Effect of long‐chain triglyceride lipid emulsion on bupivacaine‐induced changes in electrophysiological parameters of rabbit Purkinje cells

Lipid emulsions are used in the reversal of local anesthetic toxicity. The aim of this study was to investigate the cellular electrophysiological effects of long‐chain triglyceride lipid emulsion (LCTE) on cardiac action potential characteristics and conduction disturbances induced by bupivacaine. Purkinje fibers were dissected from the left ventricle of New Zealand white rabbit hearts and superfused with either Tyrode's solution during 30 min (control group), with bupivacaine 10^?6 m , 10^?5 m , and 5.10^?5 m alone, or in the presence of LCTE 0.5%, in addition, LCTE at 0.1%, 0.5%, and 1% was perfused alone. Electrophysiological parameters were recorded using the conventional microelectrode technique (37 °C, 1 Hz frequency). Bupivacaine 5.10^?5 m ‐induced conduction blocks (8/8 preparations): LCTE 0.5% suppressed the bupivacaine 5.10^?5 m ‐induced conduction blocks (1/8 preparations). Exposure to bupivacaine 10^?6 m , 10^?5 m , and 5.10^?5 m resulted in a significant decrease in the maximal rate of depolarization (V_max) (respectively, 25%, 55%, 75%; P < 0.002 vs. control group). In the presence of LCTE 0.5%, bupivacaine 10^?6 m did not significantly decreased V_max (13%; P = 0.10 vs. control group). The decrease in V_max resulting from bupivacaine 10^?5 m alone was significantly less in the presence of LCTE 0.5% (P < 0.01 vs. bupivacaine 10^?5 m alone). Exposure to bupivacaine 10^?6 m , 10^?5 m , and 5.10^?5 m alone or in the presence of LCTE 0.5% resulted in a significant decrease in action potential duration measured at 50% and 90% repolarization (APD₅₀ and APD₉₀; P < 0.01 vs. control group). LCTE inhibited the Purkinje fibers conduction blocks induced by bupivacaine. Moreover, LCTE 0.5% attenuates the decrease in V_max induced by bupivacaine 10^?6 m and 10^?5 m .     

Severe excessive daytime sleepiness induced by hydroxyurea

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented.     

Maternally acquired genotoxic Escherichia coli alters offspring’s intestinal homeostasis

The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood.     

Psoriasis from a Prosthesis: Unusual Koebner Phenomenon in a Girl with Autoamputation of the Leg

An 8‐year‐old girl showed psoriatic lesions confined to her autoamputated left thigh. She was wearing an above‐the‐knee prosthesis that induced plaque psoriasis by koebnerization. Rapid clinical remission was achieved using tacrolimus 0.03% ointment.     

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients

International Urology and Nephrology - The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent...     

TNFα protects cardiac mitochondria independently of its cell surface receptors

Our novel proposal is that TNFα exerts a direct effect on mitochondrial respiratory function in the heart, independently of its cell surface receptors. TNFα-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids. We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration of TNFα (0.5 ng/ml) was added to isolated heart mitochondria from black 6 × 129 mice (WT) and double TNF receptor knockout mice (TNFR1&2^−/−). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants, N-acetyl-l-cysteine or N-tert-butyl-α-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNFα reduced State 3 respiration from 279.3 ± 3 to 119.3 ± 2 (nmol O₂/mg protein/min), increased proton leak from 15.7 ± 0.6% (control) to 36.6 ± 4.4%, and decreased membrane potential by 20.5 ± 3.1% compared to control groups. In TNFR1&2^−/− mice, TNFα reduced State 3 respiration from 205.2 ± 4 to 75.7 ± 1 (p < 0.05 vs. respective control). In WT mice, both antioxidants added with TNFα restored State 3 respiration to 269.2 ± 2 and 257.6 ± 2, respectively. Imipramine and NOE also restored State 3 respiration to 248.4 ± 2 and 249.0 ± 2, respectively (p < 0.01 vs. TNFα alone). Similarly, both antioxidant and inhibitors of the sphingolipid pathway restored the proton leak to pre-TNF values. TNFα-treated mitochondria or isolated cardiac muscle fibers showed an increase in respiration after anoxia–reoxygenation, but this effect was lost in the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2^−/− mice. TNFα exerts a protective effect on respiratory function in isolated mitochondria subjected to an anoxia–reoxygenation insult. This effect appears to be independent of its cell surface receptors, but is likely to be mediated by ROS and sphingolipids.     

Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic leukemia from reactive monocytosis

In the absence of a cytogenetic abnormality or overt dysplasia, chronic myelomonocytic leukemia (CMML) may be difficult to be distinguished from reactive monocytosis. We have previously described a typical growth pattern in CMML patients, i.e., 'pseudonormal' colonies resembling granulocytic colonies but consisting entirely of monocytic cells when stained. To study the utility of the colony forming unit cell assay (CFU-C) as a diagnostic tool in patients with monocytosis, we analyzed a cohort of 48 consecutive patients referred to our institution with peripheral blood monocytosis. Thirty-six patients fulfilled the WHO criteria for CMML; 12 were diagnosed with reactive monocytosis. Of the patients with CMML, 28 showed pseudonormal growth with or without leukemic cluster growth, another four showed exclusively leukemic growth. None of the patients with reactive monocytosis showed either leukemic or pseudonormal growth. With a specificity of 100% and a sensitivity of 89%, the CFU-C assay has a unique potential to distinguish CMML from reactive monocytosis.     

Is the volume-outcome relation still an issue in the era of PCI with systematic stenting? Results of the greater Paris area PCI registry.

AIMS: In acute myocardial infarction (AMI), primary percutaneous transluminal angioplasty (PTCA) is the preferred option when it can be performed rapidly. Because of the limited access to high PTCA volume centres in some areas, it has been suggested that PTCA could be performed in low-volume centres on AMI patients. Little data exist on the validity of this strategy in modern era PTCA. METHODS AND RESULTS: The Greater Paris area comprises 11 million inhabitants and accounts for 18% of the French population. In 2001, the hospital agency of the Greater Paris area set up a registry of all PTCAs performed in this region. Data from 2001 and 2002 was analysed. Hospitals performing <400 PTCAs per year were classified as low-volume. A case-control analysis (propensity score) compared in-hospital mortality in low- and high-volume centres. A total of 37 848 angioplasty procedures were performed in 44 centres during the study period; 24.7% were performed in low-volume centres. A non-statistically significant trend towards reduced in-hospital mortality was noted in high-volume centres as opposed to low-volume centres: 2.01 vs. 2.42%, P = 0.057. In-hospital mortality rates were significantly different in the sub-group of emergency procedures: 6.75% in high- vs. 8.54% in low-volume centres, P = 0.028. No difference was noted between low- and high-volume centres in non-emergency procedures (0.62 vs. 0.62%, P = 0.99). CONCLUSION: In the era of modern stenting, a clear inverse relationship exists between hospital PTCA volume and in-hospital mortality after emergency procedures. Tolerance of low-volume thresholds for angioplasty centres with the purpose of providing primary PTCA in AMI should not be recommended, even in underserved areas.