Elevated hair cortisol concentrations in recently fled asylum seekers in comparison to permanently settled immigrants and non-immigrants.

Recently fled asylum seekers generally live in stressful conditions. Their residency status is mostly insecure and, similar to other immigrants, they experience stress due to acculturation. Moreover, they often suffer from traumatization and posttraumatic stress disorder (PTSD). All of these factors can result in chronic maladaptive biological stress responses in terms of hyper- or hypocortisolism and, ultimately, illness. We believe the current study is the first to compare hair cortisol concentration (HCC) of recently fled asylum seekers with PTSD to those without PTSD, and to compare HCC of asylum seekers to HCC of permanently settled immigrants and non-immigrant individuals. HCC of the previous 2 months was compared between 24 asylum seekers without PTSD, 32 asylum seekers with PTSD, 24 permanently settled healthy Turkish immigrants and 28 non-immigrant healthy Germans as the reference group. Statistical comparisons were controlled for age, sex and body mass index. No significant difference in HCC was found between asylum seekers with and without PTSD. However, the asylum seekers showed a 42% higher HCC than the reference group. In contrast, the permanently settled immigrants exhibited a 23% lower HCC than the reference group. We found relative hypercortisolism in recently fled asylum seekers, but no difference between persons with and without PTSD. These findings add to the very few studies investigating HCC in groups with recent traumatization and unsafe living conditions. Contrary to the findings in asylum seekers, permanently settled immigrants showed relative hypocortisolism. Both hyper- and hypocortisolism may set the stage for the development of stress-related illnesses.

Medium- and long-term prognostic validity of competing classification proposals for the former somatoform disorders.

BACKGROUND: DSM-5 introduced a fundamental revision of the category of somatoform disorders, which resulted in the new somatic symptom disorder (SSD) and related disorders. However, prognostic validity of SSD remains unclear, while other classification proposals, such as bodily distress disorder (BDD) or polysymptomatic distress disorder (PSDD), might be promising alternatives for the new ICD-11. Therefore, the comparison of the different approaches concerning long-term prognosis of disorder-relevant factors is of special interest. METHOD: In a longitudinal design (baseline, 1-year, and 4-year follow-up), the three proposals (SSD, BDD, PSDD) were compared in an age-representative sample of the German general population (N = 321). To this end, the baseline sample was divided into three independent pairs of groups (with/without SSD, with/without BDD, with/without PSDD). It was tested how well each approach differentiated with regard to medium- and long-term healthcare utilization, number of symptoms, and impairment. RESULTS: Criteria for BDD distinguished best with regard to future healthcare utilization resulting in a large-sized effect (f = 0.44) for the difference between persons with and without BDD, while SSD and PSDD revealed only medium-sized effects (f = 0.28 and f = 0.32) between subjects with and without diagnosis. The three proposals distinguished equally well with regard to future subjective impairment (between f = 0.39 and f = 0.41) and the number of reported symptoms (between f = 0.77 and f = 0.83). CONCLUSION: In accordance with our data regarding prognostic validity, the current draft of the WHO group is based on the BDD proposal. However, existing limitations and weaknesses of the present proposal for the ICD-11 are further discussed.

[Preventive pain therapy. Preventive tramadol infusion versus bolus application in the early postoperative phase]. / Präventive Schmerztherapie. Präventive Tramadolinfusion versus Bolusapplikation in der frühen postoperativen Phase.

Even today, adequate postoperative analgesia is still a great problem. Based on positive results of former studies using a continuous infusion of tramadol for postoperative pain relief, we aimed to improve this regimen. In order to investigate the effectiveness of preventive analgesia, one group of patients was given 100 mg tramadol (Tramal) at the time of extubation, followed by a maintenance infusion. The other group was treated with single boluses of tramadol on demand, thus representing common pain treatment. METHODS. 112 patients undergoing abdominal surgery were chosen at random for this double-blind study. Half of them (preventive group) received an injection of 100 mg tramadol at the time of extubation; the others (on-demand group) were given a placebo instead. A continuous infusion of 500 ml NaCl 0.9% (administered with 30 ml/h) followed, either containing 200 mg tramadol (preventive group) or a placebo (on-demand group) and was maintained until the end of the study. At the first expression of pain, patients in the preventive group received 50 mg tramadol (representing the first subsequent injection) whereas patients of the on-demand group were given 100 mg tramadol as a loading dose. For further treatment of pain, the members of both groups received 50 mg tramadol when necessary. The level of pain was assessed by means of VAS (visual analogue scale) every hour and additionally at first expression of pain, and finally by VRS (verbal rating scale) after eight hours at the end of the study. RESULTS. 112 patients were chosen at random. 18 had to be excluded--two treatment failures, twelve violations of the study protocol and four patients of the on-demand group, who did not ask for treatment for pain and therefore did not receive any tramadol. Hence only 94 patients could be statistically evaluated. 50% of the remaining 48 patients in the preventive group needed none or only one subsequent injection of tramadol, the other 50% needed two or more subsequent injections. However the patients in the on-demand group, now 46, split up into 71.7% who where administered up to one subsequent injection and 28.3% who received more than one subsequent injection. The number of patients who asked for treatment for pain twice or more during the study period totalled 50% in the preventive group and 58.7% in the on-demand group. The average interval between extubation and first expression of pain was 106.3 +/- 84.2 min in the preventive group, and 75.0 +/- 22.7 min in the on-demand group. The intensity of pain evaluated by VAS as that time was comparable: 55.6 +/- 22.7 (preventive) versus (63.4 +/- 18.3 (on demand). The pain relief obtained, shown by the VAS-differences between the first expression of pain and following assessment, came up to 27.7 +/- 22.9 in the preventive group and 30.3 +/- 23.4 in the on-demand group within a period of 46.2 +/- 17.2 min (preventive) and 43.7 +/- 17.2 min (on-demand). Retrograde assessment of pain (VRS) showed that 85.5% of the preventive group found pain relief excellent or good and 78.3% of the on-demand group were of the same opinion. Total consumption of tramadol totalled 281.4 +/- 53.6 mg in the preventive group in comparison with 150.0 +/- 53.7 mg in the on-demand group. CONCLUSIONS. Only 28.3% of patients of the on-demand group received more than one subsequent injection of tramadol in comparison with 50% of the preventive group--an unexpected result. However, it has to be considered that the injection of tramadol given at the first expression of pain in the preventive group was counted as the first subsequent injection already. The patients in the preventive group asked, on average, 30 min later for treatment for pain. The subsequent pain relief in both groups was comparable, although the amount of tramadol administered at that time was higher in the on demand group than in the preventive group (100 mg versus 50 mg+ amount given by infusion). These facts show the efficacy of the preventive infus

[Postoperative analgesia with tramadol. Continuous infusion versus repetitive bolus administration]. / Postoperative Analgesie mit Tramadol. Kontinuierliche Infusion versus repetitive Bolusgabe.

Postoperative pain relief can be achieved by several methods, including the use of systemic opioids and regional anaesthesia with intrathecal or epidural opioids or local anaesthetics. On-demand analgesia using a PCA (patient-controlled analgesia) system is regarded as the ideal option for systemic opioid analgesia. While PCA devices are not yet commonly used in all recovery units, the use of repetitive boluses on demand is still the most frequent form of administration in postoperative pain therapy. The objective of the present study was to show if continuous infusion of the opioid tramadol could produce better analgesia than repetitive administration of boluses. METHOD. In a study under double-blind conditions 135 ASA I and II patients were assigned at random to group I (infusion group) or group B (bolus group) when they first requested pain treatment after abdominal surgery. The patients in group I received an initial intravenous loading dose of 100 mg tramadol, followed by an infusion of 12 mg/h tramadol for 24 h; if necessary, repeated boluses of 50 mg tramadol were given. In group B the patients received a placebo infusion instead of the tramadol infusion; otherwise, the procedure was the same. Pain relief was monitored by means of a VAS (visual analogue scale) up to 6 h after surgery. We investigated the retrograde assessment of analgesia by the patients after 6 h, how often repetitive boluses were required, and the amount of analgesics administered in 6 and 24 h. RESULTS. The pain relief was assessed as excellent or good by 76.5% of group I and 65.6% of group B; 19.1% of group I and 26.9% of group B assessed the analgesic effect as satisfactory; 4.4% of group I and 7.5% of group B complained of insufficient analgesia. In group I 69.2% requested only one or no repetitive bolus, compared with 40.3% in group B, while two or more boluses were demanded by 30.8% in group I und 59.7% in group B. The average analgesic consumption after 6 h was 223.5 +/- 53.7 mg tramadol in group I and 176.6 +/- 63.1 mg tramadol in group B, respectively. After 24 h it was 449.5 +/- 66.0 mg tramadol in group I and 201.6 +/- 83.9 mg tramadol in group B. While the consumption during the first 6 h was comparable, from then on the consumption in group I increased significantly. Side effects were reported by 25% in both groups. They were clinically irrelevant and did not necessitate termination of the clinical trial in any case. During the study period pulse and blood pressure remained within the normal range and did not show any significant changes. CONCLUSION. The fact that the patients in group I requested far fewer repetitive boluses than those in group B and the assessment by the patients led to the conclusion that treatment in the infusion group is better than that in the bolus group. Concerns that a significantly higher consumption of analgesics would cause unwanted side-effects have proven unfounded. Six hours after surgery, when analgesia was evaluated by the patients, there was no significant difference between the two groups. Not until the maintenance infusion had been administered for a further 18 h, was the tramadol consumption within the infusion group significantly higher. Thus, we should consider continuing unreduced administration of the maintenance infusion 6 h after operation.

[Discontinuity resection of the colon. Indications and results]. / Die Diskontinuitätsresektion des Colons. Indikation und Ergebnisse.

In 83 patients discontinuity resection of the colon was performed. Due to negative selection factors postoperative mortality was 26.5%. In 37 patients continuity of the colon was restored, no patient died postoperatively. The only severe complication was formation of a colovesical fistula requiring a pull-through operation.

Phosphorylation of purified bovine cardiac sarcolemma and potassium-stimulated calcium uptake.

Sarcolemmal vesicles were prepared from bovine cardiac muscle by differential and discontinuous sucrose density gradient centrifugation. Na+/K+-ATPase was purified 33-fold to a specific activity of 53 +/- 0.5 (12) mumol Pi X mg-1 X h-1, binding sites for strophantin 20-fold to a density of 56.3 +/- 5.3 (14) pmol/mg and that for the calcium antagonist nitrendipine 5.5-fold to a density of 0.72 +/- 0.07 (6) pmol/mg. The specific activity of the Na+/Ca2+ exchanger was 61.1 +/- 3.7 (6) nmol/mg. The vesicles had an intravesicular volume of 20 +/- 4 (4) microliter/mg and 56.9 +/- 6 (4)% of the vesicles were right-side-out oriented. Several peptides of the purified membranes were phosphorylated in the presence of Mg . ATP and EGTA. Most of the radioactive phosphate was incorporated into a peptide with an apparent molecular mass of 22 kDa. Denaturation of the membranes at 100 degrees C changed the mobility of this peptide to 15 kDa and 11 kDa. This peptide could not be distinguished from a sarcoplasmic reticulum peptide of similar molecular mass. The phosphorylation of the sarcolemmal peptide was stimulated by Ca2+/calmodulin, cAMP and the catalytic subunit of cAMP-dependent protein kinase. A comparison of the phosphorylation of sarcolemmal membranes with that of sarcoplasmic reticulum showed that Ca2+/calmodulin stimulated in each membrane, the phosphorylation of the 22-kDa peptide and a 44-kDa peptide, and in the sarcoplasmic reticulum the phosphorylation of an additional peptide of 55-kDa. Ca2+/calmodulin-dependent phosphorylation of a 55-kDa peptide could not be demonstrated in sarcolemma, regardless if sarcolemmal membranes were incubated together with sarcoplasmic reticulum or if the phosphorylation was carried out in the presence of purified cardiac myosin light chain kinase or phosphorylase kinase. 'Depolarization' induced Ca2+ uptake which was measured according to Bartschat, D.K., Cyr, D.L. and Lindenmayer, G.E. [(1980) J. Biol. Chem. 255, 10044-10047] was 5 nmol/mg protein. This uptake was not enhanced after preincubation of the vesicles with Mg . ATP or Mg . ATP and cAMP-dependent protein kinase. The value of 5 nmol/mg protein is in agreement with the theoretical amount of Ca2+ which can be accumulated by the bovine cardiac sarcolemma in the absence of a driving force other than the Ca2+ gradient. The potassium-stimulated Ca2+ uptake was not blocked by the organic Ca2+ channel blockers. Prolonged incubation of Mg . ATP with sarcolemmal vesicles in the presence of various ATPase inhibitors led to the hydrolysis of ATP. The liberated phosphate precipitated with Ca2+ in the presence of LaCl3. These precipitates amounted to an apparent Ca2+ uptake ranging from 50 to over 1000 nmol/mg. The results suggest that potassium-stimulated Ca2+ uptake of bovine cardiac sarcolemmal vesicles is not enhanced in the presence of ATP or by phosphorylation of a 22-kDa peptide.

Identification of voltage operated calcium channels by binding studies: differentiation of subclasses of calcium antagonist drugs with 3H-nimodipine radioligand binding.

3H-Nimodipine (3H-NIM) is a high affinity radioligand suitable to study Ca2+ -channels in a variety of tissues. The binding is saturable, reversible, and stereospecific in purified bovine heart and partially purified guinea-pig brain membranes. In the latter a Bmax of 600fmol/mg protein, dissociation constants (KD) of 0.4-0.8nM and a Hill slope of 1.0 are found. At 37 degrees C the optimal pH in 50mM TRIS-HCl buffer is 7.1-7.4. The calcium channel is a metalloprotein, and the divalent cation which is essential for the binding of 3H-NIM can be removed by EDTA (EC50 20 microM); the nimodipine binding site of the channel may then be reconstituted by divalent cations with Mn2+ greater than Ca2+ greater than Mg2+ greater than Sr2+. Ca2+ -antagonist drugs can be divided into three main classes based on their interaction with the 3H-NIM binding site: Class I has one site law of mass action-displacement isotherms with 3H-NIM, Class II exhibits complex biphasic inhibition profiles and Class III drugs increase the affinity of 1,4 dihydropyridines for the Ca2+ -channel. Diltiazem is a Class III Ca2+ -antagonist. Our in vitro studies lead us to conclude that the Ca2+ -channel contains multiple regulatory sites at which drugs can act.