Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 19 recordsLinked to original sources

PubMed2007

Anger in palliative care: a clinical approach.

Anger in patients and families is a common problem in the care of persons with advanced disease. Whereas it is widely accepted that anger may be a justifiable reaction to significant illness and loss, it frequently creates difficulties for the doctors involved in care. In particular, there is often a personal impact on the doctor at whom anger is directed. This paper examines results of qualitative research with palliative care workers in the context of the broader published literature and the authors' clinical experiences. The ability to interact effectively with angry patients is a skill that is often learned with experience and is extremely useful in both transforming the patients' reaction into a more creative emotion and in developing a therapeutic relationship. Despite conscientious efforts, however, a few patients continue to be angry. A practical approach to anger, useful for the clinician directly involved in care, is outlined along with some strategies to adopt in the face of persistent anger.

Adaptation, Psychological↗

PubMed2006

Maternal bond and mother-child interaction in severe postpartum psychiatric disorders: is there a link?

Mothers in the puerperium are vulnerable to a wide spectrum of postpartum psychiatric disorders. One of the central psychological processes of the puerperium is the development of an emotional relationship with the baby. The bond to the infant as well as the interaction with the baby are two aspects of the mother-infant relationship that can be disturbed by mothers with postpartum psychiatric disorders. Dysfunctional maternal cognitions may also influence the development of an emotional bonding and the establishment of a positive interaction with the child. The aim of this study is to investigate differences in the self-perceived experience of bonding and the observed mother-child interaction of severely ill postpartum depressive and psychotic mothers. In addition the association between subjective experience of bonding and objective measurement of mother-child interaction will be described. Results show that depressive mothers perceived their bonding to the baby more negatively than psychotic mothers. No differences could be found in the objective interactional behaviour of the mothers in both groups, with the exception that the infants of psychotic mothers showed more eye contact avoidance towards their mothers. The subjective experience of motherhood clearly influences the maternal interactional behaviour with depressive mothers as well as with psychotic mothers.

Adult↗

PubMed2006

Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission.

This overview tries to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. This view is supported by genetic findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction, however, is mediated by the N-methyl-D-aspartate (NMDA)-receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYNA). Despite the NMDA receptor antagonism, KYNA also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased KYNA levels can explain psychotic symptoms and cognitive deterioration. KYNA levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. Another line of evidence suggests that a (prenatal) infection is involved in the pathogenesis of schizophrenia. Due to an early sensitization process of the immune system or to a (chronic) infection, which is not cleared through the immune response, an immune imbalance between the type-1 and the type-2 immune responses takes place in schizophrenia. The type-1 response is partially inhibited, while the type-2 response is over-activated. This immune constellation is associated with inhibition of the enzyme indoleamine dioxygenase (IDO), because IDO - located in astrocytes and microglial cells - is inhibited by type-2 cytokines. IDO catalyzes the first step in tryptophan metabolism, the degradation from tryptophan to kynurenine, as does tryptophan 2,3-dioxygenase (TDO). Due to the inhibition of IDO, tryptophan-kynurenine is predominantly metabolized by TDO, which is located in astrocytes, not in microglial or other CNS cells. In schizophrenia, astrocytes in particular are activated, as increased levels of S100B appear. Additionally, they do not have the enzymatic equipment for the normal metabolism-route of tryptophan. Due to the lack of kynurenine hydroxylase (KYN-OHase) in astrocytes, KYNA accumulates in the CNS, while the metabolic pathway in microglial cells is blocked. Accordingly, an increase of TDO activity has been observed in critical CNS regions of schizophrenics. These mechanisms result in an accumulation of KYNA in critical CNS regions. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g., the use of anti-inflammatory cyclo-oxygenase-2 inhibitors, which can also decrease KYNA directly, are discussed.

Animals↗

PubMed2006

Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity.

Concentrations of 3alpha-reduced neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs). We investigated the impact of mirtazapine on the activity of a key neurosteroidogenic enzyme, the 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), and on the levels of neuroactive steroids in relation to clinical response. A total of 23 drug-free in-patients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. Enzyme activity was determined by assessment of steroid conversion rates. Irrespective of clinical outcome, there were significant increases in 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, 5alpha-dihydroprogesterone, and 5beta-dihydroprogesterone after mirtazapine treatment, whereas 3beta,5alpha-tetrahydroprogesterone levels were significantly decreased. In vitro investigations demonstrated a dose-dependent inhibitory effect of mirtazapine on the activity of the microsomal 3alpha-HSD in the oxidative direction (conversion of 3alpha,5alpha-tetrahydroprogesterone to 5alpha-dihydroprogesterone). Mirtazapine affects neuroactive steroid composition similarly as do SSRIs. The inhibition of the oxidative pathway catalyzed by the microsomal 3alpha-HSD is compatible with an enhanced formation of 3alpha-reduced neuroactive steroids. However, the changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of this antidepressant rather than clinical improvement in general.

3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)↗

PubMed2006

[Angiographic follow-up after carotid artery stenting of bifurcation stenosis].

PURPOSE: The purpose of this prospective study was to determine the restenosis grade, the intima hyperplasia and the stent expansion via angiographic follow-up six months after carotid artery stenting. MATERIALS AND METHODS: In 100 patients, angiographic follow-up was performed 5.9 months (range: 2.9-11.4 months) after carotid artery stenting. The restenosis grade, the intima hyperplasia and the stent expansion were measured by selective angiography of the treated carotid artery. RESULTS: The mean restenosis grade was 16 % (range: 0-78 %). In 6 of 100 patients (6 %), a restenosis grade of > 50 % was measured. In 4 patients the restenosis grade was 50-70 %. In 2 patients the restenosis grade was > 70 %. In 91 of 100 patients (91 %), the restenosis was localized in the former area of stenosis of the carotid artery, and in 9 of 100 patients (9 %), the restenosis was localized in the cranial stent end. The mean grade of intima hyperplasia was 31 % (range: 2-70 %). The mean increase in stent expansion at the time of follow-up was 10 % (range: 0-59 %). No correlation was able to be determined between the grade of stenosis and the grade of restenosis (rho = 0.017, range: - 0.180-0.213), between the grade of residual stenosis and the grade of restenosis (rho = 0.257, range: 0.064-0.431) and between intima hyperplasia and the grade of restenosis (rho = 0.476, range: 0.309-0.615). CONCLUSIONS: Carotid artery stenting is associated with a low incidence of high-grade restenosis 6 months after an intervention. The intima hyperplasia, which can be observed in each Wallstent, is partly compensated by the expansion of the self-expandable stent. Without a correlation between the grade of residual stenosis and the grade of restenosis, low-grade residual stenosis can be accepted. Therefore, we recommend undersized postdilation of the Wallstent.

Aged↗

PubMed2006

[Psychometric properties of a German version of the Apathy Evaluation Scale].

Apathy is a common feature of a variety of different psychiatric, neurological, and medical disorders. It can be defined as lack of motivation affecting cognitive, emotional, and overt behavioural aspects. Despite being associated with other clinical disorders, apathy can also occur as an independent syndrome (e. g., after brain injuries), now depicting a primary loss of motivation. However, apathy is predominantly assessed within the scope of superordinate psychiatric disorders. As a syndrome-independent scale, the Apathy Evaluation Scale (AES) claims to assess levels of apathy in different disorders. The aim of the present study is to provide German speaking researchers with an authorized German translation of the AES (AES (D)). The scale was evaluated in a sample of 217 subjects, consisting of patients suffering from dementia (n=120), remission-phase schizophrenia (n=20), Parkinson's disease (n=12), stroke (n=28), as well as elderly healthy controls (n=37). Preliminary results concerning the factorial structure, item characteristics, reliability, and construct validity demonstrate favourable statistical properties and suggest that the AESD is comparable to its original. The scale seems well-suited to detect apathy in different clinical groups. Differences between informant sources (clinician interview, self-, and informant ratings) seem to be related to the severity of symptoms or expert practice.

Aged↗

PubMed2006

Identifying the affected hemisphere by (1)H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI.

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.

Adult↗

PubMed2006

Cardiocirculatory and metabolic responses at different walking intensities.

OBJECTIVES: Although walking is a common physical activity, scientifically based training guidelines using standardised tests have not been established. Therefore this explorative study investigated the cardiovascular and metabolic load resulting from different walking intensities derived from maximal velocity (Vmax) during an incremental treadmill walking test. METHODS: Oxygen uptake, heart rate (HR), blood concentrations of lactate and catecholamines, and rating of perceived exertion were recorded in 16 recreational athletes (mean (SD) age 53 (9) years) during three 30 minute walking trials at 70%, 80%, and 90% of Vmax (V70, V80, and V90) attained during an incremental treadmill walking test. RESULTS: Mean (SD) oxygen uptake was 18.2 (2.3), 22.3 (3.1), and 29.3 (5.0) ml/min/kg at V70, V80, and V90 respectively (p<0.001). V70 led to a mean HR of 110 (9) beats/min (66% HRmax), V80 to 124 (9) beats/min (75% HRmax), and V90 to 152 (13) beats/min (93% HRmax) (p<0.001). Mean (SD) lactate concentrations were 1.1 (0.2), 1.8 (0.6), and 3.9 (2.0) mmol/l at V70, V80, and V90 respectively (p<0.001). There were no significant differences between catecholamine concentrations at the different intensities. Rating of perceived exertion was 10 (2) at V70, 12 (2) at V80, and 15 (2) at V90. Twelve subjects reported muscular complaints during exercise at V90 but not at V70 and V80. CONCLUSIONS: Intensity and heart rate prescriptions for walking training can be derived from an incremental treadmill walking test. The cardiovascular and metabolic reactions observed suggest that V80 is the most efficient workload for training in recreational athletes. Further studies are needed to confirm these findings.

Energy Metabolism↗

PubMed2006

Anti-glycan antibodies as biomarkers for diagnosis and prognosis.

Glycans (sugars or carbohydrates) are predominant surface components of cells such as erythrocytes, immune cells and microorganisms. As such, they give rise to high levels of anti-glycan antibodies of all classes. Antibodies to certain defined mono, di and oligosaccharides that are common in bacterial, fungal and parasite cells exist in human sera and can be profiled using glycan arrays. The use of glycan arrays for systematic screening of blood samples from multiple sclerosis (MS) and Crohn's disease (CD) patients in versus to blood samples from control groups, have lead to the discovery of a few anti glycan antibodies biomarkers enabling diagnosis and prognosis in MS and CD patients. Anti-Glc(alpha1,4)Glc(alpha) IgM antibodies were found to be specific for MS patients, enabling differentiation between MS patients and patients with other neurological diseases, with 54% sensitivity and 85% specificity. Anti-Glc(alpha1,4)Glc(alpha) IgM were found to be predictive for the conversion of patients in first acute neurological event to clinically defined MS. Anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-chitobioside (ACCA) antibodies were found to be specific for CD. The combined use of these antibodies enables improved diagnosis of CD versus ulcerative colitis and other gastrointestinal diseases, as well as stratification of CD patients with a more complicated disease and high risk for surgery. Anti-glycan antibodies profiling (AGAP) is a new and promising approach for development of biomarkers for diagnosis and prognosis.

Antibodies↗

PubMed2006

[Inhibition of plasmatic coagulation: what is new?].

The major goal in the development of new anticoagulant drugs is a more effective action with less adverse effects. Until now the mainly used agents are heparin and phenprocoumon or warfarin. These drugs inhibit multiple coagulation factors in different stages of the coagulation cascade. Modern drug development and the knowledge about the molecular mechanisms of the coagulation cascade allow specific inhibition of distinct phases of thrombus formation. This review focuses on the new developments in this area.

Anticoagulants↗

PubMed2005

Antibiotic prophylaxis in severe acute pancreatitis.

Severe acute pancreatitis is considered to be a subgroup of acute pancreatitis with the development of local and/or systemic complications. A significant correlation exists between the development of pancreatic necrosis, the frequency of bacterial contamination of necrosis and the evolution of systemic complications. Bacterial infection and the extent of necrosis are determinants for the outcome of severe acute pancreatitis. The late course of necrotizing pancreatitis is determined by bacterial infection of pancreatic and peripancreatic necroses. Mortality increases from 5-25% in patients with sterile necrosis to 15-28% when infection has occurred. The use of prophylactic antibiotics has been recommended in patients with necrotizing pancreatitis. Several controlled clinical trials demonstrated a significant reduction in pancreatic infections or a significant reduction of hospital mortality. However, the results of these clinical trials are controversial and not convincing. Recently, the largest randomized placebo-controlled, double-blind trial has been able to demonstrate that antibiotic prophylaxis with ciprofloxacin and metronidazole has no beneficial effects with regard to the reduction of pancreatic infection and the decrease of hospital mortality. The clinical data from this placebo-controlled trial do not support antibiotic prophylaxis in all patients with necrotizing pancreatitis, but in specific subgroups of patients with pancreatic necrosis and a complicated course.

Acute Disease↗

PubMed2005

The role of the human thalamus in processing corollary discharge.

Corollary discharge signals play an important role in monitoring self-generated movements to guarantee spatial constancy. Recent work in macaques suggests that the thalamus conveys corollary discharge information of upcoming saccades passing from the superior colliculus to the frontal eye field. The present study aimed to investigate the involvement of the thalamus in humans by assessing the effect of thalamic lesions on the processing of corollary discharge information. Thirteen patients with selective thalamic lesions and 13 healthy age-matched control subjects performed a saccadic double-step task in which retino-spatial dissonance was induced, i.e. the retinal vector of the second target and the movement vector of the second saccade were different. Thus, the subjects could not rely on retinal information alone, but had to use corollary discharge information to correctly perform the second saccade. The amplitudes of first and second saccades were significantly smaller in patients than in controls. Five thalamic lesion patients showed unilateral deficits in using corollary discharge information, as revealed by asymmetries compared with the other patients and controls. Three patients with lateral thalamic lesions including the ventrolateral nucleus (VL) were impaired contralaterally to the side of damage and one patient with a lesion in the mediodorsal thalamus (MD) was impaired ipsilaterally to the lesion. The largest asymmetry was found in a patient with a bilateral thalamic lesion. The results provide evidence for a thalamic involvement in the processing of corollary discharge information in humans, with a potential role of both the VL and MD nuclei.

Adult↗

PubMed2005

Interference with MCP-1 gene expression by vector generated triple helix-forming RNA oligonucleotides.

Triple helix-forming oligonucleotides (TFOs) that specifically bind to double-stranded DNA sequences can be rationally designed, while intracellular delivery of single stranded RNA TFOs has not yet been studied in detail. In this report, we demonstrate gene and sequence-specific inhibition of MCP-1 gene expression due to interference of intracellular-generated single-stranded RNA (CU-TFO) with an overlapping SP-1/AP-1 target. Binding of synthetic 19-nucleotide (19-nt) CU-TFO to the MCP-1 promoter duplex was verified by triplex blotting. Furthermore, we confirmed binding of a 1.1-kb fusion transcript containing the 19-nt pyrimidine CU sequence to a plasmid-encoded MCP-1 promoter target duplex at pH 7.0. In tumour necrosis factor-alpha-stimulated HEK cells, CU-TFOs inhibited MCP-1 protein release by 76 +/- 10.2% compared to intracellular-generated control oligonucleotides. Interleukin-8 as a control target gene was not affected by CU-TFO, confirming both highly specific and effective chemokine gene repression by transfectable TFO-shuttle vectors.

Base Sequence↗

PubMed2005

[Guideline conformity and outcome of inpatient treatment for schizophrenia. A clinical comparison].

Patient outcome and guideline conformity in inpatient schizophrenia treatment was systematically evaluated and compared with 597 patients across seven psychiatric hospitals. Patient structure and treatment processes showed a great variability between hospitals. Patient characteristics, especially mental state, and the chronicity of the disease were the strongest predictors of clinical outcome. Outcome evaluation using quality indicators is only possible after case-mix adjustment taking into account prognostic factors. A poorer average clinical outcome was associated with lower guideline conformity in a variety of treatment domains. After case-mix adjustment, benchmarking is an opportunity to improve quality of treatment and promote guideline conformity.

Adult↗

PubMed2005

The bisphosphonate ibandronate improves implant integration in osteopenic ovariectomized rats.

Osteoporosis is known to impair the process of implant osseointegration. Bisphosphonates are drugs that inhibit osteoclast-mediated bone resorption and normalize the high rate of bone turnover that characterizes this disease. Consequently, there is a rationale for using bisphosphonates to enhance the early stabilization of implants in subjects with low bone mass. In this study, 84 rats received titanium-only or hydroxyapatite (HA)-coated titanium femoral implants, 3 months after being ovariectomized (OVX) or sham operated. They were then treated for 4 weeks. The OVX rats were randomly assigned to daily subcutaneous injections of either saline or the bisphosphonate ibandronate (at a dose of 1 microg/kg or 25 microg/kg), while the sham-operated animals received saline throughout. The 1 microg/kg or 25 microg/kg ibandronate doses are considered translatable to doses used to treat osteoporosis and metastatic bone disease (MBD), respectively, in rats, and roughly reflect those used in humans. At the end of the treatment period, bone mineral density (BMD) at the lumbar spine increased in both of the ibandronate-treated groups when compared with the OVX control animals and to a level similar to that of the sham-operated control group. Osseointegration, determined by histomorphometric analysis and expressed as percentage of osseointegration implant surface (OIS), did not differ between groups for the titanium-only implants. For the HA-coated implants, however, OIS was 113.5% and 185% higher in the groups receiving 1 microg/kg or 25 microg/kg ibandronate, respectively, relative to the OVX controls. In turn, the OIS of the HA-coated implants was 56.5% lower in the OVX control group than in the sham control group. These findings clearly demonstrate that OVX-induced osteopenia impairs the osseointegration of HA-coated titanium implants and that ibandronate, administered at doses analogous to those used to clinically treat osteoporosis and MBD, counters this harmful effect. Ibandronate may, therefore, have a role in improving the osseointegration of implants in patients with osteoporosis and MBD.

Animals↗

PubMed2005

Late acute cardiac allograft rejection: new therapeutic options?

BACKGROUND: Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection. METHODS: Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively. RESULTS: Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus. CONCLUSION: In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.

Acute Disease↗

PubMed2005

Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin.

AIM: To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases. DESIGN: Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified. FINDINGS: Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis). CONCLUSION: %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.

Adolescent↗

PubMed2004

Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.

Adolescent↗