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Biomedical subjects

D Hayes

Publications and source records attributed to D Hayes.

At least 19 recordsLinked to original sources
PubMed2006

The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii).

A disfiguring and debilitating neoplastic condition known as devil facial tumor disease (DFTD) has been discovered in wild Tasmanian Devils (Sarcophilus harrisii) across 51% of its natural range, with population declines of up to 80% in some areas (C. Hawkins, personal communication). Between 2001 and 2004, 91 cases were examined. The tumors presented as large, solid, soft tissue masses usually with flattened, centrally ulcerated, and exudative surfaces. They were typically multicentric, appearing first in the oral, face, or neck regions. Histologically, the tumors were composed of circumscribed to infiltrative nodular aggregates of round to spindle-shaped cells, often within a pseudocapsule and divided into lobules by delicate fibrous septae. They were locally aggressive and metastasized in 65% of cases. There was minimal cytologic differentiation among the tumor cell population under light and electron microscopic examination. The results indicate DFTD to be an undifferentiated soft tissue neoplasm.

Animals↗
PubMed2006

The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian Devil (Sarcophilus harrisii).

Immunohistochemical techniques were used to characterize the disfiguring and debilitating fatal neoplastic disease, devil facial tumor disease (DFTD), which has recently affected a significant proportion of the wild population of Tasmanian Devils (Sarcophilus harrisii). The diagnostic values of a number of immunohistochemical stains were employed to further characterize 50 representative cases. The neoplasms were negative for cytokeratin (0/48), epithelial membrane antigen (0/42), von Willebrand factor (vWF) (0/11), smooth muscle actin (SMA) (0/26), desmin (0/47), glial fibrillary acid protein (0/13), CD16 (0/13), CD57 (0/43), CD3 (0/18), and LSP1 (0/16). DFTD cells were positive for vimentin (50/50), S-100 (41/48), melan A (11/39), neuron specific enolase (35/35), chromogranin A (12/12) and synaptophysin (29/30). The cells were negative for amyloid (0/30) and stained negatively with Singh's silver (0/34) but were weakly argyrophilic (3/40) using Grimelius histochemical stain. These staining characteristics are consistent with cells of neuroectodermal origin.

Animals↗
PubMed2005

Obstructive sleep apnea syndrome: a potential cause of lower airway obstruction in cystic fibrosis.

A six-year-old healthy female with cystic fibrosis (CF) and pancreatic sufficiency presented with cough, weight loss, and lung function decline. Further history suggested obstructive sleep apnea, and nocturnal polysomnography (NPSG) confirmed this. Adenotonsillectomy resulted in resolution of clinical symptoms with return of normal lung function. This case establishes that obstructive sleep apnea syndrome (OSAS) may be a potential cause of lower airway inflammation and resulting weight loss in the young CF population.

Airway Obstruction↗
PubMed2005

Bayesian spatio-temporal modelling of national milk-recording data of seasonal-calving New Zealand dairy herds.

A spatio-temporal analysis was undertaken with the aim of identifying the dynamics of herd mean individual cow SCCs (MICSCC) in seasonally calving New Zealand dairy herds. Two datasets were extracted from the Livestock Improvement Corporation's extensive national dairy recording database: (1) milk-recording data aggregated at the herd-level and (2) sales questionnaire data containing information on the size, location and infrastructure of each farm. A Bayesian spatio-temporal modelling approach was applied to the analysis. The data were aggregated by 10 km(2) grid cells and linear regression models were developed with spatially structured and unstructured random effects, a linear temporal trend random effect and spatial-temporal interactions for log-transformed median MISCC (ln(median MISCC)). Significant associations were found between ln(median MISCC) and milk yield, milk fat, milk protein, farm area and number of cups in the dairy. This led us to suggest that SCCs should be adjusted for volume and constituents prior to determining a threshold MISCC for identification of subclinical mastitis (SCM) problem herds. Part, or all, of the temporal trend in MISCC in the spatio-temporal model was accounted for by inclusion of yield and milk constituents as independent variables. This supports the hypothesis of a dilution effect with potential consequences for misdiagnosis of SCM, particularly in late lactation. Unmeasured covariates were similarly likely to be spatially structured and unstructured.

Animals↗
PubMed2005

Ebstein's anomaly - review of a multifaceted congenital cardiac condition.

Ebstein's anomaly (EA) is a rare but fascinating congenital heart disorder accounting for <1% of all congenital heart defects. Since its description in 1866, dramatic advances in diagnosis and therapy have been made. In this review, we describe current diagnostic criteria and classification, natural history, clinical features, and prognosis, typical echocardiographic features and pathologic findings, and the spectrum of associated cardiac malformations including left heart anomalies associated with EA. Differences between Ebstein-like changes associated with congenitally corrected transposition and EA are described. The spectrum of typical ECG and conduction system changes, arrhythmias including accessory pathways and ectopic atrial tachycardias related to EA are also reviewed. Differential diagnosis of EA is discussed including tricuspid valve dysplasia and prolapse as well as arrhythmogenic right ventricular cardiomyopathy. The review describes management options in EA including catheter interventions, indication for operation and surgical options including tricuspid valve repair and replacement. Overall, EA is a complex congenital anomaly with a broad pathologic-anatomical and clinical spectrum and no two patients are alike. Therefore, precise knowledge of the different anatomic and hemodynamic variables, associated malformations and management options are essential. Management of EA patients is complex. Thus it is important that these patients are regularly seen by a cardiologist with expertise in congenital heart disease.

Adolescent↗
PubMed2004

General considerations for proteolytic cascades.

Proteases are involved in the regulation of a wide variety of essential physiological processes, often by participating in a highly orchestrated sequence of events termed a 'proteolytic cascade'. Four major proteolytic cascades with disease relevance are candidates for therapeutic intervention, namely caspase-mediated apoptosis, blood coagulation, the matrix metalloproteinase cascade and the complement cascade. Understanding the various steps involved in the functioning of a cascade is key to deciding possible points of intervention for the design of potential drug molecules. This brief review illustrates some of the common features of proteolytic cascades using the blood coagulation pathway as an example.

Blood Coagulation↗
PubMed2002

Geochemical evidence for atmospheric pollution derived from prehistoric copper mining at Copa Hill, Cwmystwyth, mid-Wales, UK.

This paper presents geochemical data from a blanket peat located close to a Bronze Age copper mine on the northern slopes of the Ystwyth valley, Ceredigion, mid-Wales, UK. The research objective was to explore the possibility that the peat contained a geochemical record of the pollution generateD by mining activity. Four peat monoliths were extracted from the blanket peat to reconstruct the pollution history of the prehistoric mine. Three different geochemical measurement techniques were employed and four copper profiles have been reconstructed, two of which are radiocarbon-dated. The radiocarbon dates at one profile located close to the mine confirm that copper enrichment occurs in the peat during the known period of prehistoric mining. Similar enrichment of copper concentrations is shown in one adjacent profile and a profile within 30 m away. In contrast, copper was not enriched in the other radiocarbon-dated monolith, collected approximately 1.35 km to the north of the mine. Whilst other possible explanations to explain the copper concentrations are discussed, it is argued that the high copper concentrations represent evidence of localised atmospheric pollution caused by Bronze Age copper mining in the British Isles. The results of this study suggest that copper may be immobile in blanket peat and such deposits can usefully be used to reconstruct atmospheric pollution histories in former copper mining areas.

Air Pollutants↗
PubMed2002

Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer.

PURPOSE: This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response. MATERIALS AND METHODS: One thousand three hundred fifty four women with measurable disease, previously untreated by hormonal or chemotherapy for advanced or recurrent breast cancer, were enrolled by 179 institutions in 35 countries. Patients were stratified at baseline for menopausal status. Patients receiving adjuvant hormonal therapy within I year were excluded. All patients gave written informed consent, were randomized to 40mg droloxifene or 20 mg tamoxifen daily as single-agent therapy and underwent tumor assessment every 3 months. A central committee reviewed digitized images for all cases of tumor progression or objective response. RESULTS: The hazard ratio (droloxifene/tamoxifen) for the primary endpoint, time to disease progression, was 1.287 favoring tamoxifen (95% C.I.: 1.114-1.487; p <.001). The objective response rate (CR+PR) was 22.4% for droloxifene and 28.6% for tamoxifen (p = .02). Tamoxifen was superior to droloxifene overall, among both pre- and postmenopausal patients and among patients < or =65 years; there was no difference among women >65 years. The hazard ratio for all-cause mortality was 0.871 (95% C.I.: 0.672-1.129; p = .29), favoring droloxifene but not statistically significant. CONCLUSIONS: Droloxifene was significantly less effective than tamoxifen overall and particularly among women under 65 years. Tamoxifen and droloxifene were both less effective in pre-menopausal women with receptor-positive disease compared to post-menopausal women. Further clinical development of droloxifene was stopped.

Age Factors↗
PubMed2001

Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2.

Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N(4)-(1-benzyl-1H-indazol-5-yl)-N(6),N(6)-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice.

Animals↗
PubMed2001

Feasibility and initial results of an Internet-based pacemaker and ICD pulse generator and lead registry.

The medical community has no independent source of timely information regarding the performance of pacemaker and ICD pulse generators and leads. Accordingly, the authors established an Internet-based registry of pacemaker and ICD pulse generator and lead failures (www.pacerandicregistry.com). During the first year, they found three previously unreported device problems that were promptly communicated to the participants. Of the failures reported, 11% of ICD and 10% of pacemaker pulse generator failures were heralded by signs other than the expected elective replacement indicator (ERI). Average ICD battery longevity was 4.0 +/- 0.7 years, and average dual chamber pacemaker battery longevity was 6.8 +/- 2.6 years. Disrupted insulation accounted for 54% of pacemaker and 29% of ICD lead failures. Compared to pacemaker pulse generator and lead failure, ICD device failures were more likely to cause severe clinical consequences. In conclusion, an Internet-based registry is feasible and capable of providing timely data regarding the signs, causes, and clinical consequences of pacemaker and ICD failures.

Canada↗
PubMed2001

Newborn hearing screening: selected experience in the United States.

Universal newborn hearing screening (UNHS) is rapidly becoming 'standard of care' in the United States. More than two dozen states now require, through legislative mandate, that the state establishes a system for early hearing detection and intervention (EDHI), beginning with mandated UNHS. In states with long-standing EDHI programs, the average age of identification and intervention has decreased significantly. In those states, infants are identified and intervention initiated typically before age 6 months, meeting the Joint Committee on Infant Hearing's (JCIH) recommendation for newborn hearing screening, diagnosis and intervention. Language outcome data suggest that earlier intervention results in better language outcomes for deaf and hard-of-hearing children. This article reviews the current status of UNHS in the United States, summarizes the Colorado statewide program and describes the JCIH Year 2000 position statement for developing comprehensive EDHI programs.

Guidelines as Topic↗
PubMed2001

Strategic real-estate planning can generate revenue.

Many healthcare organizations treat their real estate as liabilities rather than assets and overlook opportunities to generate significant additional revenue and reduce costs. An Ernst & Young Study found that to maximize the return on investment in their real-estate holdings, healthcare organizations need to include property management in their strategic plan, manage construction and expansion effectively, adapt and reuse their facilities where possible, and pursue innovative real-estate strategies. Managing real-estate assets effectively can free up capital to use for other core business needs.

Capital Expenditures↗
PubMed2000

HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer.

PURPOSE: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized-physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. PATIENTS AND METHODS: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. RESULTS: HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. CONCLUSION: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen.

Antineoplastic Agents, Hormonal↗
PubMed2000

Quantitative immunohistochemical analysis of cytokine profiles in Epstein-Barr virus-positive and -negative cases of Hodgkin's disease.

Hodgkin's disease (HD) is a malignant lymphoproliferative disease characterized by the presence of Hodgkin-Reed-Sternberg cells surrounded by a reactive infiltrate. In Epstein-Barr virus (EBV)-associated cases (40-60%), at least two EBV-encoded proteins [latent membrane protein 1 (LMP1) and LMP2] are expressed, which are potential targets for cytotoxic T-lymphocytes (CTLs). Although in EBV-positive cases significantly more activated (granzyme B-positive) CTLs and natural killer (NK) cells are present, the cytotoxic immune response is not sufficient for adequate killing of tumour cells. The production of immunomodulating cytokines within the tumour may be one of the mechanisms causing circumvention of the immune system. This study investigated by immunohistochemistry the presence of the immunosuppressive cytokine interleukin-10 (IL-10) and other Th1/Th2-associated cytokines [IL-2, IL-4, interferon-gamma (IFN-gamma)] in the neoplastic cells and reactive lymphocytes of nine EBV-positive and 18 EBV-negative cases of HD. The percentage of IL-10-expressing cells, both neoplastic and reactive, in EBV-positive cases was significantly higher (33.1% vs. 18.5% for the neoplastic cells and 21.6% and 12.2% for the reactive cells, p=0.003 and 0.04, respectively) than in EBV-negative cases. No difference in the percentage of IL-2-, IL-4- and IFN-gamma-expressing cells was observed. These results suggest that escape from local immune surveillance is not due to a shift from Th1 towards Th2, but may be caused by a direct effect of IL-10 on the cytotoxic cells.

Cytokines↗
PubMed2000

Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies.

The development of the human immunodeficiency virus-1 (HIV-1)/simian immunodeficiency virus (SIV) chimeric virus macaque model (SHIV) permits the in vivo evaluation of anti-HIV-1 envelope glycoprotein immune responses. Using this model, others, and we have shown that passively infused antibody can protect against an intravenous challenge. However, HIV-1 is most often transmitted across mucosal surfaces and the intravenous challenge model may not accurately predict the role of antibody in protection against mucosal exposure. After controlling the macaque estrous cycle with progesterone, anti-HIV-1 neutralizing monoclonal antibodies 2F5 and 2G12, and HIV immune globulin were tested. Whereas all five control monkeys displayed high plasma viremia and rapid CD4 cell decline, 14 antibody-treated macaques were either completely protected against infection or against pathogenic manifestations of SHIV-infection. Infusion of all three antibodies together provided the greatest amount of protection, but a single monoclonal antibody, with modest virus neutralizing activity, was also protective. Compared with our previous intravenous challenge study with the same virus and antibodies, the data indicated that greater protection was achieved after vaginal challenge. This study demonstrates that antibodies can affect transmission and subsequent disease course after vaginal SHIV-challenge; the data begin to define the type of antibody response that could play a role in protection against mucosal transmission of HIV-1.

Animals↗
PubMed2000

Squamous cell carcinoma of the finger masquerading as an abscess. Case report.

A 43-year-old man presented with an abscess on his left ring finger, which recurred despite multiple drainage procedures. Histological examination of the lesion was unhelpful; it was only on histopathological examination of the finger after ray amputation that the diagnosis of cutaneous squamous cell carcinoma was established. This case illustrates the need to consider malignancy when dealing with chronic finger infections.

Abscess↗