Medizin - Open Access LMU - Teil 13/22

Little is known about the effects of spiritual care training for professionals in palliative medicine. We therefore investigated prospectively the effects of such training over a six-month period. All 63 participants of the three and a half-day training were asked to fill out three questionnaires: before and after the training, as well as six months later. The questionnaires included demographic data, numeric rating scales about general attitudes towards the work in palliative care, the Self-Transcendence Scale (STS), the spiritual subscale of the Functional Assessment of Chronic Illness Therapy (FACIT-Sp) and the Idler Index of Religiosity (IIR). Forty-eight participants (76) completed all three questionnaires (91 women, median age 49 years; 51 nurses, 16 hospice volunteers, 14 physicians).Significant and sustained improvements were found in self-perceived compassion for the dying (after the training: P =0.002; 6 months later: P=0.025), compassion for oneself (P < 0.001; P =0.013), attitude towards one's family (P =0.001; P =0.031), satisfaction with work (P < 0.001; P =0.039), reduction in work-related stress (P < 0.001; P =0.033), and attitude towards colleagues (P =0.039; P =0.040), as well as in the FACIT-Sp (P < 0.001; P =0.040). Our results suggest that the spiritual care training had a positive influence on the spiritual well-being and the attitudes of the participating palliative care professionals which was preserved over a six-month period.

In the treatment of dysgeusia, the use of zinc has been frequently tried, with equivocal results. The aim of the present randomized clinical trial, which involved a sufficiently large sample, was therefore to determine the efficacy of zinc treatment. Fifty patients with idiopathic dysgeusia were carefully selected. Zinc gluconate (140 mg/day; n = 26) or placebo (lactose; n = 24) was randomly assigned to the patients. The patients on zinc improved in terms of gustatory function (p < 0.001) and rated the dysgeusia as being less severe (p < 0.05). Similarly, signs of depression in the zinc group were less severe (Beck Depression Inventory, p < 0.05; mood scale, p < 0.05). With the exception of the salivary calcium level, which was higher in the zinc patients (p < 0.05), no other significant group differences were found. In conclusion, zinc appears to improve general gustatory function and, consequently, general mood scores in dysgeusia patients.

Pulpotomy is the accepted therapy for the management of cariously exposed pulps in symptom-free primary molars; however, evidence is lacking about the most appropriate technique. The aim of this study was to compare the relative effectiveness of the Er:YAG laser, calcium hydroxide, and ferric sulfate techniques with that of dilute formocresol in retaining such molars symptom-free. Two hundred primary molars in 107 healthy children were included and randomly allocated to one of the techniques. The treated teeth were blindly re-evaluated after 6, 12, 18, and 24 months. Descriptive data analysis and logistic regression analysis, accounting for each patient's effect by a generalized estimating equation (GEE), were used. After 24 months, the following total and clinical success rates were determined (%): formocresol 85 (96), laser 78 (93), calcium hydroxide 53 (87), and ferric sulfate 86 (100). Only calcium hydroxide performed significantly worse than formocresol (p = 0.001, odds ratio = 5.6, 95% confidence interval 2.0-15.5). In conclusion, calcium hydroxide is less appropriate for pulpotomies than is formocresol.

Diabetic patients with acute coronary syndromes

are at high risk for cardiovascular complications

but risk stratification in these patients remains

challenging. Regularly, diabetic patients have a less typical

clinical presentation, which could lead to delayed

diagnosis and subsequent delayed initiation of treatment.

Since diabetic patients derive particular benefit

from aggressive anti-platelet therapy, early diagnostic

and therapeutic risk stratification of these patients is of

critical importance to improve their adverse outcome.

Although the electrocardiogram remains a pivotal

diagnostic tool in the evaluation of patients suspected of

having an acute coronary syndrome, only significant STsegment

changes provide reasonable prognostic information.

Therefore, repeated assessment of circulating

protein biomarkers represents a valuable diagnostic tool

for improving efficacy and safety of decision-making in

these patients. The combined use of biomarkers reflecting

distinct pathophysiological aspects, such as myocardial

necrosis, vascular inflammation, oxidative stress

and neurohumoral activation, may significantly improve

triage of patients with chest pain. These tools may identify

those patients that are at particularly high risk for

short-term and/or long-term cardiovascular events.

Eventually, tailored medical and interventional treatment

of diabetic patients should help to prevent these cardiac

events in a cost-effective manner.

Following the current hypothesis that acute schizophrenic psychotic illness is associated with a triatal ‘hyperdopaminergic state’, presynaptic integrity and dopamine transporter (DAT) density in first-episode, neuroleptic-naive schizophrenic patients was measured by single-photonemission- tomography (SPECT) and compared with that in healthy control subjects. A new SPECT-ligand for assessment of the striatal DAT, the Technetium-99m-labelled tropane TRODAT-1 ([99mTc]TRODAT-1), was used. Ten inpatients suffering from a first acute schizophrenic episode and 10 age- and sex-matched healthy control subjects underwent SPECT with [99mTc]TRODAT-1. On the day of SPECT, psychopathological ratings were performed with the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and Schedule for Assessment of Negative Symptoms (SANS). Patients had not previously received any neuroleptic or antidepressant medication. Mean specific TRODAT-1 binding in the striatum did not differ significantly between the patient and the age- and sex-matched control group (1.25 vs. 1.28). Variance was significantly higher in the patient group. The data obtained with the new ligand in first-episode, drug-naive schizophrenic patients are in line with the PET results from the group of Laakso et al. in a comparable patient sample. [99mTc]TRODAT-1 seems to be a valuable new SPECTligand in the evaluation of the presynaptic site of the striatal dopaminergic synapse in schizophrenia.

Toll-like receptor (TLR)-9 recognizes CpG motifs in microbial DNA. TLR9 signalling stimulates innate antimicrobial immunity and modulates adaptive immune responses including autoimmunity against chromatin, e.g., in systemic lupus erythematosus (SLE). This review summarizes the available data for a role of TLR9 signalling in lupus and discusses the following questions that arise from these observations: 1) Is CpG-DNA/TLR9 interaction involved in infection-induced disease activity of lupus? 2) What are the risks of CpG motifs in vaccine adjuvants for lupus patients? 3) Is TLR9 signalling involved in the pathogenesis of lupus by recognizing self DNA?

This study aimed to test the utility of the ozone challenge model for profiling novel compounds designed to reduce airway inflammation. The authors used a randomized, doubledummy, double-blind, placebo-controlled 3-period crossover design alternating single orally inhaled doses of fluticasone propionate (inhaled corticosteroids, 2mg), oral prednisolone (oral corticosteroids, 50mg), ormatched placebo. At a 2-week interval, 18 healthy ozone responders (>10% increase in sputum neutrophils) underwent a 3-hour ozone (250 ppb)/intermittent exercise challenge starting 1 hour after drug treatment. Airway inflammation was assessed at 2 hours (breath condensate) and 3 hours (induced sputum) after ozone challenge. Compared to placebo, pretreatment with inhaled corticosteroids or oral corticosteroids resulted in a significant reduction (mean [95% confidence interval]) of sputum neutrophils by 62% (35%, 77%) and 64% (39%, 79%) and of sputum supernatant myeloperoxidase by 55% (41%, 66%) and 42% (25%, 56%), respectively. The authors conclude that an optimized ozone challenge model (including ozone responders and ensuring adequate drug levels during exposure) may be useful for testing novel anti-inflammatory compounds in early development.

Background: Bile acid-induced apoptosis in hepatocytes can be antagonized by NF-κBdependent

survival pathways. Sulfasalazine modulates NF-κB in different cell types. We aimed

to determine the effects of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic

acid (5-ASA) on bile acid-induced apoptosis in hepatocytes.

Methods: Apoptosis was determined by caspase assays and immunoblotting, NF-κB activation

by EMSA and reporter gene assays, generation of reactive oxygen species (ROS)

fluorometrically, bile secretion gravimetrically and bile acid uptake radiochemically and by

gaschromatography in HepG2-Ntcp cells and isolated perfused rat livers.

Results: Glycochenodeoxycholic acid (GCDCA, 75μmol/L)-induced apoptosis was reduced by

sulfasalazine dose-dependently (1-1000 μmol/L) in HepG2-Ntcp cells, whereas its metabolites 5-

ASA and sulfapyridine had no effect. Sulfasalazine significantly reduced GCDCA-induced

activation of caspases 9 and 3. In addition, sulfasalazine activated NF-κB, and decreased

GCDCA-induced generation of ROS. Bile acid uptake was competetively inhibited by

sulfasalazine. In perfused rat livers, GCDCA (25 μmol/L)-induced liver injury and extensive

hepatocyte apoptosis were significantly reduced by simultaneous administration of 100 μmol/L

sulfasalazine: LDH and GPT activities were reduced by 82% and 87%, respectively, and

apoptotic hepatocytes were observed only occasionally. GCDCA uptake was reduced by 45±5%

when sulfasalazine was coadministered. However, when 50% of GCDCA (12.5 μmol/L) were

administered alone, marked hepatocyte apoptosis and liver injury were again observed

questioning the impact of reduced GCDCA uptake for the antiapoptotic effect of sulfasalazine.

Conclusion: Sulfasalazine is a potent inhibitor of GCDCA-induced hepatocyte apoptosis in vitro

and in the intact liver.

Background/Aims

The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes

substantially to the enterohepatic circulation of bile acids by their reabsorption from

the intestine. In the rat, its adaptive regulation was observed in the kidneys,

cholangiocytes and terminal ileum after bile duct ligation. Whether an adaptive

regulation of the human intestinal ASBT exists during obstructive cholestasis is not

known.

Methods

Human ASBT mRNA expression along the intestinal tract was analyzed by real time

PCR in biopsies of 14 control subjects undergoing both gastroscopy and

colonoscopy. Their duodenal ASBT mRNA expression was compared to 20 patients

with obstructive cholestasis. Additionally, in 4 patients with obstructive cholestasis,

duodenal ASBT mRNA expression was measured after reconstitution of bile flow.

Results

Normalized ASBT expression in control subjects was highest (mean arbitrary units±

SEM) in the terminal ileum 1010 ± 330. Low ASBT expression was found in the

colonic segments (8.3±5, 4.9±0.9, 4.8±1.7 and 1.1±0.2, ascending, transverse,

descending, and sigmoid colon, respectively). Duodenal ASBT expression of control

subjects was found with 171.8±20.3 at about four fold higher levels when compared

to 37.9±6.5 (p<0.0001) in patients with obstructive cholestasis. Individual ASBT

mRNA expression was inversely correlated with bile acid and bilirubin plasma

concentrations. In 4 cholestatic patients average ASBT mRNA increased from 76±18

before to 113±18 after relief of cholestasis (NS). Immunohistochemical assessment

indicates that ASBT protein is expressed on the apical surface of the duodenal

epithelial cells.

Conclusion

Obstructive cholestasis in humans leads to down-regulation of ASBT mRNA

expression in the distal part of the human duodenum.