Pervasive Hydrothermal Events Associated with Large Igneous Provinces Documented by the Columbia River Basaltic Province.

The degree and extent of crustal hydrothermal alteration related to the eruption of large igneous provinces is poorly known and not easily recognizable in the field. We here report a new δ18O dataset for dikes and lavas from the Columbia River Basalt Group (16-15 Ma) in the western USA, and document that dikes on average are 1-2‰ more depleted in δ18O than basalt flows. We show that this observation is best explained with the involvement of heated meteoric  waters during their cooling in the crust. The largest 6-8‰ depletion is found around and inside a 10 m-thick feeder dike that intruded the 125 Ma Wallowa tonalitic batholith. This dike likely operated as a magma conduit for 4-7 years, based on the extent of heating and melting its host rocks. We show that this dike also created a hydrothermal system around its contacts extending up to 100 m into the surrounding bedrock. A model that considers (a) hydrothermal circulation around the dike, (b) magma flow and (c) oxygen isotope exchange rates, suggests that the hydrothermal system operated for ~150 years after the cessation of magma flow. In agreement with a previously published (U-Th)/He thermochronology profile, our model shows that rocks 100 m away from such a dike can be hydrothermally altered. Collectively, our sample set is the first documentation of the widespread hydrothermal alteration of the shallow crust caused by the intrusion of dikes and sills of the Columbia River Basalt Province. It is estimated that heating and hydrothermal alteration of sediments rich in organic matter and carbonates around the dikes and sills releases 18 Gt of greenhouse gases (CH4 and CO2). Furthermore, hydrothermal δ18O depletion of rocks around dikes covers 500-600 km3, which, when scaled to the total CRB province constitutes 31,000 km3 of low-δ18O rocks. These volumes of crust depleted in δ18O are sufficient to explain the abundant low-δ18O magmas in eastern Oregon and western Idaho. This work also demonstrates that the width and magnitude of δ18O depletion around dikes can identify them as feeders. Given this, we here interpret Paleoproterozoic dikes in Karelia with the world's lowest δ18O depletions (-27.8‰) as feeders to the coeval large igneous province aged 2.2-2.4 Ga that operated under the Snowball Earth glaciation conditions.

15-Lipoxygenase-2 is expressed in macrophages in human carotid plaques and regulated by hypoxia-inducible factor-1alpha.

BACKGROUND: Macrophages are prominent in hypoxic areas of atherosclerotic lesions and their secreted cytokines, growth factors and activity of enzymes are involved in atherogenesis. Previously, we showed that 15-lipoxygenase (LOX)-2 is expressed in human monocyte-derived macrophages and that hypoxia increases 15-LOX-2 expression and secretion of pro-inflammatory molecules. Here we investigated whether human carotid plaque macrophages express 15-LOX-2 and whether its expression in macrophages is regulated by hypoxia through hypoxia-inducible factor 1alpha (HIF-1alpha). MATERIALS AND METHODS: Carotid plaques from 47 patients with high-grade symptomatic carotid artery stenosis were analysed using immunohistochemistry, and stained areas were quantified by digital image analysis. Carotid plaque macrophages were isolated with anti-CD14 immunobeads using an immunomagnetic bead technique. Primary macrophages were transfected with HIF-1alpha siRNA or control siRNA before extraction of RNA and medium analysis. RESULTS: In paired tissue sections, the extent of staining for CD68 correlated with staining for 15-LOX-2 but not for 15-LOX-1. In carotid plaque macrophages isolated with anti-CD14 immunobeads, 15-LOX-2 mRNA was expressed at high levels. In primary macrophages, 15-LOX-2 expression was significantly increased by incubation with the HIF-1alpha stabilizer dimethyloxalylglycine. Knockdown of HIF-1alpha significantly decreased production of the 15-LOX-2 enzyme products 12- and 15-hydroxyeicosatetraenoic acid. In carotid plaques, HIF-1alpha staining correlated with staining for 15-LOX-2. CONCLUSIONS: These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1alpha. 15-LOX-2 enzyme activity can be modulated by HIF-1alpha. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.

Larval therapy as a palliative treatment for severe arteriosclerotic gangrene on the feet.

Larval therapy (LT) is known to be a gentle and effective method for removing necrotic tissue and bacteria and reducing the accompanying unpleasant odour. Ischaemia has been considered a relative contraindication for LT. We report a patient with ischaemia treated with LT. Inguinal revascularization was performed on a 69-year-old man with critical limb ischaemia, diabetes mellitus, heart failure and end-stage renal disease. Areas of dry black malodorous gangrene remained on the distal areas of the feet after surgery and the patient's poor health did not allow any additional surgery. The patient was referred to the dermatology department for LT. Although patients are usually given this treatment as inpatients, the patient requested treatment at home. After the first LT, there was a marked reduction in odour. The gangrene needed repeated applications of larvae to remove the dead tissue. After eight treatments, the result was more positive than we had expected, with total lack of odour and initiation of healing. Larvae cannot penetrate eschar, thus free-range larvae were used because they can move beneath the hard necrotic tissue and dissolve it.

Effects of vascular surgery on amputation rates and mortality.

OBJECTIVES: To study the relation between rates of vascular interventions, amputations and mortality in a defined population. DESIGN: Retrospective comparison between two consecutive 4-year periods. SETTING: Swedish district hospital covering a population of 125,000. MATERIAL: Three hundred and sixty-seven lower limb amputations and 1080 vascular procedures. RESULTS: The number of legs treated for limb-threatening ischaemia with either revascularisation or amputation increased from 269 to 289. The rate of vascular interventions for limb-threatening ischaemia increased from the first to the second period by 65%, while the rate of amputations decreased by 23%. Limb salvage rate at 30 months increased from 37% to 53% (p < 0.0000). The reduced amputation rate was entirely related to primary amputations. The adjusted risk of amputation for patients treated in the second period was half of that for patients treated in the first period (relative risk = 0.49, p = 0.0001), while mortality was similar in both periods. Among survivors, the proportion of patients with intact legs was higher in the second period than in the first, while no difference was found between the two periods among deceased patients. CONCLUSIONS: Increased vascular intervention leads to improved limb salvage rates and reduced amputation rates. It is important for both ethical and economical reasons to identify good responders to revascularisation, because the choice of initial treatment will only influence limb salvage but not survival.

Oral ciprofloxacin versus intravenous cefuroxime as prophylaxis against postoperative infection in vascular surgery: a randomised double-blind, prospective multicentre study.

OBJECTIVES: To test the hypothesis that oral ciprofloxacin is equally effective as intravenous cefuroxime in preventing postoperative infectious complications in patients undergoing peripheral arterial surgery involving the groins. DESIGN: Prospective, randomised, double-blind multicentre study. MATERIALS: 580 patients undergoing arterial surgery involving the groins were randomised to ciprofloxacin (Ciproxin, Bayer) 750 mg x 2 p.o. or cefuroxime (Zinacef, Glaxo) 1.5 g x 3 i.v. given only on the day of surgery. The primary endpoint was wound/graft infection within 30 days postoperatively. Wound infection was defined as pus. RESULTS: The wound infection rate in the ciprofloxacin group was 9.2% (27 patients) and in the cefuroxime group 9.1% (26 patients) according to intention to treat. For correct treatment the corresponding numbers were 9.5% (23 patients) and 9.7% (22 patients), respectively. There were three graft infections (0.5%). The infection rate was 7.1% (31/433) in the absence and 14.9% (22/147) in the presence of distal ulcers (p < 0.05). S. allreus was the most common bacteria isolated. Forty percent of the wound infections were localised to the groins. By multivariate analysis presence of distal ulcer was the only factor of prognostic significance. CONCLUSIONS: The infection rate was similar in the two groups. Thus, oral administration of ciprofloxacin is an attractive, cost-effective and safe alternative to prophylaxis in vascular patients capable of taking oral medication on the day of surgery.

Intraluminal measurement of enteric mucosal perfusion: relationship to superior mesenteric artery flow during basal and postprandial states in the dog.

BACKGROUND: Several in vivo techniques that assess mucosal perfusion by intraluminal probes have recently been developed and validated, including laser Doppler flowmetry, reflectance spectrophotometry, and tonometry. METHODS: With these techniques, a canine model where the entire vascular supply to the jejunoileum was isolated as the superior mesenteric artery and vein was used to examine the relationship between enteric mucosal blood perfusion and adjusted decrements in arterial flow under fasting and postprandial conditions. RESULTS: Mucosal perfusion measured by laser Doppler flowmetry and reflectance spectrophotometry correlated linearly with decrements in superior mesenteric artery flow (r2 = 0.96 and 0.98, respectively); estimation of mucosal pH by tonometry decreased only after a critical level of arterial inflow was reached (less than 50% of baseline flow). Mucosal perfusion increased after the meal throughout the jejunoileum with unrestricted superior mesenteric artery flow. However, with restricted superior mesenteric artery flow, nutrient delivery to the jejunum was accompanied by increased mucosal perfusion at that level but by decreased perfusion in the distal ileum not exposed to nutrients. This latter response represents a distal to proximal redistribution of blood, i.e., an intramesenteric steal phenomenon. CONCLUSIONS: In vivo measurements of mucosal perfusion reflected changes in large mesenteric vessel blood flow. These intraluminal techniques discriminated between a normal and an impaired mesenteric circulation in an acute model and may have clinical application.

Abdominal aortic aneurysm with perianeurysmal fibrosis: experience from 11 Swedish vascular centers.

Case records of 2026 patients operated on because of abdominal aortic aneurysms from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of inflammatory abdominal aortic aneurysm. Also included in this case-control study was an analysis of a randomized group of 82 patients from the same centers who had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A higher proportion of patients with inflammatory abdominal aortic aneurysms had symptoms that led to radiographic investigations. The median erythrocyte sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50 mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8 patients (p less than 0.01) in the inflammatory and noninflammatory groups, respectively. Preoperative investigations revealed ureteral obstruction in 19 patients with inflammatory abdominal aortic aneurysms, of whom 12 had preoperative nephrostomy or ureteral catheter placement. At operation, 20 additional patients exhibited fibrosis around one or both ureters. Although ureterolysis was performed in 19 patients, preoperative and postoperative creatinine levels did not differ between these patients and the conservatively treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss (2085 vs 2400 ml) and complications did not differ significantly between the groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was increased for patients undergoing elective surgery for inflammatory abdominal aortic aneurysms (9% vs 0%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption and motility of the bypassed human ileum.

The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption +/- S.E.M. of both perfusates was poor on day 1 (-10 +/- 2 ml/25 cm x 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (-1 +/- 2 ml/25 cm x 30 min; P less than 0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6 +/- 0.6 vs. 7.2 +/- 1.0 clustered waves/hr; 7.5 +/- 0.5 vs. 9.7 +/- 0.2 motility units/30 min; P less than 0.05). The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates.

Effects of cholera toxin, Escherichia coli heat stable toxin and sodium deoxycholate on neurotensin release from the ileum in vivo.

Neurotensin (NT) is a biologically active peptide found in specialized epithelial cells (N-cells) in the distal small intestine. In this study we tested the hypothesis that NT may be released by luminal secretagogues, i.e., cholera toxin, Escherichia coli heat-stable toxin and sodium deoxycholate. Cholera toxin elicited net fluid secretion in anesthetized cats. This secretion was accompanied by an increased release of NT-like immunoreactivity (NTLI) into the mesenteric vein when NTLI was measured with either a C-terminally or a N-terminally directed antibody. An increasing plasma NTLI concentration (N-terminally directed antibody) was recorded in the mesenteric vein and femoral artery in cholera experiments. These results indicate that cholera toxin releases NT from the small intestine. Since neurotensin causes intestinal fluid secretion at least in part via an activation of enteric nerves we propose that the N-cell functions as a 'receptor cell' which activates an intramural secretory reflex upon luminal stimulation by cholera toxin. This study does not support a similar role for NT in the secretion elicited by the heat stable toxin of Escherichia coli or by sodium deoxycholate since we were unable to demonstrate any intestinal release of NTLI after exposing the intestine to these secretory agents.

Ectopic jejunal pacemakers and gastric emptying after Roux gastrectomy: effect of intestinal pacing.

The aims of this study were to determine whether ectopic pacemakers are present after meals in the Roux limbs of dogs after vagotomy and Roux gastrectomy, whether these pacemakers slow gastric emptying of liquids or solids, and whether abolishing the pacemakers with electric pacing might speed any slow emptying that occurs. In six dogs that underwent vagotomy and Roux gastrectomy and in four dogs that underwent vagotomy and Billroth gastrectomy (controls), myoelectric activity of the Roux limb or duodenum was measured during gastric emptying of a 500 kcal mixed meal of 99mTc-labeled cooked egg and 111In-labeled milk. Roux dogs were tested with and without pacing of the Roux limb. Roux dogs showed ectopic pacemaker in the Roux limb that drove the pacesetter potentials of the limb in a reverse, or orad, direction during 57% of the postprandial recordings. Billroth dogs had no ectopic pacemakers (p less than 0.05). Liquids emptied more slowly in Roux dogs (half-life (t1/2) = 121 +/- 15 minutes) than in Billroth dogs (t1/2 = 43 +/- 9 minutes; p less than 0.05), but solids emptied similarly in both groups of dogs (t1/2 approximately 8 hours). Pacing the Roux limb abolished the ectopic pacemakers, restored the slow emptying of liquids to the more rapid rate found in the Billroth dogs (t1/2: paced Roux, 72 +/- 15 minutes; Billroth, 43 +/- 9 minutes; p greater than 0.05) and did not change emptying of solids. The conclusion was that ectopic pacemakers present in the Roux limb after vagotomy and Roux gastrectomy drove the limb in a reverse direction and slowed emptying of liquids after the operation. The defect was corrected by pacing the Roux limb in a forward direction.

Ectopic jejunal pacemakers and enterogastric reflux after Roux gastrectomy: effect of intestinal pacing.

The aims of this study were to determine whether ectopic pacemakers are present in the Roux limb of dogs after vagotomy and Roux gastrectomy, whether these pacemakers lead to enterogastric reflux, and whether abolishing the pacemakers with electric pacing might correct such reflex, were it to occur. In five dogs that had undergone gastric vagotomy and Roux gastrectomy and five dogs that had undergone gastric vagotomy and Billroth I gastrectomy (controls), myoelectric activity of the Roux limb or duodenum was recorded during saline infusion (154 mmol/L NaCl) or nutrient (Meritene) infusion into the limb or the duodenum. Reflux of infusate into the stomach was determined via a gastric cannula. Tests in Roux dogs were done with and without limb pacing. Roux dogs showed ectopic pacemakers in the Roux limb that drove the pacesetter potentials of the limb in a reverse, or orad, direction during 76% of the recordings; Billroth dogs rarely had such pacemakers (p less than 0.001). Enterogastric reflux occurred in both groups of dogs but was greater during phase III of the interdigestive migrating myoelectric complex in Roux dogs (12% +/- 6%) than in Billroth dogs (3% +/- 1%; p less than 0.05). Pacing abolished the ectopic pacemakers in the Roux dogs and reduced enterogastric reflux from 12% +/- 6% to 3% +/- 2% when phase III was present (p less than 0.05). In conclusion, the Roux limb was driven by ectopic pacemakers that contributed to, but were not solely responsible for, jejunogastric reflux. Pacing abolished the ectopic pacemakers and decreased reflux when phase III was present in the limb.

Roux-Y gastrectomy for chronic gastric atony.

The aim of this study was to determine the clinical outcome after Roux-Y gastrectomy for chronic gastric atony. Forty patients (11 men, 29 women; age 47 +/- 12 years) presented with severe chronic gastric atony: 32 patients had postvagotomy atony, 6 had idiopathic atony, and 2 had diabetic gastroparesis. The patients underwent either extensive subtotal or near-total gastrectomy and Roux-Y gastrojejunostomy. No early postoperative mortality occurred. Among the 39 patients followed for a mean of 32 months, 31 patients (79 percent) had fewer symptoms postoperatively than preoperatively, with 26 patients (66 percent) improving at least one Visick grade postoperatively and 22 patients (56 percent) going from grades III and IV preoperatively to grades I and II postoperatively. In contrast, 13 patients (33 percent) did not improve after operation. We concluded that extensive subtotal Roux-Y gastrectomy and near-total Roux-Y gastrectomy were safe procedures that led to improvement in two-thirds of the patients with chronic gastric atony; however, one-third of patients did not have improvement.

Influence of sodium deoxycholate on morphology, net fluid transport and motility in the small intestine of the rat.

Intestinal fluid secretion and motility were induced by luminal perfusion of rat small intestine with sodium deoxycholate, a dihydroxy bile salt for 1-3 h. Changes in intestinal morphology were studied simultaneously with the changes in fluid transport and motility. The results suggest that the bile salt causes epithelial lesions which may lead to a reduced fluid absorption in the villi, thereby explaining part of the total change in net fluid transport caused by the bile salt. Pyrilamine and indomethacin did not influence the bile salt-induced secretion. Based on earlier studies, it is proposed that the major part of the bile salt-evoked secretion is mediated via activation of intramural nervous reflex(es), which also stimulate the intestinal smooth muscle cells.

Blood flow distribution, lymph flow, villus tissue osmolality and fluid and electrolyte transport after exposing the cat small intestine to sodium deoxycholate.

The effect of luminal perfusion of a dihydroxy bile salt (sodium deoxycholate) on net fluid transport, intestinal haemodynamics, lymph flow, electrolyte transport and villus tissue osmolality was studied in cat jejunum. Furthermore, the effects of hexamethonium and tetrodotoxin, two drugs influencing nervous activity, were investigated. Concomitant to net fluid secretion, the bile salt increased mucosal blood flow whereas capillary filtration coefficient and lymph flow remained unchanged. Net sodium and chloride transport changed from absorption to secretion. The change of sodium transport was due to both an increased flux from tissue to lumen and a reduced flux in the opposite direction. Villus tissue hyperosmolality was reduced. None of the effects on intestinal haemodynamics correlated with the change in net fluid transport. Furthermore, hexamethonium and tetrodotoxin inhibited the secretion of fluid and electrolytes without influencing the induced changes in intestinal haemodynamics. It is concluded that the bile salt induces intestinal fluid secretion by stimulating an active secretory process in the crypts via enteric nerves. A minor part of the total change in net fluid transport may be due to a reduced uptake in the villi.

Evidence of involvement of the enteric nervous system in the effects of sodium deoxycholate on small-intestinal transepithelial fluid transport and motility.

With an in vivo method, transepithelial net fluid transport and intestinal motility were recorded continuously in rat jejunal segments perfused with a modified Krebs-Henseleit solution with or without the bile salt sodium deoxycholate (4 or 8 mM). The bile salt produced a net fluid secretion and characteristic intestinal contractions. The two effects of the bile salt developed simultaneously and were quantitatively related to each other. Both effects disappeared when the bile salt was removed from the perfusate and diminished when the luminal perfusion was stopped. Hexamethonium (intravenously) and lidocaine (applied topically on the intestinal serosa) inhibited both effects, whereas indomethacin (intravenously) was ineffective. Atropine (intravenously) selectively abolished the intestinal contractions without affecting net fluid transport. Extrinsic denervation of the intestines performed 3 weeks before acute experiments did not influence the results. It is concluded that the bile salt stimulated both fluid secretion and intestinal contractions by activating a local nervous reflex mechanism consisting of a presynaptic cholinergic neuron and two postsynaptic neurons, one of which is cholinergic and innervates the intestinal smooth-muscle cell, and the other of which is noncholinergic and nonadrenergic and innervates the epithelium.

Involvement of the enteric nervous system in the intestinal secretion induced by sodium deoxycholate and sodium ricinoleate.

Rat small intestine was continuously perfused for up to 3 h with two different concentrations of sodium deoxycholate (4 and 8 mM) or with sodium ricinoleate (6 mM). The 4-mM bile salt solution produced a secretion that developed to a maximal rate within 3 h, whereas the maximal rate was reached within 1 h with the 8-mM bile salt solution. Hexamethonium, a ganglionic blocker, and lidocaine, a local anesthetic, always reduced the net fluid secretion to approximately zero irrespective of the rate of bile-salt-induced secretion, the concentration of the bile salt, or the perfusion time. Fluid secretion induced by sodium ricinoleate was, like the bile-salt-induced secretion, markedly inhibited by hexamethonium and lidocaine but not by atropine. It is concluded that the rate of secretion induced by the bile salt is related to the monomer concentration of free bile salt molecules in close proximity to or within the intestinal epithelium. The intestinal fluid secretion is mainly due to stimulation of an active secretory process via an activation of enteric nerves. Sodium ricinoleate evokes secretion via similar nervous reflex mechanisms.

Mechanisms in bile salt-induced secretion in the small intestine. An experimental study in rats and cats.

The present study was designed to test whether fluid and electrolyte secretion evoked in the small intestine by the dihydroxy bile salt sodium deoxycholate could be due to activation of a nervous reflex mechanism. The effect of the bile salt on small intestinal motility was also investigated, and an analysis was made of factors involved in passive and active transport mechanisms relevant to bile salt-induced secretion. Luminal perfusion with sodium deoxycholate changed net fluid transport from absorption to secretion. Hexamethonium, a ganglionic receptor blocker, lidocaine, a local anaesthetic and tetrodotoxin, a sodium channel blocker, inhibited the induced fluid secretion. The inhibitory effect increased in proportion to the rate of secretion. Elimination of the bile salt from the perfusate also inhibited the secretion. A minor part of the induced change in net fluid transport was resistant to nerve blockade or to bile salt elimination. The change of net fluid transport was paralleled by a change of sodium and chloride transport from absorption to secretion. The change of net sodium transport was due to both a reduced uptake and increased losses. Villus tissue hyperosmolality was reduced by the bile salt. Hexamethonium inhibited the electrolyte secretion. The bile salt caused epithelial lesions in the upper parts of the villi. The lesions persisted also after the bile salt-induced secretion had been inhibited by nerve blockade or by bile salt elimination. Lesions also appeared in intestines which failed to develop net fluid secretion. The bile salt also induced characteristic intestinal contractions which showed a good correlation with the rate of net fluid secretion. The motility was also inhibited by nerve blockade or bile salt elimination. Atropine abolished the induced motility but did not influence the secretion. Indomethacin, a prostaglandin synthesis inhibitor, or pyrilamine, a histamine 1-receptor antagonist, did not inhibit either motility or secretion. The bile salt caused a mucosal vasodilatation, total blood flow increasing about 50%. Capillary filtration coefficient remained unchanged. Lymph flow did not increase. No correlation was found between the change of intestinal blood flow and the change of net fluid transport. Hexamethonium and tetrodotoxin inhibited the induced secretion without influencing blood flow. It is concluded that sodium deoxycholate evokes intestinal secretion and motility via an enteric nervous reflex arch consisting of a presynaptic cholinergic neuron and two postganglionic neurons, one cholinergic innervating the intestinal smooth muscle cell and the other non-cholinergic, non-adrenergic influencing intestinal flu