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Biomedical subjects

C O'Keefe

Publications and source records attributed to C O'Keefe.

13 recordsLinked to original sources
PubMed2005

Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients.

In paroxysmal nocturnal hemoglobinuria (PNH), clonal expansion of glycosylphosphatidylinositol-anchored proteins (GPI-AP)-deficient cells leads to a syndrome characterized by hemolytic anemia, marrow failure, and venous thrombosis. PNH is closely related to aplastic anemia and may share its immune pathophysiology. In vivo expansion of dominant T-cell clones can reflect an antigen-driven immune response but may also represent autonomous proliferation, such as in large granular lymphocytic (LGL)-leukemia. T-cell clonality can be assessed by a combination of T-cell receptor (TCR) flow cytometry and complementarity-determining-region-3 (CDR3) molecular analysis. We studied 24 PNH patients for evidence of in vivo dominant T-cell responses by flow cytometry; TCR-Vbeta-specific expansions were identified in all patients. In four cases, extreme expansions of one Vbeta-subset of CD8+/CD28-/CD56+ (effector) phenotype mimicked subclinical LGL-disease. The monoclonality of these expansions was inferred from unique CDR3-size peak distributions and sequencing of dominant clonotypes. We conclude that the molecular analysis of TCR-beta chain may demonstrate clonal LGL-like expansions at unexpected frequency in PNH patients. Our observations blur the classical boundaries between different bone marrow failure syndromes such as AA, PNH, and LGL, and support the hypothesis that in PNH, the mutant clone may expand as a result of an immune-escape from antigen-driven lymphocyte attack on hematopoietic progenitors.

Amino Acid Sequence↗
PubMed2001

Improving prognosis following a first variceal haemorrhage over four decades.

BACKGROUND: Variceal bleeding is a frequent cause of death in patients with cirrhosis and portal hypertension. Over the past 40 years a number of new techniques have been introduced to control active variceal haemorrhage. Many randomised controlled trials were performed to evaluate these new therapies. While most have demonstrated efficacy in controlling haemorrhage few showed improved survival. AIM: The aim of this study was to investigate whether the prognosis for cirrhotic patients following a first variceal haemorrhage has improved over the past four decades. PATIENTS AND METHODS: A total of 1475 patients included in the control or untreated arms of randomised controlled prophylactic trials for the primary prevention of variceal haemorrhage between 1960 and 2000. Twenty eight eligible randomised controlled studies were included. Over the 40 year period of observation there was a reduction in bleeding related mortality over time from approximately 65% to approximately 40% (p=0.024). CONCLUSION: This study suggests that there has been a significant reduction in bleeding related mortality in patients with cirrhosis and portal hypertension over the past 40 years.

Confidence Intervals↗
PubMed2001

Six-month outcomes for patients who switched to olanzapine treatment.

OBJECTIVE: This study evaluated the outcomes of patients in a community mental health center who switched from treatment with another antipsychotic to olanzapine treatment. It also sought to determine whether simultaneous access to case management and psychosocial rehabilitation and olanzapine leads to enhanced functional improvement. METHODS: Six-month outcomes for a consecutive series of 104 patients who switched from a conventional antipsychotic medication to olanzapine were evaluated. Forty-nine patients in the same treatment program who continued to take conventional antipsychotics were also monitored as a reference group. Outcomes of the group receiving olanzapine were compared with their own baseline status and with outcomes of the reference group. RESULTS: At six months, patients in the olanzapine group demonstrated significant improvement over baseline across multiple measures of symptoms and psychosocial function. Compared with the reference group, the olanzapine group was more symptomatic at baseline and demonstrated significantly greater improvement at follow-up on the Brief Psychiatric Rating Scale and all subscales; Mini Psychiatric Rating Scale negative symptom, disorganization, anxiety, depression, and medication side effects items; and Clinical Global Improvement scale and Case Manager's Rating Scale-Plus illness factors. There was a trend toward superior improvement in psychosocial functioning among patients in the olanzapine group that achieved significance when patients in acute relapse at baseline were excluded. CONCLUSIONS: Olanzapine is effective in managing markedly to severely ill patients with psychotic disorders in a community mental health center. Simultaneous treatment with olanzapine, case management, and psychosocial rehabilitation leads to enhanced functional improvement among nonrelapsing patients.

Adult↗
PubMed1999

Plasma Cleaning and Its Applications for Electron Microscopy.

: The effectiveness of applying a high-frequency, low-energy, reactive gas plasma for the removal of hydrocarbon contamination from specimens and components for electron microscopy has been investigated with a variety of analytical techniques. Transmission electron microscopy (TEM) analysis of specimens that have been plasma cleaned shows an elimination of the carbonaceous contamination from the specimen. With extended cleaning times the removal of existing carbon contamination debris due to previously conducted microanalysis is shown. Following plasma cleaning, specimens may be examined in the electron microscope for several hours without exhibiting evidence of recontamination. The effectiveness of plasma cleaning is not limited to applications for TEM specimens. Scanning electron microscopy (SEM) specimens that have been plasma cleaned likewise show an elimination of carbonaceous contamination. Furthermore, other electron microscopy parts and accessories, such as aperture strips, specimen clamping rings, and Wehnelts, among others, can benefit from plasma cleaning.

Journal Article↗
PubMed1999

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗
PubMed1999

Effectiveness of combining atypical antipsychotics and psychosocial rehabilitation in a community mental health center setting.

This article presents a consecutive case series of 70 patients treated with olanzapine, case management, and psychosocial rehabilitation in a community mental health setting. This group demonstrated highly significant improvement on all analyzed measures of symptoms and psychosocial function at 6-month follow-up. These findings suggest that results of efficacy studies of olanzapine will generalize to the community mental health setting. Furthermore, prescribing olanzapine in combination with case management and rehabilitation yields positive functional outcomes.

Adult↗
PubMed1994

Expression of major histocompatibility complex class II antigen in NOD mouse thyroid.

Non obese diabetic (NOD) mice spontaneously develop thyroiditis in addition to diabetes. Mononuclear cells begin to infiltrate the thyroid of these animals in the first month of life. The expression of major histocompatibility complex (MHC) class II (Ia) antigens by cells in the thyroid from NOD mice of various ages with and without thyroiditis was examined. We found that only 1 of the 9 infiltrated thyroids from 18 8-33 day old NOD mice surveyed expressed MHC class II antigens. Therefore Ia antigen expression appears to be secondary to infiltration and does not initiate the autoimmune process. Fourteen of 17 (82.2%) infiltrated and 7 of 11 (63.6%) uninfiltrated thyroids from NOD mice aged 51-73 days contained cells expressing Ia antigens. Sixteen of 18 (88.9%) infiltrated and all 7 of the uninfiltrated thyroids from mice aged > 89 days contained Ia positive cells. These MHC class II expressing cells included thyroid epithelial cells (TEC), as well as interstitial cells such as macrophages. Ia positive cells in the thyroid have the potential of presenting thyroid specific antigen to infiltrating T cells and thereby maintaining or potentiating thyroid autoimmune destruction. Macrophages were observed in thyroid tissue from 9 of 11 (81.8%) infiltrated and 12 of 15 (80%) uninfiltrated 8-33 day old NOD mice, thyroids from 11 of 16 (68.7%) infiltrated and 6 of 9 (66.7%) uninfiltrated 51-73 day old NOD mice, as well as 28 of 29 (96.5%) uninfiltrated and all 9 of the uninfiltrated thyroid from NOD mice aged > 89 days. Thyroids from control age matched non autoimmune BALB/c mice were consistently Ia antigen negative while macrophages were seen in some of the animals aged > 60 days.

Age Factors↗
PubMedDate not supplied

Radionuclide uptake by red deer (Cervus elaphus) on mountain grazing.

Forty-two red deer (Cervus elaphus) were shot during the 1992 annual cull in Glenveagh National Park, Ireland. Samples of rumen, kidney and faeces were removed from each animal. Kidney samples were used to estimate flesh radiocaesium (137Cs) concentrations and the 95% confidence interval for the mean was 203 +/- 12 Bq kg-1. The maximum recorded 137Cs concentration in kidney was 367 Bq kg-1 (fresh weight). The altitude of the cull, the age and sex of each animal were recorded. Neither age nor sex correlated with concentrations of 137Cs in rumen, kidneys or faeces. Despite the limited altitudinal range of the study and the free ranging behaviour of deer, there was a highly significant positive correlation between rumen, kidney and faecal 137Cs concentrations and the altitude of the cull. 40K concentrations in rumen, kidney and faeces did not correlate with the altitude of cull, age or sex of slaughtered animals. Significant 137Cs concentration differences were identified in the sequence: rumen < faeces = faeces. 137Cs concentrations in rumen, kidney and faeces for individual animals were all significantly correlated. Statistical testing showed that the concentration sequence for 40K was: rumen < kidney = faeces; a sequence which differs from that of 137Cs. A comparison of ratios test for rumen:faecal ratios demonstrated that significantly more 137Cs was excreted in faeces than was the case for 40K. The concentration of 137Cs excreted in faeces relative to concentrations in forage (rumen), is approximately twice that for 40K. Linear regression of faecal 137Cs concentrations (y) on kidney concentrations (x) was carried out, the regression equation is y = -86.90 + 0.97x. This equation (R2 = 0.73, F1,40 = 107) may be used to predict 137Cs concentrations in flesh by measurement of faecal concentrations. This is a useful preliminary assessment method, particularly with herds of wild animals that prove difficult to capture for in vivo monitoring.

Altitude↗