Meta-analysis of COVID-19 prevalence during preoperative COVID-19 screening in asymptomatic patients.

OBJECTIVES: Patients with COVID-19 may be asymptomatic and are able to transmit COVID-19 during a surgical procedure, resulting in increased pressure on healthcare and reduced control of COVID-19 spread. There remains uncertainty about the implementation of preoperative screening for COVID-19 in asymptomatic surgical patients. Therefore, this study aims to determine the prevalence of preoperative COVID-19, confirmed by reverse transcriptase PCR (RT-PCR), in asymptomatic patients. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Pubmed and Embase databases were searched through 20 February 2022. ELIGIBILITY CRITERIA: All COVID-19 articles including preoperative asymptomatic patients were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Meta-analysis was performed to determine the prevalence of COVID-19 with 95% CI. Moreover, estimated positive predictive value (PPV), negative predictive value, false-positives (FP) and false-negatives were calculated for preoperative asymptomatic patients. RESULTS: Twenty-seven studies containing 27 256 asymptomatic preoperative screened patients were included, of which 431 were positive for COVID-19 by RT-PCR test. In addition, the meta-analysis revealed a pooled COVID-19 prevalence of 0.76% (95% CI 0.36% to 1.59%). The calculated PPV for this prevalence is 40.8%. CONCLUSIONS: The pooled COVID-19 prevalence in asymptomatic patients tested preoperatively was 0.76%, with low corresponding PPV. Consequently, nearly three-quarters of postponed surgical procedures in asymptomatic preoperative patients may be FP. In the event of similar pandemics, modification of preoperative mandatory RT-PCR COVID-19 testing in asymptomatic patients may be considered.

Intraoperative and postoperative risk factors for anastomotic leakage and pneumonia after esophagectomy for cancer.

Morbidity and mortality after esophagectomy are often related to anastomotic leakage or pneumonia. This study aimed to assess the relationship of intraoperative and postoperative vital parameters with anastomotic leakage and pneumonia after esophagectomy. Consecutive patients who underwent transthoracic esophagectomy with cervical anastomosis for esophageal cancer from January 2012 to December 2013 were analyzed. Univariable and multivariable logistic regression analyses were used to determine potential associations of hemodynamic and respiratory parameters with anastomotic leakage or pneumonia. From a total of 82 included patients, 19 (23%) developed anastomotic leakage and 31 (38%) experienced pneumonia. The single independent factor associated with an increased risk of anastomotic leakage in multivariable analysis included a lower minimum intraoperative pH (OR 0.85, 95% CI 0.77-0.94). An increased risk of pneumonia was associated with a lower mean arterial pressure (MAP) in the first 12 hours after surgery (OR 0.93, 95% CI 0.86-0.99) and a higher maximum intraoperative pH (OR 1.14, 95% CI 1.02-1.27). Interestingly, no differences were noted for the MAP and inotrope requirement between patients with and without anastomotic leakage. A lower minimum intraoperative pH (below 7.25) is associated with an increased risk of anastomotic leakage after esophagectomy, whereas a lower postoperative average MAP (below 83 mmHg) and a higher intraoperative pH (above 7.34) increase the risk of postoperative pneumonia. These parameters indicate the importance of setting strict perioperative goals to be protected intensively.

The effect of perioperative administration of glucocorticoids on pulmonary complications after transthoracic oesophagectomy: a systematic review and meta-analysis.

BACKGROUND: Severe pulmonary complications occur frequently following transthoracic oesophagectomy. An exaggerated immunological response is probably a main driving factor, and this might be prevented by perioperative administration of a glucocorticoid. OBJECTIVE: To determine the clinical benefits and harms of perioperative glucocorticoid during transthoracic oesophagectomy, using pulmonary complications as the primary outcome. Mortality, anastomotic leakage rate and infection were secondary outcomes. METHODS: A systematic review of interventional trials with a meta-analysis of randomised controlled trials (RCTs). RESULTS: The search retrieved seven RCTs and four interventional nonrandomised studies. In total, 367 patients received perioperative glucocorticoid and 415 patients did not. A meta-analysis of the RCTs showed no significant effect of glucocorticoid. For pulmonary complications, the pooled risk ratio was 0.69 [95% confidence interval (CI) 0.26 to 1.79], for anastomotic leakage 0.61 (95% CI 0.23 to 1.61) and for infections 1.09 (95% CI 0.41 to 2.93). A subgroup analysis of RCTs that used weight-dependent dosing within 30 min preoperatively showed a pooled risk ratio of 0.28 (95% CI 0.10 to 0.77) for pulmonary complications compared with placebo. CONCLUSION: In this meta-analysis, perioperative administration of glucocorticoid did not affect the risk of pulmonary complications after transthoracic oesophagectomy, nor did it cause adverse effects. A subgroup analysis showed that a weight-dependent dose of methylprednisolone 10 to 30 mg kg within 30 min preoperatively might be the most promising dosing regimen for further research.

Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy.

BACKGROUND: Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response. METHODS: Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex. RESULTS: Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1ß, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups. CONCLUSIONS: A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.

Chronic alcohol consumption induces an overproduction of NO by nNOS- and iNOS-expressing myenteric neurons in the murine small intestine.

BACKGROUND: There are indications that alterations in the nitric oxide (NO) system of relaxation mediate gastrointestinal motor disturbances induced by chronic alcohol consumption (CAC). As CAC is known to inhibit the motility of the mouse small intestine, we investigated in this model if CAC affects basal NO synthesis by myenteric neurons and which NOS isoforms are involved. METHODS: The instantaneous NO synthesis of individual neurons was optically measured in whole-mount preparations loaded with the NO synthesis indicator DAF-FM, and the expression of nNOS, iNOS and eNOS was determined by immunohistochemistry. KEY RESULTS: The DAF-FM recordings showed that CAC induced an increase in neuronal NO synthesis (absolute fluorescence: control 34±12; CAC 140±56; mean±SD; P<0.0004). Neurons of control mice expressed the nNOS (29±3% of total) and iNOS (28±1%) isoforms. eNOS expression was observed in <0.5% of the neurons. Chronic alcohol consumption caused an increase in the proportion of iNOS-expressing neurons (to 33±5%; P<0.01) and a decrease in nNOS-expressing neurons (to 22±3%; P<0.0001), without altering the proportion of NO-producing neurons (control 55±13%; CAC 56± 11%; P=0.82). CONCLUSIONS & INFERENCES: Chronic alcohol consumption induces a marked increase in NO synthesis by jejunal myenteric neurons, accompanied by an up-regulation of iNOS-expressing neurons and a downregulation of nNOS neurons. We conclude that the overproduction of NO may be a direct cause of gastrointestinal motility disturbances.

CGRP1 receptor activation induces piecemeal release of protease-1 from mouse bone marrow-derived mucosal mast cells.

BACKGROUND: The parasitized or inflamed gastrointestinal mucosa shows an increase in the number of mucosal mast cells (MMC) and the density of extrinsic primary afferent nerve fibers containing the neuropeptide, calcitonin gene-related peptide (CGRP). Currently, the mode of action of CGRP on MMC is unknown. METHODS: The effects of CGRP on mouse bone marrow-derived mucosal mast cells (BMMC) were investigated by measurements of intracellular Ca(2+)[Ca(2+)](i) and release of mMCP-1. KEY RESULTS: Bone marrow-derived mucosal mast cells responded to the application of CGRP with a single transient rise in [Ca(2+)](i). The proportion of responding cells increased concentration-dependently to a maximum of 19 ± 4% at 10(-5)mol L(-1) (mean ±SEM; C48/80 100%; EC(50)10(-8) mol L(-1) ). Preincubation with the CGRP receptor antagonist BIBN4096BS (10(-5) mol L(-1)) completely inhibited BMMC activation by CGRP [range 10(-5) to 10(-11) mol L(-1); analysis of variance (ANOVA) P < 0.001], while preincubation with LaCl(3) to block Ca(2+) entry did not affect the response (P = 0.18). The presence of the CGRP1 receptor on BMMC was confirmed by simultaneous immunofluorescent detection of RAMP1 or CRLR, the two components of the CGRP1 receptor, and mMCP-1. Application of CGRP for 1 h evoked a concentration-dependent release of mMCP-1 (at EC(50) 10% of content) but not of ß-hexosaminidase and alterations in granular density indicative of piecemeal release. CONCLUSIONS & INFERENCES: We demonstrate that BMMC express functional CGRP1 receptors and that their activation causes mobilization of Ca(2+) from intracellular stores and piecemeal release of mMCP-1. These findings support the hypothesis that the CGRP signaling from afferent nerves to MMC in the gastrointestinal wall is receptor-mediated.

Impairment of intestinal barrier and secretory function as well as egg excretion during intestinal schistosomiasis occur independently of mouse mast cell protease-1.

Deposition of Schistosoma mansoni eggs in the intestinal mucosa is associated with recruitment of mucosal mast cells (MMC) expressing mouse mast cell protease-1 (mMCP-1). We investigated the involvement of mMCP-1 in intestinal barrier disruption and egg excretion by examining BALB/c mice lacking mMCP-1 (Mcpt-1(-/-)). Tissue and faecal egg counts from 6 weeks until 12 weeks post-infection (w p.i.) revealed no differences between wild type (WT) and Mcpt-1(-/-)mice. Using chamber experiments on ileal tissue revealed that at 8 w p.i., the epithelial barrier and secretory capacity were severely impaired, whereas no difference was found between WT and Mcpt-1(-/-)mice in this respect. However, a fragmented distribution of the tight junction (TJ) protein occludin, but not of claudin-3 or ZO-1, was observed in WT mice at 8 w p.i., while no changes in TJ integrity were seen in Mcpt-1(-/-)mice. Therefore, we conclude that in contrast to the situation in Trichinella spiralis-infected mice, in schistosomiasis, mMCP-1 is not a key mediator in egg excretion or impairment of the intestinal barrier. The marked decrease in ileal secretory capacity during S. mansoni egg excretion suggests that the mechanisms facilitating the passage of schistosoma eggs through the gut wall are directed more particularly at the epithelial cells.

Vascular anatomy of the hamster retractor muscle with regard to its microvascular transfer.

BACKGROUND: The hamster retractor muscle (RET) is used as an in vivo model in studies of skeletal muscle ischemia-reperfusion injury. The RET is unique in that the muscle can be isolated while preserving the primary vascular supply so that its contractile function can be measured simultaneously with local microvascular responses to experimental interventions. The goal of this study was to understand the anatomical origin of the vascular supply to the RET and determine whether the RET can be used as a free flap after surgical isolation of the thoracodorsal vessels. METHODS: Microdissection was performed to determine the anatomy of the vasculature that supplies and drains the RET. RESULTS: Distinct numbers and patterns of feed arteries (2-4) and collecting veins (1-3) were identified (n = 26 animals). Dye injection (n = 8) of the thoracodorsal artery demonstrated that the RET remains perfused following its isolation on the thoracodorsal pedicle. Heterotopic allograft transplantation of the RET (n = 2) was performed by anastomosing the thoracodorsal vessels to the femoral vessels using the end-to-side technique. CONCLUSIONS: The anatomical relationships indicate that the RET can be used as a free flap model for evaluating the effect of preservation strategies and transplantation on skeletal muscle microcirculation and contractile function.

Venous valve reconstruction in patients with secondary chronic venous insufficiency.

OBJECTIVES: To evaluate the durability of venous valve reconstruction (VVR) and its benefits in terms of symptom improvement, ulcer healing and symptom/ulcer recurrence among patients with secondary chronic venous insufficiency (SCVI) in whom superficial venous surgery and compression treatment had failed. METHODS: During a ten year period (1993-2004) 1800 patients with chronic venous insufficiency (CVI) were evaluated by colour duplex ultrasound (CDU) and ambulatory venous pressure measurement (AVP). Approximately two thirds of patients had SCVI. Initial treatment consisted of compression therapy for a 6 month period. In addition, superficial vein and perforator surgery was performed in those presenting with reflux in these venous systems. 121 patients who did not improve with this treatment were investigated by ascending venography, descending video venography, air plethysmography and measurement of post-ischaemic venous pressure gradient. Thirty two cases having venous reflux without obstruction were selected for VVR. RESULTS: The ulcer healing rate within three months was 68% (13/19 patients). VVR resulted in valvular competence and a clinical success rate of 47% and 40% after 3 and 7 years respectively. In 8/13 (54%) of patients with a healed leg ulcer, a median post-operative AVP reduction of 33 mm Hg (range 20-38) was recorded. The durability of clinical success was numerically longer in patients with haemodynamic improvement (n=10) median 24 months (12-108), when compared with that in those without haemodynamic improvement (n=22) median 18 months (6-108). Popliteal vein reconstruction was part of the VVR procedure in all patients with haemodynamic improvement (post-op. AVP reduction >or=20 mm Hg). VVR at the popliteal level alone or combined with inguinal reconstruction seemed to be the one significant factor associated with haemodynamic improvement (P=0.014, Chi squared). CONCLUSION: VVR may lead to ulcer healing, but when performed at the popliteal level, haemodynamic improvement can be obtained along with a longer recurrence-free period (durability). VVR should be considered in the treatment of patients with SCVI who do not respond to superficial venous surgery and compression treatment.

Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study.

BACKGROUND AND AIMS: Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia in one randomized clinical study. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with stable critical limb ischaemia (CLI). DESIGN: A prospective, combined-centre pilot study. MATERIAL: Eight patients with CLI of the lower extremities, and without any other treatment options. METHODS: Bone marrow cells were harvested from the patient's iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAS) and several non-invasive circulatory physiological tests. RESULTS: There were no complications from the procedures. Two patients were amputated two months after cell injection. Five patients reported pain relief after four months. Five patients could be evaluated at eight months. According to VAS and physiological tests, they were all either stable or showed improvement. CONCLUSION: This method seems to be a safe option for treating patients with CLI. Inclusion of patients took a long time, mainly because many patients with CLI are offered endovascular treatment in our institution. While symptomatic improvement was found in individual patients, larger trials are required to investigate efficacy. This will probably require multi-centre participation.

Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study.

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.

Blood pressure in patients with intermittent claudication increases continuously during walking.

OBJECTIVES: The purpose of this study was to compare the circulatory responses to walking in patients with peripheral atherosclerotic disease (PAD) and healthy controls. METHODS: The participants were eleven patients with diagnosed PAD, and a control group of six healthy age-matched adults. Blood pressure, heart rate (HR), and acral skin perfusion were recorded continuously before, during and after a walking exercise on a treadmill. RESULTS: The patients walked to maximum claudication distance (MCD) on a treadmill, median walking distance 103 (34-223) metres [median (range)], at 3.3 (1.0-4.5) km/h. There was a steep increase in HR and mean arterial pressure (MAP) while the patients were walking. At claudication the median rise in MAP was 46.6 (10.3-61.3) mmHg, systolic blood pressure (SP) increased by 84.9 (31.4-124.9) mmHg, and diastolic blood pressure (DP) by 21.7 (-2.1-31.7) mmHg. HR increased by 34.9 (12.9-48.1) beats/min. The control group walked for 5 minutes at 3.2 (3.0-3.3) km/h. In the control group the blood pressure initially increased moderately but stabilised thereafter. Median rise in MAP during walking was 8.5 (5.6-14.6) mmHg, SP increased by 30.9 (6.6-41.5) mmHg, and DP was reduced by -1.4 (-5.4-1.5) mmHg. HR increased by 27.1 (18.8-34.9) beats/min. We found no significant differences in acral skin perfusion during walking exercise between the patients and control group. CONCLUSIONS: In patients with PAD, blood pressure increased continuously and significantly when walking to MCD (dynamic exercise). The level of increase in blood pressure was similar to that caused in response to isometric exercise.

The Oslo balloon angioplasty versus conservative treatment study (OBACT)--the 2-years results of a single centre, prospective, randomised study in patients with intermittent claudication.

OBJECTIVES: To compare the effect of optimal medical treatment only (OMT) with OMT combined with percutaneous transluminal angioplasty (OMT+PTA) in patients with intermittent claudication (IC). DESIGN: A single centre prospective, randomised study. Quality of life (QoL) was the primary outcome measure. Secondary measures were ankle-brachial-index (ABI), treadmill walking distances and mortality. METHODS: From a total of 434 patients considered for inclusion into the trial, only 56 patients with disabling IC fulfilled the inclusion criteria. The patients were randomised into treatment groups consisting of 28 patients each and followed for 2 years. ABI and treadmill walking distances were measured in addition to the visual analogue scale (VAS) for pain evaluation, and QoL assessment using the Short Form (SF-36 and Claudication Scale (CLAU-S). RESULTS: The demographic data in the 2 groups were almost identical. After 2 years of follow-up the ABI, the treadmill walking distances and the VAS were significant improved in the group treated with OMT+PTA, compared to the group treated with OMT only (p<0.01 for all). Furthermore, some variables from the QoL assessment also showed a significant improvement in favour of the OMT+PTA group (p<0.05 for all). CONCLUSION: The advantage of conducting a single centre study and adhering to very strict inclusion criteria was illustrated by the homogenous demographic data of the two groups. This partly outweighed the disadvantage of having included a relatively small number of patients. Early intervention with PTA in addition to OMT seems to have a generally more positive effect compared to OMT only, on haemodynamic, functional as well as QoL aspects during the first 2 years in patients with IC.

External venous valve plasty (EVVP) in patients with primary chronic venous insufficiency (PCVI).

OBJECTIVES: To evaluate the patency of EVVP and its effect in symptom relief, ulcer healing and ulcer-free period in patients with PCVI. METHODS: Between 1993 and 2004, 1800 patients with CVI were evaluated and seventeen with PCVI were selected for EVVP. They were all investigated with ambulatory venous pressure measurement (AVP), colour duplex ultrasound (CDU), ascending venography and descending video venography. The CEAP classification was used to group the patients. Six patients were C4, four C5 and seven C6. All had deep reflux and high levels of AVP. RESULTS: All procedures were technically successful. The ulcer healing rate was 4/7 (57%) within 3 months. All C4 patients experienced symptom improvement postoperatively and had a median recurrence free period of 72 (range 60-122) months. The C5 group had an median ulcer free period of 61 months (12-72) and the C6 of median 48 (12-72) months. Single valve plasties (4) reached a median competence period of 48 months (12-72), 12 multiple valve plasties at the same level show a median 78 months (63-122) and 10 multilevel repairs median 54 months (12-96). Multiple valve plasties at the same level (multi-station plasties) performed on the C4 group seemed to yield the longest durability with a median of 103 months (84-122). CONCLUSION: EVVP with an ulcer healing rate of 57% and satisfactory symptom improvement seems to be an alternative of surgical treatment for selected patients with PCVI. The durability of this technique seems to be related to clinical severity and the multiplicity of repairs.

Markers of vascular inflammation are associated with the extent of atherosclerosis assessed as angiographic score and treadmill walking distances in patients with peripheral arterial occlusive disease.

The importance of inflammation in atherosclerosis is well established in cardiovascular disease. However, limited data exist on the relationship between vascular inflammation and the severity of peripheral arterial occlusive disease (PAD). We investigated the relationship between biochemical markers of vascular inflammation and the diagnostic measures of PAD: ankle-brachial pressure index (ABI), maximum treadmill walking distance and angiographic score. In 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn for determination of selected soluble cell adhesion molecules, cytokines and chemokines. Tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and CD40 ligand (CD40L) were all significantly correlated with the angiographic score (p < 0.05 for all). After adjustment for relevant co-variates, MCP-1 and CD40L remained statistically significant (p < 0.01 for both). IL-6 was, independent of other risk factors, inversely correlated with the maximum treadmill walking distance (p < 0.01). Our cross-sectional study in PAD patients showed that the vascular inflammatory markers MCP-1, CD40L and IL-6 were significantly associated with the extent of atherosclerosis, assessed by angiographic score and maximum treadmill walking distance. These findings indicate that vascular inflammation is implicated in PAD, which might be of importance in future diagnosis and treatment of the disease.

Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt-induced ileal mucosa injury.

BACKGROUND: Indomethacin (Indo) exerts local toxic effects on small intestinal mucosa, possibly in association with hydrophobic bile salts. We investigated the potential toxic effects of Indo on ileal mucosa and the role of phosphatidylcholine (PC). MATERIALS AND METHODS: Transmucosal resistance and Na-fluorescein permeability of ileal mucosa segments from female Wistar rats were determined in Ussing chambers during a 30-min incubation with model systems containing: control-buffer, taurodeoxycholate (TDC), Indo, TDC-Indo, TDC-PC, or TDC-PC-Indo. Decrease of resistance and increase of permeability were considered as parameters for mucosal injury. After incubation in Ussing chambers, the histopathology was examined to quantify the extent of mucosal injury. Also, in CaCo-2 cells, LDH-release was determined as a measure of cytotoxicity, after incubation with various model systems. RESULTS: Decrease of resistance and increase of permeability were highest in systems containing TDC-Indo (P < 0.01). Phosphatidylcholine protected against the cytotoxic effects of TDC in absence of Indo only. Extent of mucosal injury by histological examination was also highest in systems containing TDC-Indo (P = 0.006). Again, PC exhibited protective effects in absence of Indo only. The LDH-release by CaCo2-cells was strongest in TDC-Indo systems (P < 0.001). CONCLUSIONS: Indomethacin disrupts protective effects of PC against bile salt-induced ileal mucosa injury. This finding is relevant for small intestinal injury induced by non-steroidal anti-inflammatory drugs.

Ion channel regulation of the dynamical instability of the resting membrane potential in saccular hair cells of the green frog (Rana esculenta).

AIMS: We investigated the ion channel regulation of the resting membrane potential of hair cells with the aim to determine if the resting membrane potential is poised close to instability and thereby a potential cause of the spontaneous afferent spike activity. METHODS: The ionic mechanism and the dynamic properties of the resting membrane potential were examined with the whole-cell patch clamp technique in dissociated saccular hair cells and in a mathematical model including all identified ion channels. RESULTS: In hair cells showing I/V curves with a low membrane conductance flanked by large inward and outward rectifying potassium conductances, the inward rectifier (K(IR)), the delayed outward rectifier (K(V)) and the large conductance, calcium-sensitive, voltage-gated potassium channel (BK(Ca)) were all activated at rest. Under current clamp conditions, the outward current through these channels balanced the inward current through mechano-electrical transduction (MET) and Ca2+ channels. In 45% (22/49) of the cells, the membrane potential fluctuated spontaneously between two voltage levels determined by the voltage extent of the low membrane conductance range. These fluctuations were not influenced by blocking the MET channels but could be reversibly stopped by increasing [K+]o or by blocking of K(IR) channels. Blocking the BK(Ca) channels induced regular voltage oscillations. CONCLUSIONS: Two intrinsic dynamical instabilities of V(m) are present in hair cells. One of these is observed as spontaneous voltage fluctuations by currents through K(IR), K(V) and h-channels in combination with a steady current through MET channels. The other instability shows as regenerative voltage changes involving Ca2+ and K(V) channels. The BK(Ca) channels prevent the spontaneous voltage fluctuations from activating the regenerative system.

Subintimal angioplasty in the treatment of patients with intermittent claudication: long term results.

OBJECTIVES: Reporting the long-term results of subintimal angioplasty (SA) in patients with intermittent claudication (IC). DESIGN: A prospective study. PATIENTS: One hundred and sixteen SA procedures were performed in 104 patients, from February 1997 to January 2000. METHODS: This is a prospective study of patients treated for IC with infrainguinal SA. Primary assisted patency rates were calculated, also on intention to treat basis. Univariate and multivariate Cox regression tests were used to assess whether patency was correlated with co-morbidities, run-off or occlusion length. RESULTS: There was no early mortality. Technical success was achieved in 101 cases (87%). Primary assisted patency rates on intention to treat basis (116 cases) at 6, 12, 36 and 60 months were 69, 62, 57 and 54%, respectively. For successfully recanalized patients (101 cases) these respective numbers are 79, 70, 66 and 64%. Length of occlusion, age and male gender were independent risk factors for reocclusion. CONCLUSIONS: The satisfactory results obtained in the present study are probably due to two main factors. First, the three participating radiologist are highly skilled and experienced. Secondly, a conscientious surveillance was adhered to, so that restenoses could be diagnosed and treated early. SA is a relevant alternative to bypass surgery in patients with disabling IC due to long femoro-popliteal occlusions. It is far less traumatic than conventional vascular reconstructions, complications are few and not serious. Very importantly, SA never interfered with later successful vascular surgery. Therefore, we have adopted SA as the primary treatment for patients with IC when medical treatment alone has not been satisfactory.

In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation.

Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close apposition. We examined interactions between primary cultured MMC and CGRP-IR DRG neurons in vitro by confocal recording of intracellular Ca(2+) concentration ([Ca(2+)](i)). The degranulatory EC(50) for the mast cell secretagogue compound 48/80 (C48/80; 10 microg/ml) and the neuropeptides CGRP (2.10(-8) M) and substance P (SP; 3.10(-8) M) were determined by measurement of extracellular release of the granule chymase, mouse mast cell protease-1. Application of C48/80 (10 microg/ml) and CGRP and SP (both 10(-7) M) to Fluo-4-loaded MMC induced a transient rise in [Ca(2+)](i) after a lag time, indicative of mast cell degranulation and/or secretion. The CGRP response could be completely blocked by pertussis toxin (2 microg/ml), indicating involvement of G(i) proteins. Application of MMC juice, obtained by C48/80 degranulation of MMC, to Fluo-4-loaded DRG neurons induced in all neurons a rise in [Ca(2+)](i), indicative of activation. Degranulation of MMC by C48/80 in culture dishes containing Fluo-4-loaded DRG neurons also caused activation of the DRG neurons. In conclusion, these results demonstrate a bidirectional cross-talk between cultured MMC and CGRP-IR DRG neurons in vitro. This indicates that such a communication may be the functional relevance for the close apposition between MMC and CGRP-IR nerve fibers in vivo.