Increased hospital costs are associated with low skeletal muscle mass in patients undergoing elective open aortic surgery

Objective

Low psoas muscle area is shown to be an indicator for worse postoperative outcome in patients undergoing vascular surgical. Additionally, it has been associated with longer durations of hospital stay in patients with cancer who undergo surgery and subsequently greater health care costs in Europe and the United States. We sought to evaluate this effect on hospital expenditure for patients undergoing vascular repair in a health care system with universal access.

EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes.

We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each). They were also significantly higher in MSA than in PD and controls (P < 0.05 each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory-supported differential diagnosis of atypical parkinsonian syndromes.     

Trade Herbal Products and Induction of CYP2C19 and CYP2E1 in Cultured Human Hepatocytes

Abstract: The aim of this study was to evaluate in vitro the dose‐dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic activities in cultured human hepatocytes. S‐mephenytoin and chlorzoxazone were used as specific CYP substrates, respectively, and rifampicin was used as a positive induction control for both enzymes. The hepatocytes were exposed to herbal extracts in increasing and biological relevant concentrations for 72 hrs and CYP substrate metabolites were quantified by validated HPLC methodologies. The major findings were that St John's wort was the most potent CYP‐modulating herb, showing a dose‐dependent induction/inhibition of both CYP2C19 and CYP2E1, with induction at low dosages and inhibition at higher. Ginkgo biloba showed an induction/inhibition profile towards CYP2C19 which was similar but weaker than that observed for St John's wort. If cooperative mechanisms are involved is still an open question. Common sage induced CYP2C19 in a log‐linear dose‐dependent manner with increasing concentrations. Common valerian was a weak inducer of CYP2C19, while horse chestnut and cone flower were characterized as non‐inducers of CYP2C19. Only St John's wort showed an inductive effect towards CYP2E1. In addition to St John's wort, Gingko biloba and common sage should be considered as possible candidates for clinically relevant drug‐herb interactions with selected CYP2C19 substrates.     

Surgical epicardial left ventricular lead versus coronary sinus lead placement in biventricular pacing.

OBJECTIVE: Biventricular pacing has demonstrated improvement in cardiac function in treating congestive heart failure (CHF). Two different operative strategies (coronary sinus vs. epicardial stimulation) for left ventricular (LV) pacing were compared. METHODS: Since April 1999, a total of 86 patients (pts, age: 63+/-10 years) with depressed systolic LV function (mean ejection fraction 24+/-9%), left bundle-branch-block (mean QRS 182+/-22 ms) and congestive heart failure NYHA III or higher were enrolled. For biventricular stimulation coronary sinus (CS) leads were placed in 79 pts. Nine of these devices were converted to surgical epicardial LV-leads, because of CS-lead failure. In 7 patients epicardial LV-leads were initially implanted surgically, accounting for a total of 16 pts with surgical placed epicardial steroid-eluting LV-leads. For these, a limited left-lateral thoracotomy (7+/-4 cm) was used. Thirty-three (38%) pts had an indication for a defibrillator. The mean follow-up time was 16.4+/-15.4 months (0.1-45 months), representing 107.1 patient-years. RESULTS: In the biventricular pacing mode, QRS duration decreased to 143+/-16 ms (P<0.001). Threshold capture of the CS-leads increased significantly compared to surgically placed epicardial leads (18 month control: 2.2+/-1.4V/0.5 ms vs. 0.7+/-0.3V/0.5 ms), which had no increase in threshold (P<0.001). At the 18 month follow-up 7 CS-leads had a threshold of >4V/0.5 ms vs. epicardial leads which were under 1.1V/0.5 ms, except for one (1.8V/0.5 ms). After CS-lead implantation 25 LV-lead related complications occurred, (failed implantation, CS-dissection, loss of pacing capture, diaphragm stimulation or lead dislodgment), vs. one dislodgement after surgical epicardial lead placement (P<0.05). Correct lead positioning (obtuse marginal branch area) was achieved in all surgical epicardial placements but only in 70% with CS-leads (P<0.03). In the follow up period, 9 pts died (4 cardiac related). Heart transplantation was necessary in 4 pts due to deterioration of the cardiomyopathy. CONCLUSIONS: Surgical epicardial lead placement revealed excellent long-term results and a lower LV-related complication rate compared to CS-leads. Although, the approach via limited thoracotomy for biventricular pacing is associated with 'more surgery', it is a safe and reliable technique and should be considered as an equal alternative.     

The effects of running and meditation on beta-endorphin, corticotropin-releasing hormone and cortisol in plasma, and on mood

The relations between three hormones of the hypothalamic-pituitary-adrenocortical (HPA) axis, beta-endorphin (β-EP), corticotropin-releasing hormone (CRH) and cortisol, and mood change were examined in 11 elite runners and 12 highly trained meditators matched in age, sex, and personality. Despite metabolic differences between running and meditation, we predicted that mood change after these activities would be similar when associated with similar hormonal change. Compared to pre-test and control values, mood was elevated after both activities but not significantly different between the two groups at post-test. There were significant elevations of β-EP and CRH after running and of CRH after meditation, but no significant differences in CRH increases between groups. CRH was correlated with positive mood changes after running and meditation. Cortisol levels were generally high but erratic in both groups. We conclude that positive affect is associated with plasma CRH immunoreactivity which itself is significantly associated with circulating β-EP supporting a role for CRH in the release of β-EP. Increased CRH immunoreactivity following meditation indicates, however, that physical exercise is not an essential requirement for CRH release.     

Syntheses of Novel Pyridazinomorphinans by Inverse Electron Demand Cycloaddition and their Binding to μ and κ Receptors

A number of novel pyridazinomorphinans have been synthesized by the inverse electron demand Diels-Alder reaction of various 3,6-disubstituted 1,2,4,5-tetrazines with enamines derived from dihydrocodeinone and with codeinone. Reduction of some of the pyridazinomorphinans did not furnish the expected pyrroloepoxymorphinans; in all cases investigated reductive cleavage of the epoxybridge was observed to yield dihydropyridazino- or pyrrolomorphinans. The structures of all new compounds were assigned by the spectral data, that of the cycloadduct of codeinone was additionally verified by X-ray crystallography. Compounds 5a, 8, 11a , and 16 have been evaluated for their affinity at μ and κ opioid receptors in radioligand binding assays. Their ability to inhibit [³H]DAMGO binding at μ and [³H]U 69.593 binding at κ receptors, respectively as compared to codeine has been found to be lower.     

EMPACT syndrome

Background: Seizure prophylaxis with phenytoin is a common measure in oncologic patients with brain metastases. In these patients, generalized severe adverse drug reactions such as erythema multiforme (EEM) may occur. However, in a subgroup of patients with brain radiation therapy, EEM‐like lesions develop particularly in the radiation field. Most recently, the acronym EMPACT ( E rythema M ultiforme associated with P henytoin A nd C ranial radiation T herapy) was proposed to specifically describe this syndrome. Patient/Method: Here, we report on EMPACT syndrome in a 46‐year‐old woman. Therapeutic measures included seizure prophylaxis with phenytoin and total brain radiation therapy of brain metastases from bronchial carcinoma. Three weeks after introduction of phenytoin, the patient presented with EEM‐like skin lesions restricted to the original radiation field and facial mucocutaneous involvement. After a few days, the rash spread to the upper part of the body. She was also in poor general condition. Results: The immediate cessation of phenytoin therapy, combined with administration of systemic corticosteroids and high dose immunoglobulins along with intensive local treatment and pain medications, resulted in complete resolution of the skin eruption. Patch testing to phenytoin was positive after 72 hours. Conclusion: EMPACT should be classified as an specific entity among the EEM‐like drug reactions as it only appears after radiotherapy and seizure prophylaxis with the anticonvulsant phenytoin. We propose including specific type IV‐sensitization to phenytoin into the definition of EMPACT.