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Biomedical subjects

M Riedel

Publications and source records attributed to M Riedel.

At least 55 records · Page 3Linked to original sources

The immune system and schizophrenia. An integrative view.

Immune alterations in schizophrenia have been described for decades. Modern immunological methods and new insights into the highly developed and functionally differentiated immune system allow an integrative view of both the older and the recent findings of immunological abnormalities in schizophrenia. Both the unspecific and the specific arms of the immune system seem to be involved in the dysfunction of the immune system in schizophrenia. The unspecific, "innate" immune system shows signs of overactivation in unmedicated schizophrenic patients, as indicated by increased monocytes and gamma delta-cells. Increased levels of interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of monocytes/macrophages, too. On the other hand, several parameters of the specific cellular immune system are blunted, such as, for example, the decreased T helper-1 (TH-1)-related immune parameters in schizophrenic patients both in vitro and in vivo. It seems that a TH-1-TH-2 imbalance with a shift to the TH-2 system is associated with schizophrenia. During antipsychotic therapy with neuroleptics, the specific TH-1-related immune answer becomes activated, but in addition the B cell system and antibody production increase.

Humans↗

Predictors of tracheobronchial invasion of suprabifurcal oesophageal cancer.

BACKGROUND: Factors possibly predicting airway invasion of oesophageal cancer in the absence of frank oesophagotracheal fistulas have not been studied. OBJECTIVES: To identify possible predictors of airway invasion by oesophageal cancer that are readily accessible in the preoperative setting. METHODS: We prospectively investigated 148 patients with newly diagnosed oesophageal cancer located at or above the level of the tracheal bifurcation and without any evidence of oesophago-respiratory fistulas or distant metastases. Demographic variables, respiratory parameters, results of bronchoscopy and other staging procedures (oesophagoscopy, swallow oesophagography, endosonography, CT and histology) and findings at surgery were compared between the patients with (n = 30) and without (n = 118) proven airway invasion and entered into a stepwise logistic regression model to evaluate their independent predictive roles. RESULTS: Univariate analysis indicated that the incidence of airway invasion increased with the presence of suspect CT findings, the presence of respiratory symptoms, tumour length, T stage on endoscopic ultrasonography, and histopathologic grading of the primary cancer. A multivariate logistic regression model indicated that suspect CT findings (odds ratio, 4.4; 95% confidence interval 1.7-11.1, p = 0.002) and maximal tumour length >8 cm (odds ratio, 3.7; 95% confidence interval 1.4-9.6, p = 0.007) were associated independently with airway invasion. The accuracy of predicting airway invasion was 82.5% with both variables combined. CONCLUSIONS: The high incidence of airway involvement by oesophageal cancer and the difficulty to predict it accurately with clinical data or other staging procedures justifies the routine use of bronchoscopy in all patients with the tumour located at or above the level of the tracheal bifurcation. A particular effort to objectively prove or exclude airway invasion should be made in patients with tumours longer than 8 cm and/or with CT findings suggesting airway invasion.

Aged↗

Influence of simultaneous neoadjuvant radiotherapy and chemotherapy on bronchoscopic findings and lung function in patients with locally advanced proximal esophageal cancer.

To assess the bronchoscopic and lung function changes induced by preoperative radiochemotherapy (30 Gy radiation and 5-fluorouracil) in patients with proximal esophageal cancer, we prospectively compared the findings in 77 consecutive patients before and after the therapy. All patients completed the radiochemotherapy protocol; toxicity was minimal. Sixty-four patients underwent surgery, 48 had total gross removal of disease, and six had a complete histologic response. Of the 13 patients who developed apparent direct macroscopic signs of tumor invasion into the airways during therapy, histologic proof of cancer was obtained in only one of the abnormalities. Bronchoscopy was falsely negative in six patients in whom airway invasion of the cancer was found at surgery. Neoadjuvant therapy led to no systematic changes in the appearance of the uninvolved tracheal mucosa; microscopically, an increase in postinflammatory changes, hyperplasia, and metaplasia was found. There was no significant change in the values of lung function parameters after the therapy. No patient developed symptoms suggestive of radiation-induced lung changes, although in one of them, subtle radiologic features consistent with radiation pneumonitis were found. No patient died of postoperative pulmonary complications. The interpretation of bronchoscopy in the assessment of airway invasion of esophageal cancer after radiochemotherapy is more difficult than at baseline staging; the positive predictive value of macroscopic abnormalities without microscopic proof of cancer is low, and even with extensive sampling for histology and cytology, the procedure was falsely negative in 9.4%. Neoadjuvant therapy did not induce radiation pneumonitis or changes in lung function that could be of concern at the following operation.

Adult↗

Cellular and humoral immune system in schizophrenia: a conceptual re-evaluation.

Immune alterations in schizophrenia have been described for decades. However, modern immunological methods and new insights into the highly developed and functionally differentiated immune system allow an integrative view of both the older and also more recent findings of immunological abnormalities in schizophrenia. The conceptual advances in immunology require the re-evaluation of elder immunological findings in schizophrenia. In this overview, recent advances in immunological research regarding the differentiation between T-Helper-1 and T-Helper-2 cells and between the so-called specific and unspecific arms of the immune system are discussed. The unspecific "innate" immune system shows signs of an over-activation in unmedicated schizophrenic patients, as increased monocytes and gamma delta-cells point to. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of monocytes/macrophages, too. In contrast, several parameters of the specific cellular immune system are blunted, e.g. the decreased T-helper-1 (TH-1) related immune parameters in schizophrenic patients, both in vitro and in vivo. It seems that a TH-1-TH-2 imbalance with a shift to the TH-2 system is associated with schizophrenia. During therapy with antipsychotics, the specific TH-1 related immune answer becomes activated, but the B-cell system and the antibody production become activated too.

Antibody Formation↗

[Clinical characteristics of pulmonary embolism].

Pulmonary embolism is nearly always a complication of deep venous thrombosis. The evaluation of risk factors for venous thromboembolism not only aids diagnosis but also guides decisions about the intensity of prophylactic measures. As both the extent and chronicity of pulmonary vascular obstruction vary widely, pulmonary embolism can produce widely differing clinical pictures. From the clinical, pathophysiological and therapeutical point of view, it is convenient to classify pulmonary embolism into four types: acute minor embolism (dyspnoea with or without pleuritic pain or haemoptysis), acute massive embolism (hemodynamic instability), subacute massive embolism (mimicking heart failure or indolent pneumonia), and chronic thromboembolic pulmonary hypertension (slowly progressing dyspnoea). This classification is of importance not only for the rational diagnosis and differential diagnosis, but also for the institution of adequate therapy. Because the disease has many nonspecific manifestations but no pathognomonic symptoms or signs, it is impossible to prove the diagnosis of pulmonary embolism alone on the basis of clinical presentation.

Humans↗

[Diagnosis of pulmonary embolism].

Accurate diagnosis of pulmonary embolism is essential to minimize morbidity and mortality caused by failure to treat when necessary or by inappropriate treatment. Because clinical symptoms and signs are nonspecific, it is impossible to prove the diagnosis solely on clinical grounds. The diagnosis requires high level of suspicion, estimation of the pretest clinical likelihood of embolism, and judicious use of objective investigations (scintigraphy, computed tomography, or angiography) to confirm or refute the suspicion. The choice of tests depends on the availability of these tests, the hemodynamic state of the patient, and the presence of other cardiopulmonary diseases. Despite the availability of most accurate tests, pulmonary embolism will continue to be missed if not first considered by the physician.

Diagnosis, Differential↗

[Evaluation of preoperative functional status in patients with lung cancer].

In view of the dismal prognosis of unresected bronchial cancer, surgical resection should be encouraged even in patients with borderline cardiopulmonary function. Accurate estimation of the cardiopulmonary reserve is therefore desirable to avoid denying potentially curative treatment on the on hand and severe postoperative disability on the other. Various parameters (lung volumes, gas exchange, pulmonary hemodynamics, exercise endurance) are reviewed concerning their predictive values to evaluate functional operatibility. No ideal test exists. During exercise both pulmonary and cardiac risk can be evaluated simultaneously. The high predictive value of maximal oxygen uptake to assess postoperative morbidity and mortality is established. The postoperative values for the forced expiratory volumes, the transfer factor, and maximal oxygen uptake can be predicted by means of quantitative lung scans. A new four-stage algorithm for the functional evaluation is presented. Patients with normal lung function and exercise electrocardiography can undergo lung resection up to a pneumonectomy without further diagnostic procedures. In others, first the predicted postoperative values of forced expiratory volume and transfer factor should be estimated by taking into account the number of segments to be resected. Patients with values < 30% predicted are regarded as inoperable, whereas values > 40% predicted quality for resection without the need for further diagnostics. Patients with values between 30-40% predicted are further differentiated with cardiopulmonary exercise testing and for those cases where diagnostic uncertainty still remains, predicted postoperative values can be calculated using quantitative lung scans.

Carcinoma, Bronchogenic↗

The role of immune function in schizophrenia: an overview.

Immune alterations in schizophrenia have been described for decades. However, modern immunological methods and new insights into the highly developed and functionally differentiated immune system allows an integrative view of both, the older and also recent findings of immunological abnormalities in schizophrenia. Both, the unspecific and the specific arm of the immune system seem to be involved in the dysfunction of the immune system in schizophrenia. The unspecific "innate" immune system shows signs of an overactivation in unmedicated schizophrenic patients, as increased monocytes and gamma delta-cells point to. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might also be the result of the activation of monocytes/macrophages. On the contrary, several parameters of the specific cellular immune system are blunted, e.g. the decreased T-helper-1 (TH-1) related immune parameters in schizophrenic patients both, in vitro and in vivo. It seems that a TH-1-TH-2 imbalance with a shift to the TH-2 system is associated with schizophrenia. During antipsychotic therapy with neuroleptics, the specific TH-1 related immune answer becomes activated, but also the B-cell system and the antibody production increases.

Antipsychotic Agents↗

[Risk assessment of patients before lung surgery].

Lung resection offers the best prospect of long-term survival in patients with nonmetastatic pulmonary neoplasia. In view of the dismal prognosis of unresected bronchial cancer, surgical resection should be encouraged even in patients with reduced cardiopulmonary function. Accurate estimation of the postoperative cardiopulmonary function is therefore desirable to avoid (a) refusal of potentially curative treatment and (b) severe postoperative disability. The origins of post-resection morbidity and mortality are multifactorial. Thus, no single pulmonary function test or hemodynamic measurement can accurately and reliably predict postoperative cardiorespiratory complications. Criteria of functional operability should be based on percent of predicted value, so that patient's age, sex, and height will be taken into consideration. Exercise testing offers the advantage that both pulmonary and cardiac risk can be evaluated simultaneously. The high predictive value of maximal oxygen uptake (VO2max) in assessing postoperative morbidity and mortality is established. The calculation of predicted postoperative lung function (ppo) is of importance. The postoperative values for the forced expiratory volume in one second (FEV1-ppo), the transfer factor (TL,CO-ppo), and VO2max-ppo can be predicted by using the same formula. Patients with nearly normal lung function (FEV1, TL,CO > 75% predicted) and no concomitant cardiac disease can undergo lung resection right up to pneumonectomy without further diagnostic procedures. In the others, FEV1-ppo and TL,CO-ppo should be estimated first by taking into account the number of segments to be resected. Patients with values < 30% predicted are usually regarded as being inoperable, whereas values > 40% predicted qualify for resection without the need for further diagnostics. VO2max < 10 ml/kg/min or < 40% predicted are prohibitive for surgery. If VO2max is > 20 ml/kg/min or > 75% predicted, functional operability without limitation is given. For those cases where diagnostic uncertainty still remains, FEV1-ppo, TL,CO-ppo, and VO2max-ppo can be calculated by means of quantitative lung scans. Patients with either FEV1-ppo and TL,CO-ppo < 30% predicted or VO2max-ppo < 8 ml/kg/min or < 35% predicted are deemed inoperable.

Exercise Test↗

Internally and externally guided voluntary saccades in unmedicated and medicated schizophrenic patients. Part I. Saccadic velocity.

Saccadic eye movements were elicited in 30 schizophrenic patients before and in 17 of these 30 during antipsychotic treatment with neuroleptics, and compared with those of 12 age-matched controls under three different conditions: (a) the gap paradigm, which tests the visually triggered and visually guided saccades; (b) the anti-task paradigm, which tests the internally guided, visually triggered saccades; and (c) the memory paradigm, which tests the internally triggered and guided saccades. Eye movements were recorded by DC electro-oculography, and the peak eye velocities for the different saccades were calculated. We found that antipsychotic treatment with neuroleptics reduces the peak saccadic eye velocity. This effect is larger for internally guided saccades than for externally triggered and guided eye movements. The saccadic velocity of the unmedicated schizophrenic patients did not differ from that of the controls. Since patients with diseases of the basal ganglia primarily show abnormalities of the internally guided and triggered saccades, our findings indicate that neuroleptics influence the oculomotor loop through the basal ganglia and that this loop, by means of neuroleptic influence on the brainstem saccadic burst generator, also influences the peak velocity of the internally guided saccades. This contradicts the current idea of the role of the cortical input to the brainstem saccadic burst generator, which is thought to not be involved in the determination of saccadic velocity.

Adult↗

Internally and externally guided voluntary saccades in unmedicated and medicated schizophrenic patients. Part II. Saccadic latency, gain, and fixation suppression errors.

Saccades were elicited in 30 schizophrenic patients before medication, in 17 of them during medication with neuroleptics, and in 12 healthy controls using six paradigms that tested different types of saccades: (a) the externally triggered and visually guided saccades; (b) the externally triggered and internally guided saccades (anti-saccades); and (c) the internally triggered and internally guided saccades (memory-guided saccades). Latency of the primary saccade, gain (eye amplitude to target amplitude), and percentage of unwanted saccades (fixation suppression errors) were calculated. The externally triggered and externally guided saccades were only slightly affected in the patients, indicating that the function of parieto-tectal pathways was preserved. In contrast, the internally guided and externally triggered saccades showed abnormally long latencies, slightly smaller gains, and an increased rate of suppression errors regardless of the medication status. These findings were even more pronounced in the internally triggered and internally guided saccades such as memory-guided saccades. According to animal experiments and studies on patients with disorders of the basal ganglia, the performance of these saccades is based on the function of the pre- and dorsolateral frontal cortex and its connections to the basal ganglia. The minimal improvement of some of the parameters after clinical improvement and during treatment with neuroleptics suggests that the eye-movement deficits are associated with abnormalities of schizophrenia, which do not basically change under medication with neuroleptics. The observed effects of neuroleptics also argue against a primary abnormality in the dopaminergic input to the frontal cortex - basal ganglia oculomotor loop and support the view that there is a primary disturbance of the cortical input to the oculomotor loop through the basal ganglia in schizophrenics.

Adult↗

Imaging of cell/substrate contacts of living cells with surface plasmon resonance microscopy.

We have developed a new method for observing cell/substrate contacts of living cells in culture based on the optical excitation of surface plasmons. Surface plasmons are quanta of an electromagnetic wave that travel along the interface between a metal and a dielectric layer. The evanescent field associated with this excitation decays exponentially perpendicular to the interface, on the order of some hundreds of nanometers. Cells were cultured on an aluminum-coated glass prism and illuminated from below with a laser beam. Because the cells interfere with the evanescent field, the intensity of the reflected light, which is projected onto a camera chip, correlates with the cell/substrate distance. Contacts between the cell membrane and the substrate can thus be visualized at high contrast with a vertical resolution in the nanometer range. The lateral resolution along the propagation direction of surface plasmons is given by their lateral momentum, whereas perpendicular to it, the resolution is determined by the optical diffraction limit. For quantitative analysis of cell/substrate distances, cells were imaged at various angles of incidence to obtain locally resolved resonance curves. By comparing our experimental data with theoretical surface plasmon curves we obtained a cell/substrate distance of 160 +/- 10 nm for most parts of the cells. Peripheral lamellipodia, in contrast, formed contacts with a cell substrate/distance of 25 +/- 10 nm.

Animals↗

T-cell subsets and expression of integrins in peripheral blood of patients with migraine.

Neurogenic inflammation is considered as an animal model of human migraine attacks. Using flow cytometry, we examined T-cell subsets and their integrin expression in the peripheral blood of 32 migraine patients in order to evaluate a possible inflammatory process in humans, as postulated in the migraine animal model. Our results show that migraine patients have a significant increased proportion of T-helper (47.4 +/- 6.3% vs 43.2 +/- 5.8%; p < 0.01) and T-helper memory cells (23.6 +/- 5.9 vs 20.3 +/- 6.5%; p < 0.01). Moreover, the 22 migraine patients without aura also exhibited an increase of LFA-1 expression of T-helper cells (34.7 +/- 11.5%) compared to the 35 controls (27.5 +/- 12.0%; p < 0.01). These preliminary results support the hypothesis that immunological mechanisms (such as an enhanced lymphocyte endothelium interaction) could be part of the migraine pathophysiology in humans.

Adult↗

Parentification and its impact on adolescent children of parents with AIDS.

Parentification refers to children or adolescents assuming adult roles before they are emotionally or developmentally ready to manage those roles successfully. We assess predictors and outcomes of parentification among adolescent children of Parents with AIDS (PWAs) in two phases. In Phase 1, relationships among parental AIDS-related illness, parent drug use, parent and adolescent demographics, and parentification indicators (parental, spousal, or adult role-taking) were assessed among 183 adolescent-parent pairs (adolescents: 11 to 18 years, M = 14.8 years, 54% female; parents: 80% female). Adult role-taking was associated with maternal PWAs, female adolescents, and greater parent drug use. Greater parental AIDS-related illness predicted more spousal and parental role-taking. Parent drug use predicted more parental role-taking. In Phase 2, we examined the impact of parentification on later adolescent psychological adjustment (N = 152 adolescents). Adult role-taking predicted more internalized emotional distress; parental role-taking predicted externalized problem behaviors: sexual behavior, alcohol and marijuana use, and conduct problems. Given these dysfunctional outcomes, we discuss interventions to mitigate parentification among children of PWAs.

Acquired Immunodeficiency Syndrome↗

Antibodies to heat shock proteins in schizophrenic patients: implications for the mechanism of the disease.

OBJECTIVE: The involvement of heat shock proteins has been determined in the pathophysiology of several disorders of the central nervous system, including multiple sclerosis. To elucidate their role in schizophrenia, the authors investigated antibody titers to heat shock proteins in unmedicated and medicated patients with schizophrenia. METHOD: Using the enzyme-linked immunosorbent assay technique, the authors measured titers of antibodies to 60 kilodaltons (kD) heat shock proteins (HSP60) and 70 kD heat shock proteins (HSP70) in 30 patients with schizophrenia before and during neuroleptic treatment and compared the titers with those of 31 healthy individuals. RESULTS: Ten (33%) of 30 patients with schizophrenia but only one (3%) of 31 healthy individuals showed immunoreactivity to HSP60 or HSP70. The authors found especially high anti-HSP70 titers in never-medicated patients. High anti-HSP60 titers were mainly found in patients who were being treated with neuroleptics. CONCLUSIONS: Since heat shock proteins are involved in diverse neuroprotective mechanisms, antibodies against heat shock proteins may inhibit neuroprotection. The authors discuss the implications of these findings for schizophrenia.

Adult↗

Increase in expression of adhesion molecule receptors on T helper cells during antipsychotic treatment and relationship to blood-brain barrier permeability in schizophrenia.

OBJECTIVE: The authors estimated the expression of adhesion molecule receptors (VLA-4 and LFA-1) on T helper (CD4+) and T suppressor/cytotoxic (CD8+) lymphocytes in schizophrenic patients before and during antipsychotic treatment and studied the relationship of these subpopulations to CSF measures and blood-brain barrier permeability. METHOD: Blood was drawn from hospitalized patients with schizophrenia before (N = 45) and after (N = 22) neuroleptic treatment and from an age-matched comparison group (N = 41). Lumbar punctures were performed on 32 of the schizophrenic patients. RESULTS: During antipsychotic treatment there were significant increases in the percentage of VLA-4+/CD4+ and VLA-4+/CD8+ cells. VLA-4+/CD4+ and LFA-1+/CD4+ cells were both closely related to disturbance of the blood-brain barrier. Higher values for VLA-4+/CD4+ and LFA-1+/CD4+ cells were found in patients with a disturbed blood-brain barrier. CONCLUSIONS: The findings suggest that adhesion molecules are involved in immunoregulation between the central nervous system and the peripheral immune system in schizophrenia.

Adult↗