Unusual presentations of germ cell tumors. Case 1. Recurrent laryngeal nerve palsyin mediastinal seminoma.
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Adult↗
Biomedical subjects
S Clarke
Publications and source records attributed to S Clarke.
Distinct pathways involved in sound recognition and localization: a human fMRI study.
Evidence from psychophysical studies in normal and brain-damaged subjects suggests that auditory information relevant to recognition and localization are processed by distinct neuronal populations. We report here on anatomical segregation of these populations. Brain activation associated with performance in sound identification and localization was investigated in 18 normal subjects using fMRI. Three conditions were used: (i) comparison of spatial stimuli simulated with interaural time differences; (ii) identification of environmental sounds; and (iii) rest. Conditions (i) and (ii) required acknowledgment of predefined targets by pressing a button. After coregistering, images were normalized and smoothed. Activation patterns were analyzed using SPM99 for individual subjects and for the whole group. Sound recognition and localization activated, as compared to rest, inferior colliculus, medial geniculate body, Heschl gyrus, and parts of the temporal, parietal, and frontal convexity bilaterally. The activation pattern on the fronto-temporo-parietal convexity differed in the two conditions. Middle temporal gyrus and precuneus bilaterally and the posterior part of left inferior frontal gyrus were more activated by recognition than by localization. Lower part of inferior parietal lobule and posterior parts of middle and inferior frontal gyri were more activated, bilaterally, by localization than by recognition. Regions selectively activated by sound recognition, but not those selectively activated by localization, were significantly larger in women. Passive listening paradigm revealed segregated pathways on superior temporal gyrus and inferior parietal lobule. Thus, anatomically distinct networks are involved in sound recognition and sound localization.
Adult↗
Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer.
The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.
Actuarial Analysis↗
Autoradiographic mapping of the opioid receptor-like 1 (ORL1) receptor in the brains of mu-, delta- or kappa-opioid receptor knockout mice.
The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence homology with the classical mu-, delta- and kappa-opioid receptors and a functional mutual opposition between these receptors has been suggested. To further address this possible interaction we have used mu-, delta- and kappa-opioid receptor knockout mice to determine autoradiographically if there are any changes in the number or distribution of the ORL1 receptor, labelled with [(3)H]nociceptin, in the brains of mice deficient in each of the opioid receptors. An up-regulation of ORL1 expression was observed across all brain regions in delta-knockouts with cortical regions typically showing a 15-30% increase in binding that was most marked in heterozygous mice. In contrast, ORL1 receptor expression was down-regulated in virtually all brain structures in heterozygous kappa-knockouts although the magnitude of this change was not as great as for the delta-knockouts. No significant alterations in ORL1 receptor expression were observed across brain regions in mu-receptor knockout mice and there were no qualitative differences in ORL1 receptor expression in any groups. These data suggest there are interactions between the ORL1 system and the classical opioid receptors and that the interactions are receptor-specific. The greater differences observed in heterozygous mice suggest that these interactions might be most relevant when there is only partial loss of receptor function.
Animals↗
Structure of Thermotoga maritima stationary phase survival protein SurE: a novel acid phosphatase.
BACKGROUND: The rpoS, nlpD, pcm, and surE genes are among many whose expression is induced during the stationary phase of bacterial growth. rpoS codes for the stationary-phase RNA polymerase sigma subunit, and nlpD codes for a lipoprotein. The pcm gene product repairs damaged proteins by converting the atypical isoaspartyl residues back to L-aspartyls. The physiological and biochemical functions of surE are unknown, but its importance in stress is supported by the duplication of the surE gene in E. coli subjected to high-temperature growth. The pcm and surE genes are highly conserved in bacteria, archaea, and plants. RESULTS: The structure of SurE from Thermotoga maritima was determined at 2.0 A. The SurE monomer is composed of two domains; a conserved N-terminal domain, a Rossman fold, and a C-terminal oligomerization domain, a new fold. Monomers form a dimer that assembles into a tetramer. Biochemical analysis suggests that SurE is an acid phosphatase, with an optimum pH of 5.5-6.2. The active site was identified in the N-terminal domain through analysis of conserved residues. Structure-based site-directed point mutations abolished phosphatase activity. T. maritima SurE intra- and intersubunit salt bridges were identified that may explain the SurE thermostability. CONCLUSIONS: The structure of SurE provided information about the protein's fold, oligomeric state, and active site. The protein possessed magnesium-dependent acid phosphatase activity, but the physiologically relevant substrate(s) remains to be identified. The importance of three of the assigned active site residues in catalysis was confirmed by site-directed mutagenesis.
Amino Acid Sequence↗
Assessing individual quality of life in amyotrophic lateral sclerosis.
BACKGROUND: Quality of life (QoL) assessment in amyotrophic lateral sclerosis (ALS) has typically involved the use of general or disease-specific health status questionnaires. This study assessed the feasibility of using a patient-centered approach to QoL measurement in ALS. OBJECTIVES: (1) To assess the internal consistency reliability and validity of the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) as a measure of QoL in ALS. (2) To provide a brief description of QoL in ALS, and to examine the relationships between QoL, illness severity and psychological distress in this group. METHODS: Twenty-six patients with ALS were recruited through the Irish Register for ALS/motor neurone disease (MND). Illness severity was assessed with the ALS Functional Rating Scale (ALSFRS). Levels of psychological distress were measured with the Hospital Anxiety and Depression Scale (HADS). Individual QoL was assessed with SEIQoL. RESULTS: Patients were at various stages of ALS. Mean levels of anxiety and depression were in the normal range. Twenty-one patients completed SEIQoL; five patients completed a shorter version, SEIQoL-Direct Weighting (SEIQoL-DW). Internal consistency reliability and validity results for SEIQoL were high. CONCLUSIONS: SEIQoL is generally acceptable for use in ALS in terms of its practical feasibility, and has high internal validity and consistency reliability in this patient group. However, patients severely disabled by ALS may not be able to complete SEIQoL; further research is required to confirm the use of SEIQoL-DW as an alternative measure of individual QoL in ALS.
Adult↗
Some is good and more is bad: getting the dose right in the critically ill.
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Critical Illness↗
Intrinsic connectivity of human auditory areas: a tracing study with DiI.
The human supratemporal plane contains the primary as well as several other auditory areas. We have investigated the intrinsic connectivity of these areas by means of antero- and retrograde labelling with the carbocyanin dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). A total of 30 injections was placed in both hemispheres of four freshly fixed postmortem brains. Labelled neurons and axons were found in cortex around the injection. The retrograde labelling varied from faint to Golgi-like; most of the retrograde labelled neurons were layers II-III pyramids and only a few were nonpyramidal neurons. Labelled axons were dense in all layers near the injection site, while they became relatively rare in layer IV further away. The tangential spread of labelling differed among auditory areas. On Heschl's gyrus (corresponding to the primary auditory cortex and cytoarchitectonic areas TD and part of TB) intrinsic connectivity involved a relatively narrow part of cortex. They spread over larger parts of cortex in plana polare and temporale (areas TG, TA and the remaining part of TB). A number of injections also produced anisotropic labelling patterns. These results reveal differences in intrinsic connectivity between auditory areas. They suggest that intrinsic connections within the primary auditory area, area TD and part of TB that is on Heschl's gyrus, involve mainly nearby units or modules, probably with similar coding properties, whereas in surrounding areas, connections spread over more distant units and may play an important role in the integration of different auditory features.
Aged↗
Haemolysis and the combined oral contraceptive pill?
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Adult↗
The changing epidemiology of HIV infection in injecting drug users in Dublin, Ireland.
INTRODUCTION: Injecting drug users (IDUs) represent 41.6% of the total cohort of HIV-infected patients in Ireland. Between January 1999 and December 2000, referrals to the largest tertiary centre for HIV infection in Dublin have increased dramatically. This has occurred on a background of a reduction in the overall incidence of HIV infection in Ireland between 1990 and 1998. Here we describe the changing epidemiology of HIV disease in IDUs and explore potential aetiological factors. METHODS: This is a retrospective study, collecting all data relating to new HIV diagnoses occurring in IDUs, referred to the GenitoUrinary Medicine and Infectious Diseases (GUIDE) clinic between 1987 and 2000. We calculated 6-month incidence rates of new HIV diagnoses in IDUs referred to the GUIDE clinic and performed a more detailed analysis of those patients diagnosed between January 1999 and December 2000, documenting age, sex, time and place of diagnosis, drug use history and primary drug of misuse, needle sharing history, attendance at a drug treatment clinic, prior HIV testing history, hepatitis B and hepatitis C status, and CD4 cell counts and HIV RNA levels at diagnosis. RESULTS: The number of new HIV diagnoses in IDUs increased fivefold between 1995 and 2000. Moreover, 40% of patients diagnosed since then have been under 22 years old. There has also been a significant reversal of the initial male to female ratio seen in the initial epidemic of the 1980s. CONCLUSION: There has been a significant increase in the incidence of HIV infection in IDUs between 1995 and 2000. Similar trends have been described recently in other risk groups. The aetiology of these trends is multifactorial, and a multidisciplinary, rejuvenated approach is required to focus on improving health education to reduce both sexual and needle sharing practices.
Adolescent↗
Anterior tarsal tunnel syndrome in the post partum period.
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Letter↗
Two types of auditory neglect.
Auditory neglect, defined as inattention to stimuli within the left hemispace, is mostly reported in association with left ear extinction in dichotic listening. However, it remains disputed as to how far dichotic extinction reflects a primary attentional deficit and is thus appropriate for the diagnosis of auditory neglect. We report here on four patients who presented left ear extinction in dichotic listening following right unilateral hemispheric lesions. Auditory spatial attention was assessed with two additional tasks: (i) diotic test by means of interaural time differences (ITDs), simulating bilateral simultaneous spatial presentation of the dichotic tasks without the inconvenience of interaural intensity or content difference; and (ii) sound localization. A hemispatial asymmetry on the ITD diotic test or a spatial bias on sound localization were found to be part of auditory neglect. Two patients (J.C.N. and M.B.) presented a marked hemispatial asymmetry favouring the ipsilesional hemispace in the ITD diotic test, but did not show any spatial bias in sound localization. Two other patients (A.J. and E.S.) had the reverse profile: no hemispatial asymmetry in the ITD diotic test, but a severe spatial bias directed to the ipsilesional side in sound localization. J.C.N. and M.B. had mainly subcortical lesions affecting the basal ganglia. A.J. and E.S. had cortical lesions in the prefrontal, superior temporal and inferior parietal areas. Thus, there are two behaviourally and anatomically distinct types of auditory neglect characterized by: (i) deficit in allocation of auditory spatial attention following lesions centred on basal ganglia; or (ii) distortion of auditory spatial representation following frontotemporoparietal lesions.
Adult↗
Nutritional and medical therapy for dyslipidemia in patients with cardiovascular disease.
Dyslipidemia is a significant risk factor for the progression of cardiovascular disease, particularly when associated with other risk factors. An understanding of the pathophysiology and risks for patients with atherosclerotic diseases of undertreated dyslipidemia is essential for the healthcare provider. In this article, a review of epidemiologic data regarding the role of lipid levels in cardiovascular disease prognosis is presented. A familiarity with current dietary and drug treatment of lipid disorders is at the core of an evidence-based approach to dyslipidemia management in the patient with established cardiovascular diseases.
Acute Disease↗
Distinct patterns of expression but similar biochemical properties of protein L-isoaspartyl methyltransferase in higher plants.
Protein L-isoaspartyl methyltransferase is a widely distributed repair enzyme that initiates the conversion of abnormal L-isoaspartyl residues to their normal L-aspartyl forms. Here we show that this activity is expressed in developing corn (Zea mays) and carrot (Daucus carota var. Danvers Half Long) plants in patterns distinct from those previously seen in winter wheat (Triticum aestivum cv Augusta) and thale cress (Arabidopsis thaliana), whereas the pattern of expression observed in rice (Oryza sativa) is similar to that of winter wheat. Although high levels of activity are found in the seeds of all of these plants, relatively high levels of activity in vegetative tissues are only found in corn and carrot. The activity in leaves was found to decrease with aging, an unexpected finding given the postulated role of this enzyme in repairing age-damaged proteins. In contrast with the situation in wheat and Arabidopsis, we found that osmotic or salt stress could increase the methyltransferase activity in newly germinated seeds (but not in seeds or seedlings), whereas abscisic acid had no effect. We found that the corn, rice, and carrot enzymes have comparable affinity for methyl-accepting substrates and similar optimal temperatures for activity of 45 degrees C to 55 degrees C as the wheat and Arabidopsis enzymes. These experiments suggest that this enzyme may have specific roles in different plant tissues despite a common catalytic function.
Daucus carota↗
Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy.
Although gestagens have been reported to influence bone metabolism, whether these contribute to the beneficial effects of hormone replacement therapy (HRT) on the skeleton of postmenopausal women is currently unclear. To address this question, we compared changes in bone turnover markers after commencing HRT in 26 postmenopausal women randomized to receive 8 weeks of treatment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baseline (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide by enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater than that in the combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion to a greater extent when given alone (P = 0.02), osteocalcin levels were significantly higher in this group than in women receiving combination therapy (P = 0.04). To assess the effect of dydrogesterone on the balance between formation and resorption in more detail, we subsequently compared the ratio between formation and resorption markers in the two treatment groups. We found that osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly higher in women treated with estradiol alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogesterone may reduce formation relative to resorption. These results suggest that gestagens may reduce estrogen's beneficial effects on the skeleton of postmenopausal women, as assessed over the first 8 weeks of replacement therapy.
Amino Acids↗
The modulation of late component event related potentials by pre-stimulus EEG theta activity in ADHD.
Electroencephalography (EEG) and Event Related Potentials (ERPs) studies in ADHD have generally been studied separately. This study examined these measures simultaneously in 54 adolescent unmedicated ADHD males and age and gender matched normal controls during an auditory oddball paradigm. Compared with controls, ADHD patients showed increased pre-stimulus EEG Theta activity and post-stimulus reduced N200 amplitude, increased P200 amplitude and delayed N200 and P300 latencies evoked to target stimuli. Moreover, Theta activity was negatively correlated with N200 amplitude and positively correlated with P200, N200 and P300 latency in ADHD. There were no correlations in the control group. Pre-stimulus preparatory state increases in Theta activity in ADHD may underlie some of the reported disturbances in information processing reflected in ADHD.
Adolescent↗
Treating personality fragmentation and dissociation in borderline personality disorder: a pilot study of the impact of cognitive analytic therapy.
Recent findings suggest that personality fragmentation may be a core component of borderline personality disorder (BPD) and that successful treatment of BPD may depend on the extent to which this is addressed. Cognitive analytic therapy (CAT) can increase integration by strengthening awareness, and hence control, of the dissociative processes maintaining fragmentation. This pilot study aimed to conduct a systematic evaluation of the impact of CAT on BPD severity and personality integration. A patient series within-subject design was used. Five BPD participants completed a series of assessments to evaluate the impact of therapy on BPD severity, fragmentation, dissociation, symptomatology and interpersonal adjustment before, during and following 16-session CAT. By follow-up, CAT had produced reductions in the severity of BPD for all five participants, and three participants showed significant changes in their levels of personality fragmentation. Improvements in comorbid disturbance were less consistent, however. Although the small number of participants involved limits these findings, they have theoretical and clinical interest. They generally support the suggestion that integration should be enhanced with BPD patients, and suggest that CAT may be a useful method to achieve this goal.
Adult↗
National guidelines for the active management of HIV in pregnancy.
The number of HIV positive women becoming pregnant in Ireland is increasing, with many pregnancies occurring in women from countries of high HIV prevalence. The management of such patients offers the challenge of reducing the risk of maternal-fetal transmission of HIV infection, avoiding fetal-infant toxicities, and maintaining future maternal antiretroviral options. Guidelines for the optimal management of HIV disease in pregnancy have been produced by a subgroup of the Irish Infection Society consisting of GenitoUrinary Medicine and Infectious Diseases Consultants. They are based on currently available international data and guidelines. The national guidelines offer a broad management outline for HIV positive pregnant patients. Ultimately, each patient is assessed individually by a multidisciplinary team, and a careful plan for antenatal, intrapartum, and postpartum care is determined.
Anti-HIV Agents↗