Isoflurane reduces glutamatergic transmission in neurons in the spinal cord superficial dorsal horn: evidence for a presynaptic site of an analgesic action

The minimum alveolar concentration (MAC) of a volatile anesthetic defines anesthetic potency in terms of a suppressed motor response to a noxious stimulus. Therefore, the MAC of an anesthetic might in part reflect depression of motor neuron excitability. In the present study we evaluated the effect of isoflurane (ISO) on neurons in the substantia gelatinosa driven synaptically by putative nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell patch-clamp recordings were performed in neurons with their soma in the substantia gelatinosa of transverse rat spinal cord slices. We investigated the effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO reversibly reduced the amplitude of eEPSC to 39% +/- 22% versus control. ISO decreased the frequency of sEPSC and mEPSC to 39% +/- 26% and 63% +/- 7%. Neither the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We conclude that ISO depresses glutamatergic synaptic transmission of putative nociceptive primary-afferent inputs, presumably by reducing the release of the excitatory transmitter. This effect may contribute to an antinociceptive action of volatile anesthetics at the spinal cord level. IMPLICATIONS: The present electrophysiological in vitro experiments provide evidence that the volatile anesthetic isoflurane reduces excitatory transmitter release at the first site of synaptic integration of nociceptive inputs, the spinal cord superficial dorsal horn. This effect may contribute to the anesthetic action of volatile anesthetics at the spinal cord level.     

Respiratory lumenal change of the pharynx and trachea in normal subjects and COPD patients: assessment by cine-MRI

The purpose of this study was to use cine-MRI during continuous respiration to measure the respiratory lumenal diameter change in the pharynx and at an upper tracheal level. Fifteen non-smokers and 23 chronic obstructive pulmonary disease (COPD) patients with smoking history (median 50 pack-years) were included. Cine-MRI with seven frames/s was performed during continuous respiration. Minimal and maximal cross-sectional lumenal diameters within the pharynx and the upper tracheal lumen area were measured. The median diameter change in the pharynx (tracheal area) was 70% (1.4 cm(2)) in volunteers and 76% (1.7 cm(2)) in smokers (P=0.98, P=0.04). Tracheal lumenal collapse was a median of 43% in volunteers and 64% in smokers (P=0.011). No clear disease-related difference of the pharynx-lumen was found. The maximal cross-sectional area of the upper trachea lumen as well as the respiratory collapse was larger in COPD patients than in normal subjects. This information is important for the modelling of ventilation and prediction of drug deposition, which are influenced by the airway diameter.     

3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent

The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40°; voxel size: 1.3×2.5×4.0 mm³; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40°; voxel size: 0.8×1.0×1.6 mm³) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n=2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21±8 vs. 13±3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer.     

The role of MRI in patients with astrocytoma WHO II treated with fractionated stereotactic radiotherapy

Aim of this study was to evaluate the role of pre-therapeutic and follow-up MRI in the clinical treatment and outcome in patients with astrocytoma WHO grade II after fractionated stereotactic radiation therapy (FSRT). One hundred thirty-nine patients with histologically proven astrocytoma WHO grade II were treated with FSRT and retrospectively evaluated. All patients had follow-up MRI studies (Gd-DTPA-enhanced T1- and T2-weighted MR images). Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed on five potential MRI related prognosticators. Median follow-up was 3.8 years. Positive contrast enhancement (CM+) prior to FSRT proved to be a significant prognosticator for PFS and OS (p<0.01). Pre-therapeutic oedema on T2-weighted images and multifocality of contrast medium (CM) enhancement did not prove to be significant prognosticators. Also, diameter and volume of CM enhancement showed no significance on clinical outcome. Negative contrast enhancing (CM–) patients developing a de novo CM enhancement during follow-up showed a significantly worse clinical outcome compared with generally CM– patients (p<0.05). Pre-therapeutic CM enhancement and the development of CM-enhancing areas during follow-up are negative prognosticators for PFS and OS. They must be interpreted as signs of secondary malignity.     

Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells

Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P < 0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6-inducer IL-1beta. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r = 0.33, P < 0.05) and total FFAs (r = 0.29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation.     

Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.     

AC-Verletzungen: konservativ-funktionelle Therapie und Ergebnisse

Injuries involving the acromoclavicular joint account for more than 10% of all injuries to the shoulder girdle, making them the second most frequent type of shoulder injury. When categorized as Tossy I or II such injuries are generally treated conservatively, whereas Rockwood IV–VI injuries are treated operatively. There is still no agreement on the best way of treating Tossy class III injuries. More than 35 conservative treatments have been proposed, and over 50 operative methods. Regardless of the method of treatment applied, relatively good functional results are obtained. Persisting prominence of the clavicle cannot reliably be reduced by strapping, but the reduced shoulder strength that has been claimed to follow conservative treatment has not been verified by strength testing. Furthermore, after surgery rehabilitation takes longer, the period of inability to work and to engage in sporting activities is extended, and the complication rate is higher, in addition to which the costs of surgical treatment are higher. "Skillful neglect" of Tossy I–III injuries combined with brief immobilization of the shoulder joint, cryotherapy and functional treatment seems to be the method of choice even in patients whose work involves hard physical labour and in active athletes.     

Risk factors for premenstrual dysphoric disorder in a community sample of young women: the role of traumatic events and posttraumatic stress disorder

BACKGROUND: There is some evidence that the onset and course of premenstrual syndrome is related to stress; however, few studies have explored the role of traumatic events and post-traumatic stress disorder (PTSD) as risk factors for the development of premenstrual dysphoric disorder (PMDD). METHOD: A community cohort of 1488 women (aged 14-24 years at baseline) were prospectively and longitudinally evaluated up to 3 times over a period of about 42 months from 1995 to 1999. The DSM-IV version of the Munich-Composite International Diagnostic Interview was used to establish PMDD and PTSD diagnostic status; stressful life events and conditions were assessed with the Munich Events List and the Daily Hassles Scale. Prevalence and incidence of either threshold or subthreshold PMDD from baseline to the second follow-up were calculated. Risk factors, including prior comorbid mental disorders and traumatic events, were examined using logistic regression analysis. RESULTS: The incidence of threshold PMDD was 3.0%. The most powerful predictors were subthreshold PMDD at baseline (OR = 11.0, 95% CI = 4.7 to 25.9). Traumatic events greatly increased the odds of developing PMDD at follow-up (OR = 4.2, 95% CI = 1.2 to 12.0). Other predictors were a history of anxiety disorder (OR = 2.5, 95% CI = 1.1 to 5.5) and elevated daily hassles scores (OR = 1.6, 95% CI = 1.1 to 2.3). Both were also associated with the risk of developing subthreshold PMDD, although the association was less robust. CONCLUSIONS: Traumatic events and pre-existing anxiety disorders are risk factors for the development of PMDD. The underlying mechanisms are unknown, making further investigation necessary.     

Is bipolar I disorder heterogeneous?

Abstract.Objectives: The question whether bipolar I disorder should be subdivided into a preponderantly manic group (M) with no depression or only mild depression (Md) and a nuclear manic-depressive group (MD) has been rarely studied although the problem was raised more than 50 years ago. This paper seeks to elucidate this question by contributing further data.Methods: 406 patients with mood disorders hospitalised at some time during the period 1959–1963 were followed-up every five years until 1985; mortality data were collected up to 1997. Data on episodes, outcome, suicides and attempted suicides, alcohol and substance abuse/dependence and long-term medication, as well as on personality (melancholic and manic type) were collected. Major mood disorders were subclassified according to their hospitalisation for depression (D) and/or mania (M).Results: 30 manic patients (M/Md), 130 bipolar I (MD), 60 bipolar II patients (Dm) and 186 major depressive patients (D) were compared. The manic group differed from the bipolar I group in several variables: better school achievement, milder course of the illness (fewer recurrences), significantly less suicidality and a trend to less chronicity and more recovery. Manic patients required less long-term medication than bipolars and they differed in personality types from bipolars, the personality of manic patients being more often of the manic rather than the melancholic type, they were also more aggressive than bipolars. The family history data showed that the overall morbidity risk of first degree relatives of manic patients was significantly lower than that of bipolar patients.Conclusions: In accord with several other studies our data point to the existence of a more manic (M/Md) group of bipolar subjects. The diagnosis predicts a better course, lower suicidality and fewer and different treatment needs than does nuclear bipolar I (MD) disorder. The M/Md groups, as clinically interesting subgroups of the mood spectrum, should become a target of further research.