Results of a French pilot database of standard of care of chronic subdural hematoma.

BACKGROUND: A registry of chronic subdural hematoma does not exist in France yet. OBJECTIVE: To present a monocentric pilot project of a French registry of surgical management of chronic subdural hematoma. METHOD: A monocentric pseudonymized formal database was created. From May 2020 to May 2021, all patients undergoing surgical evacuation of chronic subdural hematoma were entered into the database. RESULTS: One hundred and twenty four surgeries from 113 patients were entered in the database. Patients' demographic and surgical data as well as follow-up are described. CONCLUSION: A local database is easy to implement. We propose a national registry of chronic subdural hematoma management.

An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG).

Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options.

Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients' and professionals' expertise - a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative.

Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. It may affect nearly all parts of the body including extremities, trunk and abdomen. Considering the variable clinical presentations, anatomic locations and biological behaviours, an individualised treatment approach is required. No established or evidence-based approach for the treatment of this neoplasm is available as of today. Therefore, we propose a consensus treatment algorithm based on a round table meeting bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). The aim of the meeting was to develop - for the first time ever - a consensus approach based on professionals' AND patients' expertise. As a fundamental prerequisite, all patients should be discussed in a multidisciplinary setting in centres or professional networks with a specific expertise in the disease.

A compact electron cyclotron resonance proton source for the Paul Scherrer Institute's proton accelerator facility.

A compact electron cyclotron resonance proton source has been developed and installed recently at the Paul Scherrer Institute's high intensity proton accelerator. Operation at the ion source test stand and the accelerator demonstrates a high reliability and stability of the new source. When operated at a 10-12 mA net proton current the lifetime of the source exceeds 2000 h. The essential development steps towards the observed performance are described.

Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue.

A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer.

Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning.

We characterize the infiltration of interstitial cells into tissue engineering scaffolds prepared with electrospun collagen, electrospun gelatin, electrospun poly(glycolic) acid (PGA), electrospun poly(lactic) acid (PLA), and an electrospun PGA/PLA co-polymer. Electrospinning conditions were optimized to produce non-woven tissue engineering scaffolds composed of individual fibrils less than 1000 nm in diameter. Each of these materials was then electrospun into a cylindrical construct with a 2 mm inside diameter with a wall thickness of 200-250 microm. Electrospun scaffolds of collagen were rapidly, and densely, infiltrated by interstitial and endothelial cells when implanted into the interstitial space of the rat vastus lateralis muscle. Functional blood vessels were evident within 7 days. In contrast, implants composed of electrospun gelatin or the bio-resorbable synthetic polymers were not infiltrated to any great extent and induced fibrosis. Our data suggests that topographical features, unique to the electrospun collagen fibril, promote cell migration and capillary formation.

Flavor decomposition of the sea-quark helicity distributions in the nucleon from semiinclusive deep inelastic scattering.

Double-spin asymmetries of semiinclusive cross sections for the production of identified pions and kaons have been measured in deep inelastic scattering of polarized positrons on a polarized deuterium target. Five helicity distributions including those for three sea quark flavors were extracted from these data together with reanalyzed previous data for identified pions from a hydrogen target. These distributions are consistent with zero for all three sea flavors. A recently predicted flavor asymmetry in the polarization of the light quark sea appears to be disfavored by the data.

Evidence for quark-hadron duality in the proton spin asymmetry A1.

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry A1. Longitudinally polarized positrons were scattered off a longitudinally polarized hydrogen target for values of Q2 between 1.2 and 12 GeV2 and values of W2 between 1 and 4 GeV2. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable x. This finding implies that the description of A1 in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of Q2 above 1.6 GeV2.

Q2 dependence of nuclear transparency for exclusive rho0 production.

Exclusive coherent and incoherent electroproduction of the rho(0) meson from 1H and 14N targets has been studied at the HERMES experiment as a function of coherence length (l(c)), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon (-Q2). The ratio of 14N to 1H cross sections per nucleon, called nuclear transparency, was found to increase (decrease) with increasing l(c) for coherent (incoherent) rho(0) electroproduction. For fixed l(c), a rise of nuclear transparency with Q2 is observed for both coherent and incoherent rho(0) production, which is in agreement with theoretical calculations of color transparency.

Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma.

High-dose melphalan (HDM) has been adopted as standard therapy in the treatment of multiple myeloma. This treatment is associated with non-selective cytotoxicity, causing oral mucositis as the major non-hematological side-effect. Amifostine is a cytoprotector which prevents toxicity induced by anticancer therapy. We prospectively compared two groups of patients who either received (group A, n = 21) or did not receive (group B, n = 20) amifostine (740 mg/m(2)) before HDM (200 mg/m(2)) followed by autologous peripheral blood progenitor cell transplantation. The occurrence of severe oral mucositis was significantly decreased in group A in comparison to group B (33% vs 65%, P < 0.05). Six patients in group A required opioid analgesic therapy during a mean period of 4.8 days as compared to eight patients for 6.5 days in group B (P = NS). Delayed vomiting was less frequent in group A (43% vs 70%, P = 0.07) and significantly less severe in group A (grade 2-4) vomiting: two patients vs nine patients, P < 0.02). No difference was observed between the two groups in either hematological toxicity after HDM or in response rate. Grade I emesis was the only immediate side-effect observed after amifostine administration. We conclude that amifostine can reduce mucositis induced by HDM.

Modulation of cardiac Na(+) current by gadolinium, a blocker of stretch-induced arrhythmias.

Gd(3+) blocks stretch-activated channels and suppresses stretch-induced arrhythmias. We used whole cell voltage clamp to examine whether effects on Na(+) channels might contribute to the antiarrhythmic efficacy of Gd(3+). Gd(3+) inhibited Na(+) current (I(Na)) in rabbit ventricle (IC(50) = 48 microM at -35 mV, holding potential -120 mV), and block increased at more negative test potentials. Gd(3+) made the threshold for I(Na) more positive and reduced the maximum conductance. Gd(3+) (50 microM) shifted the midpoints for activation and inactivation of I(Na) 7.9 and 5.7 mV positive but did not alter the slope factor for either relationship. Activation and inactivation kinetics were slowed in a manner that could not be explained solely by altered surface potential. Paradoxically, Gd(3+) increased I(Na) under certain conditions. With membrane potential held at -75 mV, Gd(3+) still shifted threshold for activation positive, but I(Na) increased positive to -40 mV, causing the current-voltage curves to cross over. When availability initially was low, increased availability induced by Gd(3+) dominated the response at test potentials positive to -40 mV. The results indicate that Gd(3+) has complex effects on cardiac Na(+) channels. Independent of holding potential, Gd(3+) is a potent I(Na) blocker near threshold potential, and inhibition of I(Na) by Gd(3+) is likely to contribute to suppression of stretch-induced arrhythmias.

Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group.

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.

Cardioplegia-induced cell swelling: prevention by normothermic infusion.

BACKGROUND: Previous work has shown significant swelling of isolated rabbit myocytes exposed to cold hyperkalemic cardioplegia; however, the effect of warm hyperkalemic cardioplegia on myocyte volume is unknown. This study examined the effect of warm hyperkalemic cardioplegia (St. Thomas' solution) on myocyte volume. METHODS: Myocytes were enzymatically isolated and placed on an inverted video microscope. Tyrode's solution (37 degrees C) was infused for 10 minutes to establish baseline cell volumes. Subsequently, either the control Tyrode's or St. Thomas' was infused either at 37 degrees C and 9 degrees C respectively (n = 5 for all groups) for 20 minutes, followed by a 30-minute reperfusion with 37 degrees C Tyrode's. Cell volume was determined from cell images captured every 5 minutes. RESULTS: Myocyte swelling occurred rapidly on exposure to cold St. Thomas' solution to a maximum of 9.8 +/- 2.1% (p < 0.001). In contrast, myocytes exposed to warm cardioplegia did not show any volume changes during exposure to cardioplegia. However, upon reexposure to Tyrode's, these cells showed shrinkage below their baseline volume (p < 0.001). CONCLUSIONS: The cell swelling associated with hypothermic cardioplegia is prevented by normothermic infusion.

Existence of a transient outward K(+) current in guinea pig cardiac myocytes.

A novel transient outward K(+) current that exhibits inward-going rectification (I(to.ir)) was identified in guinea pig atrial and ventricular myocytes. I(to.ir) was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 micromol/l Ba(2+) or removal of external K(+). The zero current potential shifted 51-53 mV/decade change in external K(+). I(to.ir) density was twofold greater in ventricular than in atrial myocytes, and biexponential inactivation occurs in both types of myocytes. At -20 mV, the fast inactivation time constants were 7.7 +/- 1.8 and 6.1 +/- 1.2 ms and the slow inactivation time constants were 85.1 +/- 14.8 and 77.3 +/- 10.4 ms in ventricular and atrial cells, respectively. The midpoints for steady-state inactivation were -36.4 +/- 0.3 and -51.6 +/- 0.4 mV, and recovery from inactivation was rapid near the resting potential (time constants = 7.9 +/- 1.9 and 8.8 +/- 2.1 ms, respectively). I(to.ir) was detected in Na(+)-containing and Na(+)-free solutions and was not blocked by 20 nmol/l saxitoxin. Action potential clamp revealed that I(to.ir) contributed an outward current that activated rapidly on depolarization and inactivated by early phase 2 in both tissues. Although it is well known that 4-AP-sensitive transient outward current is absent in guinea pig, this Ba(2+)-sensitive and 4-AP-insensitive K(+) current has been overlooked.

Activation of mitogen-activated protein kinases is required for alpha1-adrenergic agonist-induced cell scattering in transfected HepG2 cells.

Activation of alpha1B-adrenergic receptors ((alpha1B)AR) by phenylephrine (PE) induces scattering of HepG2 cells stably transfected with the (alpha1B)AR (TFG2 cells). Scattering was also observed after stimulation of TFG2 cells with phorbol myristate acetate (PMA) but not with hepatocyte growth factor/scatter factor, epidermal growth factor, or insulin. PMA but not phenylephrine rapidly activated PKCalpha in TFG2 cells, and the highly selective PKC inhibitor bisindolylmaleimide (GFX) completely abolished PMA-induced but not PE-induced scattering. PE rapidly activated p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, c-Jun N-terminal kinase (JNK), and AP1 (c-fos/c-jun). Selective blockade of p42/44 MAPK activity by PD98059 or by transfection of a MEK1 dominant negative adenovirus significantly inhibited the PE-induced scattering of TFG2 cells. Selective inhibition of p38 MAPK by SB203850 or SB202190 also blocked PE-induced scattering, whereas treatment of TFG2 cells with the PI3 kinase inhibitors LY294002 or wortmannin did not inhibit PE-induced scattering. Blocking JNK activation with a dominant negative mutant of JNK or blocking AP1 activation with a dominant negative mutant of c-jun (TAM67) significantly inhibited PE-induced cell scattering. These data indicate that PE-induced scattering of TFG2 cells is mediated by complex mechanisms, including activation of p42/44 MAPK, p38 MAPK, and JNK. Cell spreading has been reported to play important roles in wound repair, tumor invasion, and metastasis. Therefore, catecholamines acting via the (alpha1)AR may modulate these physiological and pathological processes.

Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels.

We have identified a 35 amino acid peptide toxin of the inhibitor cysteine knot family that blocks cationic stretch-activated ion channels. The toxin, denoted GsMTx-4, was isolated from the venom of the spider Grammostola spatulata and has <50% homology to other neuroactive peptides. It was isolated by fractionating whole venom using reverse phase HPLC, and then assaying fractions on stretch-activated channels (SACs) in outside-out patches from adult rat astrocytes. Although the channel gating kinetics were different between cell-attached and outside-out patches, the properties associated with the channel pore, such as selectivity for alkali cations, conductance ( approximately 45 pS at -100 mV) and a mild rectification were unaffected by outside-out formation. GsMTx-4 produced a complete block of SACs in outside-out patches and appeared specific since it had no effect on whole-cell voltage-sensitive currents. The equilibrium dissociation constant of approximately 630 nM was calculated from the ratio of association and dissociation rate constants. In hypotonically swollen astrocytes, GsMTx-4 produces approximately 40% reduction in swelling-activated whole-cell current. Similarly, in isolated ventricular cells from a rabbit dilated cardiomyopathy model, GsMTx-4 produced a near complete block of the volume-sensitive cation-selective current, but did not affect the anion current. In the myopathic heart cells, where the swell-induced current is tonically active, GsMTx-4 also reduced the cell size. This is the first report of a peptide toxin that specifically blocks stretch-activated currents. The toxin affect on swelling-activated whole-cell currents implicates SACs in volume regulation.

Rabbit ventricular myocyte volume changes as a direct result of crystalloid cardioplegia in congestive heart failure induced by aortic regurgitation.

OBJECTIVES: We hypothesized that the cell volume of ventricular myocytes isolated from hearts in volume-overload congestive failure would respond differently to hypothermic cardioplegia than would sham-operated cohorts. METHODS: Adult rabbits underwent either valvotomy and aortic regurgitation-induced heart failure or sham surgery. Congestive failure was confirmed clinically and by means of echocardiography. Cell volumes of isolated myocytes were measured by digital video microscopy. After equilibration in 37 degrees C physiologic solution, cells were suprafused with 9 degrees C standard or low-Cl(-) St Thomas' Hospital solution followed by reperfusion in 37 degrees C physiologic solution. RESULTS: Exposure to cold St Thomas' Hospital solution for 20 minutes caused sham myocytes to swell by 8% (n = 9); cell volumes fully recovered on normothermic reperfusion. In contrast, congestive failure myocytes (n = 9) maintained their cell volume in cold St Thomas' Hospital solution and during reperfusion. Lowering the [K(+)][Cl(-)] product of St Thomas' Hospital solution by partially replacing Cl(-) with an impermeant anion prevented cellular edema in the sham group (n = 8) but caused a 4% swelling in failure myocytes (n = 10) on reperfusion. Osmotically shrinking the failure cells (n = 9) converted their behavior to that of sham cells. CONCLUSIONS: In the absence of ischemia, congestive failure myocytes are less sensitive to cardioplegia-induced edema than sham cells. Low-Cl(-) cardioplegia, which prevents edema and protects the normal heart, induced swelling and may be detrimental in myopathic hearts. Differences in volume regulation in failure and sham myocytes may be due to activation of volume-sensitive channels that are turned off by osmotic shrinkage.

Age-related effects of St Thomas' Hospital cardioplegic solution on isolated cardiomyocyte cell volume.

OBJECTIVES: We tested the hypothesis that neonatal cells are more sensitive to cardioplegia-induced cell swelling than more mature cells and spontaneous swelling in the absence of ischemia can be prevented by cardioplegia with a physiologic KCl product. METHODS: Cell volumes of isolated ventricular myocytes from neonatal (3-5 days), intermediate (10-13 days), and adult (>6 weeks) rabbits were measured by digital video microscopy. After equilibration in 37 degrees C physiologic solution, cells were suprafused with 37 degrees C or 9 degrees C St Thomas' Hospital solution (standard or low Cl(-)) or 9 degrees C physiologic solution followed by reperfusion with 37 degrees C physiologic solution. RESULTS: Neonatal cells swelled 16.2% +/- 1.8% (P <.01) in 37 degrees C St Thomas' Hospital solution and recovered during reperfusion, whereas more mature cells maintained constant volume. In contrast, 9 degrees C St Thomas' Hospital solution caused significant age-dependent swelling (neonatal, 16.8% +/- 1.5%; intermediate, 8.6% +/- 2.1%; adult, 5.6% +/- 1.1%). In contrast to more mature cells, neonatal cells remained significantly edematous throughout reperfusion (8.1% +/- 1.5%). Swelling was not due to hypothermia because 9 degrees C physiologic solution did not affect volume. Lowering the KCl product of St Thomas' Hospital solution by partially replacing Cl(-) with an impermeant anion prevented cellular edema in all groups. CONCLUSION: In the absence of ischemia, neonatal cells were more sensitive to cardioplegia-induced cellular edema than more mature cells, and edema observed in all groups was avoided by decreasing the KCl product of St Thomas' Hospital solution to the physiologic range. Differences in cell volume regulation may explain the sensitivity of neonatal hearts to hyperkalemic cardioplegic arrest and suggest novel approaches to improving myocardial protection.