Is there a need for postoperative monitoring after open carpal tunnel release under WALANT?

Open carpal tunnel release (OCTR) under wide-awake local anesthesia with no tourniquet (WALANT) is a common outpatient procedure in hand surgery worldwide. In our clinic, WALANT has replaced intravenous regional anesthesia with a tourniquet (IVRA, or 'Bier block') as standard practice in OCTR. We therefore wondered what the optimal postoperative setting after OCTR under WALANT is. In this study, we compared patient satisfaction in two postoperative settings: immediate discharge (ID) after the operation, or short postoperative monitoring (PM) period in the outpatient clinic. Our hypothesis was that older patients would prefer a brief postoperative surveillance. We retrospectively analyzed patient satisfaction with the two settings using an adjusted questionnaire based on the standard Swiss grading system. We also assessed postoperative pain, satisfaction with the perioperative preparations and the reasons for unscheduled postoperative consultations, as secondary outcomes. One hundred and nine patients (ID, n = 63; PM, n = 46) were included in this single-center retrospective observational study. Patients were highly satisfied with both postoperative settings (Mean: ID 5.1/6; PM 5.5/6; p = 0.07). Even patients aged ≥80 years reported extremely high satisfaction with both settings (ID 5.6/6; PM 6.0/6; p = 0.08). Fifteen patients (ID, n = 11 [17.5%]; PM, n = 4 [8.7%], p = 0.72) unexpectedly consulted a doctor after surgery. OCTR under WALANT as an outpatient procedure with immediate discharge was associated with high patient satisfaction. However, detailed postoperative monitoring could contribute to the patient's well-being and education on how to cope with the postoperative course, and help with any questions.

Update on experimental acute pancreatitis.

Acute pancreatitis is a disease still not fully understood. Early pathophysiologic event escape clinical observation because patients typically present only some time after the acute onset of the disease. Also, many ethiologic factors can lead to acute pancreatitis and the clinical course can range from mild, self-limiting to severe and life- threatening. Therefore, experimental models are necessary for any research into early acute pancreatitis. In accordance with the varying clinical picture of acute pancreatitis, many different model exist. In this article, we describe the most commonly used models and show their advantages and disadvantages.

Immunomodulation in a novel model of experimental chronic pancreatitis.

Chronic pancreatitis is a disease that involves the lymphocytic inflammation of the pancreatic gland, the destruction and fibrous transformation of the endocrine and ductal structures. An involvement of the immune system in the disease progression is assumed and possibly allows immune modulation as a novel treatment strategy. We used a new model of experimental chronic pancreatitis to examine the effect of immune modulation with the mTOR-inhibitor rapamycin on clinical, chemical and histological parameters of chronic pancreatitis. Pancreatitis was induced by injecting 8 mg/kg bodyweight DBTC intravenously in male Sprague Dawley rats. 24 and 72 hours later, 20 µg/kg bodyweight cerulein was injected intraperitoneally to simulate recurrent attacks of pancreatitis typical for the clinical course. 48 hours after the DBTC injection, rats were randomly allocated to placebo or sirolimus (1.5 mg/kg bw i.p.). The treatment was repeated every 24hours for 5 days. The rats were sacrificed 7, 14, 21 and 35 days after DBTC injection. Histologic examination revealed a reduced acute pancreatic damage in the treatment group in the first week and less chronic changes in the further course. ALT and amylase increased in Placebo animals over the observation period and was lower in sirolimus treated animals. Oral glucose tolerance test showed that all placebo animals were diabetic four weeks after DBTC while sirolimus treated animals were normoglycemic. An early, limited treatment with immunomodulatory and antifibrotic agents like sirolimus can positively influence the detrimental course of experimental chronic pancreatitis and may offer a treatment alternative in humans.

Everolimus and mycophenolate mofetil sensitize human pancreatic cancer cells to gemcitabine in vitro: a novel adjunct to standard chemotherapy?

BACKGROUND/AIMS: Gemcitabine improves survival in pancreatic adenocarcinoma. A variety of drugs have been tested to potentiate gemcitabine treatment for pancreatic cancer cells. Two major immunosuppressive drugs, mycophenolate mofetil (MMF) and everolimus (RAD001) have been shown to exert an anti-tumoral effect, but their ability to sensitize human pancreatic cell lines during gemcitabine treatment remains unclear. We examined the effects of everolimus and MMF on gemcitabine-treated MiaPaCa and Panc-1 cell lines. METHODS: MiaPaCa and Panc-1 human pancreatic tumor cell lines were subjected to everolimus (0.001-1 microg/ml) or MMF (0.1-100 microg/ml) treatment in combination with gemcitabine (1-10(6) nM). Western blot analysis was performed for Panc-1 cells in the presence or absence of TGF-beta1 and different treatments: 0.1-100 muicro/ml MMF and 0.1-100 microg/ml everolimus. The antiproliferative effect of the treatment was assessed by BrdU test. The results were evaluated by two-way analysis of variance followed by post-hoc tests, and nonlinear regression analysis for dose-response rates. RESULTS: As expected, standard treatment doses of gemcitabine decreased proliferation dose-dependently. Everolimus increased the actual EC(50) response to gemcitabine treatment (1-10(3) nM) to as much as 83.1 and 82.1% in MiaPaCa and Panc-1 cell lines, respectively. Likewise, concomitant administration with MMF altered the EC(50) of gemcitabine treatment in MiaPaCa cell lines to values between 76.8 and 85.2% for doses of >or=1 microg/ml. Even the minor dose of MMF (0.1 microg/ml) increased the antiproliferative effect of gemcitabine by 43.5% for MiaPaCa and 42.4% for Panc-1 cells. In addition, treatment of Panc-1 cells with MMF (0.1-100 microg/ml) dose-dependently inhibited TGF-beta1-induced collagen expression. CONCLUSION: We found an overadditive antiproliferative effect of both MMF and everolimus in gemcitabine-treated MiaPaCa and Panc-1 cells in vitro, and an additional inhibitory effect of MMF on TGF-beta1-induced collagen type I expression. Interestingly, both the sensitizing effect of pancreatic cancer cells to gemcitabine treatment and the inhibition of collagen type I expression could be achieved by clinically feasible doses of everolimus and MMF. The use of these drugs is promising as a novel adjunct to standard chemotherapy.

Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro.

BACKGROUND: Everolimus inhibits the growth of several tumor cell lines in vitro as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line Panc-1 and on a small cell lung cancer cell line ScLc. MATERIALS AND METHODS: Cells were cultured under standardized conditions. Everolimus was added in increasing doses from 0.005 to 500 microg/mL; MMF was used from 0.05 to 5000 microg/mL. For co-incubation experiments, we combined everolimus (0.005 microg/mL and 0.05 microg/mL) with five concentrations of MMF; and MMF (0.5 microg/mL and 5 microg/mL) with five concentrations of everolimus. The antiproliferative capacity was assessed by a BrdU incorporation assay. RESULTS: Everolimus and MMF inhibited BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50% inhibition was seen in Panc-1 only at 50 microg/mL everolimus, but in ScLc at 5 microg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was observed at 5 microg/L. In ScLc, 40% inhibition of BrdU incorporation was seen only at 50 microg/L MMF. In co-incubation, an effective combination for both Panc-1 and ScLc was 5 microg/mL MMF with 0.005 microg/mL everolimus resulting in 50% inhibition of BrdU incorporation (P < .001). CONCLUSIONS: Everolimus and MMF showed dose-dependent antiproliferative effects in tumor cell lines in vitro both alone and in combination. The combined use of everolimus and MMF showed supra-additive effects at concentrations used for therapeutic immunosuppression in patients.

Pseudo-thermosetting chitosan hydrogels for biomedical application.

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Pseudo-thermosetting chitosan hydrogels for biomedical application.

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Pancreas graft thrombosis: is there a role for trypsin.

PURPOSE: Thrombosis of the pancreas graft is the main cause of early graft loss in pancreas transplantation. We investigated whether hypercoagulability develops locally in the pancreas and contributes to thrombosis formation because of ischemia or reperfusion injury. It was further hypothesized that this might be induced by excessive intravascular trypsin activity. METHODS: Ten Patients undergoing pancreas transplantation were studied. In addition to the standard operation a 14 French catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were drawn simultaneously from the splenic vein of the pancreas graft (local samples) and the radial artery (systemic samples) at 0,1,2,5,10,30, and 60 minutes after reperfusion. RESULTS: After reperfusion a progressive hypercoagulability developed locally in the pancreas as seen by an increase of thrombin-antithrombin complexes and only a transient increase of plasmin-antiplasmin complexes. In addition antithrombin 3 and protein c decreased systemically. The alterations seem not to be triggered by trypsin because trypsin activity locally remained low despite trypsinogen release and activation as assessed by trypsinogen activation peptides. CONCLUSION: Local hypercoagulability might contribute to the development of graft thrombosis, however, the mechanism seems not to be related to ectopic trypsin activation.

Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.

This review presents a critical analysis of covalently and ionically crosslinked chitosan hydrogels and related networks for medical or pharmaceutical applications. The structural basis of these hydrogels is discussed with reference to the specific chemical interactions, which dictate gel formation. The synthesis and chemistry of these hydrogels is discussed using specific pharmaceutical examples. Covalent crosslinking leads to formation of hydrogels with a permanent network structure, since irreversible chemical links are formed. This type of linkage allows absorption of water and/or bioactive compounds without dissolution and permits drug release by diffusion. pH-controlled drug delivery is made possible by the addition of another polymer. Ionically crosslinked hydrogels are generally considered as biocompatible and well-tolerated. Their non-permanent network is formed by reversible links. Ionically crosslinked chitosan hydrogels exhibit a higher swelling sensitivity to pH changes compared to covalently crosslinked chitosan hydrogels. This extends their potential application, since dissolution can occur in extreme acidic or basic pH conditions.

Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications.

The aim of this review was to provide a detailed overview of physical chitosan hydrogels and related networks formed by aggregation or complexation, which are intended for biomedical applications. The structural basis of these systems is discussed with particular emphasis on the network-forming interactions, the principles governing their formation and their physicochemical properties. An earlier review discussing crosslinked chitosan hydrogels highlighted the potential negative influence on biocompatibility of covalent crosslinkers and emphasised the need for alternative hydrogel systems. A possible means to avoid the use of covalent crosslinkers is to prepare physical chitosan hydrogels by direct interactions between polymeric chains, i.e. by complexation, e.g. polyelectrolyte complexes (PEC) and chitosan/poly (vinyl alcohol) (PVA) complexes, or by aggregation, e.g. grafted chitosan hydrogels. PEC exhibit a higher swelling sensitivity towards pH changes compared to covalently crosslinked chitosan hydrogels, which extends their potential application. Certain complexed polymers, such as glycosaminoglycans, can exhibit interesting intrinsic properties. Since PEC are formed by non-permanent networks, dissolution can occur. Chitosan/PVA complexes represent an interesting alternative for preparing biocompatible drug delivery systems if pH-controlled release is n/ot required. Grafted chitosan hydrogels are more complex to prepare and do not always improve biocompatibility compared to covalently crosslinked hydrogels, but can enhance certain intrinsic properties of chitosan such as bacteriostatic and wound-healing activity.

[Radiation-induced aneurysm of the cavernous internal carotid artery]. / Anévrysme post-radique de la carotide intra-caverneuse.

We report a case of intra-cranial aneurysm of the left cavernous internal carotid artery occurring 27 years after radiotherapy of the pterygopalatine fossa for Hodgkin disease. The development of the aneurysm within the irradiation field, the long latency after radiotherapy, the normality of carotid angiography before radiotherapy and the absence of other etiologies led to the diagnosis of radiation-induced aneurysm. The main characteristics of radiation-induced intra-cranial aneurysms are reviewed.

Serum amyloid A is a better early predictor of severity than C-reactive protein in acute pancreatitis.

BACKGROUND: Serum amyloid A (SAA) is an early and sensitive marker of the extent of tissue trauma and inflammation. The aim of this study was to compare the early prognostic accuracy of SAA with that of serum C-reactive protein (CRP) in acute pancreatitis. METHODS: In a prospective multicentre trial, plasma SAA and CRP levels were measured in patients with severe and mild acute pancreatitis, and in a control group with acute abdominal pain. Plasma samples were collected on admission and at 6-h intervals for 48 h, every 12 h between 48 and 72 h, then daily for 5 days. Plasma SAA was measured by a new enzyme-linked immunosorbent assay and CRP was measured by immunoturbidometry. RESULTS: There were 137 patients with mild and 35 with severe acute pancreatitis, and 74 control patients. SAA levels were significantly higher in patients with severe acute pancreatitis than in those with mild acute pancreatitis, on admission, at 24 h or less after symptom onset, and subsequently. Whereas plasma CRP concentration was also significantly higher in patients with severe acute pancreatitis on admission, it failed to distinguish mild from severe acute pancreatitis until 30-36 h after symptom onset. SAA levels predicted severity (sensitivity 67 per cent, specificity 70 per cent, negative predictive value 89 per cent, mean(s.d.) area under curve 0.7(0.05)) significantly better than CRP (57 per cent, 60 per cent, 84 per cent, 0.59(0.06) respectively) on admission (P = 0.02) and at 24 h following symptom onset (area under curve 0.65(0.09) versus 0.58(0.09) respectively; P < or = 0.02). CONCLUSION: Plasma SAA concentration is an early marker of severity in acute pancreatitis and is superior to CRP estimation on hospital admission and at 24 h or less after symptom onset. This study suggests that plasma SAA concentration is clinically useful, with the potential to replace CRP in the management of acute pancreatitis.

Application of the Marcus cross relation to hydrogen atom transfer reactions.

The transfer of a hydrogen atom-a proton and an electron-is a fundamental process in chemistry and biology. A variety of hydrogen atom transfer reactions, involving iron complexes, phenols, hydroxylamines, tBuOOH, toluene, and related radicals, are shown to follow the Marcus cross relation. Thus, the Marcus theory formalism based on ground-state energetics and self-exchange rates, originally developed for electron transfer processes, is also valuable for hydrogen atom transfer. Compounds that undergo slow proton transfer (C-H bonds) or slow electron transfer (cobalt complexes) also undergo slow hydrogen atom transfer. Limitations of this approach are also discussed.

The esterase-like activity of serum albumin may be due to cholinesterase contamination.

PURPOSE: The "esterase-like activity" of human serum albumin (HSA) is described in the literature, but a contamination of commercially available HSA preparations by plasma cholinesterase is conceivable in some cases. The purpose of the present work was to examine this hypothesis. METHODS: The hydrolytic activity of HSA and its inhibition by physostigmine were measured fluorimetrically by monitoring the hydrolysis of the ester substrate moxisylyte. Affinity chromatography was used to separate cholinesterase and HSA. The cholinesterase activity in the eluted fractions was assessed using Ellman's reagent and butyrylthiocholine as substrate. RESULTS: A significant variation in the esterase-like activity of different albumin batches was observed. This activity was strongly inhibited by physostigmine, a well-known inhibitor of cholinesterase. Affinity chromatography led to a complete separation between HSA and the esterase activity, which was found exclusively in the cholinesterase fraction. CONCLUSIONS: The apparent esterase-like activity of HSA toward moxisylyte and butyrylthiocholine was due to a contamination by cholinesterase. With these substrates, HSA showed a total lack of esterase-like activity.

Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications.

OBJECTIVES: There is recent experimental evidence that caspase-1 activation plays an instrumental role in the pathomechanism of severe acute pancreatitis. Besides interleukin-1beta, interleukin-18, a recently described proinflammatory cytokine, is cleaved into its biologically active form by caspase-1 as well. Interleukin-18 is known to have potent properties concerning the activation of the Th1-lymphocyte subset via costimulation of interferon-gamma production. In contrast to interleukin-1beta, little is known about the clinical impact of interleukin-18 in the course of acute pancreatitis. DESIGN: Cohort study comparing patients with mild and severe acute pancreatitis associated with local and systemic complications during the course of the disease. SETTING: Surgical and anesthesiological intensive care unit as well as wards of the department of general surgery. PATIENTS: We included 68 patients with acute pancreatitis in the present study. In terms of local complications, pancreatic necrosis was present in 37 patients, of whom 21 developed pancreatic infections. Systemic complications included pulmonary, renal, or cardiocirculatory insufficiency and were observed in 40, 18, and 25 patients, respectively. Severe multiple-organ dysfunction syndrome involving all three organ systems occurred in 18 patients, all suffering from pancreatic necrosis. INTERVENTIONS: Serum samples were collected over 14 consecutive days after study inclusion. Ascites or peripancreatic exudate was obtained by ultrasound-guided fine needle aspiration in 14 cases. Sera and local aspirates were stored at -70 degrees C until analysis. MEASUREMENTS AND RESULTS: Interleukin-18 and interferon-gamma were measured by commercially available enzyme-linked immunosorbent assays. Interleukin-18 concentrations were significantly increased after the fourth day of disease onset until the end of the observation period in patients who developed pancreatic necrosis and systemic complications such as pulmonary, renal, and cardiocirculatory failure as well as severe multiple-organ dysfunction syndrome. However, no correlation was found between the development of pancreatic infections and interleukin-18 concentrations. In contrast with interleukin-18, interferon-gamma concentrations did not show any significant difference with respect to the presence or absence of either systemic or local complications. Local interleukin-18 concentrations in ascites or peripancreatic exudate were up to 20-fold higher than systemic concentrations, whereas interferon-gamma concentrations did not differ. CONCLUSIONS: Serum interleukin-18 concentrations are significantly elevated in patients with acute pancreatitis complicated by pancreatic necrosis and remote organ failure. The present data suggest an important role of caspase-1 dependent cytokine activation in the pathomechanism of severe acute pancreatitis beyond the experimental setting. In this context, interleukin-18 may serve as a potential target for new therapeutic approaches.

Reduced serum total reductive capacity in lethal severe trauma.

BACKGROUND: Risk assessment is a prerequisite for effective treatment and triage in severe injury. A novel substrate-based assay to measure total reductive capacity (TORC) in serum was used to stratify risk of lethal outcome in severe trauma in a clinical trial. METHODS: Serum of patients with severe trauma (Injury Severity Score > 19) was obtained at the accident site, at admission, and at regular intervals thereafter. TORC was determined and correlated to outcome. The TORC assay uses thiol-labeled arachidonic acid as substrate from which free thiols are released by reductive amino acids and the specific activity of phospholipase A2. Free thiols are coupled to monochrombimone, and the resulting fluorescence is proportional to TORC. RESULTS: Eighteen patients with lethal severe trauma and 16 patients who survived were studied. Injury Severity Scores (lethal, 33 (29--43); survival, 31 (25--42); p = NS) and Polytrauma Scores (lethal, 25 [18--32]; survival, 26 [23--31], p = NS) were not significantly different. At the accident site, patients with a lethal course had significantly lower TORC than nonlethal cases (59.2 +/- 5.1 ng/mL vs. 89.5 +/- 6.7 ng/mL; p < 0.001). Values at admission were similar (lethal, 51.2 +/- 7 ng/mL; survival, 73.8 +/- 9 ng/mL; p < 0.01). At the accident site and at admission, TORC < 82.3 ng/mL was prognostic of lethal outcome (sensitivity, 88%; specificity, 65%/73% and 69%, respectively, for admission). CONCLUSION: Serum reductive potential at the site of accident or at admission allows the stratification of trauma patients with respect to lethal outcome in severe trauma when severity scores fail to do so.

C--N bond formation on addition of aryl carbanions to the electrophilic nitrido ligand in TpOs(N)Cl(2).

The osmium(VI) nitrido complex TpOs(N)Cl(2) (1) has been prepared from K[Os(N)O(3)] and KTp in aqueous ethanolic HCl. It reacts rapidly with PhMgCl and related reagents with transfer of a phenyl group to the nitrido ligand. This forms Os(IV) metalla-analido complexes, which are readily protonated to give the analido complex TpOs(NHPh)Cl(2) (4). The nitrido-phenyl derivatives TpOs(N)PhCl and TpOs(N)Ph(2) react more slowly with PhMgCl and are not competent intermediates for the reaction of 1 with PhMgCl. Reactions of 1 with alkyl- and arylboranes similarly result in transfer of one organic group to nitrogen, leading to isolable borylamido complexes such as TpOs[N(Ph)(BPh(2))]Cl(2) (11). This is an unprecedented insertion of a nitrido ligand into a boron--carbon bond. Hydrolysis of 11 gives 4. Mechanistic studies suggest that both the Grignard and borane reactions proceed by initial weak coordination of Mg or B to the nitrido ligand, followed by migration of the carbanion to nitrogen. The hydrocarbyl group does not go to osmium and then move to nitrogen--there is no change in the atoms bound to the osmium during the reactions. It is suggested that there may be a general preference for nucleophiles to add directly to the metal--ligand multiple bond rather than binding to the metal first and migrating. Ab initio calculations show that the unusual reactivity of 1 results from its accessible LUMO and LUMO + 1, which are the Os = N pi* orbitals. The bonding in 1 and its reactivity with organoboranes are reminiscent of CO.