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Biomedical subjects

J Coffey

Publications and source records attributed to J Coffey.

At least 19 recordsLinked to original sources
PubMed2006

A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone.

PURPOSE: We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of (186)Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). METHODS: Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of (186)Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. RESULTS: Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq (186)Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. CONCLUSION: We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach.

Aged↗
PubMed2005

A discussion of the biology of testicular cancer and current concepts in the management of stage I and bilateral disease.

This case was the subject of a Grand Round Presentation at the Royal Marsden Hospital, Sutton, UK on 8 June 2004. A case of metachronous, bilateral testicular germ-cell tumours (TGCTs) arising in a patient with a family history of this disease was presented. The second primary was managed conservatively. The rationale and outcome of this approach was presented, along with a discussion of the management of early stage TGCTs and the genetics of familial and bilateral disease.

Adult↗
PubMed2003

Therapy of non-Hodgkin's lymphoma.

Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas, especially gastric MALT lymphoma, deserves special attention because of the high response rate to Helicobacter pylori eradication therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Topical treatment of psoriasis in children.

Psoriasis is a common dermatoses, affecting children in North America. Many papers have stressed the treatments available for adult psoriasis, but few have dealt with this disorder in children. Topical treatment modalities continue to be the first line therapy for childhood psoriasis. This paper summarizes the general topical treatments available including their clinical use, benefits, cost, and side-effects.

Child↗
PubMed2001

MRI-assessed volume of cerebellum correlates with associative learning.

Richard F. Thompson's cerebellar model of classical eyeblink conditioning highlights Purkinje cells in cerebellar cortex and principal cells in the deep cerebellar nucleus as the integrating cells for acquisition of conditioned responses (CRs). CR acquisition is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell-deficient mice that lose all cerebellar cortical Purkinje cells. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. Magnetic resonance imaging (MRI) was used to assess cerebellar volume in humans. Cerebellar volume was related to eyeblink conditioning (400-ms delay procedure) in 8 adults (21-35 years) and compared to 8 older adults (77-95 years) tested previously (Woodruff-Pak, Goldenberg, Downey-Lamb, Boyko, & Lemieux, 2000). In the young adult sample, there was a high correlation between percentage of CRs in a session and cerebellar volume (corrected for total intracranial volume [TIV], r =.58, p =.066). There were statistically significant age differences in cerebellar volume, t(14) = 8.96, p <.001, and percentage of CRs, t(14) = 3.85, p <.002, but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was.832 (p <.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume, supporting Thompson's model of a cerebellar cortical role in facilitating this form of associative learning.

Adult↗
PubMed1999

Nuclear import of hepatic glucokinase depends upon glucokinase regulatory protein, whereas export is due to a nuclear export signal sequence in glucokinase.

Hepatic glucokinase (GK) moves between the nucleus and cytoplasm in response to metabolic alterations. Here, using heterologous cell systems, we have found that at least two different mechanisms are involved in the intracellular movement of GK. In the absence of the GK regulatory protein (GKRP) GK resides only in the cytoplasm. However, in the presence of GKRP, GK moves to the nucleus and resides there in association with this protein until changes in the metabolic milieu prompt its release. GK does not contain a nuclear localization signal sequence and does not enter the nucleus in a GKRP-independent manner because cells treated with leptomycin B, a specific inhibitor of leucine-rich NES-dependent nuclear export, do not accumulate GK in the nucleus. Instead, entry of GK into the nucleus appears to occur via a piggy-back mechanism that involves binding to GKRP. Nuclear export of GK, which occurs after its release from GKRP, is due to a leucine-rich nuclear export signal within the protein ((300)ELVRLVLLKLV(310)). Thus, GKRP appears to function as both a nuclear chaperone and metabolic sensor and is a critical component of a hepatic GK translocation cycle for regulating the activity of this enzyme in response to metabolic alterations.

Adaptor Proteins, Signal Transducing↗
PubMed1997

What is the value of the lateral chest radiograph in the follow-up thoracic lymphoma?

Lateral chest radiography in the investigation of thoracic lymphoma remains a feature of the current literature. This study assessed what information the lateral chest radiograph (CXR) adds in the follow-up of such patients. Eighty-eight patients with known lymphoma who had a CXR and thoracic CT within the same 4-week period were assessed. Five radiologists scored eight mediastinal and hilar nodal groups and eight extramediastinal regions on the frontal CXR as normal, equivocal or definitely abnormal (denoted 0, 1 and 2, respectively). This was repeated 1 week later with a combination of frontal and lateral films. Results were compared with the findings on CT which were scored similarly using accepted criteria for the presence of lymphadenopathy. Where the lateral CXR caused a change in score at any site, this change was compared with CT to determine the effect on diagnostic accuracy. For four of the five observers, the lateral film made no significant difference in diagnostic accuracy in the assessment of mediastinal lymph nodes. A fifth observer derived a small benefit from the addition of the lateral film, although almost 30 % of this was accounted for by changing from a wrong to an equivocal diagnosis. The lateral film did cause a small increase in the detection of pleuro-parenchymal lung lesions, although none of these were clinically significant. We conclude that routine lateral chest radiography is unhelpful in the follow-up of patients with lymphoma.

Adult↗
PubMed1997

Classification of mild Alzheimer's disease by artificial neural network analysis of SPET data.

An evaluation of the performance of artificial neural networks (ANNs) for the classification of probable Alzheimer's disease (pAD) patients was undertaken using data extracted from four regions of interest constructed on single photon emission tomographic (SPET) cerebral perfusion images. Two studies using feed-forward neural networks (FFNNs) were undertaken. The first was to determine if it would be possible to classify pAD patients and normal subjects in a mixed group, comprising 29 patients diagnosed as having pAD varying in severity from mild, established dementia to moderate dementia and 10 healthy control subjects. The second was to determine if the networks generated in the first study could prospectively classify 15 additional patients with very mild or mild cognitive impairment. The results were compared to those obtained using the same data and discriminant analysis. The relative performances of the two analysis techniques were assessed on the basis of the area under receiver operating characteristics (ROC) curves. The FFNN successfully classified all datasets in the first study, achieving an area under the ROC curve of 1.00, whereas discriminant analysis achieved 0.94. When tested on data from the second group, the areas under the ROC curves varied between 0.86 and 1.00 for the FFNN, whereas that for discriminant analysis was 0.99. We conclude that FFNNs can accurately classify pAD patients with mild to moderate dementia using data obtained from SPET cerebral perfusion images.

Aged↗
PubMed1997

Comparison of screw retention of nine abutment systems: a pilot study.

Fracturing or loosening of abutment and retaining screws is a frequent occurrence. This study was designed to evaluate the retaining ability of nine abutment systems. Abutment and retaining screws were secured to the appropriate implant using a digital torque gauge, with the abutment screws placed at 30 N-cm and the retaining screws at 10 N-cm. Removal torque was recorded three times for each sample 10 minutes after initial placement, 20 minutes after retightening, and 24 hours after retightening. There was no statistical difference in removal torque relative to time or repeated tightening. Of the nine abutment systems, three were statistically less retentive as compared with the most retentive system. The retaining screws were less retentive as compared with the abutment screws. For maximum retention the elimination of retaining screws from the restorative design and using 30 N-cm of torque for the abutment screws is suggested.

Analysis of Variance↗
PubMed1996

Event-related potential prolongation in Alzheimer's disease signifies frontal lobe impairment: evidence from SPECT imaging.

BACKGROUND: The N2 and P3 components of auditory event-related potentials (ERPs) and single-photon emission computed tomographic (SPECT) images are separate independent biological markers of cerebral function and are abnormal in Alzheimer's disease (AD). The relationship between ERP N2 and P3 latencies and regional cerebral perfusion abnormalities in AD is unknown. METHODS: ERP and SPECT data were obtained one week apart in 18 patients with "probable" AD of mild or moderate severity, and 12 healthy age-matched elderly controls. Average premotor frontal, anterior temporal, inferior parietal, and occipital cortical/cerebellar perfusion ratios were calculated from the SPECT data and correlations with ERP N2 and P3 latencies derived for AD and control groups separately. RESULTS: ERP N2 latency was correlated significantly with the average frontal perfusion ratio (r = -.59; p < .009), but correlations with average temporal, parietal, and occipital ratios were nonsignificant in the AD group. Similarly, ERP P3 latency was correlated significantly with the average frontal perfusion ratio (r = -.65; p < .004), but not with the other perfusion ratios in the AD group. In the control group, a partial correlation between the average frontal perfusion ratio and the ERP N2 latency was noted (r = -.52; p < .09), but no other ERP/SPECT correlations approached statistical significance. CONCLUSION: ERP N2 and P3 latency delay in AD is a function of differential frontal lobe hypoperfusion.

Aged↗
PubMed1995

Emergency procedures important to the training of emergency medicine residents: who performs them in the emergency department?

OBJECTIVE: To quantify one aspect of emergency medicine (EM) training by determining the proportion of emergency procedures performed by emergency physicians (EPs) in EDs with EM residency programs (EMRPs). METHODS: Cross-sectional descriptive survey of all allopathic EMRPs accredited by the EM Residency Review Committee (RRC-EM) as of July 1, 1993. Using a modified visual analog scale, program directors indicated the proportion of ten index procedures performed in the ED by EPs vs all other physicians. RESULTS: All 98 EMRPs meeting entry criteria responded to the survey. The medians for the percentage of times index procedures were performed in the ED by an EP were as follows (parentheses following percentages enclose 95% CIs): endotracheal intubation, 97% (95%, 100%); reduction of anterior shoulder dislocation, 93% (88%, 97%); thoracostomy, 63% (50%, 75%); transvenous pacer insertion, 60% (50%, 75%); cricothyrotomy, 50% (50%, 75%); thoracotomy, 50% (25%, 50%); diagnostic peritoneal lavage, 50% (25%, 50%); fiberoptic laryngoscopy, 22% (6%, 25%); sigmoidoscopy, 0% (0%, 6%); and pelvic sonography, 0% (0%, 0%). CONCLUSION: EPs in EDs of institutions that have EMRPs perform, on average, 50% of all index procedures (95% CI 47%, 52%). This information may assist EM programs experiencing difficulty in ensuring that their residents receive an equitable share of those procedures that are critical to their training.

Cohort Studies↗
PubMed1994

Dental pain evoked by hydrostatic pressures applied to exposed dentin in man: a test of the hydrodynamic theory of dentin sensitivity.

The hydrodynamic theory of dentin sensitivity holds that pain is evoked by stimuli producing minute shifts in tubule fluid. In human volunteers hydrostatic pressures were applied to prepared dentinal cavities. The subjects reported the magnitude and quality of their sensations of pain by means of an intermodal matching technique in combination with verbal descriptors. No pain could be elicited when the smear layer was present. After removal of this layer, pressure stimuli of either direction evoked sharp pain. Rapid changes in pressure induced higher pain intensities than slow changes, indicating that the dental A-delta system is dynamic and gradient dependent. These results provide support for the hydrodynamic theory of dentin sensitivity and also lend credence to the notion that the movement of fluid across dentin induces a selective activation of the A-delta nerves in healthy pulps which is highly correlated with a sensation of sharp and/or shooting pain.

Acid Etching, Dental↗
PubMed1994

The discriminant value of semiquantitative SPECT data in mild Alzheimer's disease.

UNLABELLED: In most semiquantitative SPECT studies, overlap between groups of patients with Alzheimer's disease (AD) and age-matched elderly controls is such that single posterior cortical perfusion measurements lack sensitivity. In the present study, the value of a combination of semiquantitative temporoparietal SPECT parameters was examined. METHODS: Supratentorial transaxial perfusion measurements were obtained in frontal, anterior temporal, posterior temporoparietal and occipital cortical areas in both hemispheres, in a baseline population of 10 healthy elderly controls and 30 mild to moderately impaired AD patients, as well as in a prospective group of 15 patients with mild cognitive impairment, 12 patients with a diagnosis of probable AD and individual cases of multi-infarct dementia, dementia-frontal type and paranoid psychosis. A linear discriminant function (LDF) was calculated from the baseline subjects' data to classify control and AD subjects individually. RESULTS: Highly significant hypoperfusion was noted in both the anterior temporal and posterior temporoparietal regions of interest in the AD group compared with controls, but with significant overlap. Using an LDF incorporating these perfusion measurements in both hemispheres, 10/10 (100%) controls and 26/30 (87%) AD baseline subjects were correctly classified. Using the baseline LDF in the prospective 15 mildly impaired cases, 11/12 new mild AD cases and none of the 3 non-AD cases were classified in the AD group. CONCLUSION: These results support the use of a combination of semiquantitative SPECT perfusion estimates from cortical areas with predictable pathological involvement in AD in a linear discriminant format in the clinical assessment of patients with suspected AD.

Aged↗
PubMed1994

Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation.

Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.

Administration, Oral↗
PubMed1993

Whatever happened to abstracts from different sections of the association for research in vision and ophthalmology?

PURPOSE: The authors investigated the fate of abstracts from each ARVO section (May 1985 meeting), the overall publication percentage, and the journals in which the abstract-derived articles were published. METHODS: They performed a MEDLINE search by first author for 25 or 26 randomly selected abstracts from each section to identify those that led to full-length articles in peer-reviewed journals. RESULTS: Overall, 63% of abstracts led to full-length articles in peer-reviewed journals within our search period of 87 months. The publication rate of oral presentation abstracts (68%) was significantly higher than that of poster presentation abstracts (56%). A greater proportion of basic science-oriented abstracts (67%) led to publication than the clinically oriented abstracts (56%). The rate of publication was lowest for the Cornea section (40%) and highest for Physiology and Pharmacology (80%) and Biochemistry (76%). The abstract-derived articles were published in 67 different peer-reviewed journals, with 43% of the articles appearing in only five journals. CONCLUSIONS: The fact that the majority of abstracts led to full-length articles supports ARVO's goal of a large interdisciplinary appeal with the exchange of ideas among different investigators.

Congresses as Topic↗
PubMed1992

Level of accuracy and degree of precision in attempting to maintain steady levels of biting force.

The primary purpose of this study was to assess the level of accuracy (bias) and degree of precision for a group of 24 normal subjects attempting to maintain a constant biting force at levels of 100 gm, 500 gm, 1000 gm and 2000 gm for a period of 10 s each. Accuracy is defined as the difference between subjects' actual level of biting force and the target value they were trying to achieve. Precision is the level or range of variability demonstrated by the subjects while attempting to bite with a constant level of force. Subjects' performance relative to accuracy and precision was also compared when using the central incisors vs. the first permanent molars. Assessment of bite force was measured using a specially designed strain gauge scale which permitted subjects to visually monitor when their biting force equalled a preset resistance. Each subject was instructed to bite on the end of a plastic sheathed steel beam with enough force to activate the indicator needle on the voltage meter to its central position and to try to maintain a constant level of biting force (by attempting to keep the indicator needle steady in its central position). No significant (P > 0.05) differences were found in mean accuracy in bite force for gender or specific teeth used in the biting task. However, a significant difference (P < 0.0001) in mean accuracy in bite force was found to exist between the target levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗