Concurrent medicine: the next trend in the industrialization of health care.
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Delivery of Health Care↗
Biomedical subjects
T Miller
Publications and source records attributed to T Miller.
Inhibition of human cytomegalovirus DNA maturation by a benzimidazole ribonucleoside is mediated through the UL89 gene product.
2-Bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (BDCRB) is a member of a new class of benzimidazole ribonucleosides which inhibit human cytomegalovirus (HCMV) late in the replication cycle without inhibiting viral DNA synthesis. We show here that polygenomic concatemeric HCMV DNA does not mature to unit genome length in the presence of BDCRB. To discover the locus of action, virus resistant to BDCRB was selected by serial passage in the presence of the compound. Genetic mapping experiments with BDCRB-resistant virus demonstrated that the resistance phenotype mapped to one amino acid (Asp344Glu; low resistance) or two amino acids (Asp344Glu and Ala355Thr; high resistance) within the product of exon 2 of the HCMV U(L)89 open reading frame. The HCMV U(L)89 open reading frame and its homologs are among the most conserved open reading frames in the herpesviruses, and their products have sequence similarities to a known ATP-dependent endonuclease from the double-stranded DNA bacteriophage T4. These findings strongly suggest that BDCRB prevents viral DNA maturation by interacting with a U(L)89 gene product and that the U(L)89 open reading frame may encode an endonucleolytic subunit of the putative HCMV terminase. Further, since mammalian cell DNA replication does not involve a DNA maturation step, compounds which inhibit viral DNA maturation should be selective and safe.
Amino Acid Sequence↗
Measuring the quality of diagnostic hypothesis sets for studies of decision support.
Within medical informatics there is widespread interest in computer-based decision support and the evaluation of its impact. It is widely recognized that the measurement of dependent variables, or outcomes, represents the most challenging aspect of this work. This paper describes and reports the reliability and validity of an outcome metric for studies of diagnostic decision support. The results of this study will guide the analytic methods used in our ongoing multi-site study of the effects of decision support on diagnostic reasoning. Our measurement approach conceptualizes the quality of a diagnostic hypothesis set as having two components summed to generate a composite index: a Plausibility Component derived from ratings of each hypothesis in the set, whether correct or incorrect; and a Location Component derived from the location of the correct diagnosis if it appears in the set. The reliability of this metric is determined by the extent of interrater agreement on the plausibility of diagnostic hypotheses. Validity is determined by the extent to which the index generates scores that make sense on inspection (face validity), as well as the extent to which the component scores are non-redundant and discriminate the performance of novices and experts (construct validity). Using data from the pilot and main phases of our ongoing study (n = 124 subjects working 1116 cases), the reliability of our diagnostic quality metric was found to be 0.85-0.88. The metric was found to generate, on inspection, no clearly counterintuitive scores. Using data from the pilot phase of our study (n = 12 subjects working 108 cases), the component scores were moderately correlated (r = 0.68). The composite index, computed by equally weighting both components, was found to discriminate the hypotheses of medical students and attending physicians by 0.97 standard deviation units. Based on these findings, we have adopted this metric for use in our further research exploring the impact of decision support systems on diagnostic reasoning and will make it available to the informatics research community.
Decision Support Systems, Clinical↗
The value of imagery in perioperative nursing.
Body/mind medicine is rapidly becoming one of the catalysts that will integrate conventional and complementary health care. Interactive Imagery, in particular, offers many potent healing opportunities for nurses and patients in the perioperative continuum. Within this holistic approach, nurses play a pivotal part in providing to patients self-care tools that can be applied in and out of the hospital. Imagery adds value to the health care system by offering nurses and other health care practitioners a way to empower themselves and their patients. It is harmless, time and cost-effective, and often fun, and it focuses on patient satisfaction.
Adult↗
Association of homologous chromosomes during floral development.
Reduction in chromosome number and genetic recombination during meiosis require the prior association of homologous chromosomes, and this has been assumed to be a central event in meiosis. Various studies have suggested, however, that while the reduction division of meiosis is a universally conserved process, the pre-meiotic association of homologues differs among organisms. In the fruit fly Drosophila melanogaster, some somatic tissues also show association of homologues [1,2]. In the budding yeast Saccharomyces cerevisiae, there is some evidence for homologue association during the interphase before meiotic division [3,4], and it has been argued that such associations lead directly to meiotic homologue pairing during prophase I [5]. The available evidence for mammals suggests that homologous chromosomes do not associate in germ cells prior to meiotic prophase [6]. To study the occurrence of homologue pairing in wheat, we have used vibratome tissue sections of wheat florets to determine the location of homologous chromosomes, centromeres and telomeres in different cell types of developing anthers. Fluorescence in situ hybridization followed by confocal microscopy demonstrated that homologous chromosomes associate pre-meiotically in meiocytes (germ-line cells). Surprisingly, association of homologues was observed simultaneously in all the surrounding somatic tapetum cells. Homologues failed to associate at equivalent stages in a homologue recognition mutant. These results demonstrate that the factors responsible for the recognition and association of homologues in wheat act before the onset of meiotic prophase. The observation of homologue association in somatic tapetum cells demonstrates that this process and meiotic division are separable.
Cell Nucleus↗
Minor structural differences in Boc-CCK-4 derivatives dictate affinity and selectivity for CCK-A and CCK-B receptors.
We previously reported novel Boc-CCK-4 (Boc-Trp-Met-Asp-Phe-NH2) derivatives possessing the general structure Boc-Trp-Lys[N epsilon-CO-NH-(R-Ph)]-Asp-Phe-NH2 (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842). In contrast to Boc-CCK-4, which is 70-fold selective for the CCK-B receptor, the modified lysine-bearing tetrapeptides were highly potent and selective full agonists at the CCK-A receptor. Further investigation of the structure-activity profile following modification of the substituted phenylurea moiety appended off the lysine revealed that moving certain substituents, e.g. nitro or acetyl, from the 2- or 3-position on the phenyl ring to the 4-position, a relatively minor and subtle structural modification within the tetrapeptide, resulted in loss of CCK-A receptor selectivity and development of a trend toward CCK-B selectivity. These tetrapeptides, e.g. Boc-Trp-Lys[N epsilon-CO-NH-(4-NO2-Ph)]-Asp-Phe-NH2 and Boc-Trp-Lys[N epsilon-CO-NH-(4-Ac-Ph)]-Asp-Phe-NH2, were full agonists relative to CCK-8 in stimulating intracellular calcium mobilization in a cell line that expresses the CCK-B receptor.
Cell Line↗
Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.
OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2 tumors) and blood samples from 17 patients with head and neck squamous cell carcinoma was performed using primers flanking 16 microsatellite repeat polymorphisms spanning most of chromosome 18q. DNA was extracted only from specimens with greater than 70% tumor nuclei. SETTING: Research university. PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%) of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1-q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be more than one 18q tumor suppressor gene involved in the genesis and progression of head and neck squamous cell carcinomas.
Carcinoma, Squamous Cell↗
Picture archiving and communication system implementation: the practical considerations of adapting the technology to the real world of health care operations.
The issues discussed in this article are just some of the real-life considerations a facility's management team should address during the planning process as they make decisions about PACS implementation. We currently are working with the management teams of many facilities on PACS implementation projects that have yet to be completed. In the future, we hope to report on our experiences, including both successes and failures, as construction is completed and the systems actually are implemented.
Computer Communication Networks↗
Centromeric behaviour in wheat with high and low homoeologous chromosomal pairing.
Control of homoeologous chromosomal pairing in hexaploid wheat stems from a balance between a number of suppressor and promoter genes. This study used centromeric behaviour as a tool to investigate the mechanism. Fluorescent in situ hybridization employing centromeric and telomeric sequences as probes was applied to pollen mother cells of wheat and wheat/alien hybrids having different pairing gene combinations. It showed: association of centromeres during pre-meiotic interphase; decondensation of centromeric structure; sister chromatid disjunction of univalent chromosomes in homoeologous pairing situations at anaphase I; and centromeric stretching between univalent sister chromatids in wheat/rye hybrids deficient for pairing genes. The implications of these results are discussed.
Anaphase↗
United States passenger-vehicle crashes by crash geometry: direct costs and other losses.
The personal and societal losses caused by motor-vehicle crashes are significant. This paper provides tools that describe these losses for 30 different crash geometries. Persons involved with the development and implementation of crash countermeasures can use these tools to prioritize their countermeasure approach. Multiple vehicle crashes currently account for much larger direct costs but only slightly more years lost than single vehicle crashes. Direct expenditures on multiple vehicle crashes exceed $41 billion per year; they claim 974,000 years of life and functioning. Direct expenditures on single vehicle crashes exceed $18 billion per year; they claim 937,000 years of life and functioning.
Accidents, Traffic↗
Virtual bronchoscopy with perfluoronated hydrocarbon enhancement.
RATIONALE AND OBJECTIVES: Bronchoscopic computed tomography (CT) is limited by machine resolution and air-soft-tissue contrast. The objective of this study was to determine whether improving the contrast by using the contrast agent perflubron (PFOB) in the lung would improve the bronchoscopic CT technique and permit visualization of small airways. MATERIALS AND METHODS: Bronchoscopic CT was performed in an anesthetized 8-week-old New Zealand white rabbit before and after the endotracheal administration of PFOB. RESULTS: Bronchoscopic CT performed with PFOB permitted navigation of bronchi as small as 0.8 mm in diameter, which are much smaller than those that can be navigated without PFOB. CONCLUSION: In this example, the use of perfluorochemicals with bronchoscopic CT enhanced the capabilities of virtual bronchoscopy.
Animals↗
Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia in first remission.
The purpose of the study was to evaluate the feasibility and efficacy of high-dose cytarabine-anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for adult patients with acute myelogenous leukemia in first remission. Fifty-nine consecutive patients (median age 45, range 18-69) with acute myelogenous leukemia in first remission were enrolled on a study of high-dose cytarabine-mitoxantrone consolidation chemotherapy used as a method of in vivo purging for the purpose of autologous peripheral blood progenitor cell transplantation. A median of 7 x 10(8) peripheral blood mononuclear cells/kg were infused 1 day after preparative conditioning with 11.25 Gy total body irradiation and cyclophosphamide (120 mg/kg). Forty-six patients received myeloablative chemo-radiotherapy followed by the infusion of chemotherapy/rHu-G-CSF-mobilized autologous peripheral blood progenitor cells. The median time to both neutrophil and platelet recovery from transplant was 15 days (range, 11-36 and 5-253+ days, respectively). After a median follow-up of 27 months, 31 patients remain alive with 27 in complete remission. Median remission duration for all eligible patients is 12 months, and actuarial leukemia-free survival at 3 years is 42 +/- 14%. The actuarial risk of relapse is 54 +/- 15%. Toxicity of autologous peripheral blood progenitor cell transplant included treatment-related death in two patients and grade III/IV organ toxicity in six. Advanced age was a negative prognostic factor for leukemia-free survival. Our results demonstrate that autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible in an unselected population of adult patients with acute myelogenous leukemia in first remission producing improved leukemia-free survival with minimal toxicity.
Adult↗
Immunogenic characterization of a tissue culture-derived vaccine that affords partial protection against avian coccidiosis.
The immunogenicity of a tissue culture-derived vaccine generated from an Eimeria tenella-infected cell line in a serologically defined bird line, and the ability to confer protection against homologous challenge in young chicks was examined. The cell line, SB-CEV-1/F7, was infected with E. tenella sporozoites and the resulting 72-h postinfection cell-free supernatants were adjuvanted and used to immunize Leghorn chicks homozygous for the B19 haplotype. Peripheral blood and splenic lymphocytes from these immunized birds proliferated in vitro in response to both sporozoite and SB-CEV-1/F7 tissue culture-derived parasite antigens. In addition, splenic immune lymphocytes obtained from birds previously exposed to E. tenella in vivo responded to these tissue culture-derived parasite antigens in vitro. To evaluate the efficacy of the vaccine, B19B19 chicks were vaccinated s.c. with adjuvanted 72-h postinfection cell-free supernatants or an ammonium sulfate precipitate derivative thereof, orally boosted, and then subjected to homologous parasite challenge at 10 d of age. The level of protection (body weight gain, cecal lesions) was assessed 6 d after challenge. Performance results from four battery trials demonstrated that vaccinated birds were significantly protected against weight loss compared to unimmunized, challenged controls. In addition, in two of the four trials, vaccinated birds were significantly protected against lesions. These results provide strong evidence that tissue culture-derived parasite antigens obtained from the E. tenella-infected SB-CEV-1/F7 cell line are immunogenic in birds and can provide partial protection against E. tenella clinical coccidiosis.
Aging↗
Orbital metastases: diagnosis and course.
AIMS: Three issues were investigated in adult outpatients with orbital metastases. One, how accurate are current diagnostic methods? Two, what is the survival associated with orbital metastases? Three, did any clinical factors correlate with prognosis in this patient cohort? METHODS: Retrospective analysis of patients with orbital metastases managed in an ocular oncology unit. RESULTS: 11 of 31 (35%) patients had no known primary malignancy at the time of orbital diagnosis. In eight of 31 (26%) computed tomography and/or magnetic resonance imaging data did not yield the diagnosis of metastases. In 15 of 17 (88%) cases a fine needle aspiration biopsy was diagnostic. Several types of therapy were used. The median survival was 1.3 years. CONCLUSION: Orbital metastases, even with newer diagnostic techniques can be difficult to diagnose. Management was based on location and extent of both orbital and systemic disease as well as vision. In most cases, orbital symptoms were palliated; however, survival was dismal. No clinical factor correlated with prognosis.
Adult↗
Role of nitric oxide in modulating the long-term renal and hypertensive actions of norepinephrine.
We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-induced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-term control of renal hemodynamics and arterial pressure. To achieve this goal, we examined the effects of an intrarenal infusion of norepinephrine (NE) (0.1 microgram.kg-1.min-1) for 7 days in conscious, chronically instrumented control dogs and in dogs pretreated with a synthesis inhibitor, L-NAME (3 micrograms.kg-1.min-1 intrarenally). Both groups of dogs also received captopril (15 micrograms.kg-1.min-1) plus angiotensin I] intravenously to clamp the renin-angiotensin system throughout the protocol. In control dogs (n = 6), intrarenal infusion of NE decreased renal plasma flow by 9% (134 +/- 10 to 122 +/- 14 mL/min) and glomerular filtration rate by 16% (49 +/- 4 to 41 +/- 5 mL/min) while having no effect on mean arterial pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pretreated with intrarenal L-NAME (n = 9), NE decreased renal plasma flow by 37% (129 +/- 8 to 81 +/- 16 mL/min) and glomerular filtration rate by 32% (47 +/- 3 to 32 +/- 5 mL/min) while increasing mean arterial pressure from 104 +/- 5 to 113 +/- 6 mm Hg. The results of this study demonstrate that NO plays an important role in modulating the long-term actions of NE on renal function and arterial pressure.
Adrenergic alpha-Agonists↗
Role of endothelin in mediating the attenuated renal hemodynamics in Dahl salt-sensitive hypertension.
The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.
Animals↗
Ear dominance and telephone sales.
In a field study, three equally sized sales teams used on of three head-sets--left, right, both ears--for a day's selling of insurance by telephone. This had no effect on sales. In a retrospective study of records, daily sales performance including the percentage conversion rate for sales divided by the number of calls and the number and duration of calls was related to preference for type of head-set. Sales were markedly influenced by the choice of head-set. People who chose to wear the left earpiece significantly out sold the others wearing right and stereohead-sets. Neither the number of incoming calls nor the time spent on the telephone were influenced by the choice of head-set. When sales are analysed in terms of individual differences in personal preference for type of head-set, those who chose the left ear had an advantage. Forced use of the left, versus right ear or both ears for one day had no effect.
Commerce↗
Remote control. Facility managers and engineers guide the move to telemedicine.
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Cost Savings↗