Tracking medication dispensed from a hospital pharmacy.
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Electronic Data Processing↗
Biomedical subjects
J Osborne
Publications and source records attributed to J Osborne.
KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways.
Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a structural and functional homologue of human IL-6 called viral IL-6 (vIL-6). Expression of vIL-6 in KSHV-related lymphoproliferative disorders has been implicated in their pathogenesis. vIL-6 has been shown to mimic a number of IL-6 activities including stimulating the growth of IL-6 dependent cell lines and activating the JAK1 and STAT1/3 pathway in HepG2 cells. However, IL-6 and vIL-6 display differences in receptor usage that may give rise to underlying qualitative and quantitative differences in the signaling pathways utilized. While IL-6 has an absolute requirement for both the IL-6 Ralpha and the gp130 subunits, vIL-6 appears to require only gp130. In addition to JAK1 and STAT1/3 pathways, IL-6 activates multiple other pathways including the direct activation of STAT 5 by JAK1, the Ras-MAP kinase cascade and a novel H7-sensitive pathway. In this study we examined whether vIL-6 is capable of signaling via distinct IL-6 response elements (IL-6 RE) under the control of these different pathways. We show that vIL-6 activates both STAT1/3- and STAT5-dependent Type II IL-6 REs. In addition, vIL-6 induces transcriptional activation via a Type I IL-6 RE that binds C/EBP, indicative of Ras-MAP kinase pathway induction. Furthermore, vIL-6 is capable of activating the IL-6 response element in the c-jun promoter (RE-IL-6). vIL-6 induced activation of JRE-IL-6 requires both the Ets- and Cre-like sites, suggesting that vIL-6 is capable of stimulating the same novel serine/threonine kinase mediated pathway as IL-6. These results demonstrate that vIL-6 can stimulate all of the known IL-6-induced signaling pathways. Therefore, vIL-6 could potentially contribute to KSHV-related disease progression by continued activation of IL-6-stimulated growth and anti-apoptotic pathways even when cells attempt to protect themselves from IL-6 over-stimulation by downmodulating their IL-6Ralpha subunits.
CCAAT-Enhancer-Binding Proteins↗
The Epworth Sleepiness Scale: can it be used for sleep apnoea screening among snorers?
Snoring is a common disorder and may lead to the development of Obstructive Sleep Apnoea (OSA) with its associated hazards. Differentiation of patients with OSA from patients with simple snoring is crucial to the ENT surgeon before selecting treatment. This study aimed to assess the reliability of the Epworth Sleepiness Scale (ESS) to screen for OSA among snorers. Forty-six patients referred for treatment of snoring were studied. Each patient completed the ESS questionnaire and subsequently underwent a hospital sleep study. The ESS scores did not correlate with the apnoea/hypopnoea indices calculated from the sleep studies (correlation coefficient 0.12). The lack of correlation is mainly because simple snorers can also suffer from excessive daytime sleepiness, due to an unclear mechanism. The ESS is a useful questionnaire for assessing disability as a result of snoring but it is of no value in distinguishing simple snorers from patients with OSA.
Adult↗
A simple audio data logger for objective assessment of snoring in the home.
We have developed a portable device for patient use in logging snoring loudness in the home, for guiding treatment decisions and measuring the clinical effectiveness of treatment. The device uses a free field microphone and is positioned on a bedside table. The prototype devices contain no inherently expensive components and are simple to operate (producing only 5% patient error to date). They are portable, battery powered, rugged and produce digital data which are easily and automatically analysed, and these design parameters enable the devices to be used for first line patient assessment. Of the 75 recordings made so far from 30 patients, 85% were successful, yielding clinically useful data. Because it is sound levels which are recorded and not replayable sounds, patient privacy is maintained, resulting in excellent patient acceptance (to date no patient has refused). The device has a dynamic range of 45-90 dB sound pressure level and a frequency range of 30 Hz-5 kHz. Because snoring intensities often vary significantly throughout the night the device can measure continuously over 8 h.
Calibration↗
Novel super-high affinity sheep monoclonal antibodies against CEA bind colon and lung adenocarcinoma.
We have developed technology to create monoclonal antibodies (MAbs) using lymphocytes from immunized sheep. The affinities of these sheep monoclonal antibodies (SMA) can be several orders of magnitude higher than mouse MAbs. This paper reports the development and validation of a modified enzyme-linked immunoadsorbent assay (ELISA) method to select high-affinity antibodies of the desired specificity at the first screen. Using this method, we have isolated high affinity SMA to carcinoembryonic antigen (CEA), a marker of colon cancer. Comparisons of our novel SMA with mouse MAbs using the new ELISA and BIAcore technology (BIAcore AB, Stevenage, Herts, UK) have confirmed that we have made super-high affinity antibodies to CEA. One of these has a t(1/2) for dissociation of 8 days, which could provide a longer therapeutic window than is available with murine monoclonals currently being used in the clinic. This antibody has a specific tissue staining profile; it thus appears to be an excellent candidate for use in the clinic.
Adenocarcinoma↗
Nurses' perceptions: when is it a medication error?
This study investigates nurses' perceptions of medication errors and appropriate reporting. Results of the study suggest that nurses may not report because of fear of reprisal. Further, there may be a need to allow for nursing judgment in some instances; at those time, the term "medication error" may not be the most appropriate. Implications for nursing administration include further exploration of nonpunitive processes in response to adverse drug events.
Adult↗
Interleukin-10 and antigen-presenting cells actively suppress Th1 cells in BALB/c mice infected with the filarial parasite Brugia pahangi.
Infection with the third-stage larvae (L3) of the filarial nematode Brugia results in a Th2-biased immune response in mice and humans. Previously we have shown that the production of interleukin 4 (IL-4) is critical for down-regulating polyclonal Th1 responses in L3-infected mice. However, the in vitro neutralization of IL-4 did not fully recover the defective polyclonal Th1 responses, nor did it result in the production of any antigen (Ag)-specific Th1 cytokines, suggesting that perhaps infection with L3 does not result in priming of Th1 cells in vivo. In this study, we analyzed the role of IL-10 and Ag-presenting cells (APCs) in the spleen as additional factors controlling the Th2 bias in infected mice. Our data show that IL-10 and APCs also contribute to the suppression of mitogen-driven Th1 responses of spleen cells from infected mice. In addition, the neutralization of IL-10 or the replacement of the resident APC population from spleen cell cultures resulted in the production of Ag-specific Th1 cytokines. Irradiated spleen cells from either L3-infected or uninfected mice were able to restore Ag-specific Th1 responses in vitro. Therefore, it appears that Brugia-reactive Th1 cells are primed following infection with L3, but are actively suppressed in vivo by a mechanism that involves IL-10 and the resident APC population, but not IL-4. These results indicate that a complex interplay of cytokines and cell populations underscores the Th2-polarized response in L3-infected mice.
Aedes↗
Genotypic and phenotypic characterization of "Streptococcus milleri" group isolates from a Veterans Administration hospital population.
Because identification of the species within the "Streptococcus milleri" group is difficult for the clinical laboratory as the species share overlapping phenotypic characteristics, we wished to confirm biochemical identification with identification by 16S rRNA gene sequence analysis. Ninety-four clinical isolates previously identified as the "Streptococcus milleri" group were reclassified as S. anginosus, S. constellatus, or S. intermedius with the API 20 Strep system (bioMerieux Vikek, Hazelton, Mo.) and the Fluo-card (Key Scientific, Round Rock, Tex.). In addition, we determined the Lancefield group, hemolysis, colony size, colony texture, repetitive extragenic palindromic PCR (rep-PCR) pattern, and cellular fatty acid (CFA) profile (MIDI, Newark, Del.). 16S rRNA gene sequence analysis with 40 selected representative strains showed three distinct groups, with S. constellatus and S. intermedius found to be more closely related to each other than to S. anginosus, and further distinguished a biochemically distinct group of urogenital isolates within the S. anginosus group of isolates. Except for strains unreactive with the Fluo-card (8%), all S. anginosus and S. intermedius strains identified by sequencing were similarly identified by biochemical testing. However, 23% of the selected S. constellatus isolates identified by sequencing (9% of all S. constellatus isolates) would have been identified as S. anginosus or S. intermedius by biochemical tests. Although most S. anginosus strains formed one unique cluster by CFA analysis and most S. constellatus strains showed similar rep-PCR patterns, neither method was sufficiently dependable for identification. Whereas Lancefield group or lactose fermentation did not correspond to sequence or biochemical type, S. constellatus was most likely to be beta-hemolytic and S. intermedius was most likely to have a dry colony type. The most frequent isolate in our population was S. constellatus, followed by S. anginosus. There was an association of S. anginosus with a gastrointestinal or urogenital source, and there was an association of S. constellatus and S. intermedius with both the respiratory tract and upper-body abscesses.
Adult↗
Bacteremia caused by a novel isolate resembling leptotrichia species in a neutropenic patient.
We report a case of Leptotrichia species bacteremia in a patient undergoing treatment for acute myelogenous leukemia. Like previously reported Leptotrichia species, this is a gram-variable, pleomorphic rod that is catalase negative and utilizes glucose and sucrose. However, it is more fastidious than previously reported isolates of Leptotrichia and may represent a novel species.
Antineoplastic Combined Chemotherapy Protocols↗
Planning and accountability at AHCPR: applying the quality message at home. Agency for Health Care Policy and Research.
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Health Planning↗
Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.
We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were > or = 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or val92met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in the red/blonde cases with wild-type MC1R alleles compared with those with asp294his was significant (exact P = 0.029). No associations between val92his or asp84glu and CYP2D6 alleles were identified.
Cytochrome P-450 CYP2D6↗
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.
Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
Chromosome Mapping↗
Well-differentiated liposarcoma of the hypopharynx.
We present a case of well-differentiated liposarcoma of the hypopharynx in a 51-year-old male, with a review of the literature of this very rare condition.
Humans↗
Snoring assessment: do home studies and hospital studies give different results?
We have developed a device (Glan Clwyd Snore Box) suitable for the objective measurement of the loudness and duration of snoring. The device is simple for the patient to operate, portable, battery powered, and able to produce objective results. We have used the Snore Box to record the snoring at home and during sleep studies in the hospital. Twenty-nine patients were studied. Overall the Snore Index recorded in the home was greater than in the hospital (P < 0.001), the average difference being 67 snores/h. We conclude that snoring is more appropriately assessed at home than in the hospital. We suggest the deficit arises from sleeping in an unfamiliar environment and the presence of several wires connecting the patient to the recording monitor which interfere with natural sleep in the hospital setting.
Adult↗
Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene.
Allelic variation at the melanocyte stimulating hormone receptor (MC1R) gene has been linked with sun-sensitive skin types, suggesting it is a susceptibility candidate for melanoma. We determined the frequency of the val92met, asp294his, and asp84glu MC1R alleles in 190 Caucasian controls and 306 melanoma cases and studied their association with skin type and hair color. The percentage of controls with at least one val92met, asp294his, or asp84glu allele was 17.3%, 6.8%, and 3.5%, respectively. Individually, frequencies of the val92met, asp294his, or asp84glu alleles in the controls with skin types 3 and 4 were similar to those with skin types 1 and 2. Trend analysis, however, did identify an association (exact p = 0.048, two-sided test) between skin type and MC1R variants in the group comprising all controls with any one or more of these alleles. There was no association between MC1R alleles and hair color. Allele frequencies were not different in melanoma cases and controls. There were no associations between skin types and the proportion of cases with the asp294his or asp84glu alleles, though the association between skin type and the val92met allele approached significance (exact p = 0.09, two-sided test). Unexpectedly, in the group comprising all cases with one or more variant alleles, the proportion of subjects with variant alleles increased with skin types associated with tanning rather than burning, although trend analysis showed that this association did not quite reach statistical significance (exact p = 0.08, two-sided test). Asp84glu (but not val92met or asp294his) variant alleles were more common in subjects with blonde hair, although the relationship between the asp84glu allele and hair color did not achieve statistical significance (chi(2)3 = 6.16, exact p = 0.10). We interpret the data presented as indicating that polymorphism at MC1R does not appear a major determinant of skin type, at least in terms of these allelic variants. Furthermore, considered alone, these alleles are not susceptibility candidates for malignant melanoma.
Adult↗
The L3 of Brugia induces a Th2-polarized response following activation of an IL-4-producing CD4-CD8- alphabeta T cell population.
Lymphatic filariasis in man is characterized by a profound bias in the immune response. Parasite-specific Th1 responses are dramatically down-regulated while Th2 responses dominate. We have used the infective larval stage of the nematode parasite Brugia pahangi, a potent Th2 inducer in naive mice, to examine cytokine production during the initiation phase of the response. For comparative purposes, the early cytokine transcription pattern elicited by microfilariae (mf), another life cycle stage of the parasite known to induce a primary Th1 response, was analysed in parallel. At 24 h post-infection (p.i.) a burst of IL-4 transcription was detected in the draining popliteal lymph node of L3-infected animals. IL-4 was the only cytokine transcript detectable at this early time point and was not present in mf-infected mice. From day 4 p.i. onwards, the L3 elicited a Th2 response as defined at the level of cytokine mRNA and protein production by CD4+ cells. In contrast, mf stimulate high levels of IFN-gamma mRNA at day 4 p.i. in the absence of IL-4 or IL-10 induction. Cell selection analysis indicated that IL-4 produced at 24 h derived from a population of CD4-CD8- alphabeta T cells. These results suggest that triggering of an unusual double-negative T cell population to secrete IL-4 at the very outset of infection with the L3 of B. pahangi may be the critical factor favouring the development of antigen-specific Th2 cells in response to this stage of the parasite.
Animals↗
Minimally invasive direct coronary artery bypass: technical considerations and instrumentation.
Minimally invasive coronary artery bypass is defined as any maneuver or modification of conventional coronary bypass that decreases adverse effects. These adverse effects fall into three broad categories, which are access trauma, consequences of cardiopulmonary bypass, and aortic manipulation. In the minimally invasive direct coronary artery bypass (MIDCAB) approach, coronary revascularization is performed via a limited access incision, usually a left anterior thoracotomy, through which a left internal mammary artery is anastomosed under direct vision to the left anterior descending artery on a stabilized beating heart. Harvest of the left internal mammary artery can be performed with video assistance (two- or three-dimensional or under direct vision). A variety of offset chest wall retractors that allow internal mammary artery harvest under direct vision have simplified the procedure, and several mechanical stabilization devices (with or without suction) allow local wall immobilization for a target vessel anastomosis. Graft patency data from early series of stabilized MIDCAB procedures and published series of left internal mammary artery graft patency with conventional bypass grafting appear to be comparable. Current indications for MIDCAB include restenosis of the left anterior descending artery after catheter-based therapy and the necessity for target vessel revascularization in elderly high-risk patients with multivessel disease. Limitations of the MIDCAB procedure include mostly single vessel revascularization of the anterior aspect of the heart.
Aged↗
One-two rural residency tracks in family practice: are they getting the job done?
BACKGROUND: In the 1990s, the Residency Review Committee for Family Practice (RRCFP) and the American Board of Family Practice used the development of rural training programs as a strategy to bridge training experiences across urban referral centers and rural community hospitals. These programs are relatively small and attract trainees who are predisposed to rural practice. Aggregating data from several programs yields insight about their challenges and their ability to produce graduates who enter rural practice. METHODS: This descriptive analysis is based on self-reported data from a 1996 survey mailed to the residency program directors of rural training programs, identified by the RRCFP office as one-two programs. RESULTS: More than half of the rural training programs surveyed were located in health professions shortage areas, most in communities with little urban influence. These programs are equally likely to be sponsored by university- or community-based residency programs. Most (75%) placed two or fewer residents per year in the rural site; minorities accounted for 4% of placements. Thirty percent of programs report unfilled positions. Seventy-five percent use televideo communications and find experiences in surgery and obstetrics relatively easy to arrange but dermatology and critical care difficult. Seventy-six percent of graduates enter rural practice after graduation. CONCLUSIONS: This survey suggests that family practice rural one-two residencies are meeting the goal of providing trainees with a rural immersion experience, in anticipation of selecting rural practice after graduation.
Community Health Services↗