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Biomedical subjects

K Fassbender

Publications and source records attributed to K Fassbender.

At least 55 records · Page 3Linked to original sources
PubMed1997

Real-time control for transscleral cyclophotocoagulation.

BACKGROUND: In transscleral cyclophotocoagulation, the surgeon cannot directly observe the applied laser effects. Overdosage, possibly resulting in unwanted pop effects, or underdosage with no therapeutic effect therefore often occur. METHOD AND MATERIALS: Laser radiation passing through the sclera and ciliary body is partly reflected from the fundus and can be monitored from outside the eye by a detector system. Since all other parameters influencing the intensity of the recorded radiation are constant in time during one laser exposure, the time dependence of this radiation directly reflects the change of transmission of the treated tissue. The laser exposure therefore can be stopped by a computer when certain criteria of the recorded curves are fulfilled. In addition, the transmission curves are displayed on a monitor in real time, permitting the surgeon to interrupt the exposure. A Nd:YAG laser and a diode laser are connected to the device. After successful tests in enucleated porcine eyes which were evaluated histologically and in human cadaver eyes this method is applied to patients suffering from refractory glaucoma. RESULTS: The transmission curves from enucleated porcine eyes show that the 810-nm diode laser is more appropriate for this method than the 1064-nm. Nd:YAG laser, because the radiation output of the diode is more stable in time and the tissue absorption is higher, both resulting in a larger dynamical range of useful signal. The curves from the porcine eyes, the human cadaver eyes and the curves from patients show a typical shape which allows interruption of exposure either by the surgeon or by the computer program before a pop effect occurs. CONCLUSIONS: This new method increases the precision and safety of transscleral cyclophotocoagulation.

Adult↗
PubMed1997

Cerebrovascular involvement in the acute phase of bacterial meningitis.

Cerebral ischaemia is a common complication of bacterial meningitis. Although cerebrovascular involvement in the acute phase of inflammation may be particularly important for the still unacceptably high morbidity and mortality, only, a few studies have investigated cerebrovascular changes in bacterial meningitis. We prospectively investigated changes of intracranial cerebral blood flow velocities (CBFV) in 22 patients (12 men, 10 women, mean age 48 years, 19 years, SD) with bacterial meningitis, by means of transcranial Doppler sonography (TCD). According to previously published criteria the degree of arterial narrowing was assessed and related to the patients' outcome. Elevated CBFVs in the middle cerebral artery were documented in 18/22 patients with markedly increased systolic peak velocities (CBFV of > 210 cm/s) in 7 patients. Serial examinations performed in 11 patients showed elevated CBFV as early as day 1, reaching peak CBFV between day 3 and day 6 after onset of symptoms in most cases. Furthermore, cerebrovascular involvement was also documented by disturbances of physiological slow spontaneous oscillations of blood flow velocities in 5/10 patients examined with TCD. Low Glasgow Coma Scales (< 7) on admission (29% vs 0%), focal cerebral ischaemic deficits (29% vs 7%) and, seizures (43% vs 7%) were more frequent in patients with CBFV of > 210 cm/s. Finally, a poor clinical outcome was significantly related to severe vascular involvement (P < 0.05). In conclusion, cerebrovascular complications are frequently found in patients with bacterial meningitis. TCD is an easily applicable technique for revealing vascular changes non-invasively, even in severely ill patients. Since our data suggest an unfavourable course of the disease in association with increased CBFV in intracranial arteries, probably indicating vasospasm, TCD could potentially be used to identify high-risk patients who could benefit from adjuvant therapeutic interventions.

Adult↗
PubMed1997

Proinflammatory cytokines: indicators of infection in high-risk patients.

Proinflammatory cytokines play an eminent role in pathophysiology of infection and inflammation. Their actual clinical importance is, however, uncertain. In this study, we tested the hypothesis that inflammatory cytokines could be useful in detection of infections in high-risk patients. We prospectively studied the diagnostic value of determination of concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and the 55- and 75-kd soluble TNF receptors (sTNFR-p55 and sTNFR-p75) in detection of nosocomial infections in 52 patients with acute ischemic stroke, as an exemplary high-risk group, and compared these findings to those of conventional inflammatory indicators of inflammation (C-reactive protein and leukocyte count). After 1 week of hospitalization, 27% of the patients had minor or moderately severe nosocomial infections. This subpopulation exhibited significantly increased concentrations of IL-6 and sTNFR-p55 but not of IL-1beta, TNF-alpha, or sTNFR-p75. As expected, levels of C-reactive protein and leukocytes were increased in infected patients. The sensitivity and specificity for detection of nosocomial infections at day 7 of hospitalization was highest for IL-6, followed by C-reactive protein and the leukocyte count. The data suggest that the proinflammatory cytokine IL-6, in addition to its considerable pathophysiologic importance in systemic inflammation, may be valuable in detection of infections in high-risk patients.

Adult↗
PubMed1997

Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte-recruitment.

The release of circulating isoforms of selectin- (L-selectin, ELAM-1) and immunoglobulin-type- (ICAM-1) adhesion molecules, responsible for accumulation of leukocytes at sites of tissue injury was studied in CSF and serum of 21 patients with bacterial meningitis and in healthy subjects. Their concentrations were compared with the intrathecal leukocyte recruitment and release of inflammatory cytokines. In contrast to serum concentrations of the leukocyte-derived adhesion molecule, sL-selectin, serum concentrations of endothelial-derived adhesion molecules, sELAM-1 and sICAM-1, were significantly increased in meningitis. No intrathecal synthesis of these adhesion molecules was observed. Serum levels of sELAM-1 were associated with extent of CSF pleocytosis and with concentrations of proinflammatory cytokines IL-1beta and TNF alpha in CSF, but not in serum. Therefore, expression of endothelial adhesion molecules i.e. ELAM-1 may be responsible for the massive intrathecal recruitment of potentially harmful leukocytes in patients with bacterial meningitis. Intrathecally released proinflammatory cytokines may represent the inducing signals for their endothelial upregulation.

Adolescent↗
PubMed1996

Acute Myocardial Infarction in Canada: New Epidemiologic Insights on Incidence, Therapy, and Risk.

Objective: To define the changing incidence, risk, and therapy of acute myocardial infarction (A311). Data sources: Review of contemporary AMI data from the University of Alberta Hospitals, six other sites of the Clinical Quality Improvement Network (CQIN), and other Canadian and international centers. Data synthesis: Ischemic heart disease is age-related and the Canadian population is rapidly aging. At the University of Alberta Hospitals, the incidence of Q wave AMI (per 100,000 population) in 1985 was 113 and has remained unchanged (NS) since that time (129 in 1994). In contrast, the combined incidence of non.Q-wave AMI and unstable angina has increased markedly, from 74 in 1985 to 226 in 1994 (p < 0.05). The use of proven efficacious therapies for AMI has greatly increased in recent years, with thrombolytic drugs being given to approximately 35;percnt; of all patients by 1993; and beta-blockers and aspirin to 75;percnt; and 98;percnt; of patients, respectively. However, females and patients older than 70 years' despite their greater risk, received significantly less efficacious medication than males and younger AMI patients. The use of calcium antagonists decreased from a peak utilization rate of 60;percnt; for all AMI patients in 1989 to less than 10;percnt; by 1993. In-hospital AMI mortality risk has also decreased in the last several years, particularly among higher risk older patients (35;percnt;, 1987 vs. 19;percnt;,1993). In a population of 3896 consecutive AMI patients, recruited largely in 1992 and 1993 from seven CQIN sites, logistic regression analyses revealed aspirin was associated with the greatest relative risk reduction (61%); beta-blocker and thrombolytic therapy were related to risk reductions of 55;percnt; and 16;percnt;, respectively. Incremental age was the most important factor associated with increased relative risk in AMI, overall and in both sexes; sex was not an independent risk predictor. Qualitatively very similar AMI incidence, risk, and treatment data have also been recently observed in other centers in Canada, the United States, and elsewhere. Conclusions: Although widespread primary or secondary prevention is possibly contributory, the recent static incidence of Q-wave AMI and the marked increase in unstable angina and non-Q-wave AMI are more likely due to enhanced health awareness and diagnosis-seeking behavior in the population at risk. The decline in AMI mortality, at least for high-risk acute care patients, is compatible with a clinically relevant secondary prevention effect. There are still, however, windows of opportunity to further improve AMI outcomes by increasing the utilization of proven efficacious therapy, especially among women and older patients. Another particularly attractive epidemiologic benefit in the immediate future would accrue from the further development and effective use of efficacious therapies directed against unstable angina and n-Q-wave AMI.

Journal Article↗
PubMed1996

Circulating L-selectin in multiple sclerosis patients with active, gadolinium-enhancing brain plaques.

Leukocyte migration into inflammatory lesions is controlled by adhesion molecules. L-selectin is the adhesion molecule on leukocytes that is responsible for making the initial contact with endothelium. After establishing this contact, L-selectin is shed from the cell surface and present in the circulation as a functional soluble receptor. To investigate this initial adhesive event, we evaluated the presence of soluble L-selectin (sL-selectin) in serum and CSF of patients with multiple sclerosis (MS), viral encephalitis, and controls. MS patients with active, gadolinium-enhancing lesions on magnetic resonance imaging had significantly higher sL-selectin serum levels than controls (P < 0.05). These levels in MS patients correlated with the size of the enhancing lesions (P < 0.05), and with sL-selectin levels in CSF (P < 0.001). In viral encephalitis, in contrast, sL-selectin is elevated in CSF only (P < 0.001) and may derive from intrathecal leukocytes. These results show that the earliest adhesive events mediated by L-selectin indeed operate in active MS, and that sL-selectin will be of value in quantitating the extent of this inflammatory process.

Adult↗
PubMed1996

Inflammatory cytokines in CSF in bacterial meningitis: association with altered blood flow velocities in basal cerebral arteries.

OBJECTIVE: To investigate the association between release of humoral inflammatory mediators in CSF and blood and alterations of cerebral blood flow in patients with bacterial meningitis. METHODS: Immunomodulatory (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF alpha)) and vasoactive (thromboxane A, prostacyclin, endothelin-1) molecules of probable or confirmed leucocyte origin were determined in CSF and venous blood from 20 patients with bacterial meningitis, and matched control subjects. Their concentrations were related to the presence of increased blood flow velocities in the middle cerebral arteries, as recorded by transcranial Doppler sonography. RESULTS: Concentrations of proinflammatory cytokines and prostacyclin and leucocyte counts were significantly increased in meningitis, but concentrations of the vasoconstrictors thromboxane and endothelin-1 were not. Patients with high blood flow velocities ( > 140 cm/s) had significantly increased concentrations of IL-1 beta and IL-6 and raised cell counts in CSF. CONCLUSION: The increases of key mediators of inflammation and immunoactivation and of leucocyte count in the CSF of patients with high cerebral blood flow velocities suggest a role of excessive compartmentalised host defence in pathogenesis of disorders of cerebral blood flow in bacterial meningitis.

Adolescent↗
PubMed1995

Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke.

BACKGROUND AND PURPOSE: Cellular adhesion molecules mediate adhesion between endothelial cells and leukocytes as a precondition for extravasation of leukocytes at sites of tissue injury. The pattern of release of circulating adhesion molecules has been characterized in patients with acute ischemic stroke. METHODS: Serum concentrations of soluble selectin-type adhesion molecules (solube endothelial leukocyte adhesion molecule-1 [sELAM-1], soluble lymph node homing receptor [sL-selectin]) and immunoglobulin-type adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1]) were serially determined (at hours 4, 8, and 10 and at days 1, 3, and 5) in 22 patients with acute ischemic stroke. As control subjects, age- and sex-matched individuals with (n = 40) and without (n = 22) vascular risk factors were studied. RESULTS: We observed increased concentrations of sICAM-1 and decreased levels of sL-selectin in patients with risk factors even in the absence of stroke. Patients with acute stroke had, in addition, an initial transient increase of sELAM-1 and a persistent increase of sVCAM-1. CONCLUSIONS: The results suggest a chronic alteration of expression of adhesion molecules sICAM-1 and sL-selectin in subjects with risk factors for atherosclerosis; they also indicate acute changes of levels of sELAM-1 and sVCAM-1 in response to acute ischemic stroke. Determination of soluble adhesion molecules could allow in vivo monitoring of the initial steps of leukocyte-mediated brain damage in acute ischemic stroke.

Aged↗
PubMed1994

Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease.

The release of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha and soluble TNF-receptors p55 and p75 in peripheral blood was serially determined in 19 patients with acute cerebral ischemia. Only patients admitted within 4 h following onset of symptoms were studied. In contrast to serum levels of IL-1 beta, TNF-alpha and TNF-receptors, which did not exhibit a significant response, IL-6 showed a significant increase of serum levels already within the first hours following onset of disease and reached a plateau at 10 h until day 3 and returned to baseline by day 7. The increase of levels of this cytokine was significantly (P < 0.05) correlated with increasing volumes of brain lesion and was also significantly (P < 0.005) associated with poor functional and neurological outcome. The increase of levels of IL-6 despite a considerable dilution in peripheral blood shown in this preliminary study suggests an early inflammatory response in ischemic brain lesion.

Activities of Daily Living↗
PubMed1994

Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome.

BACKGROUND AND PURPOSE: The aim of this study was to characterize the response of the hypothalamic-pituitary-adrenal system in the first hours of ischemic stroke and to relate its extent to the occurrence of acute confusional state, volume of brain damage, and clinical outcome. METHODS: The secretion of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volumetry of computed tomographic scans), and neurological and functional outcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed. RESULTS: The massive neuroendocrine response observed consisted of an initial phase with concomitantly increased levels of ACTH and cortisol and a second phase with decreased levels of ACTH while high concentrations of cortisol persisted. Initial levels of ACTH but not cortisol were significantly increased in patients with acute confusional state and significantly correlated with volume of brain lesion and neurological and functional outcome. CONCLUSIONS: An early and persisting activation of the hypothalamic-pituitary-adrenal axis was observed in relation to severity of disease. Its characteristic biphasic pattern suggests an initial central stimulation of release of ACTH followed by feedback suppression concomitant with an increased susceptibility of the adrenal gland. Because these hormones are known to exacerbate hypoxic injury to neurons, their massive release in hyperacute stroke may increase the extent of brain damage.

Acute Disease↗
PubMed1993

Interleukin-6 and acute-phase protein concentrations in surgical intensive care unit patients: diagnostic signs in nosocomial infection.

OBJECTIVE: To determine the value of serum concentrations of interleukin-6 (IL-6), C-reactive protein, and glycosylation of alpha 1-acid glycoprotein as tools for diagnosing nosocomial infection in surgical intensive care unit (ICU) patients. DESIGN: Prospective, consecutive entry study of patients with an anticipated stay of at least 24 hrs in a surgical ICU. SETTING: University hospital, a major provider of acute surgical care. PATIENTS: One hundred four consecutive patients admitted to the surgical ICU between March and June 1990. MEASUREMENTS: Concentrations of IL-6, C-reactive protein, and glycosylation of alpha 1-acid glycoprotein were measured on days 1 and 6 after ICU admission. Clinical evaluation for infection was performed daily in a blinded fashion, i.e., without knowing the results of the acute-phase parameters. MAIN RESULTS: On day 6 after surgery or trauma, nosocomial infection could be ascertained in 13 cases. The clinical parameter of fever > 38 degrees C had a sensitivity of 54% and a specificity of 90% to demonstrate nosocomial infection. Infected patients showed increased concentrations of IL-6 (p < .001), C-reactive protein (p < .001), and increased reactivity of alpha 1-acid glycoprotein to concanavalin A (p < .001) compared with patients without infections. By choosing appropriate cutoff values, IL-6 determinations had the highest specificity (97%), and C-reactive protein values had the highest sensitivity (85%) for diagnosing nosocomial infections. In uninfected patients, 81% of the IL-6 values, but only 29% of the C-reactive protein values, were back to the normal range on day 6 after injury. CONCLUSION: Due to the rapid normalization after trauma, a single measurement of the serum IL-6 concentration may be useful to support or refute the clinical suspicion of nosocomial infection.

Adolescent↗
PubMed1993

Influence of endotoxin on nocturnal sleep in humans.

Sleepiness is a common complaint during infectious diseases, but the interaction between sleep and host defense mechanisms has been poorly explored in humans. We therefore studied the effect of endotoxin, a major pathophysiological factor in gram-negative bacterial infections, on sleep and on parameters of the primary host response in men. In a single-blind counterbalanced trial, 15 healthy volunteers received either placebo or Salmonella abortus equi endotoxin (0.4 ng/kg body wt) intravenously on two separate occasions. Nocturnal sleep was recorded, and rectal temperature and the plasma levels of tumor necrosis factor-alpha, interleukin-6, adrenocorticotropic hormone, and cortisol were monitored for 12 h. Endotoxin reduced the relative amounts of wakefulness (P < 0.05) and rapid-eye-movement (REM) sleep (P < 0.05) and increased the relative amount of non-REM sleep (P < 0.01). Electroencephalogram delta power during non-REM sleep, as measured by spectral analysis, was not altered by endotoxin. The endotoxin-induced changes in sleep structure were related temporally and quantitatively to the increases in rectal temperature and to the release of cytokines and neurohormones. It is concluded that cytokines and neurohormones mediate the effects of endotoxin upon sleep. The ensuing increase in non-REM sleep may be part of the adaptive host response to bacterial infections in humans.

Adrenocorticotropic Hormone↗
PubMed1993

Endotoxin- and corticotropin-releasing hormone-induced release of ACTH and cortisol. A comparative study in men.

The present study compares the effects of endotoxin, a key factor in gram-negative bacterial infection, and of corticotropin-releasing hormone (CRH) on ACTH and cortisol secretion in healthy male volunteers in a placebo-controlled design. Endotoxin (isolated from Salmonella abortus equi; 0.4 ng/kg body weight) induced a significantly delayed and prolonged increase of ACTH and cortisol secretion as compared to CRH (100 micrograms), supporting the hypothesis that different intermediate mechanisms are involved (baseline/peak: ACTHEndotoxin vs. ACTHCRH: 140 +/- 40 min vs. 44 +/- 17 min (p < 0.001); CortisolEndotoxin vs. CortisolCRH: 113 +/- 51 min vs. 66 +/- 31 min (p < 0.05); peak/baseline: ACTHEndotoxin vs. ACTHCRH: 244 +/- 79 min vs. 200 +/- 25 min (p < 0.05); CortisolEndotoxin vs. CortisolCRH: 278 +/- 76 min vs. 182 +/- 16 min (p < 0.001)). Activation of the hypothalamo-pituitary-adrenocortical (HPA) system by endotoxin in men is associated with increased interleukin-6 (peak value: 124 +/- 109 pg/ml) and tumor necrosis factor-alpha (peak value: 69 +/- 53 pg/ml) plasma levels which, probably together with locally produced interleukin-1, stimulate the HPA system both at the hypothalamic and (to a lesser degree) at the pituitary site. Provided that strictly controlled laboratory conditions are applied, the endotoxin challenge test presented here may serve as an appropriate and safe tool to explore an individual's capacity for neuroendocrine adaptation to a bacterial stressor, thus providing information complementary to the CRH test.

Adrenocorticotropic Hormone↗
PubMed1993

Glycosylation of acute phase proteins and interleukins following hip arthroplasty. Inflammation parameters studied in 10 patients.

We analyzed changes in glycosylation and serum concentrations of alpha 1-acid glycoprotein (AGP), antichymotrypsin (AC), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) following hip arthroplasty. Glycosylation of AGP and AC showed an increased reactivity to concanavalin A between postoperative Day 2 and Day 5 and Day 10, respectively. Serum levels of AGP and AC increased at the earliest on Day 5. The AC levels returned to baseline by Day 10. AGP, however, exhibited increased values beyond Day 14. CRP levels were elevated at Day 2 and remained increased beyond Day 14. sIL2R showed increased values at Days 5, 10 and 14. IL-6 was the first parameter to increase, and it returned to baseline in less than 5 days.

Acute-Phase Proteins↗
PubMed1993

Glycosylation of alpha 1-acid glycoprotein in systemic onset juvenile rheumatoid arthritis and acute bacterial infection: value in differential diagnosis.

Agarose based affinity immunoelectrophoresis with free concanavalin A (Con-A) as ligand was used to examine the microheterogeneity of alpha 1-acid glycoprotein in sera of patients with systemic onset juvenile rheumatoid arthritis (JRA) and acute bacterial infections. In JRA, a decreased proportion of Con-A reactive alpha 1-acid glycoprotein variants was found when compared to healthy control. In contrast, acute bacterial infection showed an increased reactivity. Investigation of glycosylation may be useful in the differential diagnosis of systemic onset JRA and acute bacterial infection.

Acute Disease↗