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Biomedical subjects

K Hayes

Publications and source records attributed to K Hayes.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluating on-line continuing education for nurses.

The rapid increase in web sites for nursing continuing education demands critical appraisal by the user. The level of anonymity of the web site authors and sponsors may lead to a laxity of accountability found in no other media. This article discusses criteria for web site evaluation and provides a rating instrument to assist learners in determining the quality and usability of an on-line nursing continuing education offering. Using the rating instrument, two web sites are reviewed. A list of selected nursing continuing education web sites is included.

Attitude to Computers↗
PubMed1999

An integrated strategy for the process development of a recombinant antibody-cytokine fusion protein expressed in BHK cells.

Recombinant fusion proteins offer important new therapeutic approaches for the future. This report describes the use of three different genetic strategies (i.e. "mono-", "bi-" and "tri-cistronic" vectors) to achieve stable secretion from BHK cells of a glycosylated antibody-cytokine fusion protein designed for use in antitumour therapy. It describes selection of a robust and effective production cell line based on stability of secretion of the product, quality of mRNA and protein products and performance in in vitro bioassays for potency. The data obtained at this stage were utilised in the selection of a suitable candidate production cell line. The relative productivity and general performance of the cells in stirred tank and fixed bed culture systems indicated that a variety of cell culture technologies provided robust tools for production of a highly selected cell clone. Consistency of the product glycosylation was determined by analysis of released oligosaccharides using matrix-assisted laser desorption ionisation-time of flight mass spectrometry and high-performance anion exchange chromatography. These investigations showed consistent expression of three glycoforms of the fusion protein which varied in their relative proportions in different culture systems and at different time points in a fixed bed reactor with continuous perfusion. In conclusion, this study dealt with a range of important scientific and technical issues which are essential for regulatory approval and commercial success of a recombinant protein and elucidates some useful markers for process development for similar recombinant biologicals.

Animals↗
PubMed1999

Deletions and losses in chromosomes 5 or 7 in adult acute lymphocytic leukemia: incidence, associations and implications.

Deletions or losses in chromosomes 5 or 7 are recurrent non-random abnormalities in acute myeloid leukemia (AML), and are associated with prior exposure to carcinogens or leukemogenic agents, and with poor prognosis. Their occurrence and significance in adult acute lymphocytic leukemia (ALL) is not well described. The aim of the study was to evaluate the incidence, associations and implications of chromosome 5 or 7 abnormalities in adult ALL. Patients with newly diagnosed ALL referred to MD Anderson Cancer Center between 1980 and 1996 were analyzed. Characteristics and outcome of patients with or without chromosome 5 or 7 abnormalities were compared by standard statistical methods. Thirty-one of 468 patients (6.6%) had chromosome 5 or 7 abnormalities. Loss of chromosome 5 occurred in six cases, three of them had both chromosome 5 and 7 abnormalities. Deletion or loss of chromosome 7 occurred as a single abnormality in three patients; in 28 patients it was associated with other abnormalities. The most significant cytogenetic association was with the Philadelphia chromosome (Ph) abnormality occurring in nine patients (29%). Compared with patients without the abnormalities, patients with chromosome 5 or 7 abnormalities tended to express CD34 more frequently (74% vs 54% P = 0.07), to be older (age >60 years 29% vs 18% P = 0.14), and to be associated with Ph (29% vs 11% P = 0.004). With therapy, the complete response (CR) rate with chromosome 5 or 7 abnormalities was lower (64% vs 79% P = 0.038) but the survival rate was similar (3-year survival rate 32% vs 36% P = 0.14). When the 22 patients without Ph were considered separately, the CR and survival rates were similar among patients with or without chromosome 5 or 7 abnormalities. Abnormalities in chromosome 5 or 7 are not specific for AML, and may occur in ALL. Unlike in AML, chromosome 5 or 7 abnormalities in ALL were not predictive of worse prognosis, which is accounted for mostly by the association with Ph.

Adolescent↗
PubMed1999

Use of peripheral blood blasts vs bone marrow blasts for diagnosis of acute leukemia.

Acute leukemia can be diagnosed when blasts constitute 30% or more of the nucleated cells in a patient's peripheral blood (PB) sample. To determine whether in such cases bone marrow (BM) aspirates are still necessary, we compared the results of diagnostic studies performed on PB samples with blast counts of 30% or more with those performed on the same patients' BM samples. We found no differences in morphologic features, cytochemistry, or immunophenotype between the blasts in PB and BM samples in any of 30 cases studied. However, in 10 (23%) of 44 cases in which cytogenetic analysis was performed, PB but not BM samples were insufficient for analysis. The converse never occurred. Five of the 10 cases had acute lymphoblastic leukemia and 5 had acute myeloid leukemia (41% of the patients with acute lymphoblastic leukemia and 17% of the patients with acute myeloid leukemia). In cases with adequate metaphases, there was strong correlation between the cytogenetic results for PB and BM samples. Some PB samples with blast counts of 30% or more are adequate for diagnosis of acute leukemia, especially when therapy can be delayed until it is known that an adequate number of analyzable metaphases are recovered from the PB samples.

Acute Disease↗
PubMed1999

Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia.

PURPOSE: To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Fifty-nine patients with MDSs and 27 with CMML were enrolled. They were either previously untreated (66%) or had received only biologic agents (14%) or chemotherapy with or without biologic agents (20%). Treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous infusion daily for 5 days and cytarabine 1. 0 g/m(2) by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiviral agents. At a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. RESULTS: Complete remission (CR) was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P =.15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively). The treatment effectively induced CR in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. The median number of continuation courses was two. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks for CMML). The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refractory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infections in 49% of patients. Six patients (7%) died during induction therapy. CONCLUSION: Topotecan and cytarabine induced high CR rates in unselected patients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active induction regimen in MDS and CMML patients, is well tolerated, and is associated with a low mortality rate.

Adult↗
PubMed1998

A simple efficient method of sequential G-banding and fluorescence in situ hybridization.

Several methods of chromosome identification to be used in combination with G-banding by the trypsin technique with Giemsa staining (G-banding) and fluorescence in situ hybridization (FISH) have been developed in the past few years. Unfortunately, these methods are impractical to use in the clinical laboratory and can provide inconsistent results. We report a simple, efficient, and reliable method of G-banding and FISH for use in clinical cytogenetics. G-banded chromosomes are codenatured with a direct- or indirect-labeled DNA prove (by using either chromosome painting or a chromosome centromeric probe) followed by a hybridization and signal detection. The procedure requires no pretreatment or additional fixation and results in good preservation of chromosome morphology and good intensity of the FISH signal.

Azure Stains↗
PubMed1998

Prognostic value of cytogenetics in multiple myeloma.

Karyotypic studies of bone marrow were conducted in 79 previously untreated patients with multiple myeloma who received a standard programme of chemotherapy. An abnormal karyotype was observed in 46% of patients, virtually all showing multiple abnormalities consistent with a long period of preclinical clonal evolution. Patients with an abnormal pattern showed various aberrations with hyperdiploidy in 64%, pseudodiploidy in 5% and hypodiploidy in 31%. The number of chromosomes affected ranged from two to 19 (median 10), with at least one trisomy in 83%, one monosomy in 75%, and one translocation in 42% of patients. Lymphoma-like karyotypes were present in 17% of patients with an abnormality but were not associated with atypical clinical features, such as an extramedullary mass, leukaemia, or increased serum lactate dehydrogenase. Monosomy or deletion of chromosome 13 was present in 47% of patients with an abnormal pattern, who lived for a shorter duration (median 10 months) than patients with other abnormalities (median 34 months) or with diploidy (median 35 months). The cause of the short survival of patients with monosomy or deletion of chromosome 13 was not clear, but further studies on the relationship with specific oncogenes are indicated.

Bone Marrow Cells↗
PubMed1998

PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics.

Mutation of the PTEN tumor suppressor gene is a frequent event in endometrial cancers. In other types of cancers, PTEN mutation has been associated with metastatic behavior and advanced stage. To examine the relationship between PTEN mutation and clinical features of endometrial cancers, we screened 136 cases for mutations in the nine exons and intronic splice sites of the PTEN gene, using single-strand conformation analysis, and aberrant bands were sequenced. Mutations were noted in 44 of 136 (32%) endometrial cancers, and two mutations were present in 8 cases. There were 36 cases with mutations resulting in truncated protein products, 6 cases with missense mutations in the phosphatase domain, 1 case with an in-frame deletion, and 1 case with a large insertion. Mutation of the PTEN gene correlated most closely with endometrioid histology; mutations were seen in only 5% (1 of 21) of serous/clear cell cancers compared with 37% (43 of 115) of endometrioid cancers (P = 0.004). PTEN mutation was associated with early stage, nonmetastatic disease and more favorable survival in both the entire group of 136 cases and in the 115 endometrioid cases. In addition, PTEN mutation correlated with other molecular features associated with favorable clinical behavior, including microsatellite instability and absence of p53 overexpression. Microsatellite instability was found in 60% of cases with PTEN mutations compared with only 25% of cases without mutations (P = 0.004). Overexpression of p53 was seen in only 14% of cases with PTEN mutations compared to 39% of cases without mutations (P = 0.006). In conclusion, PTEN mutation is associated with endometrioid histology and other favorable pathological, clinical, and molecular features rather than with increased metastatic potential as has been noted in some other types of cancers.

Adult↗
PubMed1997

Progressive encephalopathy associated with CD4/CD8 inversion in adult FIV-infected cats.

Experimental intravenous challenge of five adult cats with the feline immunodeficiency virus Maryland isolate (FIV-MD) was investigated for its ability to induce neurologic abnormalities associated with the onset of immunodeficiency. Five 8-month-old cats were inoculated with 1000 median tissue culture infective dose of FIV-MD isolate, with five age-matched cats serving as uninfected controls. All FIV-MD-infected cats tested positive for serum antiviral antibodies and plasma viral DNA as detected by polymerase chain reaction at 2, 4, 10, and 16 months postinfection (PI). At 10 and 16 months PI, there was a significant reduction in the CD4/CD8 lymphocyte ratio, with all cats having a CD4/CD8 ratio of 1 or less. Total protein electrophoretic analysis of cerebrospinal fluid demonstrated a significantly increased albumin quotient at 4 and 16 months PI, representing a disrupted blood-brain barrier (BBB). At 16 months PI, all cats demonstrated a preferential increase in frontal cortical slow-wave activity compared with control cats. Serial evaluation of brainstem auditory evoked potential recordings revealed a prolongation of the interpeak latencies times over the study time. At least one abnormality was found over time in visual and somatosensory evoked potential testing in three and four infected cats, respectively. Comparing lymphocyte subtype ratios with neurologic testing revealed that every FIV-MD-infected cat exhibited an abnormality in at least one neurologic functional test with a concurrent CD4/CD8 count ratio of 1 or less. Overall, this study demonstrated that FIV-MD infection in adult cats results in a delayed-onset, progressive encephalopathy that parallels the decline in the CD4/CD8 lymphocyte ratio. Compared with prior information from pediatric FIV-MD-infected cats, these results indicate that age of infection influences the onset and severity of disease and may be associated with CD4 cell depletion in FIV-MD-infected cats, as seen in HIV-1-infected humans.

Analysis of Variance↗
PubMed1997

Usefulness of detection of minimal residual disease by 'hypermetaphase' fluorescent in situ hybridization after allogeneic BMT for chronic myelogenous leukemia.

Hypermetaphase FISH (HMF), a molecular cytogenetic procedure combining the long term mitotic arrest of bone marrow cultures with detection of a specific chromosomal rearrangement by fluorescence in situ hybridization (FISH), has recently been shown to be effective in determining the frequency of Philadelphia chromosome positive (Ph+) cells in the bone marrow of chronic myelogenous leukemia (CML) patients undergoing treatment. By combining the probe for the Ph chromosome with one for the detection of the X chromosome, we used HMF to monitor the presence of malignant cells within the emerging host cell population in the marrow of a CML patient that had undergone sex-mismatched allogeneic bone marrow transplantation. In successive studies, we detected 0.5% and 1.75% Ph+ cells, respectively, confirmed by Western blot analysis for p210 protein. These readings occurred concordantly with a repopulation of host-derived diploid female cells. Standard G-band cytogenetic analyses did not detect any Ph+ cells at these time points. Intervention with donor lymphocyte infusion reinduced complete remission. This experience indicates that HMF is useful to identify low levels of repopulation by Ph+ cells in the marrow post-BMT at a stage when intervention is most efficacious.

ABO Blood-Group System↗
PubMed1997

Pressure ulcer prevention: review of literature.

Much has been written about the causes, prevention, and nursing management of pressure ulcers. A review of current literature on the subject reveals that, in spite of the enormity of information available, the problem continues to consume a large percentage of nursing time and energy. Studies of aggressive prevention and ongoing continuing education programs have demonstrated significant reduction of incidence and time of treatment, as well as dramatic cost savings. The Agency for Health Care Policy and Research (AHCPR) has recommended that all patients at risk for pressure ulcer development be placed on some form of pressure-reducing support surface. There is a wide variety of these products available, but a surprisingly limited quantity of published articles specifically compare the efficacy of one product to another.

Adolescent↗
PubMed1996

Risk indicators for hospitalization during the last year of life.

OBJECTIVE: High levels of hospital expenditures for older people during their last year of life are widely documented. However, evidence of the association between prospectively measured indicators and subsequent hospitalization is sparse. This article investigates the pattern of hospitalization for a sample of Medicare enrollees during their last year of life. DATA SOURCES: Data from the Longitudinal Study of Aging, a national study of persons age 70 and older, are used. Only data on decedents are used. STUDY DESIGN: We determine individual characteristics (including functional status, evidence of disease, living arrangement, and prior hospitalization) shortly before the last year of life. A distinction is made between terminal and nonterminal admissions. National estimates and regression analyses using survey weights are conducted. PRINCIPAL FINDINGS: The likelihood of any use is high regardless of age, functional status, or the presence of major diseases. Although only a few indicators are associated with having a terminal stay, a number of indicators are associated with nonterminal use. Nonterminal stays and total nights hospitalized are positively associated with prior evidence of disease, prior hospitalization, and age, although the probability of nonterminal use decreases with age for persons over 82 years old. The relationship between use and functional status depends on whether persons lived alone, were institutionalized, or had private health insurance. CONCLUSIONS: This study demonstrates that while it is difficult to predict who will be admitted to the hospital at the time of death, a number of characteristics existing before the last year of life are associated with nonterminal hospitalization and total nights hospitalized during the last year of life.

Age Factors↗
PubMed1995

HIV-1 infection of human macrophages impairs phagocytosis and killing of Toxoplasma gondii.

The susceptibility of patients with AIDS to certain opportunistic infections is due to defective cell-mediated immunity. The contribution of direct infection of macrophages with HIV-1 to this defect is unknown. To address this issue, we infected normal human monocyte-derived macrophages with a monocytotropic strain of HIV-1 and examined their ability to phagocytose and kill the opportunistic pathogen, Toxoplasma gondii. Phagocytosis of heat-killed T. gondii was reduced in HIV-infected macrophages compared with mock-infected controls. Opsonization of heat-killed T. gondii increased phagocytosis by both mock- and HIV-infected macrophages, but phagocytosis in HIV-infected cultures remained lower than in controls. Internalization of live T. gondii by macrophages was unaffected by HIV infection. Intracellular replication of live T. gondii was enhanced by HIV infection, as shown in four experiments, each using monocyte-derived macrophages from a different donor. Treatment of HIV-infected macrophages with IFN-gamma decreased parasite replication but not to control levels. These findings suggest that infection of macrophages by HIV may be a contributing factor to the reactivation of T. gondii infection in patients with AIDS.

Animals↗
PubMed1995

Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse.

The translocation between chromosomes 15 and 17, t(15;17)(q22-24;q11-21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

Base Sequence↗
PubMed1994

Pontine reticular neurons provide tonic excitation to neurons in rostral ventrolateral medulla in rats.

To determine whether the pontine reticular formation (PRF) is a source of tonic activity for cardiovascular neurons in the rostral ventrolateral medulla (RVLM), the discharge of PRF neurons was inhibited by unilateral microinjections of glycine (1.0 M; 60 nl) while recording the discharge of single neurons in the RVLM in 14 Saffan-anesthetized rats. RVLM units were characterized as cardiovascular if their spontaneous activity was changed by baroreceptor activation and was synchronized to the cardiac cycle. Glycine injection into the ipsilateral PRF eliminated the ongoing activity of six cardiovascular units and reduced the activity of four (mean decrease -91 +/- 4%). Inhibition of these units lasted 20-115 s (mean 59 +/- 9 s). Glycine injection into the PRF had no effect on the discharge of five cardiovascular units. Activity of six noncardiovascular units did not respond to PRF blockade. Glycine injection into the PRF caused decreases in arterial pressure (-28 +/- 5 mmHg), heart rate (-23 +/- 3 beats/min), and renal nerve activity (-42 +/- 7%) that also returned to control values between 25 and 120 s (mean 55 +/- 5 s). These results indicate that PRF neurons provide tonic excitatory drive to some cardiovascular neurons located in the RVLM.

Animals↗
PubMed1993

High-dose oral acyclovir reduces the incidence of cytomegalovirus infection in liver transplant recipients.

To determine the impact of high-dose oral acyclovir on cytomegalovirus (CMV) infection or disease after liver transplantation, CMV cultures were prospectively collected for 6 months after transplantation. The incidence and timing of infection and disease in patients receiving high-dose oral acyclovir (3200 mg/day) from day 7 until 3 months after transplantation were compared with an historical control group who received no acyclovir. All patients who did not receive acyclovir (group 1, n = 12) but only 57% of those who did (group 2, n = 22) had CMV infection (P = .008). Nine (75%) group 1 but only 3 (14%) group 2 patients had positive leucocyte cultures (P = .0007). Three group 1 patients developed CMV disease; 1 group 2 patient developed CMV hepatitis. Each of these 4 patients had CMV viremia (P = .01). The frequency of CMV infection after liver transplantation appears to be reduced by high-dose oral acyclovir.

Acyclovir↗
PubMed1993

Caring for the community.

Humboldt Home Health Services, in Eureka, California, has stretched its vision of "good business" to include the development of many new programs that not only respond directly to patient and community needs, but are also economically viable, self-sustaining, and builders of staff self-esteem.

Acquired Immunodeficiency Syndrome↗