Search

BACKGROUND AND PURPOSE: Obesity is a risk factor for osteoarthritis in the lower limb, yet the cardiovascular risks associated with obesity in hip or knee replacement surgery are unknown. We examined associations between body mass index (BMI) and the risk of a major adverse cardiovascular event (MACE: ischemic stroke, acute myocardial infarction, or cardiovascular death) or the risk of all-cause mortality in a nationwide Danish cohort of patients who underwent primary hip or knee replacement surgery.METHODS: Using Danish nationwide registries, we identified 34,744 patients aged ≥ 20 years who underwent elective primary hip or knee replacement surgery between 2005 and 2011. We used multivariable Cox regression models to calculate the 30-day risks of MACE and mortality associated with 5 BMI groups (underweight (BMI < 18.5 kg/m(2)), normal weight (18.5-24 kg/m(2)), overweight (25-29 kg/m(2)), obese 1 (30-34 kg/m(2)), and obese 2 (≥ 35 kg/m(2))).RESULTS: In total, 232 patients (0.7%) had a MACE and 111 (0.3%) died. Compared with overweight, adjusted hazard ratios (HRs) were 1.2 (95% CI: 0.4-3.3), 1.3 (0.95-1.8), 1.6 (1.1-2.2), and 1.0 (0.6-1.9) for underweight, normal weight, obese 1, and obese 2 regarding MACE. Regarding mortality, the corresponding HRs were 7.0 (2.8-15), 2.0 (1.2-3.2), 1.5 (0.9-2.7), and 1.9 (0.9-4.2). Cubic splines suggested a significant U-shaped relationship between BMI and risks with nadir around 27-28.INTERPRETATION: In an unselected cohort of patients undergoing elective primary hip or knee replacement surgery, U-shaped risks of perioperative MACE and mortality were found in relation to BMI. Patients within the extreme ranges of BMI may warrant further attention.

AIMS: Pharmacological and revascularization strategies following myocardial infarction (MI) have changed substantially during the last two decades. We investigated the temporal trends in heart failure (HF) incidence and mortality during the first 90 days following first-time MI between 1997 and 2010 in Denmark.METHODS AND RESULTS: Through administrative nationwide registers we identified 89,389 patients without prior HF hospitalized with first MI. The number of patients treated with percutaneous coronary intervention (PCI) days 0-1 after index MI increased from 2.5% in 1997-98 to 38.2% in 2009-10. Treatment with clopidogrel increased from 0.02% in 1997-98 to 68.1% in 2009-10 and statins from 8.1% in 1997-98 to 78.3% in 2009-10. The incidence of HF (defined as HF diagnosis or incident use of loop diuretics) decreased from 23.6% in 1997-98 to 19.6% in 2009-10 (pCONCLUSION: We found a temporal decrease in HF incidence and mortality during the first 90 days after MI in 1997-2010. This could partly be explained by changes in interventional and pharmacological treatment strategies.

To study separation of wound edges in midline laparotomy incisions closed with either a mass stitch or a stitch incorporating only aponeurosis.Experimental study in pig.University hospital, Norway.8 domestic pigs.Steel sutures were used and metallic clips were placed in the aponeurosis. After increasing the intra-abdominal pressure the distance between the lateral edge of stitches and between pairs of clips was measured on sequential radiographs.After three hours with raised intra-abdominal pressure the lateral edge of stitches became separated by a mean (SD) of 5.6 (1.3) mm with a mass stitch and by 0.5 (0.6) mm with stitches placed only in the aponeurosis (p0.001). Corresponding figures for separation of clips was 3.6 (1.5) mm and 0.1 (0.3) mm (p0.001). The suture cut through the muscle by more than 3mm in 25 out of 36 mass stitches. Muscle and peritoneum included in the mass stitch was compressed, darkly discoloured, and there were signs of haemorrhage.Wound edges become separated with a mass stitch but not with stitches placed only in the aponeurosis when the intra-abdominal pressure is raised after closure of midline laparotomy incisions. This results from sutures compressing or cutting through subcuticular fat, muscle, and peritoneum enclosed in a mass stitch.

Quality of life is receiving increasing attention as a criterion for the assessment of treatment, not least for surgery, in pancreatic cancer. In exocrine pancreatic cancer there are three main symptoms that must be dealt with: pain, loss of weight and jaundice. All of them seriously impair quality of life, but most often pain is the most feared by the patients. Despite this, the intensity and the quality of the pain is all too often only scantly described. In 85 consecutive patients with newly diagnosed pancreatic cancer we have prospectively registered the quality and quantity of their pain and correlated it to tumor and patient characteristics. It was found that about one fourth of the patients were totally pain free and half of all suffered a pain described by two or less on a Visual Analogue Scale. Only one in ten had severe pain. Although more and more patients were treated with morphine, it was still about one third of all patients that had no or only little pain in the last part of their life. Pain had a strong correlation to survival. This may be due to secondary effects like depressing the mood of the patient and reducing the food intake, but is probably more often a reflection of that generalized cancer induces more pain. Analgesic drugs are the cornerstone of the pharmacologic management of pain due to pancreatic cancer. A significant part of the patients do well with only paracetamol and nonsteroidal antiinflammatory agents. Combining these agents with narcotic analgesics can enhance pain control while lessening the dose of narcotics. A wide range of narcotics are available as well as different modes for delivery: regular pills, slow release forms, injections, subcutaneous injections, epidural etc. Each patient's pain management should be individualized, based on the intensity of pain, the type of pain and the side effects. It is essential not only to describe the medication, but also to follow-up the development of the pain and the patient's total experience of the situation. As an alternative to narcotics, plexus celiac blocks have been used with somewhat different result; in the hands of the experts the percutaneous approach is usually sufficient, but in the hands of other also poor results are reported. During the last years thoracoscopic splanchnicectomy has been tried as a complement giving long-standing pain relief with little or no side effects in the majority of patients. With this approach the sympathetic fibers lead by the symphathetic chain and further by the nervus splanchnicus major, minor and minors are divided. The denervation is easily done and can be performed bilateraly in one seance. This method will probably be used more often as the technique is now well described.

To compare survival on different beta-blockers in heart failure.We identified all Danish patients ≥35 years of age who were hospitalized with a first admission for heart failure and who initiated treatment with a beta-blocker within 60 days of discharge. The study period was 1995-2011. The main outcome was all-cause mortality and all-cause hospitalization. Cox proportional hazard models were used to compare survival. The study included 58 634 patients of whom 30.121 (51.4%) died and 46.990 (80.1%) were hospitalized during follow-up. The mean follow-up time was 4.1 years. In an unadjusted model carvedilol was associated with a lower mortality [hazard ratio (HR) 0.737, 0.714-0.761] compared with metoprolol (reference) while bisoprolol was not associated with an increased mortality (HR 1.020, 0.973-1.069). In a model adjusted for possible confounders and stratified according to beta-blocker dosages, patients that received high-dose carvedilol (≥50 mg daily) had a lower all-cause mortality risk (HR 0.873, 0.789-0.966) than patients receiving high-dose (≥200 mg daily) metoprolol (reference). High-dose bisoprolol (≥10 mg daily) was associated with a greater risk of death (HR 1.125, 1.004-1.261). High-dose carvedilol was associated with significantly lower all-cause hospitalization risk (HR 0.842, 0.774-0.915) than high-dose metoprolol (reference), while high-dose bisoprolol had insignificantly lower risk than high-dose metoprolol (HR 0.948, 0.850-1.057).Heart failure patients receiving high-dose carvedilol (≥50 mg daily) showed significantly lower all-cause mortality risk and hospitalization risk, compared with other beta-blockers.

The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease.HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial.In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables.A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy.In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.

Purpose: Heart failure (HF), vascular disease and atrial fibrillation (AF) are all pathophysiological related and understanding antithrombotic therapy is crucial. Our aim was to investigate the impact of AF and antithrombotic therapy on prognosis in HF patients with co-existing vascular disease. Methods: In a nationwide cohort of patients hospitalized with HF and vascular disease (coronary artery disease and peripheral arterial disease), AF status was categorized as prevalent, incident and no AF. Patients were followed from 1997 to 2009 and risks of thromboembolism (TE) and serious bleeding were assessed by Cox regression models with antithrombotic therapy (single antiplatelet, vitamin K antagonist (VKA) or both) and AF as time-dependent variables. Crude rates are events per 100 person-years. Results: A total of 37,464 patients were included (mean age 74.5 [SD 10.7] years, 36.3% females) and mean follow-up of was 3.0 years. Of these, 7,804 (20.7%) had prevalent AF while incident AF occurred in 6,432 (17.2%). Impact of AF and antithrombotic therapy on TE and bleeding risk is shown below. Relative to VKA therapy, consistent increased risk of TE was present in AF patients on single antiplatelet therapy with no decrease in risk when combining antiplatelet with VKA therapy. In patients without AF, no difference in TE risk was found between antithrombotic regimens. Bleeding risk was significantly raised in all patients on dual therapy with antiplatelet and VKA. ![Figure][1] Impact of AF and antithrombotic therapy Conclusions: In patients with co-existing HF and vascular disease, AF has an adverse effect on thromboembolism and bleeding. Adding antiplatelet therapy on top of VKA therapy is not associated with additional benefit on thromboembolic risk, but notably increased risk of bleeding. [1]: pending:yes

This study was performed to examine if the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) or tumor necrosis factor (TNF) are released from the gastric mucosa during acute mucosal damage, and if the generation of these cytokines is affected by indomethacin. Cat stomachs were exposed to 2 M NaCl for 10 min followed by luminal perfusion at pH 1. Gastric mucosal blood flow was determined by radioactive microspheres, portal vein blood flow by transit-time flowmetry, and H+ back diffusion/secretion by pH-stat titration. Concentrations of active cytokines and of histamine in aortic and portal vein blood were measured by bioassay and RIA, respectively. Active IL-6, but not IL-1 and TNF, is released from the gastric mucosa during acute mucosal damage by 2 M NaCl and acid back diffusion. Indomethacin increased mucosal injury and enhanced the TNF generation but reduced the release of IL-6 from the gastric mucosa. We conclude that IL-1 and TNF probably do not play an important modulating role during acute gastric mucosal damage. The generation of IL-6 may, however, contribute to mucosal protection.

This study was undertaken to examine the role of prostaglandins and histamine in the hyperemic response to gastric mucosal damage followed by H+ back-diffusion. Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the surface epithelium, increased gastric mucosal blood flow, and increased release of histamine, PGE2, and 6-keto PGF1 alpha (prostacyclin) into portal venous blood. The effect of indomethacin and histamine blockers (H1 + H2) on the hyperemic response to acid back-diffusion was related to the depth of the mucosal injury and the region of the stomach. In the corpus, indomethacin enhanced mucosal injury. In areas with superficial damage, the hyperemia was inhibited by indomethacin and antihistamines and eliminated by the combination of both. In corpus areas with indomethacin-induced deep lesions, the blood flow was very high, and this hyperemia was partly inhibited by antihistamines. In the antrum the hyperemic response was reduced by antihistamines. Indomethacin increased the release of histamine into portal venous blood (baseline recordings) and reduced basal gastric mucosal blood flow.

Anthracycline based chemotherapy improves survival in breast cancer patients but is associated with an increased risk of heart failure (HF). The risk of late onset HF is, however, debatable and based on observational studies. This study determines the risk of clinical HF more than 10 years after

The present study was undertaken to measure the output of histamine and calcitonin gene-related peptide (CGRP) from injured and restituting gastric mucosa into venous blood and to study the effect of acid back-diffusion on the release of these mediators and their role in the hyperemic response to injury.Stomachs of cats were perfused with saline at pH 1.0 or 7.4. Gastric mucosal blood flow (GMBF) was determined with radioactive microspheres, and blood flow in the portal vein and celiac artery was determined by transit-time flowmetry. H+ back-diffusion/secretion was measured by pH-stat titration and by measuring the arteriovenous base excess difference. Mucosal injury was produced by exposure to 2 M NaCl. Histamine and CGRP in portal venous blood were measured by radioimmunoassay.During mucosal exposure to 2 M NaCl GMBF increased, and histamine (0.23 nmol/min) and CGRP (1.2 pmol/min) were released from the mucosa into blood. The hyperemic response was reduced by pretreatment with H1 and H2 blockers and still further by addition of the blocker CGRP8-37. After mucosal damage and luminal perfusion at pH 7.4, GMBF and output of CGRP and histamine decreased towards base-line levels within 30 min. During luminal perfusion at pH 1.0 associated with acid back-diffusion, GMBF and histamine output remained high, whereas the output of CGRP decreased to base-line level. Pretreatment with H1 and H2 blockers reduced the hyperemic response as measured 30 min after damage.The hyperemic response caused by 2 M NaCl is most likely mediated by histamine and CGRP and maintained by histamine released by back-diffusion of H+ through the superficially damaged gastric mucosa.

Background: Non steroidal anti-inflammatory drugs(NSAIDs) utilization has been associated with worsened outcomes among patients with established cardiovascular disease.We analyzed the cause-specific cardiovascular risk associated with use of NSAIDs in a nationwide cohort of patients with prior myocardial infarction (MI). Methods: By individual-level linkage of nationwide registries of hospitalizations and drug dispenses from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified. The risk of cardiovascular death, a composite of coronary death or nonfatal MI, and fatal or nonfatal stroke with NSAID use was analyzed by adjusted Cox proportional hazard models. Results: Of 97,698 patients included (mean age 69 years (SD 13.0), 63.0% men),44.0% received NSAIDs during follow-up. Relative to no NSAID use, overall NSAID was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.52 95% confidence interval [CI] 1.34-1.73). In particular, use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 2.05 95% confidence interval CI 1.88-2.23) and HR 1.74(CI.1.53-1.98), respectively) with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of fatal/nonfatal stroke (HR 1.27(CI. 1.14-1.41)).Naproxen was associated with the lowest risk of all outcomes, although higher than no NSAID use. Conclusion: The cause specific cardiovascular risks associated with the use of individual NSAIDs found to differ and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results further support caution in use of NSAIDs in patients with prior MI.

Background: Use of NSAID has shown to be associated with a substantially increased risk of athero-thrombotic adverse events in patients with a history of myocardial infarction. Whether a similar increase in risk is found for VTE is unknown. Methods: Patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. The risk of VTE associated with NSAID use was analyzed by time-dependent Cox proportional hazard models adjusted for age, gender, calendar year, concomitant drug use, and comorbidity. Results A total of 98,901 patients were included (mean age 68 years (SD 13.0), 64.0% men), 44.0% received NSAIDs during follow-up. There were 1847 VTEs. Relative to no NSAID use, the Cox-analyses showed increased risk of VTE with use of any NSAIDs. Overall NSAID use was associated with increased risk of VTE (Hazard ratio [HR] 1.75 95% confidence interval [CI] 1.52-2.02). In particular use of the selective cyclooxygenase-2 (COX-2) inhibitors rofecoxib and the nonselective NSAID diclofenac was associated with significantly increased risk of VTE (HR 2.56 (CI 1.60-4.08) and HR 2.03(CI.1.50-2.74), respectively). Conclusion: Use of most NSAIDs was associated with an increased risk of VTE. The use of rofecoxib and diclofenac was associated with highest risk. Further studies, preferably randomized clinical studies, are warranted to establish the cardiovascular safety of NSAIDs, however this study suggests that risk of VTE should be considered when prescribing NSAIDs patients with MI.

Background: Anxiety and sleep deprivation is associated with higher levels of circulating catecholamines and adrenergic stress, which may increase cardiovascular risk. We examined risk of recurrent myocardial infarction and death related to use of sedatives as a proxy for anxiety and sleeplessness in patients after first-time myocardial infarction. Methods and population: Patients, without prior psychiatric disease, surviving 30 days after discharge from first-time MI 1997-2009 and their subsequent drug use was identified by individual-level-linkage of nationwide registers hospitalization and drug dispensing from pharmacies in Denmark. Propensity scores for use of sedatives within the first year were calculated by logistic regression analysis conditional on baseline characteristics. Patients using sedatives were matched on propensity scores with 1 control not receiving sedatives and risk of recurrent myocardial infarction and death within the first-year after discharge was compared using cumulative incidence curves and Cox proportional-hazard models. Results: A total of 24,217 patients using sedatives after discharge and 24,217 matched controls, who were balanced in baseline characteristics, were included. The mean age was 71 years (SD 12.5 years) and 55% were males. Recurrent myocardial infarction by 1 year was observed in 2,411 (10%) patients using sedatives and 1,928 (8%) controls (Fig.); adjusted hazard Ratio (HR) 1.26 (1.18-1.36). In a separate analysis, dividing sedatives into anxiolytics and hypnotics yielded a HR of 1.18 (1.10-1.26) and 1.21 (1.14-1.29), respectively. Patients using sedatives had increased 1 year mortality relative to controls, HR 1.15 (1.09-1.21), but mortality was higher in patients using anxiolytics compared to hypnotics, HR 1.24 (1.16-1.33). Conclusion: Patients using sedatives after MI are at increased risk of recurrent myocardial infarction and death and may be targets for more aggressive approach to secondary preventive interventions.

We have studied the effect of intragastric instillation of 4.5 M NaCl on cell proliferation and carcinogen penetration into the forestomach of Wistar rats at different time intervals after salt exposure. Cells in the S-phase were labelled by incorporation of bromodeoxyuridine and located after immunohistochemistry. N-[3H]Methyl-N'-nitro-N-nitrosoguanidine ([3H]MNNG) was used as the carcinogen and penetration of [3H]MNNG to proliferative cells was determined by autoradiography. The number of cells in S-phase per millimetre epithelium length 12 h and 24 h after salt exposure (32.2 +/- 11.9 and 20.6 +/- 7.4) was significantly higher than in the control animals (9.4 +/- 3.6). No increase in cell proliferation occurred during the first 2 h after salt exposure. Microscopy also revealed oedema in the lamina propia. The forestomach blood flow was not influenced by the application of hypertonic saline. [3H]MNNG at a concentration of 40 micrograms/ml did not penetrate to the proliferative cells in the forestomach and no effect of salt pretreatment on carcinogen penetration was seen. The low penetration of [3H]MNNG to proliferative cells in the forestomach epithelium may explain why this concentration of MNNG given in drinking water over several weeks usually does not induce squamous cell carcinomas in the forestomach. The previously observed cocarcinogenic effect of salt on squamous cell cercinogenesis in the upper gastrointestinal tract could be due to the observed increase in cell proliferation after salt exposure.

Background/Aims: The hyperemic response after superficial gastric mucosal damage is essential for repair of the mucosa. Only indirect evidence suggests that this is caused by supply of bicarbonate. Therefore, this study tested the effect of maintaining the availability of bicarbonate after prevention of the hyperemic response after damage by 2 mol/L NaCl. Methods: Celiac artery flow was reduced, as monitored by Doppler ultrasonography, by gradual constriction of the vessel after mucosal damage. Saline (pH 1.0) was perfused through the stomach lumen and thereafter through a closed chamber with pH and Pco 2 electrodes. Results: Exposure to 2 mol/L NaCl produced a marked increase of mucosal blood flow as measured by microspheres (P $0.025) and a high degree of mucosal restitution 90 minutes after damage as judged by microscopy, whereas prevention of the hyperemic response caused extensive erosions and much less restitution ( P ⩽ 0.001). The latter effect was completely counteracted by intravenous bicarbonate. High blood concentration of bicarbonate increased luminal release of bicarbonate, whereas high mucosal blood flow did not. Conclusions: These data show that bicarbonate is an important factor in blood flow-mediated protection and repair of damaged gastric mucosa and suggest that concentration gradients are the major determinants for transport of bicarbonate across the damaged and restituted mucosa.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT).Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis and Transplantation, including etiological diagnosis. The use of NSAID before the start of RRT was studied by linkage to the National Prescription Register and comorbidity by linkage to the National Patient Registry.A total of 6663 patients were included in the study, and 2407 patients (36.1%) were prescribed NSAID in the 3 years before the start of RRT. These patients were older (mean age = 63.0 vs 61.4 years) and had a significantly higher degree of comorbidity (Charlson score = 2.85 vs 2.61, p 0.05) compared with patients not treated with NSAIDs. In the 3 years leading up to RRT, the number of patients treated with NSAID each year and the cumulated median length of treatment including all NSAIDs were stable at approximately 20% and 40 days, respectively.In this study of a nationwide group of patients, we observed a widespread use of NSAID with an unaffected high annual incidence in the 3 years leading up to the initiation of RRT.

The magnitude of cardiovascular risk associated with psoriasis has been debated and the prognostic impact of psoriasis following myocardial infarction (MI) is unknown. Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients with psoriasis following first-time MI.Cohort study of the entire Danish population including all individuals who experienced first-time MI during the period 2002-2006. Multivariable Cox regression models were used to assess the post-MI prognostic impact of psoriasis. Main outcome measures. All-cause mortality and a composite cardiovascular end-point of recurrent MI, stroke and cardiovascular death.A total of 462 patients with psoriasis and 48 935 controls (mean age 69.5 and 70.6 years, respectively) were identified with first-time MI during the study period. The mean follow-up was 19.5 months [standard deviation (SD) 16.5] for patients with psoriasis and 22 .0 months (SD 18.7) for those without psoriasis. Incidence rates (IRs) per 1000 patient-years for all-cause mortality were 119.4 [95% confidence interval (CI) 117.2-138.3] and 138.3 (95% CI 114.1-167.7) for patients without and with psoriasis, respectively, and the adjusted hazard ratio (HR) associated with psoriasis was 1.18 (95% CI 0.97-1.43). For the composite end-point, the IRs were 149.7 (95% CI 147.1-152.4) and 185.6 (95% CI 155.8-221.0) for patients without and with psoriasis, respectively, with an HR of 1.26 (95% CI 1.04-1.54) for patients with psoriasis.This first study of the impact of psoriasis on prognosis after first-time MI indicated a significantly impaired prognosis in patients with psoriasis. Further studies of this novel association are warranted.

Dimethyl sulfoxide applied intragastrically for 10 min in rats caused extensive mucosal damage. In concentrations of 5%, 10%, or 100%, dimethyl sulfoxide caused superficial damage to 33%, 36%, and 97%, respectively, of the corpus mucosa, and 28%, 44%, and 96%, respectively, of the antral mucosa. Concentrated dimethyl sulfoxide also caused damage to the pits and glands in some areas of the mucosa. The amount of fluid in the stomach increased by 0.24 ml, 0.48 ml, and 2.07 ml during application of 5%, 10%, and 100% dimethyl sulfoxide. The 10% dimethyl sulfoxide increased mucosal blood flow by 0.57 ml/min/g in the antrum, and 100% dimethyl sulfoxide increased mucosal blood flow by 2.21 ml/min/g in the antrum and by 1.17 ml/min/g in the corpus. We conclude that dimethyl sulfoxide is a gastric irritant, which should be considered when it is used as an oxygen radical scavenger, as a drug or carcinogen vehicle, or as oral medication in patients. The protective effect of intragastric dimethyl sulfoxide against stress and various drug-induced gastric injury may be due to "adaptive cytoprotection" rather than an oxyradical scavenger effect.

This study was designed to test the hypothesis that hyperemia after exposure to 2 M NaCl protects the gastric mucosa against damage caused by absolute ethanol by removing ethanol diffusing from the gastric lumen into the mucosa. The stomach of anesthetized cats was perfused with saline at pH 1.0. Gastric mucosal blood flow was determined by radioactive microspheres, and portal vein blood flow was measured by Doppler ultrasound flowmetry. The concentration of ethanol in the corpus mucosa and the amount of ethanol transported away from the stomach in portal blood were measured by using absolute ethanol containing trace amounts of 14C-labeled ethanol. Pretreatment with 2 M NaCl for 10 min increased mucosal blood flow and prevented the development of deep mucosal lesions after subsequent application of absolute ethanol. An inverse correlation was found between mucosal blood flow and the degree of ethanol-induced damage. The mucosal content of ethanol was low in animals pretreated with hyperosmolar NaCl, and the degree of mucosal damage was related to the tissue concentration of ethanol. The amount of ethanol transported by blood from the stomach increased with increasing mucosal blood flow. We conclude that the mild irritant, 2 M NaCl, increases mucosal blood flow, which protects the mucosa by removing ethanol diffusing from the lumen. Thus, the mucosal ethanol concentration remains below a level that causes damage.

The purpose of this study was to determine the risk of adverse cardiovascular events associated with concomitant use of clopidogrel and calcium-channel blockers (CCBs) in patients with myocardial infarction (MI).CCBs inhibit a variety of cytochrome P-450 enzymes, some of which contribute to clopidogrel metabolic activation. This interaction may diminish the efficacy of clopidogrel.All patients surviving 30 days after a first-time MI in the period 2000 to 2006 in Denmark were identified by individual-level linkage of nationwide administrative registers. The cohort was divided into patients treated with and without clopidogrel and followed for 1 year after discharge. The risk of a composite of cardiovascular death, MI, or stroke and the risk of the individual components of the composite end point and all-cause death associated with CCBs were analyzed with multivariable Cox proportional hazard models and in univariate propensity score-matched models.A total of 56,800 patients were included, of whom 24,923 were treated with clopidogrel and 13,380 with CCBs. In the Cox analyses, the risk of the composite end point associated with CCBs was increased in both patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI]: 1.07 to 1.24) and 1.05 (95% CI: 1.01 to 1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI: 0.99 to 1.18). Analyses of all additional adverse end points and propensity score-matched models provided similar results.The clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment. This potential drug interaction is unlikely to have clinical significance.

In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

Bariatric surgery for morbid obesity implies challenges in anaesthesiological handling. We report our experience from 500 consecutive patients during 3 years.The patients were due for laparoscopic Roux-en-Y gastric bypass and enteral bypass. Sleep was induced after pre-oxygenation with target control infusions (TCI) of remifentanil and propofol; vecuronium was supplied for facilitating endotracheal intubation. The propofol infusion was stopped and desflurane 3-6% was given for BIS-titrated anaesthetic maintenance together with remifentanil TCI. Antiemetic prophylaxis was supplied with intravenous (IV) droperidol, ondansetron and dexamethasone; post-operative pain prophylaxis was IV paracetamol, parecoxib and bupivacaine infiltration. The patients were extubated in the operating room and kept in the post-operative care unit for 3-4 h, being tested for a 20 m walk before discharge to the ward.The procedure was uncomplicated peri-operatively in all 500 cases and in 497 patients (99.4%) post-operatively. Three patients had one complication, which resolved without sequelae: oesophageal rupture from gastric tubing, reoperation for anastomosis leakage and pneumonia. The mean duration of surgery was 57 min (range 37-91). The mean time from the start of anaesthesia until the start of surgery and time from the end of surgery until the end of anaesthesia were both significantly reduced throughout the study period, from 23 to 7.8 and 5.8 to 1.9 min, respectively (P0.001). The mean total hospital stay was reduced from 3 days at start to 2 days in the end of the series (P0.05).Safe bariatric short-stay surgery is feasible with a dedicated anaesthesiological concept in an expert surgical team.

Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Treatment with clopidogrel after myocardial infarction (MI) is recommended to almost all patients for 12 months. • There is interpatient variation in the effect of clopidogrel treatment, one possible explanation for this being low initiation or poor persistence with therapy. WHAT THIS STUDY ADDS • We found remarkably high initiation and persistence with clopidogrel treatment among MI patients treated with percutaneous coronary intervention (PCI); interpatient variation cannot be explained by poor initiation and persistence in these patients. • Among MI patients without PCI and among MI patients with concomitant heart failure we found substantial underuse; therefore, focus on these groups is important. AIMS To identify possible underuse by analysing initiation and persistence with clopidogrel treatment in an unselected population of patients admitted with myocardial infarction (MI) with or without subsequent percutaneous coronary intervention (PCI). METHODS Patients admitted with first-time MI from 2000 to 2005 and subsequent prescription claims of clopidogrel were identified by individual-level linkage of nationwide administrative registries in Denmark. Independent factors affecting initiation and persistence with treatment were analysed by multivariable logistic regression models and Cox proportional hazard models. RESULTS A total of 46 190 MI patients were included in the study, of whom 14 939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3% among MI patients without PCI. MI patients with concomitant heart failure received less treatment [odds ratio (OR) 0.49, confidence interval (CI) 0.43, 0.56 among patients with PCI and OR 0.90, CI 0.81, 0.99 among patients without PCI in 2002–2003, and OR 0.89, CI 0.80, 1.00 in 2004–2005, respectively]. Of MI patients with PCI, 77.5% completed 9 months' clopidogrel treatment in 2004–2005, the corresponding figures for MI patients without PCI being 53.9%. CONCLUSIONS Initiation and persistence with clopidogrel treatment is high in MI patients with PCI. However, we found substantial underuse among MI patients without PCI and in MI patients with heart failure.

With improvements in management of chronic heart failure (CHF) more patients survive for extended periods, thus increasing the importance of detection and management of non-cardiac diseases. This study aimed to assess the prognosis after a diagnosis of cancer in a large Danish CHF cohort compared to

The aim was to study prospectively primary endoscopic treatment of CBD stones and further the long-term need for renewed gallstone disease interventions, defined as short- and long-term outcome.Seven years prospective follow-up of 101 consecutive patients with CBD stones who underwent endoscopic treatment with the intent of primarily achieving duct clearance.Many patients underwent several endoscopy sessions before stone clearance was completed in 83%. Eleven patients were treated surgically, 2 patients received a permanent stent, and the remaining 3 became stone free with other means. Complications occurred in 47 patients. During follow-up, 31 patients were readmitted for gallstone disease and 15 of these had recurrent CBD stones. Ten percent (8/78) of patients with the gallbladder in situ had acute cholecystitis during follow-up and late cholecystectomy was carried out in 22%. Risk factors for new gallstone disease were an in situ gallbladder containing stones and previous episodes of CBD stones.A goal of complete CBD stone clearance with ERC and ES proved to be relatively resource consuming. Subsequent cholecystectomy after duct clearance for CBD should be advised when the gallbladder lodges gallstones, especially in younger patients. Recurrent CBD stones were not influenced by cholecystectomy.

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole population-based incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990-2003 were evaluated with an immunohistochemical panel including staining for c-kit. The age-adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty-seven of the mesenchymal gastrointestinal tumors were positive for c-kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high-risk category while half of the nongastric tumors (11 of 22) fall into this high-risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high-risk category is 46%. The negative predictive value of low- and very-low-risk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This population-based GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs.

We investigated two series of MOCVD-grown Al/sub x/Ga1-xN samples with Al compositions x=0.1 and x=0.3 before and after hydrogenation. Shallow and deep centers were investigated using electrical characterization methods. We observe a dominant donor level with a larger binding energy in the sample with x=0.3. We also observe interface defects between An and the AlGaN layer which become more significant with increasing x. Their presence is related to the high Al mole fraction which creates potential fluctuations at the surface of the sample. Hydrogenation results in (i) a partial passivation of the shallow donors, (ii) disappearance of interface defects, and (iii) creation of a new shallow donor center.

To investigate effects of prolonged increased intra-abdominal pressure (IAP) on diuresis, renal blood flow, and hormones that influence renal function, in particular endothelin.Experimental study.Haukeland University Hospital, Norway.21 domestic pigs.The TAP was maintained at normal (n = 7) or at 20 mmHg (n = 7) or 30 mmHg (n = 7) for three hours.Urine output, renal venous pressure, renal artery blood flow (transit-time flowmetry), renal cortex blood flow (microspheres), and renin, aldosterone, atrial natriuretic factor (ANF), adrenaline, noradrenaline, cortisol, and endothelin-1 (ET-1) in renal venous blood.An IAP of 20 mmHg was followed by no significant changes in the variables studied. An IAP of 30mmHg was associated with anuria, considerably reduced renal blood flow and increased renal vascular resistance. The renin activity and the blood concentrations of ET-1, aldosterone, noradrenaline, adrenaline, and cortisol increased during the three hours that IAP was at 30 mmHg.An IAP of 20 mmHg did not influence renal haemodynamics or diuresis. The low renal blood flow observed at an IAP of 30 mmHg probably results from reduced arteriovenous pressure difference and vasoconstriction. Increased concentrations of endothelin, angiotensin II, and noradrenaline may account for the vasoconstriction. The anuria can be explained by low renal blood flow and increased reabsorption of sodium in renal tubules caused by aldosterone.

Wound complications occur quite often after abdominal operations. Numerous studies have been performed in the last decades focusing on closure methods, incisions and suture materials. However, the most important factor, the individual surgeon, has hardly been taken into account in these studies.This study presents results from a prospective randomised study on abdominal wall closure focusing on the results of the individual surgeon.We found no differences in the complication rate between different suture materials or between continuous and interrupted closure techniques. There are marked individual differences in complication rates between surgeons. Regular audit with feedback to individual surgeons is an important instrument for quality improvement.

Suture material and suture technique may affect wound healing. Most surgeons now use a continuous or interrupted mass closure technique, and most studies performed have not shown differences in wound complication rates between these methods. Most authors favour the continuous technique because it is faster and cheaper [1–5].

Wound complications are still a challenging problem after major gastrointestinal operations. Prospective trials performed in recent years show burst abdomen rates of 1%–3%, wound infection rates of 10%–15% and incisional hernia rates of 4%–21% [1–9]. Burst abdomen is a complication associated with mortality rates of 10%–30%, high morbidity, and increased hospital stay and cost of treatment. In an effort to reduce the rate of this complication, many prospective randomized studies have been performed comparing different closure methods and suture materials [1–9]. with the incidence of burst abdomen that low, the problem with these studies is often the small number of patients included, leading to inconclusive results.

Cleaved edge overgrowth (CEO) is a molecular beam epitaxy (MBE) process which can produce laterally confined semiconductor nanostructures1. The basic idea of the CEO is to utilize the atomic layer precision of the MBE process to control the dimensions of a low-dimensional structure (dimensions < 10 nm!). First a multiple quantum well (MQW) structure is made by standard MBE growth on a (100) GaAs substrate. The (100) GaAs samples are then thinned to ~100–200 µm thickness and cleaved in ultra high vacuum in the MBE machine. The cleave exposes an exact (110) surface of GaAs and the final step is a MBE overgrowth on the cleaved edge. High quality MBE growth on (110) GaAs is not trivial. We have made growth tests on (110) GaAs substrates which indicates that an improved quality (110) GaAs/AlGaAs is achieved using molecular beams of As2 instead of As4 in the MBE growth. We are currently interested in the concept of T-shaped quantum wires2–5. Photoluminescence characterization at 4 K of our first CEO sample with T-shaped intersections between 70 A thick (100) MQW’s and a 70 A (110) single quantum well (SQW) indicates formation of quantum wires ~14 meV below the (100) MQW luminescence and ~7 meV below the (110) SQW luminescence.

Purpose: The optimal antithrombotic treatment strategy is unresolved in patients with multiple indications. We investigated the risk of thrombosis and bleeding according to multiple antithrombotic treatment regimes in atrial fibrillation (AF) patients after myocardial infarction (MI) or coronary intervention (PCI). Methods: A total of 12,165 AF patients hospitalized with MI and/or undergoing PCI between 2001-2009 were identified by nationwide registries (60.7% males, mean age 75.6 years). Risk of MI or coronary death, ischemic stroke, bleeding and all-cause death according to antithrombotic treatment regimen was estimated by Cox regression models. Results: Within one year, MI or coronary death, ischemic stroke, and bleeding events occurred in 2,255 (18.5%), 680 (5.6%), and 769 (6.3%) patients, respectively. Crude rates for MI or coronary death were 16.2, 9.6, and 17.7 events per 100 person-years for triple therapy (oral anticoagulation (OAC) + aspirin + clopidogrel), OAC + clopidogrel and OAC + aspirin, respectively. The corresponding crude rates for ischemic stroke were 4.1, 2.8 and 5.6, while for bleeding 14.3, 10.9 and 9.7 events per 100 person-years. Crude rates for triple therapy (8.9 per 100 person-years) and OAC plus clopidogrel (7.1 per 100 person-years) were lower than for OAC plus aspirin. Adjusted HRs are shown in the Figure. ![Figure][1] Effectiveness and safety Conclusion: In a nationwide cohort of AF patients with indication for triple therapy after MI/PCI, the combination of OAC and clopidogrel was equal or better on both effectiveness and safety outcomes compared to other multiple antithrombotic treatment regimes including recommended triple therapy. [1]: pending:yes

Purpose: Psoriasis is associated with increased prevalence of cardiovascular risk factors and increased risk of cardiovascular adverse events. Heart failure (HF) is a major cause of cardiovascular morbidity and mortality but the association between psoriasis and HF has not been investigated in detail. We investigated the risk of new-onset HF in a nationwide cohort of psoriasis patients compared to the background population. Methods: The study included the entire Danish population aged ≥ 18 years that was followed from 1st January 1997 until HF, death or 31st December 2009. Information on comorbidity and concomitant medication was identified by individual-level linkage of administrative registers. Incidence rates (events per 1000 person-years) for development of HF were calculated and adjusted hazard ratios (HRs) were estimated by multivariable Cox hazard regression models adjusted for age, gender, comorbidity and cardiovascular medications. Results: A total of 5,845,758 subjects were eligible for analysis with a maximum follow-up of 13 years. In the study period 66,659 patients with psoriasis, including 6,823 patients with severe psoriasis, were identified. The overall incidence rates for new-onset HF were 2.27 (confidence interval [CI] 2.26–2.28), 4.01 (CI 3.82–4.24), and 4.50 (CI 4.00–5.12) for the reference population, mild psoriasis and severe psoriasis, respectively. Compared to the reference population, the age- and gender-adjusted HRs for HF were increased in all patients with psoriasis, i.e., HR 1.63 (CI 1.54–1.72) and HR 1.70 (CI 1.50–1.94) for those with mild and severe psoriasis, respectively. Conclusion: In this nationwide cohort, psoriasis was associated with increased risk of new-onset HF. The association remained statistically significant after adjustment for confounding factors.

Purpose: The aldosterone antagonist eplerenone reduces mortality and readmissions after acute myocardial infarction (MI) in patients with LVEF≤40% and either symptomatic heart failure or diabetes mellitus, and is recommended by ESC guidelines. We investigated evidence-based use of eplerenone in a nationwide cohort of patients after first-time MI in Denmark. Methods: From national registers we included all patients with MI, aged ≥30 years and surviving ≥30 days. Indication for eplerenone was defined as claimed prescription of loop-diuretics in addition to either ACE-inhibitor or antidiabetic drugs, within 90 days after discharge. Use of eplerenone and other aldosterone antagonists was identified, and survival compared by Kaplan-Meier analysis. Results: We included 49,479 patients (63% men, mean age 68.1±13.6 years) with a median follow-up of 1003 (IQR 420-1716) days. Treatment with eplerenone was indicated in 9,115 (18.4%) patients, of which 93 (1.02%) received eplerenone, and 2,157 (23.7%) received spironolactone. Mortality rates for groups with and without indication for eplerenone at one-year were 1,096 (16.0%) and 3,115 (8.1%), and at end of follow-up 2,871 (41.8%) and 8,680 (22.5%), respectively (Figure). Applying the evidence-based mortality reducing effect of eplerenone to our results, a potential of 164 and 431 deaths within the first year, and during long-term follow-up, respectively, could have been saved by guideline-recommended use of eplerenone. ![Figure][1] Survival by eplerenone indication Conclusions: In a nationwide cohort of post-MI patients, a low use of eplerenone was observed in patients with indication for treatment. Our findings suggest an unexploited potential in the treatment of high-risk group of patients, and therefore focus on initiation of evidence-based treatment is warranted. [1]: pending:yes

Background Safety data from clinical trials have raised concerns over the cardiovascular (CV) safety of non-steroidal anti-inflammatory drug (NSAID) use in general. Despite the widespread use of NSAIDs in RA patients, the few reports available from RA populations have not indicated an increased CV risk associated with commonly used NSAIDs. This suggests that the benefits of NSAID use (eg. improved mobility and pain relief) to some extent may balance the adverse CV effects observed in non-RA individuals. Objectives To evaluate the CV risk associated with use of several NSAIDs in RA patients and controls. Methods The study was designed as a register-based, longitudinal, nationwide cohort study in the period 1997 to 2009. Data were gathered from in- and out-hospital records (diagnoses), pharmacy records (prescriptions) and several civil registers (vital status, emigration and annual income). RA patients were identified by the combination of RA diagnoses and DMARD treatment and matched with 4 randomly selected controls based on age and sex. Individuals with prior myocardial infarction (MI) and stroke were excluded. Overall NSAID exposure and exposure to distinct NSAIDs were determined from redeemed prescriptions. Outcome of interest was the combined endpoint of myocardial infarction, stroke and/or CV mortality (primary cause of death). Risk was assessed by fitting Cox regression models stratified by RA status. Results 17 320 RA patients were included (71% females, mean age 59 years) and 69 280 matched control. 6 284 events occurred during follow-up (801 during NSAID use). RA patients were exposed to NSAID in 25% of follow-up compared to 5% in the control group. The overall risk associated with NSAID use was significantly lower in RA patients than in controls (hazard ratio 1.21 vs. 1.49, p Conclusions This study found that NSAID use in RA patients is frequent and may be associated with an increased risk of CV disease. However, the magnitude of such risks is significantly lower than non-RA individuals and differed among NSAIDs. The results support a strongly individualised approach to NSAID treatment in RA patients based on the need for pain relief, the individual characteristics of the RA patient and the safety profile of the various NSAIDs available. Disclosure of Interest None Declared

This study was undertaken to examine the role of adenosine and nitric oxide (NO) in the hyperemic response to H+ back-diffusion into superficially or deeply injured gastric mucosa, and the role of adenosine in mucosa when blood flow was reduced with indomethacin.Cat stomachs were exposed to 2 M NaCl for 10 min followed by luminal perfusion at pH 1. Gastric mucosal blood flow was determined by radioactive microspheres, portal vein blood flow by transit-time flowmetry, and H+ back-diffusion/secretion by pH-stat titration, and concentrations of histamine in aortic and portal vein blood were measured.In the antrum pretreatment with the adenosine blocker 8-phenyltheophylline (8-PT) or with NG-methyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, had no effect on the hyperemic response or mucosal injury. However, pretreatment with 8-PT in addition to indomethacin produced extensive deep lesions in the antrum. In the corpus/fundus 8-PT had no effect on the hyperemic response and did not increase indomethacin-induced lesions. L-NMMA significantly reduced the hyperemic response in corpus/fundus. In areas with deep lesions very high blood flow was observed in the vital part of the mucosa below the necrotic tissue. This hyperemia was reduced by L-NMMA but not by 8-PT. Indomethacin increased the release of histamine during base-line conditions, whereas 8-PT reduced histamine release after damage.This study indicates that usually adenosine is not involved in the hyperemic response to mucosal damage, but it appears to have important protective functions in the antral mucosa under marginal circulatory conditions. NO is one of the mediators of the hyperemic response to mucosal injury in the corpus/fundus.

While changes in blood flow associated with simple intestinal obstruction have been studied extensively, little is known about blood flow changes associated with strangulation obstruction. Closed loop strangulation was produced in anesthetized cats by means of a baby pressure gasket. Intestinal blood flow was measured by transit time flowmetry. Blood pressure was measured in a carotid artery and in veins of a closed loop of small intestine. The gasket pressure was increased stepwise in 10 mm Hg increments after which the intestinal venous pressure was kept constant at 50 mm Hg for 5 h. Increasing gasket pressure was followed by a corresponding increase in venous pressure in the closed bowel loop. Blood flow in the closed loop decreased with increasing venous pressure and was closely related to the arteriovenous perfusion pressure under stepwise increase of the gasket pressure and during prolonged periods with increased venous pressure. At constant elevated venous pressure the intestinal blood flow was determined by the arterial pressure. The vascular resistance in the closed loop increased exponentially with increasing venous pressure and especially at very low blood flow. In conclusion, we have found that strangulation obstruction is associated with increased venous pressure in the closed loop which contributes to maintaining intestinal blood flow during the obstruction.

In this study we tested the influence of blood flow and the mucoid cap on the penetration of carcinogens to the proliferative cells in the injures rat gastric mucosa. Ten minutes after mucosal exposure to 4.5 mol/liter NaCl, N-[3H]methyl-N'-nitro-N-nitrosoguanidine was instilled intragastrically. Hypertonic saline caused superficial mucosal damage, formation of a mucoid cap, high gastric mucosal blood flow, and a large flux of fluid into the gastric lumen. The mean percentage of S-phase cells labeled with carcinogen (the cell population at risk for N-methyl-N'nitro-N-nitrosoguanidine-induced carcinogenesis) in the antrum and corpus was 0.2 and 0.2, respectively, in the injury control group, 10.1 and 2.0 after removal of the mucoid cap, 1.5 and 9.8 after celiac artery ligation, and 28.2 and 21.9 after removal of the mucoid cap and celiac artery ligation. These results show that both the mucoid cap and gastric mucosal blood flow protect against penetration of carcinogens into the superficially injured gastric mucosa.