These data clearly show that obesity is associated with a relative insensitivity to glucocorticoid feedback, which is most marked during the night, and suggest that this condition is characterized by a decreased mineralocorticoid receptor response to circulating corticosteroids.

Adrenocorticotropic Hormone↗

PubMed2001

Effect of active limb movements on symptoms in patients with low back pain.

STUDY DESIGN: A descriptive, correlational study of patients with mechanical low back pain (LBP). OBJECTIVES: To assess the effect of active limb movements on symptoms in patients with LBP and to examine the relationship between symptoms with limb movements and select patient characteristics. BACKGROUND: Limb movements result in forces applied to the spine and, thus, may be important in the examination and treatment of patients with LBP. METHODS AND MEASURES: A total of 188 people with LBP, 84 men and 104 women, participated in a standardized examination. Six of the items required patients to move their limbs and note LBP symptoms as increased, remained the same, or decreased. The prevalence of various symptom responses with each limb movement test was calculated. Relationships between patient characteristics and reports of increased symptoms were examined with Cochran's linear trend statistic and the Spearman and Pearson correlation coefficients. Differences in characteristics of patients with and without increased symptoms were examined with chi2 test, Mann-Whitney U test, or Student's t test for independent groups. RESULTS: An increase in symptoms was reported by 149 patients with at least 1 of the limb movement tests, and 3 of the patients reported a decrease in symptoms. Across the patient sample, the mean number of limb movement tests for which symptoms were reported as increased was 2.30 +/- 1.64. Patients with an increase in symptoms reported higher average pain intensity the week prior to the examination (median = 2; range: 1-5) and higher functional disability (mean = 0.25; SD = 0.15) than those without a change in symptoms (pain intensity: median = 1; range: 0-2 and functional disability: mean = 0.16; SD = 0.12). The correlation between the number of increased symptoms and the person's average pain intensity was r = 0.23; the correlation with the functional disability score was r = 0.36. Patients with a history of LBP tended to report an increase in symptoms with more of the limb movement tests (mean = 3.5; SD = 1.40) than those without a previous history of LBP (mean = 2.0; SD = 1.11). CONCLUSIONS: Active limb movements performed during the examination primarily resulted in increased LBP symptoms. The presence and number of increased symptoms with the active limb movements was related to the patient's report of average pain intensity and functional disability. Tests of symptoms with active limb movements may provide insight into factors contributing to a LBP problem, as well as information to guide the treatment of patients with LBP.

Adolescent↗

PubMed2000

Rapid antibody response to influenza vaccination in "at risk" groups.

Persons attending for routine influenza vaccination in an urban practice each provided three specimens of blood for evaluating their immunological response. 138 (67%) of the 206 persons were defined as "at risk" by reason of morbidity as given in the guidelines published by the Chief Medical Officer. The mean age was 67 yr and 65% were aged 65 yr or more. By day 7, 71% of 31 persons had protective H(1)N(1) titres, 61% H(3)N(2) and 42% B. These proportions were similar to those found at day 14 and at day 21 based on 159 persons. These findings suggest that an effective immune response is mounted within seven days of vaccination indicating that the vaccination of persons "at risk" is worthwhile even after an epidemic has established itself. This is not a reason to modify present policy of routine vaccination in early winter well before epidemics are likely to occur.

Adult↗

PubMed2000

Scope and organization of the Guide to Community Preventive Services. The Task Force on Community Preventive Services.

BACKGROUND: The diverse nature of the target audience (i.e., public health decision-makers) for the Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide) dictates that it must be broad in scope. In addition, for the Guide to be most useful for its target audience, its organization and format must be carefully considered. DETERMINING THE SCOPE OF THE GUIDE: Healthy People objectives and actual causes of death were used to determine the contents of the Guide. A priority setting exercise resulted in the selection of 15 topics for systematic reviews using the following criteria: burden of the problem, preventability, relationship to other public health initiatives, usefulness of the package of topics selected and level of current research and intervention activity in public and private sectors. Interventions within each topic target state and local levels and include population-based strategies, individual strategies in other than clinical settings and group strategies. ORGANIZATION OF THE GUIDE: The Guide is organized into: Introduction, Reviews and Recommendations (three sections: Changing Risk Behaviors, Reducing Diseases, Injuries, or Impairments, and Addressing Environmental and Ecosystem Challenges), Appendixes, and Indexes. DISCUSSION: The scope and organization of the Guide were determined using relevant public health criteria and expert opinion to provide a useful and accessible document to a broad target audience. While the final contents of the Guide may change during development, the working table of contents described in this paper provides a framework for development of the Guide and conveys its scope and intention.

Decision Making↗

PubMed2000

Myelophthisis as a solitary manifestation of failure from rectal carcinoma. A Batson phenomenon?

Rectal carcinoma is uncommonly associated with systemic metastases in the absence of liver metastases, reflecting the predilection for spread via the portal system. Occasionally, isolated lung metastases are seen, which are usually attributed to spread via the portosystemic anastomoses in the distal rectum. However, myelophthisis is an unreported complication of rectal cancer as an isolated form of systemic failure. We present a case of fatal myelophthisis associated with otherwise localized rectal carcinoma secondary to metastatic rectal cancer. This observation led to the hypothesis that spread to the bone marrow occurred via a "third circulation," the Batson plexus, a network of deep pelvic veins with rich anastomoses to the vertebral plexus.

Adenocarcinoma, Mucinous↗

PubMed2000

Neuraminidase inhibitors: progress in the management of influenza.

Influenza is a serious respiratory illness and represents a significant clinical burden. As well as being debilitating, influenza can often cause complications leading to hospitalisation and death. Prophylaxis by vaccination is the preferred method of disease management, but because influenza viruses are constantly changing their antigenic properties, influenza outbreaks occur regularly as epidemics. Neuraminidase inhibitors are a new class of anti-influenza drugs designed to block influenza virus replication. Two neuraminidase inhibitors, zanamivir and oseltamivir, have been licensed for clinical use in the treatment of influenza. Both drugs significantly reduce the severity and duration of the illness when treatment is started within two days of the onset of symptoms. However, while zanamivir and oseltamivir have apparently similar efficacy, they differ in their modes of delivery and tolerability. Zanamivir is delivered direct to the lungs by inhalation and is well tolerated. Oseltamivir is taken in the form of a pill but has the side-effect of producing nausea and vomiting in some patients. In the absence of a demonstrable difference in efficacy, uptake of the two drugs will depend on evaluation of the relative merits of mode of delivery and tolerability.

Acetamides↗

PubMed2000

Influenza surveillance in England and Wales: October 1999 to May 2000.

The period of increased influenza activity in England and Wales in the winter of 1999/2000 was associated with considerable morbidity and mortality and well-publicized pressure on hospital services. The influenza activity coincided with the regular annual increase in respiratory syncytial virus infections and the Christmas and New Year holiday period. Consultation rates with general practitioners for influenza-like illness did not reach 'epidemic' levels but were higher than seen in many winters and comparable with those seen in two out of the previous three winters. In common with those winters, attack rates for influenza-like illness and acute bronchitis were especially high in elderly people among whom complications of acute infection and hospital admissions increased. Excess mortality due to influenza during this period appeared to be substantial but was not as high as seen in the last epidemic (1989/90).

Adolescent↗

PubMed1999

Mandatory reporting of diseases and conditions by health care professionals and laboratories.

CONTEXT: Surveillance is a key component of the core public health function of health assessment. Systematic reporting by health care professionals and laboratories, which may vary by state law, statute, or regulation, continues to provide essential data for assessing public health. OBJECTIVE: To describe the state and territorial reporting requirements for diseases and conditions recommended for national public health surveillance. DESIGN, SETTING, AND PARTICIPANTS: Between May and August 1997, the state and territorial epidemiologists from all 50 states, in addition to New York City, Puerto Rico, and Guam, completed questionnaires indicating which diseases and conditions were reportable by health care professionals and laboratories in their jurisdictions. The surveys were subsequently updated to reflect reporting requirements current as of January 1, 1999. The overall response rate for the survey was 100% for US states and 90% overall, including the territories. MAIN OUTCOME MEASURE: State and territorial reporting requirements for diseases and conditions of public health concern. RESULTS: Of the 58 diseases and conditions recommended for national reporting, 35 (60%) were reportable in greater than 90% of the states and territories, 15 (26%) were reportable in 75% to 90%, and 8 (14%) were reportable in less than 75%. Nineteen of the infectious diseases were reportable in all of the states and territories that responded. CONCLUSIONS: Required reporting varies substantially by state or territory. Health care professionals are integral to public health efforts at the local, state, and national levels.

Communicable Diseases↗

PubMed1999

Epidemic serogroup B meningococcal disease in Oregon: the evolving epidemiology of the ET-5 strain.

CONTEXT: In 1993, Oregon's incidence of serogroup B meningococcal disease began to rise because of a highly clonal group of strains designated enzyme type 5 (ET-5), the first such increase observed in the United States. OBJECTIVE: To evaluate the impact that the ET-5 strain has had on the epidemiology of meningococcal disease in Oregon. DESIGN AND SETTING: Epidemiologic analysis of surveillance data on Oregon meningococcal disease cases from 1987 through 1996 and multilocus enzyme electrophoresis typing of serogroup B isolates from June 1993 through April 1995 and from April through June 1996. PATIENTS: A total of 836 persons with invasive meningococcal disease. MAIN OUTCOME MEASURES: Disease frequency and clonality of strains. RESULTS: Serogroup B disease incidence rates more than doubled from the preepidemic period in 1987-1992 (1.0 case per 100000 population) to the recent epidemic period in 1995-1996 (2.2 cases per 100000). The age-specific incidence rate of serogroup B disease among those 15 through 19 years old increased 13-fold between the preepidemic period (0.5 case per 100000) and 1995-1996 (6.4 cases per 100000). However, the proportion of cases with meningococcemia and the case-fatality rate did not change. Of 99 Neisseria meningitidis isolates obtained from 1993-1995, 88 (89%) belonged to the ET-5 complex. Of these, 69 (78%) were a single clone, designated 301. Of 20 serogroup B isolates from 1996, 18 (90%) belonged to the ET-5 complex; 17 (94%) were the 301 clone. CONCLUSION: Serogroup B meningococcal disease incidence continues at high levels in Oregon with increasing predominance of the ET-5 clonal strains.

Adolescent↗

PubMed1999

Multinational outbreak of Salmonella enterica serotype Newport infections due to contaminated alfalfa sprouts.

CONTEXT: In December 1995, reported Salmonella enterica serotype Newport (SN) infections increased sharply in Oregon and British Columbia but not elsewhere in North America. Similar unexplained increases had been noted in 6 other states in the fall of 1995. OBJECTIVE: To determine the source of the outbreak(s). DESIGN: Case-control studies, environmental investigations, bacterial subtyping, and surveillance information review. SETTINGS: Oregon and British Columbia communities (winter 1995-1996) and Georgia, Oklahoma, Pennsylvania, Vermont, Virginia, and West Virginia (fall 1995). PARTICIPANTS: Oregon and British Columbia residents with culture-confirmed SN infections and onset from December 1, 1995, through February 29, 1996, and healthy community controls. MAIN OUTCOME MEASURES: Odds ratio (OR) of illness associated with exposures; distribution patterns and culture of alfalfa seeds and sprouts; subtyping of SN isolates. RESULTS: We identified 133 cases in Oregon and British Columbia; 124 (93%) occurred in patients older than 18 years; 87 (65%) were female. Case patients were more likely than community control subjects to report having eaten alfalfa sprouts in the 5 days preceding illness (41% [17/41] vs 4% [3/75]; OR, 17.0; 95% confidence interval, 4.3-96.0). Case isolates shared a distinctive pulsed-field gel electrophoresis (PFGE) pattern. The SN was grown from seeds and alfalfa sprouts. The distribution of 1 seed lot to multiple growers corresponded to the distribution of cases. Distribution of a second seed lot from the same European wholesaler corresponded to the location of the fall outbreak, which was characterized by a similar demographic profile. The PFGE pattern of fall outbreak isolates and confiscated sprouts and seeds was indistinguishable from the Oregon and British Columbia outbreak and differed from background isolates. CONCLUSIONS: The SN-contaminated alfalfa seeds were distributed to multiple growers across North America in 1995 and resulted in a protracted international outbreak scattered over many months. Current sprouting methods are inadequate to protect consumers from such events. Alfalfa sprouts may be an elusive but important vehicle for salmonellosis and other enteric infections.

Case-Control Studies↗

PubMed1999

Controversies in skin resurfacing: the role of erbium.

Carbon dioxide laser resurfacing has been a valuable procedure for facial skin rejuvenation since the early 1990s, largely replacing medium and deep chemical peels and dermabrasion. The introduction of the erbium:YAG laser for resurfacing has caused confusion about its role. Because of its ability to resurface very superficially it has been limited by many laser surgeons to treating only superficial rhytides and sun damage. However, it is the equal of CO2 in improving deep rhytides but with quicker healing and fewer side-effects.

Erbium↗

PubMed1999

Do influenza epidemics affect patterns of sickness absence among British hospital staff?

Influenza vaccination for healthcare workers is not recommended in Britain, but some hospitals offer vaccine to reduce sickness absence. However, in Nottingham, the influenza epidemics of 1993-94 and 1996-97 made no impact on staff absence. Annual vaccination of healthcare workers against influenza is unlikely to reduce absence most winters, but there may be gains in terms of preventing nosocomial infection.

Disease Outbreaks↗