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Biomedical subjects

A McNamara

Publications and source records attributed to A McNamara.

At least 19 recordsLinked to original sources

Improved pelvicalyceal visualization with multidetector computed tomography urography; comparison with helical computed tomography.

Our aim was to compare the quality of pelvicalyceal visualization on computed tomography (CT) urography using a small intravenous contrast material dose, hydration, and high-resolution multidetector CT (MDCT) with that of conventional helical CT. The test (MDCT) group (49 consecutive patients, 98 kidneys) was scanned 5 min following an intravenous bolus of 30 ml of iodinated contrast material. The control (helical CT) group (50 consecutive patients, 95 kidneys) was scanned 5 min following injection of 120-150 ml of intravenous contrast material. Enhancement and quality of calyceal detail were measured using a five-scale grading system (1 for no detail, 5 for cupped calyces). Calyceal attenuation was substantial in both groups (more than 220 Hounsfield units, HU) but less in the test group compared with the control group (mean 475 and 920 HU, respectively), p<0.0001. In the test group, the calyceal attenuation was less than 500 HU in the majority of cases (65/98 kidneys), while the opposite was true for the control group, where calyceal attenuation was more than 750 HU in 50/95 kidneys (p<0.001). The quality of calyceal detail was 3.4/5 in the test group compared with 1.8/5 in the control group (p<0.0001). The combination of hydration, low-contrast dose, and the high image resolution achieved with MDCT significantly improves calyceal visualization in CT urography.

Adult↗

Real-time functional magnetic resonance imaging (rt-fMRI) in patients with brain tumours: preliminary findings using motor and language paradigms.

Functional MRI (fMRI) shows areas of the brain that are active during a task, but the standard approach (offline analysis after the imaging has finished) precludes tailoring of the imaging to the individual patient, e.g. for assessing normal function around an individual lesion. The aims of the study were to explore the technical feasibility of acquiring functional images in real-time (rt-fMRI), develop the necessary software interfaces and protocols for image acquisition, and to compare images of functional activation acquired in real-time with the standard offline statistical parametric method in patients with solitary brain tumours. Patients with a solitary supratentorial lesion were studied. The rt-fMRI paradigms were sequential finger opposition, ankle movement and language function (correct recognition of grammatically violated sentences). Datasets were analysed using AFNI software (National Institute of Mental Health, Bethesda, Maryland, USA) for the real-time analysis and SPM99 (Functional Imaging Laboratory, University College, London, UK) for the offline analysis. From 11 patients, useful data were obtained in nine. The finger tapping task produced most consistent activation between real-time and offline analysis with good anatomic localization to the primary motor cortex contralateral to the tapping finger. Ankle movement produced weaker activation and correlation with real-time analysis. For the language task the offline analysis provided reproducible activation patterns, but the real-time method showed no activation at the chosen threshold of p = 0.001. Tumourous areas of brain did not show any activation with either method of analysis during any task. rt-fMRI is feasible and could be a valuable functional evaluation tool in the planning of surgery for tumours in motor regions of the brain. Further paradigm development is required for evaluation of language, and possibly other more complex executive functions.

Adult↗

Human brucellosis in the Mid-West 2002-3.

Human brucellosis remains a serious public health issue in Ireland. Clinical notifications in the Mid-Western Area (HSE-MWA) underestimate the burden of illness and attendant morbidity in the region. The diagnosis of acute and chronic human brucellosis depends on the clinical evidence and the results from laboratory serological testing or culture on rare occasion. This study examined the clinical evidence behind locally defined serological "positives" in the HSE-MWA from 2002 to 2003. Ninety cases were detected in 2002 and 31 in 2003. While sampling bias is likely to be present, aspects of brucellosis in Ireland were confirmed. Middle-aged males were most commonly affected. The majority of cases were linked to farming or veterinary practice. Symptoms such as sweats, fever and weight loss were commonly associated with acute brucellosis infection while malaise was common in acute and chronic brucellosis. A clear definition of what is notifiable is needed. Surveillance systems must appreciate the importance of both clinical and laboratory evidence to classify confirmed or probable brucellosis as paired sera were not common. Public health authorities must follow-up the clinical aspects for accurate national statistics. General practitioners in the Mid-West appear to be vigilant regarding brucellosis in their patients. Regional zoonoses committees are useful in monitoring disease prevalence in human and animal populations without compromising confidentiality.

Adolescent↗

Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation.

Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities.

3,4-Dihydroxyphenylacetic Acid↗

Anesthesia induced retrograde amnesia is ameliorated by ephrinA5-IgG in mice: EphA receptor tyrosine kinases are involved in mammalian memory.

EphA receptors and their ephrin-A ligands were previously thought to play a role only in embryonic development of the brain. Recently, however, these proteins were shown to be expressed in the adult mouse brain, primarily in the hippocampus, and were implicated in hippocampal synaptic plasticity and learning. What aspects of learning EphA receptors mediate have not been studied? Using the fear conditioning paradigm we demonstrate that EphA receptors play roles in memory. We show that post-training surgical anesthesia leads to robust context specific retrograde amnesia in mice, and post-anesthesia activation of EphA receptors induces a significant amelioration of this amnesia. As acquisition was left unaffected and performance factors were found unaltered, we suggest that the amelioration was due to changes in cognition leading to improved memory. Our data represent the first pieces of evidence for the involvement of EphA receptor tyrosine kinase receptors in mammalian memory, a finding that opens a new avenue into the functional analysis of the largest receptor tyrosine kinase subfamily in the brain.

Amnesia, Retrograde↗

The Chlamydomonas zygospore: mutant strains of Chlamydomonas monoica blocked in zygospore morphogenesis comprise 46 complementation groups.

Chlamydomonas monoica undergoes homothallic sexual reproduction in response to nitrogen starvation. Mating pairs are established in clonal culture via flagellar agglutination and fuse by way of activated mating structures to form the quadriflagellate zygote. The zygote further matures into a dormant diploid zygospore through a series of events that we collectively refer to as zygosporulation. Mutants that arrest development prior to the completion of zygosporulation have been obtained through the use of a variety of mutagens, including ultraviolet irradiation, 5-fluorodeoxyuridine, ethyl methanesulfonate, and methyl methanesulfonate. Complementation analysis indicates that the present mutant collection includes alleles affecting 46 distinct zygote-specific functions. The frequency with which alleles at previously defined loci have been recovered in the most recent mutant searches suggests that as many as 30 additional zygote-specific loci may still remain to be identified. Nevertheless, the present collection should provide a powerful base for ultrastructural, biochemical, and molecular analysis of zygospore morphogenesis and dormancy in Chlamydomonas.

Animals↗

Improved clinical outcomes with liver transplantation for hepatitis B-induced chronic liver failure using passive immunization.

OBJECTIVE: The goals were to summarize the results of liver transplantation for chronic hepatitis B disease (HBV) at the University of Virginia, correlate pretransplant viral markers with posttransplant hepatitis B immunoglobulin (HBIg) requirements, and identify the relation between viral protein in the liver and clinical reinfection. SUMMARY BACKGROUND DATA: Liver transplantation is an accepted treatment for end-stage liver disease from chronic HBV infection, although lifelong antiviral treatment (with HBIg or antiviral agents) is still necessary. Patients with evidence of active viral replication (detectable serum HBV-DNA or e antigen) at the time of transplant have a higher rate of allograft infection. Whether clinically stable patients receiving HBIg immunoprophylaxis have detectable viral products in their grafts remains unknown. METHODS: Forty-four transplants performed for HBV disease at the University of Virginia since March 1990 were reviewed. Most patients underwent aggressive passive immunoprophylaxis with HBIg to maintain serum HBV surface antibody (HBsAb) levels > or =500 IU/l for the first 6 months after the transplant, and > or =150 IU/l thereafter. Patients had viral markers quantified, underwent pharmacokinetic analysis of HBsAb levels to adjust dosing, and were biopsied routinely every 3 to 6 months and when indicated. RESULTS: Forty-four transplants were performed in 39 patients. Actual 1-year and 3-year graft survival was 95% and 81%, respectively, and 1-year and 3-year patient survival was 98% and 96%, respectively. After the adoption of indefinite HBIg prophylaxis, nine grafts became infected (all in recipients positive for HBV e antigen). Three occurred within 8 weeks of transplantation and were associated with a short HBsAb half-life and a wild-type virus. Six occurred >8 months after the transplant, and most of these were associated with viral mutation. Quantification of pretransplant markers was an overall poor predictor of HBIg requirements after the transplant. Immunohistochemistry demonstrated transient low-level expression of core protein in the liver in 23% of patients without serum or clinical evidence of recurrent hepatitis. CONCLUSIONS: An excellent outcome is possible after liver transplantation for chronic HBV disease using HBIg dosed by pharmacokinetic parameters. Currently, quantification of pretransplant serum markers of the HBV antigen load does not predict the intensity of posttransplant treatment required for good clinical outcomes. Because HBV is not eradicated from the patient, some form of indefinite antiviral therapy continues to be warranted.

Adult↗

Covered lives and seamless systems: nursing workforce development and integration in Arizona's managed-care environment.

Responding to demands that nursing leaders conduct business in creative proactive ways, the authors of this department share the work of The Robert Wood Johnson Foundation's national program, Colleagues in Caring: Regional Collaboratives for Nursing Work Force Development. The purpose of this initiative is to enhance regional and state collaborative planning and implement actions and policies to address the rapid changes occurring in the United States nursing labor market. This department, edited by Mary Fry Rapson, PhD, RN, CS, National Program Director and Rebecca B. Rice, EdD, RN, National Deputy Director, presents the ongoing work of the program, highlighting the work of the 20 individual collaboratives. Regional approaches to the expected program outcomes and specific challenges and opportunities that are unique to each region's environment are included.

Arizona↗

Rapid diagnosis and identification of cross-over sites in patients with glucocorticoid remediable aldosteronism.

Glucocorticoid remediable aldosteronism (GRA) is an autosomal dominant cause of primary aldosteronism and high blood pressure resulting from a chimeric 11beta-hydroxylase/aldosterone synthase gene. Abnormal expression of aldosterone synthase causes primary aldosteronism, which can be inhibited by glucocorticoids. Diagnosis of GRA has depended on the identification of a restriction enzyme product in genomic DNA of affected individuals. Recently, a two-tube long PCR method was described that allowed diagnosis of GRA in a kindred in Australia. A similar long PCR method confirmed the diagnosis of GRA in members of five northeastern Scotland families previously identified by Southern blotting and detected affected members of five GRA families previously identified in Glasgow. A multiplex PCR protocol is described here that allows the control aldosterone synthase amplification and chimeric gene amplification to be carried out in the same tube. We describe the regions of cross-over in each of 10 kindreds identified in Scotland. To identify cross-over regions in each of the kindreds, the chimeric long PCR product was cloned and sequenced. Five cross-over sites were identified ranging from intron 2 to exon 4, indicating the reliability of the method in identifying chimeric genes resulting from different sites of cross-over.

Base Sequence↗

Chronic fenoterol exposure increases in vivo and in vitro airway responses in guinea pigs.

We tested the hypothesis that the regular inhalation of a beta 2-adrenergic receptor (beta 2AR) agonist increases airway responsiveness in guinea pigs. A potent beta 2AR agonist, fenoterol hydrobromide, in sublaryngeal doses equivalent to maximal doses used in the treatment of asthma on a weight basis (5.28 micrograms/kg), was administered by nebulizer three times a day for 6 weeks to normal adolescent guinea pigs (FEN, n = 10) and to ovalbuminsensitized guinea pigs challenged twice weekly with ovalbumin (OA + FEN, n = 20), although not in the 12 h prior to or 4 h after antigen challenge. Controls included saline-treated normal animals (CON, n = 10) and ovalbumin-sensitized animals treated with repeated antigen challenge and saline (OA, n = 20). At 72 h after the last administration of saline, fenoterol, and ovalbumin, the dose-response relationship between pulmonary resistance (RL) and nebulized acetylcholine (ACh) was measured. RLmax increased 2-fold and the ACh concentration causing a 10-fold increase in RL (PC10) decreased 4-fold in the FEN, OA, and OA + FEN groups as compared to the CON group. In the FEN, OA, and OA + FEN groups, in vitro tracheal smooth-muscle contractile responses to maximal concentrations of acetylcholine increased 2-fold, and this increase was not due to increased smooth-muscle mass. There was no evidence for beta 2AR desensitization as judged by in vitro tracheal smooth-muscle relaxant responses to fenoterol. These results suggest that chronic beta 2AR stimulation increases airway smooth-muscle contractility and in vivo airways responsiveness to a degree similar to that induced by chronic antigen exposure. A similar effect in human asthmatics may explain the adverse effects observed during prolonged treatment with these drugs.

Aerosols↗

Detection of hepatitis C virus RNA in hemodialysis patients.

The clinical significance of the high prevalence of antibodies to hepatitis C virus (HCV) in dialysis patients remains undefined. In order to assess the relationship between seropositivity and potential infectivity, 63 patients undergoing maintenance hemodialysis were evaluated between April and May 1990. The mean duration of maintenance hemodialysis was 45 mo (range, 13 to 144). Eighty-two percent (52 of 63) had received blood transfusions, and 16% (10 of 63) had a history of iv drug abuse. Serum samples were analyzed by HCV-cDNA polymerase chain reaction; antibodies to HCV structural (core) and nonstructural regions NS3 and NS4 were determined by enzyme immunoassay. Specimens repeatedly reactive for anti-HCV and HCV-RNA-positive samples were tested by HCV MATRIX dot immunoblot assay and HBV-DNA PCR. Twenty-five percent (16 of 63) were anti-HCV-positive. Of the 16 anti-HCV-positive patients, HCV-RNA was detected in 5 (31%) with the NS3 primers and in 12 (75%) with 5'-noncoding primers. Among the anti-HCV-negative patients, HCV-RNA was detected in 2 (4.3%) of 47 patients. Eleven of the 18 patients with HCV infection (anti-HCV and/or HCV-RNA-positive) had evidence of additional present or past viral infections (human immunodeficiency virus and/or hepatitis B virus). In summary, HCV-RNA is present in at least 75% of anti-HCV-positive patients, suggesting that they may be infectious. The detection of HCV-RNA in anti-HCV-negative patients may indicate early or chronic HCV infection not detected by current antibody assays or the inability of these patients to mount or sustain a significant antibody response.

Adult↗

Haemospermia: how to proceed?

Haemospermia is an alarming symptom but does it signify serious disease and how should it be investigated? A retrospective review of 44 men showed no evidence of malignancy and infection as the commonest cause. Standard investigation with midstream specimen of urine, intravenous pyelogram and cystoscopy is unhelpful. Microscopy and culture of a first stream specimen of urine or expressed prostatic secretions is the investigation of choice. Cystoscopy should be reserved for patients with recurrent haemospermia.

Adult↗

Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen.

Polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA in the sera and livers of nine patients with chronic hepatitis B after treatment-induced or spontaneous loss of serum hepatitis B surface antigen. Patients were evaluated at intervals ranging from 3 to 67 months after disappearance of hepatitis B surface antigen. PCR was performed using primer pairs from the surface and core gene regions, and surface gene products were quantitated. Liver tissue was also evaluated by in situ hybridization to assess viral transcription. Five of the nine patients had viral DNA detectable in serum by PCR. Quantitation of polymerase chain reaction products in serum and liver showed that the DNA levels tended to decline progressively after antiviral therapy. Six of seven surface antigen-negative patients tested had detectable viral DNA in the liver, and four of the six DNA-positive patients were negative for DNA in serum by PCR. None had surface gene messenger RNA. Thus, it is concluded that hepatitis B virus DNA may be detectable by PCR in liver tissue years after the disappearance of hepatitis B surface antigen, even in the absence of detectable hepatitis B virus DNA in serum.

Alanine Transaminase↗

Optimum duration of transtelephonic ECG monitoring when used for transient symptomatic event detection.

Transtelephonic electrocardiographic monitoring (TTM) has been used for postpacemaker follow-up study, postmyocardial infarction monitoring, and transient symptomatic event detection (TSED). For postpacemaker follow-up study, TTM is continued indefinitely. For postmyocardial infarction monitoring, TTM is continued for 1 year or more. For TSED, the appropriate duration for TTM has not yet been adequately assessed. Accordingly, the authors determined the yield, by week, of TTM for TSED. Five thousand fifty-two patients who made 20,590 calls were analyzed for this investigation. Ninety-five percent of patients making symptomatic calls or making a call in which an arrhythmia was documented did so within 5 weeks. Shorter periods would sacrifice yield, longer periods may not be cost-effective.

Arrhythmias, Cardiac↗

Complement and antibody mediate enhancement of HIV infection by increasing virus binding and provirus formation.

Previous studies have shown that infection of complement receptor (CR2)-bearing cells with HIV pretreated with antibody (Ab) plus complement (C) resulted in increased virus expression. The current study was designed to determine whether C-mediated 'enhancement' of HIV-1 production was the result of increased virus infection of cells as assessed by provirus formation and virus binding. Virus was incubated with anti-HIV Ab and/or C and added to CR2-positive MT-2 cells. Increased virus expression by MT-2 cells correlated with increased numbers of HIV-immunofluorescent-positive cells at 24 and 48 h and higher levels of provirus detected 8-28 h after infection. MT-2 cells also bound threefold more Ab-plus-C-treated virus than untreated virus. Serial dilutions of C showed that high levels of C with Ab did not enhance but rather suppressed virus expression. Studies were also performed which showed that terminal C components C5 and C8 were not necessary for the enhancing effect. The increased binding of C-coated HIV to CR-positive cells has important implications for the fate of virus in vivo.

Antigens, Differentiation, B-Lymphocyte↗

Ambulation status of adults with myelomeningocoele.

The current ambulation status of 87 adults with myelomeningocoele who had been ambulant with calipers as children was reviewed--23 patients were community ambulators, while 58 had become wheelchair-bound. The majority of patients in the study group found calipers uncomfortable to wear, and almost half of the group developed pressure sores directly related to their calipers.

Adolescent↗