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Biomedical subjects

M Coffey

Publications and source records attributed to M Coffey.

At least 37 records · Page 2Linked to original sources

Impaired motion sensitivity as a predictor of subsequent field loss in glaucoma suspects: the Roscommon Glaucoma Study.

AIM: To determine if impaired motion sensitivity is a significant predictor of subsequent field loss in glaucoma suspects. METHOD: A population based prospective study; a 5 year follow up of all glaucoma suspects who had been identified from a population based random sample survey in the west of Ireland. 78 glaucoma suspects whose visual field function was annually measured by Henson CFS 2000 and for whom data on family history of glaucoma, ocular status, and motion impairment had been recorded. Visual field loss was defined as Henson visual field survival score of 94 or less. RESULTS: 18 people developed visual field loss in at least one eye. Motion impairment at baseline was associated with a 2-18 times greater risk of development of the visual field loss (p < 0.001). This association was independent of sex, family history of glaucoma, intraocular pressure, and C/D ratio at baseline. The Cox's proportional hazards regression analysis confirmed the above results after adjustment for age and the C/D ratio. CONCLUSION: Motion impairment is an independent predictor of visual field loss in glaucoma suspects, although it is not clear how long motion impairment precedes visual field loss.

Age Factors↗

Pulsed low dose rate brachytherapy in a rat model: dependence of late rectal injury on radiation pulse size.

PURPOSE: Clinical protocols utilizing pulsed low dose rate brachytherapy (PDR) to replace traditional continuous low dose rate brachytherapy (CLDR) employ irradiation in individual pulses given at intervals of a few hours. A critical factor in determining whether PDR will produce equivalent or greater late-occurring normal tissue toxicity is the dose per pulse. A rat rectal model was used to determine the role of pulse size in modifying dose effectiveness in producing late-occurring toxicity. METHODS AND MATERIALS: A rat model in which the rectum is irradiated with 192Ir sources was used in conjunction with an intracavitary applicator. A section of rectum 1.3 cm in length was irradiated with either 0.75 Gy/h CLDR or one of five schemes of PDR. The schemes applied 0.375, 0.75, 1.5, 3.0, or 6.0 Gy pulses at 0.5, 1.0, 2.0, 4.0, or 8.0 h intervals, respectively. Rats were observed for up to 300 days after completion of irradiation for rectal obstruction. Rectal specimens were taken at the time of sacrifice for obstruction or at the end of follow-up and analyzed histologically for injury. RESULTS: Effectiveness of irradiation was analyzed by calculating the ED50 for incidence of obstruction and severe histological injury. The ED50 for obstruction after treatment with CLDR and pulse sizes of 0.375, 0.75, and 1.5 Gy were 70.5, 68.0, 68.6, and 68.8 Gy, respectively. These values were not significantly different. Compared to CLDR, the ED50 for obstruction after pulse sizes of 3.0 and 6.0 Gy were significantly different at 60.9 and 46.3 Gy, respectively. The relative changes in ED50 for the different radiation schemes in producing ulceration, fibrosis, and vascular sclerosis injury were similar to that observed for obstruction. The endpoints of colitis cystica profunda and atypical epithelial regeneration varied less with increasing pulse size. CONCLUSIONS: We have demonstrated that for late rat rectal injury, dose responses to PDR pulse sizes up to 1.5 Gy at 2-h intervals are not distinguishable from that seen with CLDR at a dose rate of 0.75 Gy/h.

Animals↗

The European core curriculum for radiotherapy technologists.

BACKGROUND: The Radiotherapy Technologist is the third member of the team responsible for the accurate delivery of radiotherapy to the cancer patient. Educational standards have been established for both radiotherapists and medical physicists and our group recognised the need to also standardise the education of radiotherapy technologists. MATERIALS AND METHODS: The project commenced in 1990 and was completed by 1994 when an agreed core curriculum was presented at a consensus conference. All aspects of curriculum development and education delivery were reviewed during this four year period. RESULTS: Core topics were identified. educational entry standards described and a duration of three years, consistent with European Union mobility regulations, agreed. CONCLUSIONS: The core curriculum describes the standard necessary to be achieved for entry into the profession to ensure the optimum treatment is offered to all patients throughout the European Union. Regular review of the core curriculum should be carried out to ensure the defined standards are maintained.

Curriculum↗

Eye care utilisation patterns in a rural county in Ireland: implications for service delivery.

AIMS/BACKGROUND: This investigation determined eye care utilisation patterns in a rural county in Ireland. Population based estimates of visual impairment and glaucoma were available, so the two studies will optimise planning for eye care services for the county. METHODS: Roscommon has a population of 55,000 served by one ophthalmologist and two optometrists. Data were collected on all outpatient visits for all providers for a 3 month period. Information was abstracted on demographics, presenting and final diagnoses. Expected number of visits for glaucoma were calculated using the population structure and rates of glaucoma, and assuming one visit per year per glaucoma patient. RESULTS: 1398 patients had a total of 1442 visits in 3 months. A third of the visits were to optometrists, and all but 21 visits were for normal eye examinations or glasses. The majority of children aged less than 16 years, and people older than 60 years were seen by the ophthalmologist. Among children, 81% of all visits were to the ophthalmologist and 92% were classified as a normal examination. Only an estimated 188 visits per year for glaucoma were observed, compared with 1100 expected. CONCLUSION: In this rural county, many of the visits to the ophthalmologist were for normal eye examination, particularly among children. Screening algorithms which would free the ophthalmologist to see more complicated problems could be considered. There is an underutilisation of services by glaucoma patients. Reasons for this are described.

Adolescent↗

Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno-associated viral vector delivery of AT1-R mRNA antisense.

To produce a prolonged decrease in blood pressure, we have developed a nonpathogenic adeno-associated viral vector (AAV) with the antisense DNA for AT1-R. AAV has many advantages over other viral vectors. AAV does not stimulate inflammation or immune reaction. AAV enters nondividing cells and does not replicate. Therefore, it is an appropriate choice for gene therapy. Recombinant AAV was prepared with a cassette containing a cytomegalovirus promoter and the cDNA for the AT1 receptor inserted in the antisense direction. The cassette was packaged in the virion. Stable transfection of NG108-15 cells with the PAAV-AS (plasmid AAV) antisense to AT1-R produced a significant reduction in AT1 receptors. A single injection of the rAAV-AS (viral vector) was made in adult spontaneously hypertensive rats, either directly in the hypothalamus (1 microL) or in the lateral ventricles (5 microL). The result shows that there is a significant decrease of blood pressure (approximately 23 +/- 2 mm Hg) for up to 9 weeks after injection. Control injections of mock vector produced no change in blood pressure during the same time period in age-matched controls. In young spontaneously hypertensive rats (3 weeks), a single intracardiac injection of recombinant rAAV-AS reduced blood pressure and slowed the development of hypertension compared with controls (P < .01). The results suggest that a prolonged reduction in high blood pressure can be achieved with AAV vectors delivering antisense to inhibit AT1 receptors with a single administration.

Animals↗

Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by inflammation, fibroblast proliferation, and accumulation of extracellular matrix proteins. Leukotrienes (LTs) are pro-inflammatory and pro-fibrogenic mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. They are thought to play a role in a number of disease processes, but have received relatively little attention in investigations into the pathogenesis of IPF. In this study, we measured the levels of immunoreactive LTs B(4) and C(4) in homogenates of lung tissue obtained from patients with newly diagnosed, untreated IPF, as compared to levels measured in homogenates of uninvolved nonfibrotic lung tissue from patients undergoing resectional surgery for bronchogenic carcinoma. Compared to homogenates on nonfibrotic control lung, homogenates from IPF patients contained 15-fold more LTB(4) and 5-fold more LTC(4). IPF homogenate levels of LTB(4) were significantly correlated with histologic indices of both inflammation (r=0.861) and fibrosis (r=0.926). Activation of 5-LO is known from in vitro studies to be associated with localization of the enzyme at the nuclear membrane. Immunohistochemical staining for 5-LO protein in alveolar macrophages (AMs) demonstrated that such an "activated" localization pattern was significantly more frequent in IPF lung (19.2+/-3.3% of cells) than in control lung (9.3+/-0.9%); this localization pattern was rarely seen (3.2%) in sections from a truly normal transplant donor lung. Consistent with these data, AMs obtained from IPF patients by bronchoalveolar lavage, purified by adherence, and cultured in the absence of a stimulus for 16 h elaborated significantly greater amounts of LTB(4) and LTC(4) than did control AMs obtained from normal volunteers. These data indicate that the 5-LO pathway is constitutively activated in the lungs of patients with IPF, and the AM represents at least one cellular source of LT overproduction in this disorder. We speculate that LTs participate in the pathogenesis of IPF, and their overproduction in this disorder may be amenable to specific pharmacotherapy.

Adult↗

Lymph node recovery from colorectal resection specimens removed for adenocarcinoma. Trends over time and a recommendation for a minimum number of lymph nodes to be recovered.

Recovery of pericolorectal lymph nodes from colectomy specimens has long been part of colorectal cancer staging. Recently, adjuvant therapy has been added for high stage carcinomas, providing further impetus for performing careful lymph node dissections. Pericolorectal lymph nodes were examined to determine if there has been a change over time in the number of lymph nodes recovered and proportion of specimens with pericolonic lymph node metastases from colorectal carcinoma resection specimens. Also, the authors attempted to establish a recommendation for a minimum number of lymph nodes that should be recovered before a colon can be considered free of metastases. Slides and reports of the first 20 consecutive pT3 colorectal carcinoma resections in each year from 1955 to 1995 at William Beaumont Hospital that did not have known metastases at the time of surgery were reviewed (750 specimens total). The mean number of lymph nodes recovered per specimen and incidence of detected lymph node metastases increased over the 41-year period, with the greatest increase occurring during 1992-1995. The greatest proportion of patients with lymph node metastases detected occurred in the 17 to 20 lymph nodes recovered per specimen group. Specimens with more than 20 lymph nodes did not have a higher proportion of lymph node metastases detected compared to specimens with 17 to 20 lymph nodes. Approximately 20% of the specimens with metastases had more than 17 lymph nodes recovered. These results suggest that pathologists should retrieve all the lymph nodes that can be recovered, but at least 17 lymph nodes should be recovered to insure accurate documentation of nodal metastases when present.

Adenocarcinoma↗

Microculture of western white pine (Pinus monticola) by induction of shoots on bud explants from 1- to 7-year-old trees.

We developed a protocol for the production of shoots from bud explants from 1- to 7-year-old trees of western white pine (Pinus monticola Dougl.). The best explant was a 2-mm-thick cross-sectional slice of the early winter bud. Genotype of the donor tree was a significant factor affecting shoot production, but more than 80% of the genotypes tested produced shoots. Of the media tested, bud slices from 1- to 3-year-old trees grew best in Litvay's medium containing N(6)-benzyladenine in the range of 1 to 30 micro M, whereas bud slices from older trees grew best in Gupta and Durzan's DCR medium with zeatin riboside. Up to 400 shoots more than 3 mm in height were obtained from 100 bud-slice explants taken from 7-year-old western white pine trees.

Journal Article↗

A brief mental health outcome scale: relationships between scale scores and diagnostic/sociodemographic variables in the long-term mentally ill.

The Global Assessment of Functioning (GAF) scale is a quick and simple measure of overall psychological disturbance. A recent study by our group reported the reliability and validity of the scale in a population of severely mentally ill people. The current study extends the analysis of this population to consider a number of questions, i.e. what are the associations for this group between variations in GAF scores and sociodemographic variables? Are lower scores associated with particular diagnoses for the group assessed? What are the characteristics of those patients whose scores were most variable? What were the completion rates for use of the scale? No associations were observed between GAF score and the sociodemographic variables used in this study. Lower GAF scores were associated with psychotic diagnoses. Those with most varying scores were, in the main, white European non-immigrant males with a diagnosis of schizophrenia. Completion rates for the study were reasonable at 73.8%. This study involved the repeated assessment of a large number of clients by a changing multidisciplinary team. Inspite of the extended nature of the study, completion rates remained reasonable, suggesting that the scale was acceptable for routine clinical use. The GAF in itself, however, appears to be unsuitable for making individual treatment decision but could be used as a first step before using more sophisticated scales.

Adult↗

A brief mental health outcome scale-reliability and validity of the Global Assessment of Functioning (GAF).

BACKGROUND: The Global Assessment of Functioning (GAF) is a quick and simple measure of overall psychological disturbance. However, there is little research on the reliability and validity of this measure in severely mentally ill populations. METHOD: Multidisciplinary keyworkers assessed 103 patients at monthly intervals over a 6-month period. Overall GAF scores were obtained, with additional separate ratings for symptoms and disability. These were compared with changes in antipsychotic medication and support needs over the same period. RESULTS: Satisfactory reliability was obtained for total GAF score and for symptom and disability measures, in spite of raters having only one brief training session. All GAF scores were associated with current support needs of patients. Symptom and disability scores were associated with changes in antipsychotic medication in the previous month. Only symptom score was associated with increases in antipsychotic medication at time of rating. CONCLUSION: GAF proved to be a reliable and, within the limits of the indicators used, a valid measure of psychiatric disturbance in our sample of the severely mentally ill. Differences in relationships between the three GAF scores and medication/support needs indicate the usefulness of obtaining all three scores for monitoring levels and type of psychiatric disturbance in this population.

Activities of Daily Living↗

The role of Hispanic race/ethnicity and poverty in breast cancer survival.

The association of Hispanic race/ethnicity and poverty with general survival time and breast cancer survival time was examined for a total of 14,896 breast cancer patients (14,035 White and 861 Hispanic) included in the National Cancer Institute Surveillance Epidemiology and End Results (NCI SEER) program in New Mexico and San Francisco between 1975 and 1984. Variables examined included: age, marital status, stage at diagnosis, tumor histology, delay, treatment, period of diagnosis (1975-79 vs. 1980-84), and poverty. Univariate analysis of 14,896 patients indicated that a greater proportion of Hispanics (vs. Whites) with breast cancer were: younger than age 50, married, diagnosed at a later stage, diagnosed in New Mexico, lived in greater poverty, were diagnosed between 1980-84, and died from breast cancer. Univariate Cox Proportion Hazards analysis indicated that poverty was a significant predictor for reduced general survival time. Being diagnosed in the 1980-84 period was a predictor for improved general survival time. Poverty and Hispanic race/ethnicity were significant predictors of reduced breast cancer survival time. Multivariate Cox Proportional Hazards models indicated that Hispanic race/ethnicity was a significant risk factor for breast cancer survival time for women aged 50 and older. For White women: state, marital status, poverty, surgery, radiation/hormonal treatments, and histology were significant risk factors for breast cancer survival time. For Hispanic women: stage, surgery, hormonal treatment and period of diagnosis were significant risk factors for breast cancer survival time. For White breast cancer patients, period of diagnosis was not a significant risk factor for reduced breast cancer survival time; but for Hispanics, it was a significant risk factor. In the age and race/ethnicity-stratified models of breast cancer survival time, similar risk factors emerged for both Whites and Hispanics. For both younger and older Hispanics, being diagnosed in the early 1980's (vs. the late 1970's) was associated with reduced breast cancer survival time--vs. Whites, who experienced no significant change in breast cancer survival time in the same time period. Poverty was not a predictor for Hispanic survival time in any of the models; however, it was a predictor for younger Whites for breast cancer survival time. These results fueled discussion in three areas targeting breast cancer in underserved women: the development of racial/ethnic-specific cancer control guidelines, the development of a breast cancer integrated delivery system, and population management.

Adult↗

A prospective study to identify high-yield criteria associated with acute intracranial computed tomography findings in head-injured patients.

We conducted a multicenter, prospective study of head-injured patients to identify high-yield clinical criteria for acute intracranial injuries. Emergency patients with a history of blunt head trauma occurring within 2 weeks and who underwent nonenhanced cranial computed tomography (CT) were entered onto the study during a 12-month period. Of the 264 patients, 32 (12%) had abnormal CT findings. Nine high-yield variables were associated with abnormal CT findings: alcohol use before injury, antegrade amnesia, prolonged loss of consciousness, anisocoria and/or fixed and dilated pupils, abnormal Babinski reflex, focal motor paralysis, cranial nerve deficit, Glasgow coma scale score of less than 15, and clinical signs of basilar skull fracture. Patients 2 years old or younger or older than 60 years of age showed a significantly greater prevalence of abnormal CT findings than patients of other ages.

Acute Disease↗

Prevalence of glaucoma in the west of Ireland.

County Roscommon in the west of Ireland is a relatively remote rural area whose population of 55,000 is served by two community medical ophthalmologists and three optometrists. Eye surgical services are not available within the county. In order to assess the needs of the community for prevention of blindness from glaucoma, a simple random sample of the population of County Roscommon was taken for a community based glaucoma survey. A total of 2186 people over the age of 50 were examined which represented a 99.5% response rate. The high response rate was achieved by the community basis of the study and vigorous follow up of non-attenders. Intraocular pressure was measured using applanation tonometry, disc evaluation by both direct ophthalmoscopy and stereoscopic biomicroscopy, and visual field analysis using the Henson CFS 2000 and experimental computer controlled video perimetry. Diagnostic criteria were consistent with the preferred practice pattern of the American Academy of Ophthalmology. A crude prevalence of approximately 2% for primary open angle and normal tension glaucoma was found. The population profile of intraocular pressure showed a pattern which decreased with increasing age unlike the Framingham and Ferndale studies but similar to Japanese data.

Age Factors↗

Effects of nasal airflow on breathing during sleep in normal humans.

The nasal airway is a common route for oxygen delivery to hypoxemic patients, and it has been advocated as a suitable route for intermittent positive pressure ventilation to patients in respiratory failure. There is, however, conflicting evidence on the question of whether nasal airflow has a stimulant or a depressant effect on ventilation. We therefore studied the effects on ventilation of increasing and decreasing nasal airflow during sleep, thereby avoiding the voluntary and behavioral influences on breathing seen during wakefulness. After an acclimatization night, each of nine normal male volunteers (20 to 28 yr of age) underwent overnight sleep studies using standard techniques. Each sleep study had three phases of at least 2-h durations: (1) control nasal breathing (CNB); (2) added nasal flow of 4 L of compressed air via nasal prongs (ANF); (3) predominant mouth breathing (PMB). Significant differences were found by ANOVA for the three experimental periods for both minute ventilation (Vl) and mean inspiratory flow rate (VT/Tl) during Stage 2 sleep, with the highest values occurring during ANF. Vl was 5.40 +/- 0.58 L/min (mean +/- SD) during ANF, 5.35 +/- 0.82 during CNB, and 4.92 +/- 0.71 during PMB (p < 0.05 by ANOVA). VT/Tl was 266 +/- 23 ml/s during ANF, 248 +/- 39 during CNB, and 241 +/- 30 during PMB (p < 0.02 by ANOVA). VT also tended to be higher during ANF (p < 0.1 by ANOVA). Respiratory frequency did not differ significantly during the three study periods. There was insufficient slow-wave and REM sleep to allow ventilatory comparisons in these sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Membrane association of active 5-lipoxygenase in resting cells. Evidence for novel regulation of the enzyme in the rat alveolar macrophage.

The enzyme 5-lipoxygenase (5-LO) catalyzes the first two steps in the metabolism of arachidonic acid to leukotrienes, substances which play pivotal roles both in normal host defense and in pathologic states of inflammation. Recent studies in granulocytic cells have shown that activation of 5-LO involves its Ca(2+)-dependent translocation from cytosol to membrane compartments. However, little information exists about the molecular regulation of 5-LO in macrophages, even though these cells comprise the resident effector cell population of most organs. We therefore examined the levels of 5-LO activity and immunoreactive protein in cytosol and membrane fractions of resident rat alveolar (AM) and peritoneal macrophages (PM) and compared them with the well studied human neutrophil (polymorphonuclear leukocyte). In the resting state, PM resembled polymorphonuclear leukocyte in that most of their cell-free 5-LO activity, as well as protein content, were localized to the cytosol fraction. By contrast, resting AM contained most of their activity and almost half of their immunoreactive protein in the crude membrane fraction. The inability of the drug MK-886 to reverse this membrane association suggested that the 5-LO-activating protein was not the site of binding in the resting cell; however, this drug completely inhibited leukotriene B4 synthesis in ionophore A23187-stimulated AM, indicating that an interaction between 5-LO and 5-LO-activating protein was nonetheless required for product synthesis upon stimulation. Translocation of cytosolic 5-LO protein could not be convincingly demonstrated in A23187-stimulated AM, suggesting that the pool of 5-LO enzyme responsible for product formation originated in the membrane rather than the cytosol fraction of the resting cell. The AM therefore represents the first mammalian cell in which 5-LO has been recovered from the membrane fraction (a) of a resting cell and (b) in active form. These novel findings extend our understanding of the molecular regulation of 5-LO and may be of importance in designing strategies to limit inflammation in the lung and other sites.

Animals↗

A chest radiograph scoring system in adult cystic fibrosis: correlation with pulmonary function.

The Birmingham scoring system for chest radiographs was assessed in 40 adult cystic fibrosis patients, with particular reference to correlation with pulmonary function values. Forty 'initial' and forty 'follow-up' chest radiographs were scored. The mean initial age of the group was 17.5 +/- 5.0 years, and the mean age at follow-up was 23.3 +/- 5.3 years. The cross-sectional radiographic score correlated significantly with the values of three commonly measured, pulmonary function parameters (r = 0.65, 0.67, 0.58, P less than 0.0001). There was a significant correlation (r = 0.64, P less than 0.0001), between the change in radiographic score, and the change in percent predicted forced vital capacity (FVC%). There was a less significant correlation (r = 0.45, P less than 0.006) between the change in radiographic score and the change in per cent predicted forced expiratory volume in one second (FEV1%). We conclude that the Birmingham radiographic scoring system is suitable for quantitative radiological evaluation in adult cystic fibrosis.

Adolescent↗

Cystic fibrosis in adolescents and adults.

A cystic fibrosis (CF) clinic for adults was established in 1977. We have reviewed the data on 164 patients who attended between 1977 and 1989. Twenty four patients had died, 11 being over 20 years after time of death. Of the 140 patients still alive, 61% were male and 53% were aged over 20 years. Only 55% were diagnosed by 1 year and 88% by 10 years. Almost all patients had respiratory symptoms and sputum culture yielded Pseudomonas species in 69%. Other respiratory problems included major haemoptysis and pneumothorax, each in 10%. We found a wide range of respiratory impairment among older patients. Among 3 patients aged over 23 years the mean (+/- S.D.) percent predicted FEV1 and FVC were 53.3% (+/- 18%) and 71.4% (+/- 20%) respectively. Mean weight in this group was 92.5% (+/- 14) of predicted. Malabsorption occurred in most patients and meconium ileus equivalent occurred in most patients and meconium ileus equivalent occurred in 34%. Other complications were clinical hepatomegaly (16%), diabetes mellitus (9%) and arthropathy (20%). Most patients were taking continuous antibiotics by mouth (89%) and by nebuliser (48%), beta-2 agonists by inhaler (57%) and oral steroids (29%). Almost all were taking multivitamins, pancreatic replacement therapy and multiple nutritional supplements. The number of CF "bed days" grew 12 fold since 1979 and the mean stay in hospital was double the hospital mean. The economic impact was such that over 1/4 of the annual hospital antibiotic budget was expended on CF patients.

Adolescent↗

EMS pilots: selecting the very best.

This article has reviewed factors that should be taken into account when screening prospective pilots for EMS flight programs. While all may not apply directly to all programs, assessing the elements relevant to a particular program will enhance the quality of the selection process. Additionally, the orientation process can be shortened considerably when pilots who already have the necessary skills and experience are hired. This can prove more cost-effective, by shortening the time it takes for a pilot to meet the program's requirements. Safety is also impacted positively, as pilots with experience and skills in all elements are less likely to make potentially life-threatening mistakes through lack of knowledge. If pilots truly are the most critical factor in maintaining the safety of flight operations, it makes sense to choose the very best available. Hospital program managers should determine who is responsible for pilot selection, and take steps to ensure that the most qualified pilots are being recruited. Consideration of the factors mentioned here in the selection process will give managers a better shot at choosing the very best.

Aircraft↗