[Subtle, temporary, homonymous visual field defect--fatal causes?].
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Adult↗
Biomedical subjects
J Paulsen
Publications and source records attributed to J Paulsen.
Polyethylene glycol versus sodium phosphate in bowel cleansing for colonoscopy: a randomized trial.
BACKGROUND AND STUDY AIMS: There have been conflicting results regarding the adverse effects of established bowel cleansing regimens. The aim of the present study was to compare the effects of three bowel cleansing regimens on subjective well-being, electrolyte balance, cardiac arrhythmia, and the microscopic post-cleansing appearance of the colonic mucosa. PATIENTS AND METHODS: A total of 231 consecutive outpatients were randomly assigned to receive bowel preparation for colonoscopy with either 4 l polyethylene glycol (PEG; group I, n = 76); 2 l PEG plus 10 mg Bisacodyl (group II, n = 71); or 90 ml sodium phosphate (group III, n = 84). After bowel preparation, the participants completed a questionnaire on symptoms. Endoscopists blinded to the regimen used gave scores for the quality of cleansing at endoscopy, ranging from poor (0) to very good (5). Blood samples were taken before and after bowel cleansing, electrocardiographic monitoring was used during colonoscopy, and mucosal biopsy samples were taken in the sigmoid colon. RESULTS: Bowel preparation in group II was poorer (mean score 3.26) than in groups I (3.88) and III (4.01); P < 0.001 (II vs. III), P < 0.001 (I vs. II). The frequency of arrhythmias and post-cleansing mucosal inflammation was similar in all three groups. Lower serum potassium and higher serum phosphate concentrations were found in group III in comparison with the other groups ( P < 0.001). CONCLUSIONS: No differences were detected regarding the effectiveness and safety of bowel preparation with PEG alone and sodium phosphate in individuals without cardiac, renal, or hepatic failure, despite a significantly stronger alteration of the electrolyte balance with sodium phosphate.
Biopsy↗
Evaluation of a novel colonoscope designed for easier passage through flexures: a randomized study.
BACKGROUND AND STUDY AIMS: A new colonoscope (XCF-Q160AW prototype, Olympus, Tokyo, Japan) has been developed, designed with an additional passive bending function to ease intubation through the left colonic flexure. In this study we investigated whether this function could be included in a standard colonoscope without jeopardizing general performance, particularly passage through the sigmoid colon. PATIENTS AND METHODS: 280 outpatients referred for routine colonoscopy at Telemark Hospital were randomly allocated to colonoscopy with a standard colonoscope (Olympus 140 series) or the XCF-Q160AW prototype. Sedation was given on demand. End points were cecal intubation and the patients' grading of pain in a questionnaire. RESULTS: Cecal intubation rates were 85% and 87% for standard and prototype endoscopes, respectively (P = 0.57). On-demand sedation was given to nine (7%) and 15 (11%) of the patients, respectively (P = 0.17). Of the patients, 256 (85%) returned their questionnaire, with 87 (63%) in the standard group and 109 (77%) in the prototype group reporting that they had experienced 'no pain/slight pain' (P < 0.001). In a multiple logistic regression analysis, this difference in experienced pain remained statistically significant after adjustment for interendoscopist variation and the use of the endoscope-stiffening function. Two patients in the study, in whom there had previously been several unsuccessful attempts at negotiating the splenic flexure, were successfully examined with the prototype colonoscope. CONCLUSION: Examination with the Olympus XCF-Q160AW prototype with a passive bending function caused less pain than use of a standard Olympus 140 series colonoscope, without compromising other endoscope functions for colonic intubation.
Colon↗
Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
Adolescent↗
Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging males: implications for testosterone replacement therapy.
Andropause is a syndrome described in aging males, is composed of a constellation of physical, sexual, and emotional symptoms, and is thought to be related to declining concentrations of serum testosterone. Numerous studies of testosterone replacement therapy in elderly hypogonadal males have documented the physical benefits of such treatment, but have failed to assess cognition, psychological functioning, and quality of life. Male outpatients greater or equal to 55 years of age completed cognitive, psychological, sexual, and quality of life assessments. A serum sample was provided for bioavailable testosterone assay. The associations between bioavailable testosterone concentrations and neuropsychological testing were assessed using Spearman rank correlation. Overall, bioavailable testosterone was not an important determinant of cognitive, psychological, or sexual functioning or of quality of life. The implications for future studies involving testosterone replacement therapy are discussed.
Aged↗
Correction of tetralogy of Fallot: does the time period of surgery influence the outcome?
BACKGROUND: The perioperative outcome of patients with tetralogy of Fallot (TOF) seems to have improved over the last four decades. METHODS: To prove this hypothesis, we retrospectively analysed the data of 269 TOF patients operated on between 1975 and 1999 in our institution. RESULTS: Over the years, younger patients (median age 1975 - 1980: 4.5 years, 1995 - 1999: 0.9 years) were operated on with a lower mortality (1975 - 1980: 8.6 %, 1995 - 1999: 2.4 %). Residual defects such as pulmonary stenosis or insufficiency and VSD occurred with a similar frequency over time, whereas rhythm disturbances were significantly reduced (1981 - 1985: 51.2 %, 1995 - 1999: 24.4 %, p = 0.012). Postoperative length of hospital stay was significantly (p < 0.05) shorter in the years 1995 - 1999 (11.0 - 11.4 days) than in 1975 - 1980 (16.9 +/- 16.5 days). CONCLUSIONS: Over time periods, there was a trend towards lower mortality and towards operating on patients in a younger age. The rate of rhythm disturbances and the LOS after surgery proved to be reduced during the last decade. These differences did not turn out to be statistically significant. Therefore, we conclude that the time period of surgery has only little impact on the early outcome of patients after definitive correction of TOF.
Age Factors↗
Tetralogy of Fallot: influence of surgical technique on survival and reoperation rate.
BACKGROUND: The influence of different surgical techniques in patients with Tetralogy of Fallot (TOF) on long-term survival and reoperation rate is still a matter of controversy. PATIENTS AND METHODS: The data of 266 patients (152 male, 114 female, mean body weight: 13.4 +/- 11.9 kg, mean age 4.1 +/- 6.0 years) with TOF, including 30 patients (11.2 %) with TOF/pulmonary atresia, were analyzed retrospectively. A palliative surgical procedure preceded definite correction between 1975 and 1999 in 46 patients (17.5 %). The surgical technique consisted of a transannular patch in 103 patients (40.1 %); in 133 patients (51.8 %), a non-transvalvular technique was used. In 33 patients (12.3 %), a conduit was implanted into the right ventricular outflow tract (RVOT). For surgical access to the cardiac defects, a transventricular approach was used in 138 patients, and a transatrial/trans-pulmonary approach in 26 patients. The mean follow-up time of all patients was 6.6 years. RESULTS: Kaplan-Meier survival for the entire group was 86.2 % at one year and remained stable at 85.6 % after 5 years. The 30-day mortality was 10.1 % (27 patients). Fatal risk factors were: previous cardiac surgery, preoperative oxygen saturation (SO(2)) < 80 %, diagnosis of pulmonary atresia, prolonged aortic clamping or bypass time, postoperative infections, and early revisions. Freedom from reoperation was 91.6 % after 5, 84.5 % after 10, and 52.6 % after 20 years. There was no correlation between the different surgical techniques (transannular patch, non-transvalvular techniques, transventricular approach) applied and the mortality or the rate of reoperations. CONCLUSIONS: In our series of TOF patients operated over a period of 25 years, we were unable to assess an influence of the surgical technique used for definite correction on mortality or reoperation rate. Pulmonary atresia in patients with TOF is associated with a higher risk of death and reoperation.
Adolescent↗
Caenorhabditis elegans MES-3 is a target of GLD-1 and functions epigenetically in germline development.
The maternal-effect sterile (MES) proteins are maternally supplied regulators of germline development in Caenorhabditis elegans. In the hermaphrodite progeny from mes mutant mothers, the germline dies during larval development. On the basis of the similarities of MES-2 and MES-6 to known transcriptional regulators and on the basis of the effects of mes mutations on transgene expression in the germline, the MES proteins are predicted to be transcriptional repressors. One of the MES proteins, MES-3, is a novel protein with no recognizable motifs. In this article we show that MES-3 is localized in the nuclei of embryos and germ cells, consistent with its predicted role in transcriptional regulation. Its distribution in the germline and in early embryos does not depend on the wild-type functions of the other MES proteins. However, its nuclear localization in midstage embryos and its persistence in the primordial germ cells depend on wild-type MES-2 and MES-6. These results are consistent with biochemical data showing that MES-2, MES-3, and MES-6 associate in a complex in embryos. The distribution of MES-3 in the adult germline is regulated by the translational repressor GLD-1: MES-3 is absent from the region of the germline where GLD-1 is known to be present, MES-3 is overexpressed in the germline of gld-1 mutants, and GLD-1 specifically binds the mes-3 3' untranslated region (3' UTR). Analysis of temperature-shifted mes-3(bn21ts) worms and embryos indicates that MES-3 function is required in the mother's germline and during embryogenesis to ensure subsequent normal germline development. We propose that MES-3 acts epigenetically to induce a germline state that is inherited through both meiosis and mitosis and that is essential for survival of the germline.
3' Untranslated Regions↗
Rate of functional decline in Huntington's disease. Huntington Study Group.
OBJECTIVE: To determine the rate of functional decline in a large cohort of patients with Huntington's disease (HD) followed at 43 sites by the Huntington Study Group (HSG). METHODS: The annual rate of functional decline was measured using the Total Functional Capacity Scale (TFC) and the Independence Scale (IS) in 960 patients with definite HD followed prospectively for a mean of 18.3 months. All patients were rated with the Unified Huntington's Disease Rating Scale (UHDRS). Sample size calculations for hypothetical clinical trials were calculated. RESULTS: A factor analysis of the UHDRS at baseline yielded 15 factors accounting for 77% of the variance. The TFC score declined at a rate of 0.72 units/year (standard error [SE] 0.04) and the IS score declined at a rate of 4.52 units/year (SE 0.23). Lower TFC score at baseline, indicating more severe impairment, was associated with less rapid annual decline in TFC score, perhaps reflecting the floor effect of the scale. The annual rate of decline for 575 patients with baseline TFC scores of 7 to 13 was 0.97 (SE 0.06), was 0.38 (SE 0.08) for 270 patients with baseline TFC scores of 3 to 6, and was 0.06 (SE 0.1) for 101 patients with TFC scores of 0 to 2. In multivariate analysis (n = 960), longer disease duration and better cognitive status at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology was the only factor associated with more rapid decline on the IS score. Age at onset of HD, sex, weight, and education did not affect decline on either score. CONCLUSIONS: The comparable rates of decline on the TFC and the IS scores with other published studies suggest that these estimates of functional decline are representative of HD patients who are evaluated at HSG research sites. In longitudinal analysis, longer disease duration and better neuropsychological performance at baseline were associated with a less rapid rate of decline in TFC score, whereas depressive symptomatology at baseline was associated with a more rapid decline in the IS score. These rates of functional decline and the covariates that modify them should be considered in estimating statistical power and designing future therapeutic trials involving HD patients with early or moderately severe disease.
Activities of Daily Living↗
Innervation of the cavernous body of the human efferent tear ducts and function in tear outflow mechanism.
The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries comparable to a cavernous body. The present study aimed to demonstrate the ultrastructure of the nervous tissue and the localisation of neuropeptides involved in the innervation of the cavernous body, a topic not previously investigated. Different S-100 protein antisera, neuronal markers (neuron-specific enolase, anti-200 kDa neurofilament), neuropeptides (substance P, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide) and the neuronal enzyme tyrosine hydroxylase were used to demonstrate the distribution pattern of the nervous tissue. The ultrastructure of the innervating nerve fibres was also examined by means of standard transmission electron microscopy. The cavernous body contained specialised arteries and veins known as barrier arteries, capacitance veins, and throttle veins. Perivascularly, the tissue was rich in myelinated and unmyelinated nerve fibres in a plexus-like network. Small seromucous glands found in the region of the fundus of the lacrimal sac were contacted by nerve fibres forming a plexus around their alveoli. Many nerve fibres were positive for S-100 protein (S 100), neuron-specific enolase (NSE), anti-200 kDa neurofilament (RT 97), calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY). Vasoactive intestinal polypeptide (VIP) immunoreactivity was only demonstrated adjacent to the seromucous glands. Both the density of nerve fibres as well as the presence of various neuropeptides emphasises the neural control of the cavernous body of the human efferent tear ducts. By means of this innervation, the specialised blood vessels permit regulation of blood flow by opening and closing the lumen of the lacrimal passage as effected by the engorgement and subsidence of the cavernous body, at the same time regulating tear outflow. Related functions such as a role in the occurrence of epiphora related to emotional responses are relevant. Moreover, malfunction in the innervation of the cavernous body may lead to disturbances in the tear outflow cycle, ocular congestion or total occlusion of the lacrimal passages.
Adult↗
Cytokine profiles in Wegener's granulomatosis: predominance of type 1 (Th1) in the granulomatous inflammation.
OBJECTIVE: To determine whether a specific cytokine pattern (type 1 [Th1] or type 2 [Th2]) predominates in Wegener's granulomatosis (WG), by evaluating interferon-gamma (IFNgamma) and interleukin-4 (IL-4) expression in different compartments of the body (i.e., biopsied nasal mucosal tissue [NBS], bronchoalveolar lavage [BAL] fluid, and peripheral blood [PB]) and comparing the findings with those in disease and healthy control subjects. METHODS: Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay were used to assess IFNgamma and IL-4 expression in T cell clones (TCC), T cell lines (TCL), and polyclonal CD4+ and CD8+ cells derived from NBS, BAL, and PB. RESULTS: Patients with WG and chronic rhinitis were found to share in situ production of messenger RNA (mRNA) specific for IFNgamma (Th1). Only 2 patients with WG expressed IL-4, whereas IL-4 mRNA PCR products were found in inflamed tissues of the disease control patients. The granuloma-derived T cells of WG patients produced only IFNgamma, while TCC, TCL, and CD4+ and CD8+ T cells from BAL and PB produced mainly IFNgamma. CONCLUSION: Our data indicate that a Thl cytokine pattern predominates in the granulomatous inflammation in patients with WG.
Adult↗
Is there a "subcortical" profile of attentional dysfunction? A comparison of patients with Huntington's and Parkinson's diseases on a global-local focused attention task.
This study investigated focused attention in two subcortical degenerative disorders by examining the performance of patients with Huntington's disease (HD) and Parkinson's disease (PD) on a task utilizing global-local stimuli. Participants were presented with global-local figures and were instructed to focus their attention on either the global or local level. Stimuli were either "consistent", with the same form at the global and local levels, or "inconsistent", with different forms at the global and local levels. It was found that response times (RTs) of patients with PD were comparable to those of similarly-aged controls regardless of stimulus consistency. In contrast, patients with HD demonstrated disproportionately longer RTs to inconsistent stimuli relative to their age-matched control group. Difference scores between RTs for inconsistent versus consistent stimuli were not correlated with overall level of dementia or disease severity for either the HD or PD group. These results provide further evidence for the heterogeneity of attentional dysfunction among subcortical degenerative illnesses.
Adult↗
Induction of remission in Wegener's granulomatosis with low dose methotrexate.
OBJECTIVE: To study the efficacy of methotrexate (MTX) plus low dose corticosteroids for induction of remission in generalized Wegener's granulomatosis (WG) and to possibly identify predictive factors for the outcome under this therapy. METHODS: We conducted a prospective, open label study, including 17 patients with not immediately life threatening, generalized WG. Treatment consisted of intravenous MTX 0.3 mg/kg once weekly plus daily oral low dose prednisone for initial diagnosis of WG in 11 and for a generalized relapse of WG in 6 patients. Interdisciplinary, standardized assessments of disease activity and extent were done 3-monthly. RESULTS: Within a median treatment period of 24.5 months remission could be achieved in 10/17 patients (59%), their median corticosteroid dose during that time was 1.75 mg/day. Seven patients with a median concomitant prednisone dose of 7.5 mg/day did not respond, among them 4 patients who were treated for a relapse of WG. Signs of de novo glomerulonephritis occurred in 5 of the 7 nonresponders. Significant side effects, including opportunistic infections, did not occur. CONCLUSION: Weekly low dose MTX in combination with low dose corticosteroids leads to an acceptable remission rate of almost 60% without significant side effects. Patients treated for a relapse of WG and patients with a need for a higher concomitant prednisone dose seem to be at risk for nonresponse, with a high likelihood of developing de novo glomerulonephritis.
Anti-Inflammatory Agents↗
Evaluation of the recombinant 38-kilodalton antigen of Mycobacterium tuberculosis as a potential immunodiagnostic reagent.
The diagnosis of infection caused by Mycobacterium tuberculosis is of increased public health concern following increases in the number of cases in developed countries and major increases in developing countries associated with the spread of human immunodeficiency virus (HIV) infection. The specificity of purified protein derivative skin testing for the detection of infection is compromised by exposure to environmental mycobacteria. Examination of sputum detects the most infectious patients, but not those with extrapulmonary disease. The 38-kDa antigen of M. tuberculosis contains two M. tuberculosis-specific B-cell epitopes. We overexpressed the gene for this antigen in Escherichia coli and evaluated the recombinant product in in vitro assays of T-cell function and as a target for the antibody response in humans. The sensitivity and specificity of the antigen as a skin test reagent were also assessed in outbred guinea pigs. We found that 69% of healthy sensitized humans recognize the antigen in vitro, as manifested by both cell proliferation and the production of gamma interferon. Untreated patients initially have a lower frequency of response (38%); this recovers to 72% during therapy. A total of 292 patients (20 with HIV coinfection) and 58 controls were examined for production of antibody to the 38-kDa antigen by using a commercially available kit. The sensitivity of the test in comparison with that of culture was 72.6%, and the specificity was 94.9%. The antigen was also tested for its ability to induce skin reactions in outbred guinea pigs sensitized by various mycobacterial species. The antigen provoked significant skin reactions in M. tuberculosis-, M. bovis BCG-, and M. intracellulare-sensitized animals. The significance of these findings and the usefulness of this antigen in immunodiagnosis are discussed.
AIDS-Related Opportunistic Infections↗
[ANCA-associated vasculitis. Wegener disease, microscopic poly-angiitis and Churg-Strauss syndrome].
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Antibodies, Antineutrophil Cytoplasmic↗
Therapy for the maintenance of remission in sixty-five patients with generalized Wegener's granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole.
OBJECTIVE: To compare the efficacy of low-dose intravenous (IV) methotrexate (MTX; 0.3 mg/kg once weekly), both with and without concomitant prednisone, versus daily oral trimethoprim/sulfamethoxazole (T/S; 160 mg of trimethoprim + 800 mg of sulfamethoxazole twice a day), with and without prednisone, in maintaining remission in patients with generalized Wegener's granulomatosis (WG). METHODS: In this study, 65 patients with generalized WG whose disease had entered remission with cyclophosphamide (CYC) and prednisone therapy were started on one of the following remission-maintenance regimens: MTX alone (group A; n = 22), T/S alone (group B; n = 24), MTX plus concomitant prednisone (group C; n = 11), and T/S plus concomitant prednisone (group D; n = 8). Clinical, radiographic, and seroimmunologic data were evaluated to assess the efficacy of the 4 regimens and to seek possible predictive factors concerning outcome in each group. RESULTS: Partial or complete remission was maintained in 86% of the patients in group A, but in only 58% of those in group B (P < 0.05). In group C, 91% of patients remained in remission, which is in sharp contrast to group D, in which all patients experienced a relapse after a median of 14.5 months (P < 0.005). Side effects occurred twice as often with MTX (n = 12) as with T/S (n = 6) treatment and could usually be resolved by supplemental folinic acid. Two patients taking MTX and 3 patients taking T/S were withdrawn from the study medication because of side effects. In none of the patients were the adverse effects life threatening. No statistically significant factors predictive of poor outcome emerged in any group. CONCLUSION: Low-dose MTX was found to be superior to T/S for the safe and effective maintenance of remission in patients with generalized WG. The use of concomitant prednisone was not associated with a worse outcome with MTX treatment. Since T/S, especially with concomitant prednisone, seemed to increase the chance of relapse, neither T/S alone nor T/S plus prednisone can be recommended for the maintenance of remission in patients with generalized WG.
Adolescent↗
Structure of recombinant human parathyroid hormone in solution using multidimensional NMR spectroscopy.
The solution structure of human parathyroid hormone, in the form of recombinant prolyl-hPTH(1-84), has been investigated by multidimensional NMR spectroscopy under conditions (aqueous trifluoroethanol) which favour the structured-state of the protein. Spin systems were identified from 3D 1H DQF (double-quantum filtered)-COSY and TOCSY spectra and sequence-specific assignments were from 2D 1H phase-sensitive NOESY spectra. Signal overlap was resolved in a 3D-NOESY-TOCSY spectrum and assignments were confirmed with 2D NOESY-15N-HMQC (heteronuclear multiple-quantum coherence) spectra taken of a sample universally labeled with 15N. A satisfactory set of final structures was calculated from the quantitative NOE data using restrained molecular dynamics and energy minimization calculations. The N-terminus is dominated by three, well defined helices between Ser-3 to Asn-10, Ser-17 to Lys-27 and Asp-30 to Leu-37, while the most significant structural features in the C-terminus are a short, less-well defined helix between Asn-57 to Ser-62 and a series of loose turns. These two terminal units are joined by an unstructured mid-region. The molecule shows a tendency towards tertiary structure, defined by a number of long-range NOEs. A detailed RMS deviation analysis allowed the final refined structures to be classified into a limited ensemble of stable conformations that reflect the inherent flexibility of the hormone in solution.
Amino Acid Sequence↗
Large-scale preparation and biological activity of recombinant human parathyroid hormone.
Human parathyroid hormone (hPTH) has been bacterially expressed in bioreactors as cro-beta-galactosidase-hPTH fusion protein. We have developed a large-scale purification scheme that exploits the pH-dependent differential solubility of hPTH and a two-step chromatographic procedure. We demonstrate that in a number of assay systems, the recombinant material obtained by this procedure is biologically active.
Animals↗