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Biomedical subjects

A Schultz

Publications and source records attributed to A Schultz.

At least 37 records · Page 2Linked to original sources

Resistance of previously infected chimpanzees to successive challenges with a heterologous intraclade B strain of human immunodeficiency virus type 1.

To test whether the protective effects of attenuated simian immunodeficiency virus vaccines in macaques were applicable to the human immunodeficiency virus type 1 (HIV-1)-chimpanzee system, two groups of animals, previously infected with HIV-1(IIIB) or HIV-1(SF2) were each challenged with a heterologous clade B virus, HIV-1(DH12). Following challenge, the parameters measured included virus isolation (from plasma, peripheral blood mononuclear cells, and lymph node tissue); quantitative DNA PCR using primers capable of distinguishing HIV-1(IIIB), HIV-1(SF2), and HIV-1(DH12) from one another; and serologic assays to monitor changes in binding and neutralizing antibodies. In contrast to an HIV-1-naive chimpanzee that rapidly became infected following the inoculation of HIV-1(DH12), the two chimpanzees previously infected with HIV-1(IIIB) resisted repeated and escalating inoculations of HIV-1(DH12), as monitored by virus isolation and PCR. The two animals previously infected with HIV-1(SF2) became infected with HIV-1(DH12) but in contrast to the case with the HIV-1-naive chimpanzee, no cell-free viral RNA was detected in the plasma by the branched DNA procedure and levels of peripheral blood mononuclear cell-associated viral DNA were reduced 35- to 50-fold.

AIDS Vaccines

Interventional radiologic procedures with CT guidance in cancer pain management.

Reduction of pain without systematic side effects can be achieved in advanced stages of cancer with precise percutaneous techniques guided with computed tomography (CT). CT guidance allows exact needle positioning, reducing complications and improving the results. Regional analgesia with neurolytic block (neurolysis) is achieved by injection of alcohol or phenol and involves intentional destruction of a nerve or nerves to interrupt nociceptive pathways for weeks or months. Percutaneous alcoholization of bone metastasis is indicated in patients with painful, severe, osteolytic bone metastasis if conventional anticancer therapy is ineffective and high doses of opiates are necessary to control pain and when rapid pain relief is necessary. Bone packing with acrylic glue (methyl methacrylate) is used to prevent pathologic fractures and pain in patients with vertebral body tumors and acetabular metastasis. With these techniques, the radiologist is able to play an active role in pain management and in improving the quality of life of patients with malignancies.

Bone Cements

Expression of neurofilaments and of a titin epitope in thymic epithelial tumors. Implications for the pathogenesis of myasthenia gravis.

Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.

Adolescent

Regulation of rat kidney mesangial cell phospholipase A2.

1. The precursor of eicosanoids is arachidonic acid, which emanates from the cleavage of the sn-2 position of phospholipids by phospholipase A2 (PLA2). Eicosanoids have diverse physiological and pathophysiological effects in the kidney. The regulation of phospholipase A2 has important implications for kidney function. 2. In the current communication we focus our attention on mesangial cell cytosolic PLA2 (cPLA2) and its regulation at the post-translational and post-transcriptional level. 3. At the post-translational level, using site directed mutagenesis of cPLA2 and a dominant negative ras, we have demonstrated that cPLA2 can be phosphorylated by mitogen activated protein (MAP-2) kinase leading to increased cPLA2 enzymatic activity. 4. At the post-transcriptional level we show that the half-life of cPLA2 mRNA in mesangial cells is significantly increased when mesangial cells are stimulated by mitogens. We further demonstrate the presence of three ATTTA motifs in the 3' untranslated region (3' UTR) of the cPLA2 cDNA. 5. Using chimeric constructs bearing the 3' UTR from rat cPLA2 fused downstream of the luciferase reporter, we demonstrate that this region exerts a destabilizing effect on cPLA2. 6. We have isolated and mapped genomic DNA and polymorphic markers for cPLA2 in the human and rat.

Animals

Continent urinary diversion in patients with dysfunction of the lower urinary tract. Experience with the detubularized right colonic segment as urinary reservoir.

The experience with a continent urinary diversion in patients with dysfunction of the lower urinary tract is reported. The right detubularized colonic segment was used as urinary reservoir and an intussucepted ileal valve as outlet. Thirty seven patients were studied with a mean followup of 37 months. All patients except one were continent with a well-functioning diversion. The kidney function was not reduced in any of the patients and the acid-base balance was within normal limits. Twelve patients (32%) had had complications resulting in surgical revision. The majority were simple corrections, but 3 patients experienced a spontaneous perforation of the reservoir needing emergency laparotomy.

Adult

Arterial high flow priapism role of radiology in diagnosis and treatment.

Radiological methods for diagnosis and treatment of arterial high flow priapism are described based on experience with 7 patients, 6 with lesions of the cavernous and 1 with a lesion of the spongious body and glans. Arteriography (7 patients) and cavernosography (6 patients) indicated the site of the lesion in all cases. Color Doppler was useful in the two patients examined. Embolisation was successfully performed in 4 patients and resulted in complete or partial detumescence in all Two patients had a 10 year history without complete loss of erectile function. They had markedly dilated veins at cavernosography, and one responded favorably to venoablative surgery.

Adult

Myasthenia gravis.

Myasthenia gravis (MG) is the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. It is almost invariably associated with pathological alterations of the thymus. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis B cells are increased in the medulla forming germinal centers or diffuse B cell infiltrates. Intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and involves AChR on myoid cells as the triggering (myasthenogenic) antigen. In thymomas no intratumorous immune reaction occurs and the AChR is not the myasthenogenic antigen. Instead, an abnormal neurofilament that shares epitopes with the AChR is expressed in thymomas and may trigger AChR-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of MG take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. The etiology of MG remains enigmatic.

Adolescent

[CD40 as a mediator of proliferation in normal ans neoplastic thymic epithelium].

AIMS AND METHODS: While CD40 is a costimulatory molecule of utmost importance for B-cell proliferation and Ig class switch its role has not been elucidated in the human thymus and in thymic epithelial tumors. To investigate, whether CD40 is functionally active there, we investigated the proliferative response by 3H-Thymidin incorporation of primary normal and neoplastic thymic epithelial cell cultures to CD40 triggering by soluble CD40 ligand (CD40L). RESULTS: Normal thymic epithelial cells exhibited proliferation in response to CD40 ligand in a dose dependent manner, while a CD40 ligand specific monoclonal antibody prevented this effect. This response was not significantly different from the response of neoplastic thymic epithelial cells derived from myasthenia gravis-associated thymomas. CONCLUSION: Our data demonstrate that CD40 is expressed on the surface of normal and neoplastic epithelial cells of the thymus and is a functional molecule in terms of epithelial cell proliferation in vitro. Given the differential expression of CD40 in the various histological thymoma subtypes in vivo, the finding suggests a role of CD40 in the different mechanisms of tolerance breakdown in thymomas.

Antigens, CD

[Abnormal T cell maturation in myasthenia gravis associated thymomas].

AIMS AND METHODS: Paraneoplastic myasthenia gravis is a thymoma-associated autoimmune disease, characterized by autoantibodies against the acetylcholine receptor (AChR). CD4+ AChR-specific T cells play a pivotal role in the production of autoantibodies. However, it is not known how the tumor is involved in the pathogenesis of autoimmunity. To address this question thymocyte maturation was followed in medullary, mixed and cortical thymomas using three-color FACS analysis. RESULTS: Compared to normal thymuses medullary thymomas were almost devoid of immature T cells and most intratumorous lymphocytes appeared to be of peripheral origin. In mixed and cortical thymomas maturation of thymocytes took place from the most immature precursors to thymomcytes with a mature phenotype. Only in the latter tumor subtypes immature CD4+/CD8-/CD3-thymocytes were significantly increased. In addition, a reduced production of mature CD4+ T cells suggests ineffective positive selection. Activated T cells were present in one medullary but none of the mixed or cortical thymomas. CONCLUSION: Each histological thymoma subtype is associated with a characteristic defect of T cell maturation. The contribution of medullary thymomas to the pathogenesis of myasthenia gravis (MG) might be a pathological intratumorous T cell activation. By contrast, an abnormal antigen-specific T cell selection may be the contribution of cortical and mixed thymomas to anti-AChR autoimmunity.

Antigens, CD

[Molecular mimicry between neurofilaments and titin as the basis for autoimmunity towards skeletal muscle in paraneoplastic myasthenia gravis].

AIMS AND METHODS: Autoantibodies against striated muscle proteins, particularly titin, characteristically distinguish thymoma-associated from non-paraneoplastic myasthenia gravis (MG) patients. However, the stimulus for this autoimmunity remains enigmatic since whole titin is not detectable in these tumors. Since Neurofilaments (NF) contain titin epitopes, MG-associated thymomas were investigated for NF expression using immunohistochemistry and Western blotting. RESULTS: In thymomas with cortical differentiation many of the neoplastic epithelial cells expressed medium molecular weight NF at the protein level. In sharp contrast, in medullary and mixed thymomas and in normal thymuses immunoreactivity with anti-NF antibodies was rare. CONCLUSION: The overexpression of NFs with titin epitopes by neoplastic cells in an inappropriate cortical environment may be the basis for the autosensitization of developing T-cells against titin in MG-associated cortical type thymomas.

Autoantibodies

Transmembrane signaling in kidney health and disease.

Transmembrane signal transduction is the process whereby a ligand binds to the external surface of the cell membrane and elicits a physiological response specific for that ligand and cell type. It is now appreciated that numerous disease states represent disturbances in normal transmembrane signaling mechanisms. In the current paper, we focus our attention on the mesangial cell of the glomerular microcirculation as a prototypical model system for understanding normal and abnormal transmembrane signaling processes. Among the major receptor and effector mechanisms for transmembrane signal transduction in the mesangial cell, this paper emphasizes the phospholipase effector response to growth factors and vasoactive hormones. The post-translational and transcriptional pathways for regulation of phospholipase C and phospholipase A2 are described, including consideration of perturbations in these systems that characterize two disease models, namely: acute cyclosporine nephrotoxicity and early diabetic glomerulopathy.

Animals

[Changes with age in EEG during anesthesia].

The number of older persons who have to undergo surgical procedures is steadily growing. For these patients the risks of anaesthesia are often increased because of their past medical history and their restricted physiological resources. Apart from parameters of the cardiovascular system, the electroencephalogram (EEG) represents a supplementary method for intraoperative monitoring, because cerebral alterations caused by anaesthetics or narcotics are directly reflected in the EEG. In routinely conducted registrations of the EEG in the operating theatre it appeared that the EEG of older persons differed from the EEG of younger patients. The aim of the present study was to further investigate the effect of patients' age on the EEG during anaesthesia. METHODS. Three data sets from different EEG registrations were analysed. The first data set consisted of inductions of anaesthesia with 7 mg/kg body weight thiopental in 43 patients from 17 to 80 years of age (mean 53.6 +/- 16.7 years) using derivations C3-P3 and Cz-A1. The second data set included 69 EEG registrations of general anaesthesia induced with barbiturates and maintained with enflurane in patients from 16 to 83 years (mean 51.4 +/- 17.7 years). The third data set comprised inductions of anaesthesia with 2 mg/kg body weight propofol. EEGs of the second and third data set were recorded with the EEG monitor 'Narkograph' using derivation C3-P3 and derivations C3-P3/C4-P4, respectively. Classification of the EEGs was performed according to the proposals of Kugler [12]. The basis for the statistical analysis of all data sets was formed by parameters from the power spectra of the EEG recordings. RESULTS. The data from inductions of anaesthesia with thiopental and propofol showed EEG patterns from alpha-EEG to burst suppression activity, whereby periods with burst suppressions could more often be observed in the EEG of older people. Under thiopental burst suppression activity occurred in 20% of patients up to 50 years, in 47% of those between 50 and 70 years and in 89% over 70 years. The corresponding figures for propofol were 0%, 5% and 54%, respectively. Figure 2 depicts the correlation between age and power for the thiopental data. The power decreases with increasing age of the patients. This result led to further investigations of the effect of patients' age on the power in different EEG stages. Of special interest were deep stages of anaesthesia, because especially in these stages visual inspections revealed smaller amplitudes of the EEG signal for older patients than for younger persons. Figure 3 shows the power in the delta frequency band in deep stages of barbiturate-induced enflurane anaesthesia for patients of different age groups. The power in the delta frequency band distinctly decreases for geriatric patients. The same effect could be observed for the propofol data (Fig. 4). CONCLUSIONS. The EEG represents an important method for effective intraoperative monitoring and contributes to an individually adjusted course of anaesthesia, especially for geriatric patients. In these patients, clinical signs such as parameters of the cardiovascular system, which are usually used to judge the depth of anaesthesia, are often altered by the patient's past medical history or by drugs. Furthermore, geriatric patients show a reduced need for narcotic agents. However, the variation of the required dosage is greater in older than in younger persons. The results of the present study show that with regard to an automatic classification of the EEG during anaesthesia, alterations of the EEG with age have to be taken into account.

Adolescent

[Channel selection for EEG-monitoring in anesthesia].

The conventional multichannel electroencephalogram is quite inconvenient for long-term monitoring in the operating theatre or intensive care unit. Recording of the EEG would be easier if a small number of channels was sufficient. Aiming at reduction of channels, leads from different regions of the scalp were analysed visually and with regard to their spectral content. METHODS. Electrode placements corresponded to the International 10/20 System (Fig. 1). EEG recordings were made with a conventional device (ES 12,000), a personal computer, and a spectral analyser. TWO-CHANNEL RECORDINGS. Retrospective analysis was performed on data from 392 patients (age 14-90 years) whose anaesthesia was induced with various anaesthetics/narcotics, for instance thiopental, ketamine, etomidate, halothane, and enflurane. The EEG was recorded using C3-P3 and Cz-A1. For each patient the changes of spectral parameters during the course of the induction were plotted and visually analysed. For statistical analyses a 30-s epoch of each patient was randomly selected from the first few minutes after the beginning of induction. TEN-CHANNEL RECORDINGS. In ten gynaecological patients (age 26-55 years) EEG recordings were performed during induction of anaesthesia with thiopental in combination with fentanyl, N2O and O2. The set of channels consisted of Fz'-Cb1, F3'-Cb1, Cz-Cb1, C3-Cb1, P3-Cb1, Oz-Cb1, Fz'-F3', F3'-C3, C3-P3, and P3-Oz. The electrodes Fz' and F3' were positioned on the forehead near to Fz and F3, respectively. These sites were chosen because they allow easy application of electrodes. The relationship between channels was calculated with Bravais-Person's coefficient of correlation for the power and the absolute power in the frequency bands delta (0.5-3.5 Hz), theta (3.5-7.5 Hz), alpha (7.5-12.5 Hz), and beta (> 12.5 Hz). RESULTS. In visual and statistical analyses of the two- and ten-channel recordings under the influence of anaesthetics/narcotics, similar changes of EEG activity could be observed in all channels. Although differences in the absolute power of the frequency bands were present, there was high conformity in the composition of the spectral content of the different channels. Classification of the EEG into stages of anaesthesia by means of a single channel led to consistent results for all channels. Alpha activity as leading feature of the awake state predominated occipitally. In channels including the region around the ears, contamination with EKG artifacts was observed. CONCLUSIONS. EEG patterns under the influence of different anaesthetics/narcotics are adequately represented by a reduced number of channels. For the choice of an appropriate set of channels the following aspects should be considered. Contamination with artifacts should be as low as possible, electrode sites should easily be accessible, and special features of the awake state should be identifiable. Experience with routinely conducted EEG recordings in the operating theatre and the intensive care unit showed that the channels C3-P3 or C4-P4 provide a sufficient basis for automatic staging of the depth of anaesthesia, which is implemented in the EEG monitor Narkograph.

Adolescent

A PC program for unbiased and predictive linear and quadratic discriminant analysis.

Discriminant analysis plays an important role in biological and medical research. The most popular methods of discrimination in practical applications are parametric methods like linear and quadratic discriminant analysis. However, there exist modifications of these approaches, namely unbiased and predictive discriminant analysis, which lead to reduced error rates in certain situations. In this paper a menu-driven, user-friendly PC program written in Borland Pascal 7.0 is introduced which performs unbiased and predictive linear and quadratic discriminant analysis.

Bias

A new system for descriptive classification of stones in the upper urinary tract.

A descriptive classification is proposed to stratify upper urinary tract stones by their number, size and location. The system considers the minimal but most important factors regarding the choice of surgical treatment and its success. Its principle is adaptable to more complex staging systems already existing. Practical use of the system has shown it to reflect clinical events, and its simplicity offers an opportunity for compliance in routine clinical study. It facilitates easy computerized stratification of stones in the upper urinary tract.

Humans

Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo.

Fresh human immunodeficiency virus type 1 (HIV-1) isolates from patients with AIDS were screened for infectivity in chimpanzee peripheral blood mononuclear cells (PBMC) to identify strains potentially able to generate high virus loads in an inoculated animal. Only 3 of 23 isolates obtained were infectious in chimpanzee cells. Of these three, only one (HIV-1DH12) was able to initiate a productive infection in PBMC samples from all 25 chimpanzees tested. HIV-1DH12 tissue culture infections were characterized by extremely rapid replication kinetics, profound cytopathicity, and tropism for chimp and human PBMC, primary human macrophage, and several human T-cell lines. An infection was established within 1 week of inoculating a chimpanzee with 50 50% tissue culture infective doses of HIV-1DH12; cell-free virus was recovered from the plasma at weeks 1, 2, and 4 and was associated with the development of lymphadenopathy. Virus loads during the primary infection and at 6 months postinoculation were comparable to those reported in HIV-1-seropositive individuals.

Acquired Immunodeficiency Syndrome

What is health promotion?

With change abounding in Canada's health care system, nurses must redefine their roles. One role is in health promotion, a field where nurses have created a unique identity for themselves. But before advocating, the concept must be fully understood.

Health Care Reform

The outcomes of elective laparoscopic and open cholecystectomies.

BACKGROUND: The demand for evidence of effectiveness for medical care has prompted the development of epidemiologic approaches to relating the outcomes of care to treatment. This study compares the outcomes of care for patients undergoing the newly introduced laparoscopic cholecystectomy with the results from conventional open cholecystectomies. METHODS: Consecutive cases of elective cholecystectomy from 35 hospitals (all of the metropolitan and selected rural hospitals in Minnesota) were enrolled in the study. Patients were interviewed on admission to establish baseline symptoms and functional status and to confirm risk factors. Their medical records were abstracted to yield information on risk factors, treatment, and hospital complications. To establish outcomes, patients were sent a questionnaire about their symptoms and functional status six months postoperatively. RESULTS: Of 3,448 patients studied, 2,490 (72 percent) had a laparoscopic procedure, including 195 cases that were converted to open cholecystectomies. Functional status data were obtained on 2,481 cases (76 percent). Laparoscopic operation was associated with more operative complications (odds ratio 3.02, p < 0.001), but with fewer general complications (odds ratio 0.32, p < 0.001). The mean time to return to work was 15 days for laparoscopic cases compared to 31 days for open procedures (p < 0.001). The only functional outcome difference between the two procedures was that patients who underwent laparoscopic cholecystectomies were more likely than those with conventional cholecystectomies to be able to perform their usual activities at follow-up evaluation (p < .001). There was evidence of a learning curve; the more laparoscopic procedures a surgeon performed, the fewer the operative (p < 0.01) and general (p < 0.0001) complications. There was no indication that the availability of laparoscopic operation was associated with more operations being performed. CONCLUSIONS: Laparoscopic operation seems to represent a significant advance in getting patients back to a normal life sooner. More attention needs to be given to which patients are most likely to benefit from cholecystectomy of either type. Epidemiologic approaches can be useful in assessing the effectiveness of care. Partnerships between providers and researchers can produce useful effectiveness data by supplementing available clinical records with more detailed outcome data.

Cholecystectomy