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Biomedical subjects

K Abel

Publications and source records attributed to K Abel.

At least 19 recordsLinked to original sources

[The use of diagnosis-related-groups data for external benchmarking of anesthesia and intensive care services].

Measurement and assessment of the economic efficiency of clinical departments is still an unresolved, yet important problem in hospital management. Benchmarking with other providers can help to evaluate one's own efficacy in anaesthesia and intensive care services. In this article we describe a method for using the diagnosis-related-groups (DRG) cost breakdown data, to achieve a case mix adjusted comparison of own costs for anaesthesia and intensive care services with the average costs in German hospitals. On the basis of 19,401 cases from 10 different surgical departments, we compared our own costs with the German-wide benchmark. Major factors for profit optimisation are discussed. Special attention is given to the close interaction of surgical, anaesthesiological and intensive care process performance and costs and its impact on benchmarking studies.

Anesthesia↗

[Economic evaluation of angiographic interventions including a whole-radiology in- and outpatient care].

PURPOSE: To determine the economic efficiency of a whole-radiology in- and outpatient treatment with angiographic interventions performed as the main or sole therapy. MATERIALS AND METHODS: The calculations represent the data of a university radiology department, including the following angiographic interventions (neuroradiology not considered): Vascular intervention (PTA, stent implantation) of kidneys and extremities, recanalization of hemodialysis access, chemoembolization, diagnostic arterioportal liver CT, port implantation, varicocele embolization, PTCD, percutaneous implantation of biliary stent. First, the different angiographic interventions are categorized with reference to the German DRG system 2005. Considering the example of a university hospital, the individual cost of each intervention is calculated and correlated with reimbursements by G-DRG2005 and so-called "ambulant operation" (EBM200plus). With these data, profits and losses are calculated for both in- and outpatient care. RESULTS: Radiologic interventions of inpatients yield a profit in the majority of cases. With a base rate of 2900 euros, the profits in our university hospital range between - 872 euros and + 3411 euros (mean: + 1348 euros). On the other hand, those angiographic interventions suitable for "ambulant operation" generate average profits of + 372 euros, if only direct costs are considered. The data of outpatient radiological interventions average between 381 euros up to 1612 euros lower than compared with profits obtained from in patient care. CONCLUSION: Once an angiographic intervention represents the major or sole therapy, German radiologists are advised to operate out- and inpatient care by themselves. In Germany, the G-DRG-system and EBM enable radiology departments to generate considerable proceeds for their hospitals and, secondly, to yield a valuable add-on profit for their own department budget, which then is partly detached from the inflexible conventional reimbursement of radiological services.

Angiography↗

A national audit of joint mother and baby admissions to UK psychiatric hospitals: an overview of findings.

The Marcé Clinical Audit is an ongoing data collection exercise that gathers socio-demographic and clinical information about mothers and their infants, admitted jointly to specialist units in UK psychiatric hospitals. The maternal and parenting outcomes, in particular of mothers with schizophrenia and mothers who harm themselves and/or their infants, were determined and analysed. The majority of women had a primary diagnosis of either depression (43%) or schizophrenia (21%). Mothers with schizophrenia were three times more likely to experience a poor outcome than non-schizophrenic mothers, were more likely to be separated from their infant at discharge and were perceived, by staff, to be at greater risk of harming their infant. They were, however, shown to be no more likely to cause actual harm to their infant, or themselves, than non-schizophrenic mothers.

Adolescent↗

Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women.

OBJECTIVE: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. METHOD: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT naïve. RESULTS: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT naïve women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. CONCLUSIONS: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women.

Aged↗

The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T cells under the influence of ovarian steroid hormones.

To understand more clearly how mucosal and systemic immunity is regulated by ovarian steroid hormones during the menstrual cycle, we evaluated the frequency of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency of ISC and AbSC was significantly higher in tissues collected from animals in the periovulatory period of the menstrual cycle than in tissues collected from animals at other stages of the cycle. The observed changes were not due to changes in the relative frequency of lymphocyte subsets and B cells in tissues, as these did not change during the menstrual cycle. In vitro, progesterone had a dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC) cultures. The in vitro effect of progesterone and oestrogen on ISC frequency could not be produced by incubating enriched B cells alone with hormone, but required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+ enriched cell population expressed high levels of IFN-gamma and IL-12. The changes in B cell Ig secretory activity that we document in the tissues of female rhesus macaques during the menstrual cycle is due apparently to the action of ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell secretory activity in both mucosal and systemic immune compartments. Understanding, and eventually manipulating, the CD8+ regulatory cell-B cell interactions in females may produce novel therapeutic approaches for autoimmune diseases and new vaccine strategies to prevent sexually transmitted diseases.

Animals↗

Anatomic site and immune function correlate with relative cytokine mRNA expression levels in lymphoid tissues of normal rhesus macaques.

Reverse transcriptase real-time polymerase chain reaction was used to determine pro-inflammatory, anti-viral and immunoregulatory cytokine mRNA expression levels in peripheral blood mononuclear cells (PBMC) of healthy juvenile, adolescent and adult rhesus macaques. Few age-related changes in cytokine mRNA expression levels were observed. Expression of interleukin 2 and Mx, a type I interferon-inducible gene, decreased with age, whereas interleukin 4 and macrophage inflammatory protein 1 (MIP-1) alpha and beta mRNA levels increased in older monkeys. Independent of age, the pro-inflammatory cytokines [tumour necrosis factor alpha (TNF-alpha) and chemokines] were expressed at higher mRNA levels in PBMC than the immunoregulatory cytokines (interleukins 2, 4, 12). Pro-inflammatory cytokine mRNA expression levels were highest in lymphoid tissues draining mucosal surfaces. Thus, a correlation exists between cytokine mRNA levels in lymphoid tissues and the anatomical site.

Animals↗

Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry.

RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a quantitative assessment of sequence heterogeneities. For example, in quality control of live attenuated viral vaccines, the presence of even small quantities of mutants or revertants may indicate incomplete or unstable attenuation that may influence vaccine safety. Previously, we demonstrated the monitoring of oral poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme cleavage (MAPREC). In this report, we investigate genetic variation in live attenuated mumps virus vaccine by using both MAPREC and a platform (DNA MassArray) based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain typically contain at least two distinct viral substrains, JL1 and JL2, which have been characterized by full length sequencing. We report the development of assays for characterizing sequence variants in these substrains and demonstrate their use in quantitative analysis of substrains and sequence variations in mixed virus cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI-TOF methods showed excellent correlation. This suggests the potential utility of MALDI-TOF for routine quality control of live viral vaccines and for assessment of genetic stability and quantitative monitoring of genetic changes in other RNA viruses of clinical interest.

Animals↗

Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates.

Auto-reactive T cells present in healthy subjects remain in a state of unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG-reactive T cell responses are present in the blood of both healthy subjects and MS-affected individuals. To investigate the disease-inducing potential and regulation of these autoreactive T cells in healthy outbred populations, we have characterized MOG-reactive T cell clones obtained by limiting dilution from peripheral blood of unimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circulating MOG-reactive T cells in these naive animals (2.6 +/- 1.4 / 10(5) PBMC), and a broadly diverse repertoire of epitope recognition encompassing at least three regions within the extracellular domain of MOG. Adoptive transfer of a MOG21-40-specific T cell clone resulted in mild clinical experimental allergic encephalomyelitis, characterized pathologically by rare foci of inflammation and minimal demyelination. We conclude that MOG-reactive T cells are present in healthy primates at a highly prevalent frequency, and are potentially capable of triggering central nervous system autoimmunity. Expansion of these autoreactive T cells must be tightly controlled to maintain immune homeostasis in healthy individuals.

Animals↗

Drugs in pregnancy. Prescribing for psychiatric disorders in pregnancy and lactation.

The most recent Confidential Enquiry into the causes of maternal deaths during the perinatal period in England and Wales (1994-1996) revealed that psychological illness was at least as important as hypertensive disorders. It is therefore important for obstetricians to be aware of a variety of psychiatric conditions as well as the psychotropic medication prescribed and sequelae of continuation or withdrawal of these drugs. Best management, of this particularly vulnerable group of women, requires close liaison with the psychiatric team. This chapter considers four groups of women most likely to be prescribed psychoactive drugs during the perinatal period: (i) women with mental illness wishing to conceive, (ii) women with mental illness who conceive while taking medication, (iii) those who become mentally ill while pregnant, and (iv) those who become unwell postnatally. Guidelines for treatment are discussed.

Antipsychotic Agents↗

Melanocortin 3 receptor (MC3R) gene variants in extremely obese women.

OBJECTIVE: Following several reports of linkage of obesity related phenotypes to human chromosome 20q we sought to determine whether variations of the melanocortin 3 receptor (MC3R) gene are associated with obesity. DESIGN: We screened the MC3R gene coding region and approximately 2 kb of 5' and 3' flanking sequences for DNA variants in unrelated extremely obese women and average weight controls using polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) analysis and DNA sequencing. SUBJECTS: 124 unrelated extremely obese women (body mass index, (BMI)>/=40 kg/m2) and 85 average weight controls (BMI<27 kg/m2). MEASUREMENTS: Radiation hybrid (RH) mapping was performed to localize the MC3R gene. 5' and 3' flanking sequences of MC3R gene were cloned. PCR-SSCP and DNA sequencing were used to detect mutations in the MC3R gene coding region and flanking sequences. RESULTS: RH mapping localized the MC3R gene to 20q13, between markers D20S100 and D20S149. 1083 bp 5' and 653 bp 3' flanking region of the MC3R gene were cloned. A missense mutation (+241, codon 81 ATT/GTT, Ile-->Val) was found in the MC3R coding region. Four more variants were detected in the 5' flanking sequence: -201(C-->G), -239 (A-->G), -762(A-->T) and -769(T-->C). Compared with controls, no significant allele frequency differences were found. Racial differences were found for the +241, -201, -239 and -762 polymorphisms. CONCLUSIONS: Several sequence variants were found in the MC3R gene coding region and in 5' flanking sequences. However, none of the variants were associated with obesity phenotypes. The linkage of extreme human obesity on 20q13 is likely caused by genes other than MC3R. International Journal of Obesity (2000) 24, 206-210

Adult↗

Phenothiazine, butyrophenone, and other psychotropic medication poisonings in children and adolescents.

OBJECTIVE: To describe the presentation, epidemiology, management, and outcome of phenothiazine and butyrophenone ingestions in children requiring hospitalization. METHOD: Retrospective case series in two pediatric hospitals. RESULTS: Eighty-six cases were identified among 83 patients. The majority (69.7%) of ingestions occurred in children <6 years of age and there was no gender predominance. These ingestions were more common in African Americans (65.1%). They occurred more commonly in the patient's (64.0%) or a relative's (22.1%) home and haloperidol and thioridazine accounted for 58.1% of exposures. Depressed levels of consciousness and dystonia were the most common presenting signs, present in 90.7% and 51.2% of patients, respectively. Miosis occurred in only 13.9% of the patients. Fluid boluses were administered to 28.7% of the patients but about a quarter of these had coingested potentially cardiotoxic drugs. In addition, 2 of the 12 (13.9%) patients with abnormal electrocardiograms had also ingested potentially cardiotoxic drugs. Numerous diagnostic tests were performed in these patients including electrolyte panels (80.2%), complete blood counts (69.8%), liver function tests (31.4%), serum osmolality (20.9%), blood cultures (10.5%), lumbar punctures (17.4%), head computed tomographies (15.1%), and electroencephalograms (3.5%). The median length of hospitalization was 1.78 (range 1-9) days and there were no deaths. Patients presenting with dystonias were more likely to have extensive diagnostic testing for neurologic disease than those presenting without dystonias. CONCLUSION: The presentation of phenothiazine and butyrophenone ingestions in children and adolescents may be nonspecific and confounded by coingestants. Patients with dystonias had more extensive neurologic testing than patients without dystonias, suggesting that physicians may not recognize dystonias as a clinical finding characteristic of phenothiazine or butyrophenone exposure.

Accidents, Home↗

UTP-preferring P2 receptor mediates inhibition of sodium transport in porcine thyroid epithelial cells.

1. The effects of adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP) and analogues on forskolin-stimulated absorption of Na+ by porcine thyroid epithelial cells were analysed in cultures grown as confluent monolayers on permeable supports in Transwell Ussing chambers. 2. 85% of the forskolin (10 microM)-stimulated short-circuit current was inhibited by phenamil (1 microM), which is a selective antagonist for epithelial type Na+ channels. 3. Phenamil-sensitive current was inhibited in a dose dependent manner by nucleotides added to the apical compartment of Ussing chambers. In contrast, the phenamil-resistant current, previously shown to represent anion secretion, was unaffected by nucleotides. 4. The order of potency (with EC50 values given in microM) was UTP (0.08)>>ATP (6.3)=uridine 5'-diphosphate (UDP) (6. 6)>2methyl-thio-adenosine-5'-triphosphate (2MeSATP) (84.5)>adenosine 5'-diphosphate (ADP) (147.8)>alpha,beta-methylene ATP (>150)>>adenosine (>1000). 5. P2 receptors mediating inhibition of sodium absorption were present on the apical membrane of the cells since addition of UTP (1-1000 microM) to the basal compartment of the Ussing chambers had little effect while subsequent addition to the apical compartment produced a normal response. 6. Cibachron blue (Reactive blue 2) (1-100 microM), an antagonist at some P2 receptor subtypes, inhibited phenamil sensitive current in a dose dependent manner with half maximal inhibition occurring at 14.25 microM. 7. Suramin (100 microM), pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) (100 microM) and pyridoxal 5'-phosphate (P5P) (100 microM) showed only slight competitive antagonism against the response to UTP. 8 These results indicate that a UTP-preferring P2 receptor located on the apical membrane of thyroid epithelial cells mediates inhibition of Na+ absorption.

Animals↗

High-throughput isolation of Caenorhabditis elegans deletion mutants.

The nematode Caenorhabditis elegans is the first animal whose genome is completely sequenced, providing a rich source of gene information relevant to metazoan biology and human disease. This abundant sequence information permits a broad-based gene inactivation approach in C. elegans, in which chemically mutagenized nematode populations are screened by PCR for deletion mutations in a specific targeted gene. By handling mutagenized worm growth, genomic DNA templates, PCR screens, and mutant recovery all in 96-well microtiter plates, we have scaled up this approach to isolate deletion mutations in >100 genes to date. Four chemical mutagens, including ethyl methane sulfonate, ethlynitrosourea, diepoxyoctane, and ultraviolet-activated trimethylpsoralen, induced detectable deletions at comparable frequencies. The deletions averaged approximately 1400 bp in size when using a approximately 3 kb screening window. The vast majority of detected deletions removed portions of one or more exons, likely resulting in loss of gene function. This approach requires only the knowledge of a target gene sequence and a suitable mutagen, and thus provides a scalable systematic approach to gene inactivation for any organism that can be handled in high density arrays.

Algorithms↗

Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls.

The aim of this study was to examine the effect of repeated testing on prepulse inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control subjects (eight males, mean age 30 years; seven females, mean age 29 years) were tested on three occasions across the same day separated by a minimum of 2 h. An acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous background noise of 70 dB(A) was presented binaurally through headphones and the eye-blink component of the startle response was measured taking electromyographic recordings from the right orbicularis oculi. The test session was identical at each time point and consisted of two blocks of 12 randomly mixed trials of four pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by two blocks each of six pulse-alone trials. There was huge variation in individual response magnitude that was independent of subsequent PPI in both women and men. Women showed greater PPI in the second half of sessions with the 120-msec prepulse only; but PPI was not altered significantly in either group between sessions across the day. In general, there was good test-retest reliability of PPI especially within trial type. Normal reflex habituation occurred across sessions and this effect was preserved in sessions across the day. Latency of response was significantly reduced in a session by the 60-msec trial type compared to the 120-msec trial type, as previously reported. Our results suggest that measures of PPI and habituation of the startle response are appropriate and reliable for a within-subject, test-retest design.

Acoustic Stimulation↗

Late complications of immune deviation therapy in a nonhuman primate.

The administration of antigens in soluble form can induce antigen-specific immune tolerance and suppress experimental autoimmune diseases. In a marmoset model of multiple sclerosis induced by myelin oligodendrocyte glycoprotein (MOG), marmosets tolerized to MOG were protected against acute disease, but after tolerization treatment a lethal demyelinating disorder emerged. In these animals, MOG-specific T cell proliferative responses were transiently suppressed, cytokine production was shifted from a T helper type 1 (TH1) to a TH2 pattern, and titers of autoantibodies to MOG were enhanced. Thus, immune deviation can increase concentrations of pathogenic autoantibodies and in some circumstances exacerbate autoimmune disease.

Animals↗

An alpha to beta conformational switch in EF-Tu.

BACKGROUND: The bacterial elongation factor EF-Tu recognizes and transports aminoacyl-tRNAs to mRNA-programmed ribosomes. EF-Tu shares many structural and functional properties with other GTPases whose conformations are regulated by guanine nucleotides. RESULTS: An intact form of Escherichia coli EF-Tu complexed with GDP has been crystallized in the presence of the EF-Tu-specific antibiotic GE2270 A. The three-dimensional structure has been solved by X-ray diffraction analysis and refined to a final crystallographic R factor of 17.2% at a resolution of 2.5 A. The location of the GE2270 A antibiotic-binding site could not be identified. CONCLUSIONS: The structure of EF-Tu-GDP is nearly identical to that of a trypsin-modified form of EF-Tu-GDP, demonstrating conclusively that the protease treatment had not altered any essential structural features. The present structure represents the first view of an ordered Switch I region in EF-Tu-GDP and reveals similarities with two other GTPases complexed with GDP: Ran and ADP-ribosylation factor-1. A comparison of the Switch I regions of the GTP and GDP forms of EF-Tu also reveals that a segment, six amino acids in length, completely converts from an alpha helix in the GTP complex to beta secondary structure in the GDP form. The alpha to beta switch in EF-Tu may represent a prototypical activation mechanism for other protein families.

Anti-Bacterial Agents↗

Relationship of birth season to clinical features, family history, and obstetric complication in schizophrenia.

Birth in late winter and spring has been consistently shown to be a risk factor of schizophrenia. The relationship of late winter/spring birth to clinical characteristics and other putative risk factors, such as family history and obstetric complications, may provide clues to etiology. Data relating to season of birth, clinical features, family history, and obstetric complications were analyzed for 192 patients with schizophrenia as defined by Research Diagnostic Criteria (including schizoaffective disorder). There was no significant association of season of birth with any of the psychopathological dimensions nor was there a significant association with obstetric variables or family history. However, winter-born schizophrenic patients who had a negative family history were more likely to have a history of obstetric complications. These findings suggest that obstetric complications associated with schizophrenia are perhaps the result of some seasonal risk factors important in those without a family history of the disorder.

Adolescent↗