Early life origins of chronic obstructive pulmonary disease.

BACKGROUND: Early life development may influence subsequent respiratory morbidity. The impact of factors determined in childhood on adult lung function, decline in lung function and chronic obstructive pulmonary disease (COPD) was investigated. METHODS: European Community Respiratory Health Survey participants aged 20-45 years randomly selected from general populations in 29 centres underwent spirometry in 1991-3 (n = 13 359) and 9 years later (n = 7738). Associations of early life factors with adult forced expiratory volume in 1 s (FEV(1)), FEV(1) decline and COPD (FEV(1)/FVC ratio <70% and FEV(1) <80% predicted) were analysed with generalised estimating equation models and random effects linear models. RESULTS: Maternal asthma, paternal asthma, childhood asthma, maternal smoking and childhood respiratory infections were significantly associated with lower FEV(1) and defined as "childhood disadvantage factors"; 40% had one or more childhood disadvantage factors which were associated with lower FEV(1) (men: adjusted difference 95 ml (95% CI 67 to 124); women: adjusted difference 60 ml (95% CI 40 to 80)). FEV(1) decreased with increasing number of childhood disadvantage factors (> or =3 factors, men: 274 ml (95% CI 154 to 395), women: 208 ml (95% CI 124 to 292)). Childhood disadvantage was associated with a larger FEV(1) decline (1 factor: 2.0 ml (95% CI 0.4 to 3.6) per year; 2 factors: 3.8 ml (95% CI 1.0 to 6.6); > or =3 factors: 2.2 ml (95% CI -4.8 to 9.2)). COPD increased with increasing childhood disadvantage (1 factor, men: OR 1.7 (95% CI 1.1 to 2.6), women: OR 1.6 (95% CI 1.01 to 2.6); > or =3 factors, men: OR 6.3 (95% CI 2.4 to 17), women: OR 7.2 (95% CI 2.8 to 19)). These findings were consistent between centres and when subjects with asthma were excluded. CONCLUSIONS: People with early life disadvantage have permanently lower lung function, no catch-up with age but a slightly larger decline in lung function and a substantially increased COPD risk. The impact of childhood disadvantage was as large as that of heavy smoking. Increased focus on the early life environment may contribute to the prevention of COPD.

Fluid resuscitation improves intestinal blood flow and reduces the mucosal damage associated with strangulation obstruction in pigs.

BACKGROUND: Strangulation obstruction of the small bowel is associated with local and systemic circulatory changes, local loss of fluid, and damage of the strangulated bowel segment. We wanted to examine to which extent these changes can be prevented by intravenous fluid administration. MATERIALS AND METHODS: In anesthetized pigs, strangulation obstruction was induced by increasing the pressure in a baby pressure gasket placed around a loop of ileum until venous pressure in the loop reached 50 mm Hg. During the strangulation period (180 min), a group of eight animals (Fluid(min) group) received 10 ml. kg(-1). hour(-1) Ringer acetate solution intravenously, whereas another eight animals (Fluid(max) group) received 55 ml. kg(-1). hour(-1) Ringer acetate solution intravenously. Blood flow to the strangulated bowel was measured by transit time flowmetry and colored microspheres. After completed experiments, whole wall samples of the strangulated loop were selected for microscopy. RESULTS: In the Fluid(min) group, the heart rate increased, the arterial pressure decreased markedly, and the urine output decreased toward zero. In the Fluid(max) group, the heart rate and arterial pressure remained fairly constant and the urine output increased. Blood flow to the strangulated bowel decreased in both groups, but significantly more in the Fluid(min) group. The intestinal blood flow was highly dependent on the arterial blood pressure. The strangulated mucosa showed markedly more damage in the Fluid(min) group than the Fluid(max) group. The degree of mucosal damage correlated linearly with the mucosal blood flow. CONCLUSION: The administration of large amounts of fluid to animals with strangulation obstruction normalized the arterial pressure and improved the intestinal blood flow thus minimizing damage to the intestinal mucosa.

Effects of the aldosterone receptor antagonist potassium canrenoate on renal blood flow and urinary output during prolonged increased intraabdominal pressure (IAP) in pigs.

BACKGROUND: Increased intraabdominal pressure can be found after major abdominal trauma and necrotizing pancreatitis and is used during laparoscopic surgery. The purpose of this study was to investigate the effect of the aldosterone receptor antagonist (potassium canrenoate) on renal hemodynamics and urinary output in pigs during increased intraabdominal pressure (IAP). METHODS: The IAP was kept at 30 mmHg for 3 h by instillation of Ringer's solution into the peritoneal cavity. Eight animals were treated with potassium canrenoate and eight animals served as controls. Renal blood flow, hormones in femoral artery blood, and the urinary output were measured. RESULTS: The administration of potassium canrenoate was followed by increased aldosterone concentrations in arterial blood, increased blood concentration of potassium, and increased concentration of sodium in the urine, indicating satisfactory inhibition of aldosterone. Potassium canrenoate did not cause changes in cardiac output and arterial pressure. It did not affect the renal vascular resistance that increased at an IAP of 30 mmHg, or the renal blood flow that remained constant during the experiments. The group treated with potassium canrenoate had higher mean urinary output than the controls, but the difference was not significant. CONCLUSION: Increased IAP in pigs is associated with markedly reduced urinary output and increased serum concentrations of aldosterone. Although the urinary output did not increase significantly, the increased sodium concentration in the urine of canrenoate-treated animals suggests that the high blood level of aldosterone contributes to the oliguria under increased IAP.

Delay in operative treatment among patients with small bowel obstruction.

BACKGROUND AND AIMS: Delay in operative treatment for small bowel obstruction (SBO) has been shown to affect outcome adversely. The objective of this study was to detect time trends in treatment delay for patients with SBO during the study period 1961 to 1995 and to investigate factors influencing and factors affected by delay. MATERIALS AND METHODS: The records of 815 patients with 921 operations for SBO from 1961-1995 were studied. Patients with large bowel obstruction, paralytic ileus and SBO caused by abdominal cancer or intussusception were excluded. Data were analysed with descriptive statistics and multiple linear regression analyses. RESULTS: Old age and female sex were associated with increased treatment delay. Delay in hospital increased from 5 hours (median) in the 1960'ies to 16 hours (median) in the 1990'ies. Treatment delay correlated significantly with postoperative morbidity and hospital stay. Mortality increased after prolonged treatment delay in SBO caused by hernias whereas no significant increase in mortality was observed among adhesive obstructions. CONCLUSIONS: Hospital delay increased throughout the study period. Old patients and women had a longer median treatment delay than did young ones and men. Treatment delay led to an increase in postoperative morbidity and hospital stay after surgery for SBO.

Role of angiotensin II under prolonged increased intraabdominal pressure (IAP) in pigs.

BACKGROUND: The aim of the study was to investigate the effect of the angiotensin II receptor antagonist losartan on renal hemodynamics and diuresis in pigs with increased intraabdominal pressure (IAP). METHODS: The IAP was maintained at 30 mmHg for 3 h by intraperitoneal instillation of Ringer's solution. Ten animals were treated with losartan; another 10 animals served as controls. Renal blood flow, hormones in renal vein blood, and diuresis were measured. RESULTS: In control animals, the renal vascular resistance increased renal blood flow remained constant, the blood concentration of aldosterone increased and the diuresis decreased during increased IAP. Losartan prevented the increase in vascular resistance and improved renal blood flow under increased IAP. It also prevented the rise in aldosterone concentration and increased the urine output to baseline level. CONCLUSION: Our results suggest that the renal vasoconstriction associated with increased IAP is due to increased production of angiotensin II. The oliguria associated with increased IAP is probably due, at least partly, to increased reabsorbtion of sodium and water in the renal tubuli caused by increased tissue concentration of aldosterone.

Comparison of different methods for measuring intra-abdominal pressure.

OBJECTIVE: Intra-abdominal pressure (IAP) can be measured in different ways but is usually measured indirectly via the urinary bladder. The aim of the study was to: 1) compare urinary bladder pressure, femoral vein pressure, and inferior caval vein pressure with IAP at different levels of IAP; and 2) try to find an optimal amount of fluid to be instilled into the urinary bladder before measurement of the bladder pressure, and to compare changes in blood flow in the femoral vein with that in the caval vein at different pressure levels. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Eight domestic swine of both sexes, weighing 30.6+/-2.9 kg (mean+/-SD). INTERVENTIONS: Catheters connected to pressure transducers were placed into the urinary bladder, the inferior caval vein, the femoral vein, and the superior caval vein. Transit time flow probes were placed around the inferior caval vein and the femoral vein. After a stabilizing period, the abdominal pressure was increased stepwise by instillation of Ringer's solution into the abdomen and then decreased. Thereafter, we instilled fluid into the bladder at an IAP of 8 mmHg and at 20 mmHg and measured the amount of fluid needed to elevate the intra-vesical pressure by 2 mmHg. RESULTS: The pressures recorded in the urinary bladder, the inferior caval vein, and the femoral vein reflected the pressure in the abdominal cavity very well. The fluid volume needed to increase the bladder pressure by 2 mmHg was significantly lower at 20 mmHg IAP than at 8 mmHg. Blood flow in the femoral vein and the inferior caval vein showed a similar pattern and decreased when the intra-abdominal pressure increased. CONCLUSIONS: In our porcine model, and increasing the IAP by means of instillation of Ringer's solution, a reliable estimation of the IAP was obtained by measuring the pressure in the urinary bladder, the femoral vein or the inferior caval vein. The IAP estimated indirectly as the urinary bladder pressure is affected by the amount of fluid in the bladder, which should not exceed 10-15 ml. The decrease in femoral vein blood flow reflects the changes in inferior caval vein flow during increased IAP.

Early operation or conservative management of patients with small bowel obstruction?

OBJECTIVE: To evaluate the outcome after initial non-operative treatment in patients with small bowel obstruction (SBO). DESIGN: Prospective study. SETTING: University hospital, Norway. PATIENTS: One hundred and fifty-four patients with 166 episodes of SBO admitted during the period (1994-1995). Patients younger than 10 years as well as patients with large bowel obstruction, paralytic ileus, incarcerated hernia or SBO caused by cancer were excluded from the study. INTERVENTIONS: Patients with signs of strangulation were operated on early. The rest were given a trial of conservative treatment. MAIN OUTCOME MEASURES: Need of operative treatment. Incidence of bowel strangulation, complications and death. RESULTS: There were 166 cases of SBO. Twenty patients were operated on early among whom bowel was strangulated in 9. Among the 146 patients initially treated conservatively 93 (64%) settled without operation, 9 (6%) had strangulated bowel and 3 (2%) died. Of the 91 patients with partial obstruction but no sign of strangulation, 72 (79%) resolved on conservative treatment. CONCLUSIONS: Patients with partial obstruction with no sign of strangulation should initially be treated conservatively. When complete obstruction is present, it may settle on conservative management, but the use of supplementary diagnostic tools might be desirable to find the patients who will need early operative treatment.

Effects of prolonged increased intra-abdominal pressure on gastrointestinal blood flow in pigs.

BACKGROUND: The aim of the study was to investigate the effects of prolonged intra-abdominal pressure on systemic hemodynamics and gastrointestinal blood circulation. METHODS: The intra-abdominal pressure in anesthetized pigs was elevated to 20 mmHg (7 animals), 30 mmHg (7 animals), and 40 mmHg (4 animals), respectively. These pressures were maintained for 3 h by intra-abdominal infusion of Ringer's solution. A control group of seven animals had normal intra-abdominal pressure (IAP). Transit time flowmetry and colored microspheres were used to measure blood flow. RESULTS: An IAP of 20 mmHg did not cause significant changes in systemic hemodynamics or tissue blood flow. An IAP of 30 mmHg caused reduced blood flow in the portal vein, gastric mucosa, small bowel mucosa, pancreas, spleen, and liver. Serum lactate increased in animals with an IAP of 30 mmHg, but microscopy did not disclose mucosal damage in the stomach or small bowel. An IAP of 40 mmHg was followed by severe circulatory changes. CONCLUSIONS: Prolonged IAP at 20 mmHg did not cause changes in general hemodynamics or gastrointestinal blood flow. Prolonged IAP at 30 mmHg caused reduced portal venous blood flow and reduced tissue flow in various abdominal organs, but no mucosal injury. A prolonged IAP of 40 mmHg represented a dangerous trauma to the animals.

Role of endothelin in the circulatory changes associated with small bowel strangulation obstruction in pigs: effects of the endothelin receptor antagonist bosentan.

BACKGROUND: We have previously shown that experimental strangulation obstruction leads to increased release and concentration of endothelin-1 (ET-1) in venous blood from the strangulated bowel loop. The present study focuses on the microcirculatory effects of the released ET-1 in strangulation obstruction. METHODS: In anesthetized pigs strangulation obstruction was induced by increasing pressure in a baby pressure gasket placed around a loop of ileum until venous pressure reached 45 mm Hg. The pigs were randomly allocated into two groups. The nonselective ET(A)/ET(B) antagonist bosentan was administered intravenously (5 mg kg(-1)) to eight pigs (bosentan group) 30 min before strangulation, which was maintained for 90 min. Another eight pigs were treated in same manner except for the bosentan injection (control group). RESULTS: The concentration of ET in arterial and intestinal venous blood increased markedly after intravenous administration of bosentan. Intravenous infusion of bosentan was followed by a reduction in systemic arterial blood pressure. Bosentan reduced vascular resistance and increased blood flow in the normal intestinal mucosa. It also reduced muscularis blood flow in the beginning of the experiment. In strangulated small bowel bosentan inhibited the increase in vascular resistance usually caused by strangulation obstruction. Muscularis blood flow in strangulated small bowel was not affected by bosentan. CONCLUSION: Endothelin is involved in the normal regulation of arterial blood pressure. The increase in vascular resistance associated with strangulation obstruction is caused mainly by locally released endothelin.

Mass closure technique: an experimental study on separation of wound edge.

OBJECTIVE: To study separation of wound edges in midline laparotomy incisions closed with either a mass stitch or a stitch incorporating only aponeurosis. DESIGN: Experimental study in pig. SETTING: University hospital, Norway. ANIMALS: 8 domestic pigs. METHODS: 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. RESULTS: 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 (p < 0.001). Corresponding figures for separation of clips was 3.6 (1.5) mm and 0.1 (0.3) mm (p < 0.001). 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. CONCLUSIONS: 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.

Comparison of a linear miniature ultrasound probe and a radial-scanning echoendoscope in TN staging of esophageal cancer.

BACKGROUND: Endoscopic ultrasonography is a precise method for TN staging of esophageal cancer. We explored the staging properties of a linear miniprobe as compared with a radial-scanning echoendoscope. METHODS: Sixty-eight patients with esophageal cancer underwent preoperative TN staging using a 20-MHz linear miniprobe and a 7.5/12-MHz radial-scanning echoendoscope. Tumor stage was verified by surgery and/or histology. RESULTS: T and N stages were verified in 53 and 54 patients, respectively. T-staging accuracy using the echoendoscope was 70%. The high-frequency miniprobe could not differentiate between T3 and T4 tumors, but both systems had an accuracy of 87% in discriminating between T1, T2, and T3/4 stages. With traversable tumors, the accuracy of N staging was significantly better with the echoendoscope than with the miniprobe (90% vs. 48%, P = 0.008). CONCLUSIONS: The two endosonographic systems had similar accuracy for assessing transmural tumor growth, but the echoendoscope was superior in staging advanced transmural tumors and in predicting lymph node metastasis with traversable tumors.

Complications and death after surgical treatment of small bowel obstruction: A 35-year institutional experience.

OBJECTIVE: To study factors influencing complications and death after operations for small bowel obstruction (SBO) using multifactorial statistical methods. SUMMARY BACKGROUND DATA: Death after surgery for SBO is believed to be influenced by factors such as old age, comorbidities, bowel gangrene, and delay in treatment. No studies have been reported in which adverse factors related to death and complications have been systematically investigated with modern statistical methods. METHODS: The authors studied retrospectively 877 patients who underwent 1,007 operations for SBO from 1961 to 1995. Patients with paralytic ileus, intussusception, and abdominal cancer were excluded. Odds ratios for death, complications, postoperative hospital stay, and strangulation were calculated by means of logistic regression analyses. RESULTS: Death and complication rates decreased during the study period. Old age, comorbidity, nonviable strangulation, and a treatment delay of more than 24 hours were significantly associated with an increased death rate. The rate of nonviable strangulation increased markedly with patient age. Major factors increasing the complication rate were old age, comorbidity, a treatment delay of more than 24 hours, and the need for repeat surgery. CONCLUSION: Death and complication rates after SBO decreased from 1961 to 1995. Major factors influencing the rates were age, comorbidity, nonviable strangulation, and treatment delay. Nonviable strangulation was more common in old patients.

Upper gastrointestinal contrast study in the management of small bowel obstruction--a prospective randomised study.

OBJECTIVE: To find out whether contrast radiography helps to resolve small bowel obstruction. DESIGN: Prospective randomised trial. SETTING: University hospital, Norway. SUBJECTS: 98 consecutive patients with symptoms of small bowel obstruction and a plain abdominal radiograph that confirmed the diagnosis. INTERVENTIONS: The patients were randomly allocated to receive a mixture of barium and sodium diatrizoate (Gastrografin) (n = 48) or not (n = 50). Both groups were followed up clinically and by repeated abdominal films. MAIN OUTCOME MEASURES: Non-operative resolution of small bowel obstruction; number of patients with strangulated bowel; bowel resections; mortality; complications; hospital stay; and time from admission to operation. RESULTS: No significant differences were observed between the groups in the incidence of non-operative resolution (31/48 in contrast group, 35/50 in control group, OR: 0.89), strangulation obstruction (1/48 in contrast group, 4/50 in control group, OR: 0.24), bowel resection (3/48 in contrast group, 4/50 in control group, OR: 0.76), complications (8/48 in contrast group, 5/50 in control group, OR: 1.80), mortality (3/48 in contrast group, 1/50 in control group, OR: 3.26), and hospital stay (0-7 days: 34/48 in contrast group, 38/50 in control group, p = 0.95). The contrast group had a shorter interval between admission and operation than the control group (0-24 hours: 12/48 in contrast group, 3/50 in control group, p = 0.005). CONCLUSION: The contrast examination did not contribute to the resolution of small bowel obstruction.

Glutathione modulation changes the penetration of N-[3H]methyl-N-nitro-N-nitrosoguanidine into gastric mucosa of rats.

Glutathione plays a role in gastric mucosal protection and the glutathione level is elevated in some forms of gastritis. We studied the relevance of glutathione for the penetration of N-methyl-N-nitro-N-nitrosoguanidine in the glandular mucosa of the stomach. Male Wistar rats were treated with glutathione (0.5 mmol/kg intravenously), N-acetylcysteine (0.5 mmol/kg intravenously), or L-buthionine-[S,R,]-sulfoximine (BSO, 2 mmol/kg intraperitoneally), before the gastric mucosa was exposed to N-[3H]methyl-N-nitro-N-nitrosoguanidine for 10 min. Penetration of the carcinogen was evaluated by light microscopic identification of cells labeled with bromodeoxyuridine and N-[3H]methyl-N-nitro-N-nitrosoguanidine (double-labeled cells). Thiol substances were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The percentage double-labeled cells was higher in antrum mucosa (11.7 +/- 3.1%) than in corpus mucosa (1.1 +/- 0.2%) (P < 0.05). Total glutathione level was 1853 +/- 101 nmol/g in antrum and 1560 +/- 76 nmol/g in corpus mucosa. BSO administration reduced the amount of glutathione in antrum to 495 +/- 14 nmol/g (P < 0.05) and reduced the percentage double-labeled cells in antrum mucosa to 6.1 +/- 1.3% (P < 0.05). A positive correlation was found between the percentage of double-labeled cells in the antrum mucosa and the total amount of glutathione (r = 0.451, P = 0.002), and the amount of reduced glutathione (r = 0.449, P = 0.002). Glutathione modulation effects the penetration of N-[3H]methyl-N-nitro-N-nitrosoguanidine in the antrum but not in the corpus mucosa. Thiols do not explain the different penetration of carcinogen in antrum and corpus mucosa.

Endotoxin and cytokine release in strangulation obstruction and in partial occlusion of the mesenteric artery in pigs.

BACKGROUND: The study was performed to determine if endotoxin or the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) are liberated from strangulated or partially ischemic small bowel. METHODS: Strangulation obstruction was induced by elevating pressure in a gasket placed around a loop of ileum until venous pressure reached 50 mm Hg. Low arterial flow in a loop of ileum was produced by arterial clamping reducing blood flow by 70%. A proximal bowel loop was used for control. Arterial blood flow was measured by transit time flowmetry. Blood samples were collected before and after 30, 90 and 180 min of strangulation or clamping. Plasma levels of endotoxin and cytokines (TNF, IL-1 and IL-6) were measured by limulus amebocyte lysate test and bioassays, respectively. RESULTS: Strangulation obstruction caused more extensive mucosal damage than arterial clamping. Strangulation was followed by markedly increased venous concentration and release of IL-6 in the strangulated loop. Partial arterial occlusion did not cause increased release of IL-6. Strangulation or partial clamping did not influence the concentration of endotoxin, IL-1 or TNF in intestinal venous blood. CONCLUSIONS: Strangulation obstruction causes increased release of IL-6 to intestinal venous blood. IL-6 levels did not increase after 70% reduction of arterial blood flow. The early IL-6 increase was not detected in systemic blood. Strangulation did not cause early changes in plasma levels of endotoxin, TNF or IL-1.

Causes of death in patients with peptic ulcer perforation: a long-term follow-up study.

BACKGROUND: Survival is lower in ulcer perforation patients than in the general population. This study assesses the causes of death in patients treated for peptic ulcer perforation. METHODS: Cause-specific mortality in a population-based cohort of 817 patients treated for ulcer perforation in western Norway during the period 1962-1990 was compared with cause-specific population death rates. Analyses were based on observed and expected mortality curves for major causes of death and on standardized mortality rates (SMRs). Cox regression models were used to analyse possible differences on the basis of sex, birth cohort, surgical procedure, and ulcer location. RESULTS: Ulcer perforation patients experienced increased mortality from neoplasms (SMR = 1.8; 95% confidence interval (CI) = 1.4-2.1), lung cancer (SMR = 3.6; 95% CI = 2.3-4.9), circulatory diseases (SMR = 1.3; 95% CI = 1.1-1.6), ischaemic heart disease (SMR = 1.3; 95% CI = 1.03-1.6), and respiratory diseases (SMR = 1.9; 95% CI = 1.3-2.6). Postoperative deaths accounted for 38% of all excess deaths. Death from recurrent peptic ulcer was increased also in subjects who survived the 1st year after the perforation (SMR = 5.8; 95% CI = 1.2-10.4) but accounted for only a few deaths. The increase in mortality from lung cancer was higher in subjects born after 1910 than in patients of older generations. Excess mortality from lung cancer and from circulatory diseases was higher in male than in female patients. CONCLUSIONS: Increased mortality in ulcer perforation patients could mainly be attributed to smoking-related diseases. This is indirect evidence that smoking may be an important aetiologic factor for ulcer perforation.

Release of endothelin-1 in strangulation obstruction of the small bowel in pigs.

Evidence has been provided that increased portal vein pressure results in increased release of endothelin-1 (ET-1). Strangulation obstruction is associated with increased venous pressure, and we wanted to determine if it is associated with increased local release of ET-1 and elevated concentration of ET-1 in systemic blood. Strangulation obstruction was induced by elevating pressure in a gasket placed around a loop of ileum until venous pressure reached 50 mm Hg. Ischemia in a bowel loop was induced by arterial clamping, reducing blood flow by 70%. Blood samples were collected before and after 30, 90, and 180 min of strangulation or ischemia. ET-1 was determined by radioimmunoassay following acidification and extraction on C18 columns. In strangulated loop the blood flow decreased by 70%. ET-1 concentration remained around 5 pg/ml in arterial blood, increased fourfold in strangulated venous blood, and remained unchanged in venous blood from control bowel. The release of ET-1 from the strangulated loop to blood increased twofold. Ischemia resulted in reduced release of ET-1. It is concluded that strangulation obstruction causes increased release of ET-1 to venous blood in the strangulated loop, but not increased ET-1 concentration in systemic blood. The increased ET-1 release was probably due to increased venous pressure, not to low blood flow.

Effect of gastric secretion on penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine into gastric mucosa of rats.

Clinical conditions with low gastric acid secretion have been associated with increased risk of gastric cancer. There has also been concern about gastric acid inhibition and N-nitroso compound formation in the stomach. This study investigates the effect of gastric acid secretion on the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine, an N-nitroso compound and gastric carcinogen, into the gastric mucosa of rats. Gastric acid secretion was stimulated by pentagastrin (40 microg/kg/hr) and inhibited by omeprazole (40 micromol/kg) before mucosal exposure to N-3H-methyl-N-nitro-N-nitrosoguanidine. Penetration of the carcinogen was evaluated by light microscopic identification of cells in the S-phase labeled with N-3H-methyl-N-nitro-N-nitrosoguanidine. This population of double-labeled cells is considered at risk from N-methyl-N-nitro-N-nitrosoguanidine-induced carcinogenesis. The percentage of double-labeled cells was significantly higher in antrum than in corpus mucosa (P < 0.0001). Stimulation or inhibition of gastric acid secretion did not affect the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine in antrum or corpus mucosa. We conclude that modulation of gastric acid secretion does not affect the penetration of the carcinogen into the gastric mucosa nor does it explain the different penetration of the carcinogen into corpus and antrum mucosa.

Gastroesophageal reflux in morbidly obese patients treated with gastric banding or vertical banded gastroplasty.

OBJECTIVE: To compare gastric banding (GB) and vertical banded gastroplasty (VBG) with respect to postsurgical gastroesophageal reflux (GER) and to investigate the role of preexisting hiatus hernia. SUMMARY BACKGROUND DATA: GB and VBG have for a long time been used in the treatment of morbidly obese patients. The introduction of laparoscopic techniques has renewed the interest in these operations. The long-term results after GB have, however, been poor. VBG was suggested to have antireflux properties because it involves repositioning and retaining the gastroesophageal junction within the abdomen and constructing an elongated intraabdominal tube. METHODS: Forty-three morbidly obese patients accepted for GB or VBG were evaluated for GER before and at regular intervals after surgery. All patients were questioned about adverse symptoms and need for antireflux medication. Both before and after surgery, 24-hour pH measurement and upper gastrointestinal endoscopies were performed. RESULTS: The prevalence of heartburn and acid regurgitation among patients treated with GB increased from 14% and 13% to 63% and 69%, respectively. Heartburn and acid regurgitation were present before surgery in 32% and 23% of patients treated with VBG, percentages unchanged by the procedure. The 24-hour reflux time increased significantly from 6.4% to 30.9% in patients treated with GB but was essentially unchanged in patients treated with VBG. The prevalence of esophagitis after GB and VBG was 75% and 20%. Acid inhibitors were needed in 81% of patients after GB and 29% of patients after VBG. CONCLUSIONS: The prevalence of GER was unchanged by VBG, but VBG did not demonstrate antireflux properties. The incidence of GER increased markedly after GB.

Glutathione and N-acetylcysteine reduce gastric mucosal blood flow in rats.

Glutathione has been studied as a possible mediator in gastric mucosal protection and healing, but its extracellular function is not fully understood. This study evaluates blood flow changes in normal gastric mucosa secondary to glutathione modulation under stable central hemodynamic conditions. Thiol substances were quantified by reverse-phase ion-pair liquid chromatography and fluorescence detection. Central hemodynamics remained stable when glutathione and N-acetylcysteine were administered in a dose of 0.5 mmol/kg. Higher doses than 0.5 mmol/kg of glutathione and N-acetylcysteine caused unstable hemodynamics. Glutathione (0.5 mmol/kg intravenously) and N-acetylcysteine (0.5 mmol/kg intravenously) reduced corpus mucosal blood flow by 28% and 26% (P < 0.0005), respectively, and glutathione reduced antral mucosa blood flow by 22% (P < 0.01). L-Buthionine-[S,R]-sulfoximine (2 mmol/kg intravenously) did not effect gastric mucosal blood flow. Cysteine content in mucosa and plasma increased while mucosal glutathione levels were largely unchanged after administration of reduced glutathione and N-acetylcysteine. Plasma glutathione only increased after injection of glutathione. L-Buthionine-[S,R]-sulfoximine reduced the glutathione level in both plasma and mucosa. We conclude that glutathione and N-acetylcysteine reduce gastric mucosal blood flow and that the effect may be related to increased cysteine levels in plasma or mucosa.