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Biomedical subjects

D Turner

Publications and source records attributed to D Turner.

At least 55 records · Page 3Linked to original sources

District nurse-led beds: an alternative to care at home.

Intermediate care is a key feature of the Government's plans for the development of the health service. The intermediate care scheme described here offers a district nurse-led bed (DNLB) stay in a community hospital to patients in the community who require short-term nursing help. District nurses are given the opportunity to admit patients from their community caseloads into a DNLB in a community hospital and are responsible for their admission, care and discharge. This article describes the pilot study that monitored the first 30 patients who used the DNLBs. Patients included younger people with multiple sclerosis who were admitted for respite care, but the principal beneficiaries were those aged over 65 years with chronic conditions.

Adult↗

Economics of lower urinary tract symptoms (LUTS) in older people.

Urinary incontinence is an area of clinical and social importance to older people and providers of care. This article provides an update on the 'symptom' of urinary incontinence and reviews the concept of lower urinary tract symptoms (LUTS). The challenges facing health services researchers working in this field are also discussed in terms of trying to quantify the size and extent of the underlying problem. Economic issues and work undertaken to evaluate the cost of LUTS are appraised and the common nonsurgical treatments for LUTS are described together with associated conditions and their cost implications. The cost to individuals and society of LUTS is generally underestimated and the importance of reducing its severity (if cure is not achievable) makes clinical and economic sense.

Aged↗

[The sensitivity of common bacteria to antibiotics in children in southern Israel].

BACKGROUND: Many reports describe an increasing antibiotic resistance among various pathogenic bacteria. Since every empiric antibiotic treatment is also based on the expected antibiogram of the probable isolate, it is essential to frequently monitor the resistance trends at different ages and contexts. AIM: The purpose of this study was to monitor the antibiogram of a large bacterial population isolated from pediatric bacteremia episodes. METHODS: All bacteremia episodes of children under the age of 18 years in the Soroka Medical Center, Beer Sheva, Israel, were prospectively documented from January 1990 to December 1998. RESULTS: Of the 5,373 positive blood cultures that were noted during the study period, 1,689 were considered as true different episodes. During the years 1990-92, 1993-95 and 1996-98 454, 538 and 697 episodes were noted, respectively. The most common pathogens were Streptococcus pneumoniae (447 isolates), Staphylococcus aureus (224 isolates), Escherichia coli (187 isolates) and Klebsiella spp (180 isolates). The antibiotic sensitivity of the pathogens declined with time in some of the cases and increased in others. The major problems raised were the development of ESBL (extended spectrum beta lactamase) and MRSA (methacillin resistant Staphylococcus aureus) producing isolates, high level of resistance of coagulase negative Staphylococci and Acinetobacter to most of the antibiotic agents, and increasing resistance of Streptococcus pneumoniae to various agents. CONCLUSION: Despite the significant increase in the antibiotic resistance of many of the pathogens tested, there are still various therapeutic options available.

Bacteremia↗

Changes in electromyogram during upper limb muscle contraction induced by resistive loaded breathing in humans.

Expiratory only resistive loaded breathing (RL) reduces high energy electromyogram (EMG) power (EH) during an isometric contraction of a leg extensor muscle, but not an arm flexor. An interaction between afferent activity during expiratory RL and inspiratory non-loaded phases of breathing, which the contraction spanned, could have accounted for the reduced EH in these long contractions. Therefore this study tested the hypothesis that brief arm extensor muscle contractions (70% of maximal force), performed during a single phase of expiratory RL, would also exhibit reduced EH. Surprisingly, EH in triceps, but not biceps brachii was reduced significantly when the contraction was performed during inspiratory RL rather than expiratory RL. The results suggest that either (a) short and prolonged contractions or (b) motor drive to arm and leg extensors are affected differently by RL.

Adult↗

Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK.

Cytokine gene polymorphisms affecting cytokine production may influence rejection and graft-versus-host disease following solid organ and haemopoietic stem cell (HSC) transplantation, respectively. Polymorphisms in the regulatory regions of several cytokine genes have been described; for example, tumour necrosis factor-alpha (TNF-alpha) has a G/A substitution at position -308, interleukin-2 (IL-2) has a T/G substitution at position -330 and interleukin-10 (IL-10) has substitutions at positions -1082(G/A), -819(C/T) and -592(C/A). Microsatellites associated with cytokine production have been detected in the first intron of the IFN-gamma gene and flanking the TNF-alpha gene. In this study, we have genotyped a single panel of healthy Northern European Caucasoids living in the south-east of England for the above-mentioned polymorphisms and compared the results to those published for other populations. A PCR method using sequence-specific primers (SSP) was developed for genotyping the IL-2 polymorphism, and the ABI PRISMtrade mark 310 genetic analyser was used to detect the TNF-alpha and IFN-gamma microsatellites. The allele frequencies of all the studied polymorphisms were consistent with those reported for other UK Caucasoid populations, but differences were observed when compared to other Oriental, African and Caucasoid groups. If these cytokine polymorphisms prove to have functional consequences, then any differences across population groups may have significant clinical relevance in disease and in the outcome of solid organ and HSC transplantation.

Alleles↗

Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus.

CST (BART BARF0) family viral RNAs are expressed in several types of Epstein-Barr virus (EBV) infection, including EBV-associated cancers. Many different spliced forms of these RNAs have been described; here we have clarified the structures of some of the more abundant splicing patterns. We report the first cDNAs representing a full-length CST mRNA from a clone library and further characterize the transcription start. The relative abundance of splicing patterns and genomic analysis of the open reading frames (ORFs) suggest that, in addition to the much studied BARF0 ORF, there may be important products made from some of the upstream ORFs in the CST RNAs. Potential biological functions are identified for two of these. The product of the RPMS1 ORF is shown to be a nuclear protein that can bind to the CBF1 component of Notch signal transduction. RPMS1 can inhibit the transcription activation induced through CBF1 by NotchIC or EBNA-2. The protein product of another CST ORF, A73, is shown to be a cytoplasmic protein which can interact with the cell RACK1 protein. Since RACK1 modulates signaling from protein kinase C and Src tyrosine kinases, the results suggest a possible role for CST products in growth control, perhaps consistent with the abundant transcription of CST RNAs in cancers such as nasopharyngeal carcinoma.

Amino Acid Sequence↗

Surgical correction of lumbar kyphotic deformity: posterior reduction "eggshell" osteotomy.

OBJECT: Progressive kyphotic deformity of the lumbar or thoracolumbar spine may lead to back pain, cosmetic deformity, and risk of neurological compromise. The authors describe a series of patients in whom they performed a single-stage, posterior reduction ("eggshell") osteotomy procedure to improve sagittal contour by creating lordosis within a single vertebral body. METHODS: From 1995 to 1997 the authors performed 12 osteotomy procedures in 11 patients with thoracolumbar or lumbar kyphosis. Seven patients presented with iatrogenic deformity, three with deformity secondary to traumatic injury, and one patient with ankylosing spondylitis. Their mean age at time of surgery was 46.6 years (range 23-78 years). All patients suffered from back pain and were unable to stand upright, but in only one patient were neurological findings demonstrated. The mean preoperative deformity was -26 degrees (range -90 to 0 degrees). At 6-month follow-up examination the mean sagittal contour measured 17.5 degrees (range - 17 to 44 degrees), indicating that the mean surgical correction was 40.1 degrees (range 25 to 58 degrees). All patients reported decreased back pain at follow up, and none required narcotic analgesic medication. Complications included a dense paresis that developed immediately postoperatively in a patient who was found to have residual dural compression, which was corrected by emergency decompressive surgery. One elderly patient suffered a perioperative cerebrovascular accident, and three patients suffered neurapraxia with transient muscle weakness of the quadriceps. There was one case of a dural tear. There were no deaths, and prolonged intensive care stays were not required. CONCLUSIONS: Single-level posterior reduction osteotomy provides excellent sagittal correction of kyphotic deformity in the lumbar region, with a risk of cauda equina and root and plexus compromise due to the extensive neural exposure.

Adult↗

Increased intracellular accumulation of macrophage inflammatory protein 1beta and its decreased secretion correlate with advanced HIV disease.

Considering that the chemokine macrophage inflammatory protein 1beta (MIP1beta) may serve as a competitive inhibitor for HIV entry, the objective of this study was to compare intracellular and extracellular levels of MIP1beta, in untreated HIV-infected individuals. HIV patients and healthy controls were tested by two-color flow cytometry for intracellular MIP1beta, in freshly explanted CD4 and CD8 lymphocytes, and in monocytes. Sera and plasma collected on the same day were tested, respectively, by enzyme-linked immunosorbent assay (ELISA) for MIP1beta concentration and for number of HIV-RNA copies, using nucleic acid sequence-based amplification procedure (NASBA) methodology. Results demonstrate that a high intracellular level of MIP1beta appears to be linked to a deterioration in the immune status of HIV patients (i.e., low CD4 counts) and to a high viral load. Moreover, an inverse relationship exists between the intracellular and the "secreted" form of MIP1beta, thus leading to the hypothesis that the regulation of cellular accumulation and secretion of MIP1beta and of other chemokines may be disrupted during AIDS development.

Case-Control Studies↗

Protease inhibitor-based therapy is associated with decreased HIV-related health care costs in men treated at a Veterans Administration hospital.

BACKGROUND: Protease inhibitor (PI) therapy for HIV infection is associated with decreased rates of opportunistic infections and death. Statistical models predict that decreased complications will be associated with decreased hospitalization costs. A recent report suggested that the decrease in the HIV hospitalization costs were offset by increases in demand for outpatient services. We performed a study of hospital use and HIV-associated health care costs in our center to determine the following: whether PI therapy is associated with decreased inpatient use; whether PI therapy is associated with decreased outpatient use and costs; whether decreased HIV health care costs are associated with increased use of nucleoside analogues. METHODS: The Dallas Veteran Affairs Medical Center provides comprehensive inpatient and outpatient HIV care and thus can evaluate the relation between inpatient and outpatient costs. The mean monthly number of hospital days, Infectious Diseases clinic visits, emergency department visits, other outpatient clinic visits, inpatient costs, outpatient costs, and PI costs were determined from January 1, 1995 through July 31, 1997. This time period was then divided into three intervals. Comparisons of PI use and HIV-related health care costs were during the three intervals was performed using analysis of variance (ANOVA). Significant differences between the baseline characteristics were further analyzed through multiple linear regression. RESULTS: A decrease in hospital days, and all outpatient visits including emergency visits, and HIV clinic visits was determined. No difference was found in the rate of use of other outpatient services. The per patient costs of HIV care decreased from a monthly average of $1905 U.S. in the first interval to $1122 U.S. in the last interval (p < .01). Linear regression demonstrated an inverse relation between PI use and total HIV costs (B=-0.67, p=.00, adjusted R2=0.52) but no relation between nucleoside use, stage of disease or financial class. CONCLUSIONS: PI therapy is associated with decreased hospital days and use of outpatient services. Total patient costs decreased, but a concomitant rise in outpatient costs took place. This increase was primarily a result of increased costs of acquiring PI. Increases in the number of nucleoside agents prescribed were not associated with decreased costs.

Adult↗

Pulmonary adiaspiromycosis in a patient with acquired immunodeficiency syndrome.

Adiaspiromycosis is a noninfectious, nonarthropod-transmitted fungal infection that occurs worldwide in lower vertebrates, especially rodents. However, humans may become accidental hosts. Reported here is a case of adiaspiromycosis of the lung in an HIV-positive, 40-year-old, bisexual man who first presented with cough and dyspnea. Cultures of a bronchoalveolar lavage and protected brush specimen revealed the presence of fungal elements that were identified as Emmonsia parva var. parva. The patient was successfully treated with amphotericin B and thereafter with fluconazole. This organism should be added to the list of pathogens that cause pulmonary infection in AIDS patients.

AIDS-Related Opportunistic Infections↗

Endothelin-1 stimulates c-fos mRNA expression in C6 glioma cells via MAP kinase pathway.

Exposure of C6 glioma cells to endothelin-1 (ET-1) caused dose-dependent (10(-11) M to 10(-7) M) increments in intracellular calcium concentration ([Ca2+]i) and c-fos mRNA expression (4.5-fold) that were abolished by the endothelinA receptor antagonist, BQ610, and by inhibition of phospholipase C with U73122. ET-1 stimulated c-fos mRNA expression was also inhibited by protein kinase C inhibition (chelerythrine) and by the MAP kinase kinase inhibitor PD98059, but not by inhibitors of tyrosine kinases, protein kinase A type I or II, calmodulin kinase II, or calcium channel blockade. C6 cells treated with ET-1 demonstrated a significant increase in MAP kinase activity as evidenced by Western blotting. These results indicate a mechanism of long-term signaling by ET-1 involving an ET(A) receptor-mediated, phospholipase C(beta)-linked pathway that is dependent on protein kinase C and MAP kinase activation.

Alkaloids↗

Detection of the DeltaF508 mutation in the CFTR gene by means of time-resolved fluorescence methods.

A rapid recognition in the base sequence of nucleic acids is an important prerequisite toward the diagnosis of genetic diseases and their carrier states. We have developed a hybridisation method in which a fluorescently labeled oligonucleotide is used to detect point mutations in a target by a simple fluorescence lifetime analysis of the emission of the fluorescent label. We applied this method to detect the deltaF508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a model system and with biologically derived PCR product and discuss the potential generality of this method.

Base Sequence↗

Combination therapy with fludarabine and cyclophosphamide as salvage treatment in lymphoproliferative disorders.

Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven patients) were treated with a combination of fludarabine 25 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had previously received purine analogue therapy of which four had progressive disease during treatment. The overall response rate of patients with CLL was 71% (28% CR, 43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and vomiting which was maximal in the 3 d after therapy, infections and haematological suppression which was prolonged in some patients. This combination, which is based on a rational prediction of synergistic activity, is highly effective but associated with significant problems with tolerance.

Aged↗

Interindividual variation in mitotic recombination.

Mitotic recombination (MR) between homologous chromosomes is a mutational event that results in loss of heterozygosity in half of the segregants at mitosis. Loss of heterozygosity may have important biological consequences. The purpose of this study was to describe human variation in the spontaneous frequency of MR. Using an immunoselection technique for isolating the somatic mutations that result in loss of expression of one of the codominant alleles at the HLA-A locus, we have measured the frequency and molecular basis of somatic mutations in lymphocytes from a population of young adults. Mutations were classified as being the result of intragenic changes, major deletions, or MR. Here we show that the MR mutation frequency in females was significantly greater than that in males but that intragenic mutation frequency showed no association with sex. Individual variation in MR frequency ranged over more than two orders of magnitude and was not normally distributed. Furthermore, the observed number of individuals from whom no mutants resulting from MR were obtained was significantly greater than was expected. The endogenous level of MR may be under genetic control. Given the association of loss of heterozygosity with cancer initiation and progression, low endogenous MR may confer a reduced lifetime risk of cancer, and the converse may apply.

Adult↗

Delivering prevention: the role of public programs in delivering care to high-risk populations.

A successful program of prevention or early detection should have a high level of population coverage and should ensure that high-risk populations are targeted. In practice, relatively little attention has been paid to the tendency toward greater use of preventive care by populations at lower risk, in other words, for higher use by the wealthy than by the poor. Current delivery patterns of preventive care raise questions as to how to organize these services more effectively. Physician-based delivery of preventive care in a fee-for-service system seems to result in Canadian patterns of use that are fairly similar to those found in the United States. Universal free insurance alone does not appear to be enough to counteract the failure to target preventive care toward the least-healthy groups. Appropriately-run Canadian provincial programs may be able both to expand coverage and to target high-risk populations. The population coverage for three measures directed toward prevention or early detection--childhood immunization (which in Manitoba has been offered through a long-standing provincial program), screening mammography (a new provincial program), and cervical cancer screening (no provincial program)-are compared using longitudinal administrative data from Manitoba. The discussion emphasizes the role of provincial programs and the possibilities for using population-based data to help provide cost-effective care to high-risk populations.

Adolescent↗

A comparison of two automated external defibrillator algorithms.

OBJECTIVE: To compare the interval to delivery of the first shock by first responders in mannequin-based cardiac arrest scenarios using two automated external defibrillator (AED) algorithms. METHODS: Thirty-six (18 pairs) of Toronto firefighters (FFs) trained in two AED algorithms, algorithm I (A-I) and algorithm II (A-II), were studied. A-II mandates the immediate application of the AED once pulselessness is established. In contrast to A-I, A-II dictates that no CPR be initiated until it is required by the AED voice prompts. Each FF pair alternated roles while performing "shock-indicated," mannequin-based scenarios according to A-I and A-II. The interval from mannequin contact to delivery of the first shock was recorded. Five pairs were videotaped. The intervals to complete predetermined steps were compared between algorithms to determine in which step(s) time saving occurred. RESULTS: The mean (+/-SD) interval to the first shock in A-I was 80.7 seconds (+/-10.5 sec) (95% CI = 77.2 to 84.2 sec) vs 61.1 seconds (+/-8.75 sec) (95% CI = 58.2 to 64.0 sec) in A-II (p < 0.001). A-II shortened the interval to the first shock by 19.6 sec (+/-11.5) (95% CI = 15.8 to 23.4 sec). The time saving was a direct result of delaying CPR in A-II. CONCLUSION: A-II reduced the interval from mannequin contact to the first shock in standard training scenarios.

Algorithms↗

The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation.

The heart defect (hdf) mouse is a recessive lethal that arose from a transgene insertional mutation on chromosome 13. Embryos homozygous for the transgene die in utero by embryonic day 10.5 postcoitus and exhibit specific defects along the anterior-posterior cardiac axis. The future right ventricle and conus/truncus of the single heart tube fail to form and the endocardial cushions in the atrioventricular and conus/truncus regions are absent. Because the hdf mouse mutation provided the opportunity to identify a gene required for endocardial cushion formation and for specification or maintenance of the anterior most segments of the heart, we initiated studies to further characterize the phenotype, clone the insertion site, and identify the gene disrupted. Chromosome mapping studies first identified the gene, Cspg2 (versican), as a candidate hdf gene. In addition, an antibody recognizing a glycosaminoglycan epitope on versican was found to be positive by immunohistochemistry in the extracellular matrix of normal wild-type embryonic hearts, but absent in homozygous hearts. Expression analysis of the Cspg2 gene showed that the 6/8, 6/9, and 7/9 Cspg2 exon boundaries were present in mRNA of normal wild-type embryonic hearts but absent in the homozygous mutant embryos. DNA sequence flanking the transgene was used to isolate from a normal mouse library overlapping genomic DNA segments that span the transgene insertion site. The contiguous genomic DNA segment was found to contain exon 7 of the Cspg2 in a position 3' to the transgene insertion site. These four separate lines of evidence support the hypothesis that Cspg2 is the gene disrupted by the transgene insertion in the hdf mouse line. The findings of this study and our previous studies of the hdf insertional mutant mouse have shown that normal expression of the Cspg2 gene is required for the successful development of the endocardial cushion swellings and the embryonic heart segments that give rise to the right ventricle and conus/truncus in the outlet of the looped heart.

Alternative Splicing↗