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Biomedical subjects

A Schultz

Publications and source records attributed to A Schultz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neurofilament is an autoantigenic determinant in myasthenia gravis.

Intratumorous expression of a 153-kd protein (p153), which contains an acetylcholine receptor-like epitope, is the only tumor marker described to date that significantly associates with thymoma in paraneoplastic myasthenia gravis (MG). Here, we report that p153 is identical to the midsize neurofilament, as verified by immunohistochemistry, immunofluorescence, and western blot analysis. Furthermore, the acetylcholine receptor-like epitope of the midsize neurofilament (NF-M) was identified by peptide epitope mapping. We also show, using T-cell proliferation assays, a significantly increased response of intratumorous T cells to a recombinant midsize neurofilament fragment in thymoma patients with MG compared with MG patients with thymic follicular hyperplasia or thymoma patients without MG. The T cells of thymic follicular hyperplasia and thymoma patients without MG seem to be unresponsive to NF-M. In contrast, we found increased T-cell responses to recombinant acetylcholine receptor fragments in MG patients in general compared with non-MG patients. Increased T-cell responses to NF-M in patients with paraneoplastic MG might be the result of an abnormal positive selection of immature T cells within thymomas, caused by the expression of NF-M in neoplastic thymic epithelial cells. Our results offer further evidence that NF-M expression in thymomas is an autoantigenic determinant in MG.

Epitopes↗
PubMed1999

Mental health, psychosocial functioning, and quality of life in patients with bladder exstrophy and epispadias - an overview.

Although there has been only limited clinical research on mental or psychosocial implications in patients with bladder exstrophy and epispadias, questions have been raised as to whether their life is of such questionable quality that a termination of pregnancy should be considered. A systematic overview of outcome studies published over the past three decades was carried out. In all, 1208 abstracts and 52 papers were read; only 10 (0.8%) papers focused on the mental or psychosocial outcome, but with diverse findings. However, most of the studies suffered from serious methodological deficiencies. Physical, mental, and psychosocial problems revealed in studies with reliable and valid instruments have clinical implications and underline the need for the further development of surgical and psychosocial interventions. Multicenter studies with a multimodal, prospective, and longitudinal design, based on semistructured interviews and specific questionnaires related to the disorder, are appropriate.

Abortion, Therapeutic↗
PubMed1999

Etiology and incidence of pressure ulcers in surgical patients.

This experimental study was designed to identify the etiology of pressure ulcers in a surgical sample and to evaluate a special OR mattress overlay in preventing pressure ulcer development. Surgical patients (N = 413) were randomized to receive "usual perioperative care" or the new mattress overlay. Over six postoperative days, 89 patients (21.5%) developed pressure ulcers, primarily stage I. Only 2% developed stage II or IV ulcers. Patients with ulcers were statistically older, had diabetes, were smaller in body mass, had lower Braden Scale scores on admission, and used the new mattress overlay (P < .02). Pressure ulcers that presented as "burns" or ecchymosis did not deteriorate to stage III or IV ulcers during the study. The mattress overlay was not effective in preventing pressure ulcer development.

Age Factors↗
PubMed1999

Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies.

OBJECTIVES: To determine the efficacy and safety of fixed-dose oral sildenafil in patients with erectile dysfunction (ED) of various etiologies. METHODS: In a 12-week, double-blind, randomized, placebo-controlled, fixed-dose study, 514 men (mean age 56 years) with ED were randomized to receive 25, 50, or 100 mg of sildenafil or placebo. The primary etiology of ED was determined to be organic in 32% of men, psychogenic in 25%, or mixed in 43%. Sildenafil or placebo was taken in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of the IIEF, a global efficacy question, event log data, and a partner questionnaire. RESULTS: Sildenafil significantly increased patients' ability to achieve and maintain erections (P <0.0001), with efficacy increasing with increasing dose. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction, and overall sexual satisfaction (P <0.0001). The proportion of subjects who felt that treatment with sildenafil improved their erections was significantly greater (67% to 86%) than that with placebo treatment (24%, P <0.0001). The proportion of successful attempts at sexual intercourse also increased significantly with sildenafil treatment (P <0.001). Partner responses corroborated patient reports. Sildenafil was well tolerated at the three doses studied. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for ED of various etiologies.

Administration, Oral↗
PubMed1999

Persistence of haloperidol in human brain tissue.

OBJECTIVE: After discontinuation of neuroleptic drugs, their antipsychotic and antiparkinsonian effects are still present for a prolonged period. It is not known whether the extended effects of neuroleptic drugs in humans are due to the continued presence of drug in brain tissue or to long-lasting drug-induced physiologic changes. The aim of this study was to directly examine haloperidol concentrations in human brain tissue in relation to drug-free time. METHOD: Haloperidol concentrations were measured in five regions (temporal cortex, cingulate gyrus, caudate nucleus, dentate nucleus, corpus callosum) of the postmortem brains of 11 patients previously treated with haloperidol. Haloperidol was analyzed by means of high-performance liquid chromatography with ultraviolet detection. The half-life in brain tissue was estimated by a population kinetic analysis. RESULTS: Haloperidol concentrations in the human brain tissue were 10-30 times higher than optimal serum concentrations used in the treatment of schizophrenia. Haloperidol concentrations appeared to be homogeneously distributed across different brain areas within a single patient. There was no apparent relation between duration of treatment and mean haloperidol concentration. Higher doses of haloperidol seemed to be related to higher concentrations in brain tissue. The elimination half-life from brain tissue was calculated to be 6.8 days. CONCLUSIONS: The results may have implications for clinical treatment decisions and the design of clinical research protocols. Patients exposed to haloperidol cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.

Antipsychotic Agents↗
PubMed1999

Metabolic evaluation and medical management of upper urinary tract stone disease. Guidelines from the Scandinavian Cooperative Group for Urinary Stones.

A set of simple guidelines for metabolic evaluation and medical/dietary management of patients with urolithiasis is presented. The evaluation scheme is based on the documented risk factors in the Nordic area and the results of controlled clinical trials, and takes its basis in the severity of the stone disease in the individual stone patient. The initial evaluation in all patients aims at diagnosing conditions with a definitive metabolic, infectious or anatomical/functional cause of stone formation (MIAF urolithiasis). Patients with MIAF urolithiasis are treated according to the nature of the underlying disease. Having excluded/diagnosed MIAF urolithiasis, patients with idiopathic calcium nephrolithiasis remain, and in this group, which comprises approximately 85% of the total stone population in the Scandinavian region, only those with a complicated stone disease are subjected to additional evaluation, which aims at identifying underlying pathophysiological derangements for which medical therapy has been proven to be effective in controlled clinical trials.

Dietary Proteins↗
PubMed1998

A pyrophosphate synthase gene: molecular cloning and sequencing of the cDNA encoding the inorganic pyrophosphate synthase from Rhodospirillum rubrum.

The integrally membrane-bound, proton-pumping inorganic pyrophosphate (PPi) synthase in phototrophic bacteria is hitherto the only described alternative to the ATP synthase in biological electron transport phosphorylation. We have identified and sequenced the first gene coding for a pyrophosphate synthase. The deduced protein contains 660 amino acid residues and 15 putative membrane-spanning segments. It is homologous to the vacuolar pyrophosphatases from plants.

Amino Acid Sequence↗
PubMed1998

Somatic function, mental health and psychosocial functioning in 22 adolescents with bladder exstrophy and epispadias.

PURPOSE: We report the long-term somatic outcome, mental health and psychosocial adjustment in adolescents with bladder exstrophy and epispadias. MATERIALS AND METHODS: A total of 22 adolescents 11 to 20 years old (median age 14.5), including 19 with bladder exstrophy and 3 with epispadias, were assessed for urogenital status, stoma, renal and bowel function, anorectal physiology, mental health and psychosocial functioning by physical examinations, semistructured interviews and standardized questionnaires. The parents of 21 patients were interviewed and completed questionnaires. Information was also obtained on control groups. RESULTS: Of the 22 patients 9 (41%) had no urinary diversion and were urinary incontinent, 6 (27%) had persistent fecal staining and anal canal pressures that were lower than the controls, 10 (59%) were dissatisfied with the penile appearance and 11 (50%) met the criteria for psychiatric diagnoses. The main predictors of mental health were parental warmth and patient genital appraisal in the 11 to 14-year age group, and parental warmth and urinary continence function in the 15 to 20-year age group. Psychosocial dysfunction was predicted by fecal incontinence in the younger group and worries about future sexual relationships in the older group. CONCLUSIONS: The present multimodal outcome study revealed that adolescents with bladder exstrophy and epispadias had significant physical and mental problems. Genital malformation, and urinary and fecal incontinence may have a negative impact on mental health and psychosocial functioning. Our findings emphasize the need to include psychosocial experts on health care teams to reveal the amount of distress caused by these anomalies and to offer psychosocial support.

Adolescent↗
PubMed1998

CD40 ligand and autoantigen are involved in the pathogenesis of low-grade B-cell lymphomas of mucosa-associated lymphoid tissue.

Low-grade MALT-type lymphomas are malignancies of mucosal marginal-zone B cells and preceded by reactive inflammatory lymphoid tissue. Experimental observations suggest that antigen and CD40 Ligand act during cognate T/B cell interaction and are crucial for germinal center B-cell maturation generating marginal-zone B cells. To investigate the mechanisms underlying the development of extranodal MALT-type lymphomas, the immunoglobulin receptor was sequenced and analyzed for antigen specificity using heterohybridoma technology. Furthermore, CD40 ligand expression was evaluated by immunohistochemistry and by semiquantitative RT-PCR, and ligand binding to the CD40 of tumor B cells was studied using the CD40 system. Hypermutations were found in low-grade lymphomas throughout CDR1-CDR3 suggestive of positive selection through their antigen receptor. Different VH families were used and more than 69% of tumor immunoglobulins bound different mucosal antigens. CD40L expression was found in the tumor marginal zone in substantial amounts. The in vitro proliferation response of all low-grade MALT-type lymphomas was dependent on anti-CD40-mediated signals and cytokines. Our data provide evidence that autoantigen as well as the CD40L expressed by activated nonneoplastic T cells may drive the evolution of low-grade MALT-type lymphomas either directly or by paracrine mechanisms and that antigen may contribute to lymphoma pathogenesis.

Animals↗
PubMed1998

Paraneoplastic autoimmunity in thymus tumors.

Autoimmune phenomena are more frequent in thymic epithelial tumors (TET) than in any other human tumor. Mysthenia gravis (MG) is by far the most common autoimmune disease in thymoma patients. MG is characterized by muscle weakness due to autoantibodies against the acetylcholine receptor (AChR), and CD4+ AChR-specific T cells play a pivotal role for the production of these autoantibodies. About 10% of MG patients have a thymoma and, interestingly, only such thymomas exhibit an MG association that maintains thymuslike morphological and functional features with respect to the homing and differentiation of immature T cells. Since AChR protein is not expressed in thymomas, the specificity of the autoimmunity in thymoma-associated MG is thought to be determined by nonreceptor proteins with AChR epitopes. Such proteins are overexpressed in cortical-type MG-associated thymomas, and medullary thymomas express these proteins at barely detectable levels. Aside from this quantitative difference, the pathogenesis of anti-AChR autoimmunity might be qualitatively different in these thymoma subtypes. Our findings suggest that an antigen-specific abnormal T-cell selection by cortical-type TET may contribute to the pathogenesis of paraneoplastic MG. In contrast, an abnormal (intratumorous) activation of autoreactive T cells may be operative in medullary thymomas.

Adolescent↗
PubMed1998

Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas.

To gain insight into the pathogenesis of thymoma-associated myasthenia gravis, thymocyte maturation was investigated in mixed and cortical thymomas by three-color flow cytometry. Although we detected cells at all recognizable stages, we noted an unusual increased percentage of early CD4+/CD3- thymocytes--especially in mixed thymoma--and a pronounced decreased percentage of mature CD4+/CD3+ cells in cortical thymomas as well. The percentage of CD3+/CD69+ cells that arose after positive selection was reduced in both thymoma subtypes compared with control thymuses, which suggests differences in the rate or efficiency of positive selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas were not activated in situ as shown by the absence of CD25 expression. After stimulation with recombinant human acetylcholine receptor alpha-subunit fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more strongly than those from controls, regardless of whether the donors were myasthenic. Responses of residual thymus cells to tetanus toxoid correlated well with those of autologous blood T cells, whereas those from the thymomas clearly did not--implying minimal colonization of thymomas by mature recirculating T cells. In conclusion, our results show that cortical and mixed thymomas exhibited differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating naive but potentially autoaggressive T cells; in some thymomas, these cells may then be actively immunized inside the tumor.

Autoantigens↗
PubMed1998

Encouraging vaccine results from primate models of HIV type 1 infection.

Challenge studies in primates have established that vaccine-induced protection against immunodeficiency viruses, even against mucosal routes of challenge, is attainable, and that "sterile" immunity is not required for protection. Intelligent use of such studies in primate models, coupled with in vitro measurements of immunity, is the best tool for establishing which vaccine concepts have promise.

AIDS Vaccines↗
PubMed1997

Psychometric analysis of the Functional Assessment of Cancer Therapy-General (FACT-G) scale in a rural sample.

BACKGROUND: Quality of life for persons with cancer has been studied extensively in urban populations. The Functional Assessment of Cancer Therapy-General (FACT-G) scale was developed for use in clinical trials. The authors tested the psychometric properties of the FACT-G scale in a sample of rural cancer patients. METHODS: A systematic replication of the 1993 study by Cella et al., in which FACT-G was developed, was employed to assess the reliability, validity, and factor structure of the scale. RESULTS: The reliability and validity of the FACT-G scale for evaluating rural cancer patients was determined to be sufficient for research purposes. The factor structure was the same as that reported by Cella et al. CONCLUSIONS: The FACT-G scale is appropriate for use in studies of the quality of life of rural cancer patients.

Aged↗
PubMed1997

Pathogenesis of myasthenia gravis.

Various studies over the last 25 years in Man and animal models have revealed many steps in the pathogenesis of myasthenia gravis (MG) which is now considered the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. Though not a disease entity, MG is associated with pathological alterations of the thymus in about 80% of cases. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and probably involves AChR on myoid cells as the triggering (myasthenogenic) antigen. Genetic factors contribute essentially to the pathogenesis of this form of MG. In thymoma-associated MG genetic factors are probably of marginal significance. Neither intratumour autoantibody production nor T cell activation seem to occur and the AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that share epitopes with the AChR and other auto-antigen targets in paraneoplastic MG are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of most MG cases take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. Where these initial steps occur in MG cases without thymic pathology is not known. Likewise, the factors involved in the initial triggering of MG remain enigmatic in all MG subtypes.

Adolescent↗
PubMed1997

Intrinsic rectification of ion flux in alamethicin channels: studies with an alamethicin dimer.

Covalent dimers of alamethicin form conducting structures with gating properties that permit measurement of current-voltage (I-V) relationships during the lifetime of a single channel. These I-V curves demonstrate that the alamethicin channel is a rectifier that passes current preferentially, with voltages of the same sign as that of the voltage that induced opening of the channel. The degree of rectification depends on the salt concentration; single-channel I-V relationships become almost linear in 3 M potassium chloride. These properties may be qualitatively understood by using Poisson-Nernst-Planck theory and a modeled structure of the alamethicin pore.

Alamethicin↗
PubMed1997

Characterization of the human thymic microenvironment: lymphoepithelial interaction in normal thymus and thymoma.

Recent advances in tissue culture technology and molecular biology have extended our understanding of the functional morphology of the thymus. The importance of a crosstalk between lymphoid cells and stroma has been appreciated as a prerequisite for the normal development of both. The network of direct cellular interactions and soluble factors comprising part of the microenvironment is far from being elucidated but the highly ordered thymic architecture clearly plays a pivotal role in normal thymic function. Insight into the genetic control of stroma development is only emerging while knowledge on the genetic control of the various steps in T cell development is already advanced and rapidly expanding. The present paper gives an overview on the cellular components and matrix molecules of the human thymic microenvironment and their development during ontogeny. The intrathymic cytokine network is shortly reviewed. Special emphasis is put on molecules mediating lymphoepithelial interactions that are necessary for the expansion and early selection of immature thymocytes from precursor cells and for the generation of an MHC restricted and self tolerant T cell repertoire by positive and negative selection. Considering these physiological mechanisms we summarize the molecular pathology of the microenvironment and lymphocyte/stroma interactions in thymic epithelial tumors (thymomas). Finally, a pathogenetic model for paraneoplastic myasthenia gravis is given. We suggest abnormal auto-antigen-specific positive selection of naive T cells as the essential molecular mechanism by which thymomas contribute to the autoimmunization against the acetylcholine receptor and other muscle proteins.

Apoptosis↗