Long-term outcome of patients with acute non-specific abdominal pain compared to acute appendicitis: prospective symptom audit after two decades.

BACKGROUND: Non-specific abdominal pain (NSAP) and acute appendicitis (AA) are the two most frequent diagnoses of acute abdomen in the emergency wards. The long-term morbidity, mortality and quality of life of the patients with NSAP compared to AA are unknown. METHODS: The study group consisted of 186 patients with acute NSAP compared to 147 patients with AA initially treated during 1985-1986. Medical history, social background, quality of life and abdominal symptoms were assessed with standardized questionnaires in both groups during 2006-2009. The patients who continued to have abdominal symptoms were invited to a check-up visit. RESULTS: During 1985-6, the NSAP group had more previous abdominal symptoms and operations than the AA group. Some 29% of patients with NSAP and 11% of patients with AA had still abdominal symptoms at long-term check-up (p < 0.0001). Chronic abdominal pain (38 vs 17) and peptic ulcer disease (18 vs 2) occurred more often in the NSAP group than in the controls, respectively (p = 0.001). After five years of follow-up, 11 patients in the NSAP group and 6 patients in the AA group had died (ns). During the twenty years of follow-up, mortality was higher (46/22, 25/15%) in the patients with NSAP than in controls (p = 0.013). Ischaemic heart disease was the leading cause of death in both groups (18 NSAP vs 5 AA, p = 0.017). The quality of life scores were comparable in both study groups. CONCLUSION: Over 70% of NSAP- and almost 90% of AA-patients were free of symptoms after 20 years of follow-up. Mortality was higher and various alimentary track diseases were more frequent in patients with NSAP than in AA.

Strong claudin 5 expression is a poor prognostic sign in pancreatic adenocarcinoma.

We investigated the expression of claudin 5 in 88 ductal adenocarcinomas of the pancreas. The results were correlated with patient prognosis, with claudin 5 expression in blood vessels, with the expression level of bcl2 and bax and with apoptosis. Claudin 5 expression was detected in 24 (38%) cases. It was not associated with tumour size or spread, but strong claudin 5 expression correlated with a worse survival (p = 0.005). Claudin 5 also associated with a higher extent of apoptosis and greater expression of bax protein. In the tumour vasculature, some vessels displayed a loss of claudin 5 expression. The presence of this loss was associated with tumour grade and the presence of nodal metastases (p = 0.02, p = 0.022, respectively). These results indicate that claudin 5 is upregulated in a proportion of pancreatic ductal adenocarcinomas. The association of strong claudin 5 expression with a worse survival is in line with some earlier reports indicating that this protein is involved with increased locomotion and more aggressive spread of carcinomas. The association of claudin 5 with apoptosis and bax might be due to stronger cellular kinetics found in such tumours. The loss of claudin 5 expression in the tumour vasculature points to a leaky vessel type; this might also ease the access of tumours to vessels and be reflected in its association with the presence of nodal metastases.

Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma.

The aim of this study was to investigate the expression of Nrf2, sulfiredoxin and DJ1 in pancreatic cancer. The expression of Nrf2, sulfiredoxin and DJ1 was studied immunohistochemically in a large set of pancreatic adenocarcinomas consisting of 103 cases. Eighty six percent of the cases showed cytoplasmic Nrf2 and 24% nuclear Nrf2 positivity. Sulfiredoxin positivity was observed in 54% and DJ1 positivity in all cases. Nuclear Nrf2 positivity had an association with sulfiredoxin (p=0.019) and was associated with a poor survival (p=0.010). Stage IV tumors tended to have a more nuclear Nrf2 expression (p=0.080). DJ1 expression was more often found in well-differentiated tumors (p=0.012), and DJ1 expression was associated with better survival (p=0.020). According to the results, nuclear Nrf2 expression predicts a worse survival in pancreatic adenocarcinoma, which is in keeping with its protection of cells against oxidative or xenobiotic stress. In accordance with Nrf2's regulation of the synthesis of sulfiredoxin, there was an association between them (p=0.019). DJ1 had no association with Nrf2, and its expression predicted a better survival of patients.

Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma: association with features of differentiation.

AIM: This study was undertaken to evaluate the expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma. METHODS AND RESULTS: Material tested included 111 operated samples and 47 additional biopsy samples consisting of 26 cases of pancreatitis, 3 cases of pancreatic intraepithelial neoplasia and 18 ductal adenocarcinomas. Samples were stained with antibodies to claudins 7 and 18 and analysed for membranous and cytoplasmic expression. Membrane bound claudin 7 and 18 expression was detected in 62 of 105 (59%) and 78 of 111 (70%) cases, respectively. Membrane bound claudin 7 and 18 were associated with large or intermediate neoplastic ducts (p=0.01, p=0.002, respectively). Well differentiated pancreatic adenocarcinomas displayed more cases with membrane bound claudin 7 or 18 immunopositivity (p=0.003, p=0.03, respectively). All pancreatic intraepithelial neoplasias studied expressed membrane bound claudin 18. Membrane bound claudin 7 or 18 positivity was not associated with survival (p=0.17, p=0.98). In the biopsy cases membrane bound claudin 18 had 100% specificity and 51% sensitivity for a tumour marker. CONCLUSION: Claudin 7 and 18 expression is related to gland size of neoplastic cells and is especially found in tumours with intermediate and large ducts and well differentiated tumours. Membrane bound claudin 18, when present, is a useful marker for diagnosis of pancreatic cancer. Claudins 7 and 18 were not associated with patient survival or spread of tumours.

Factors associated with successful establishment of breastfeeding in very preterm infants.

AIM: To describe feeding practices at hospital discharge in relation to characteristics of the very preterm infants (VPI) and their mothers. METHODS: Design. Prospective hospital-based registration of very preterm infants born with a gestational age < or =32 weeks in Denmark during 2004-2008. Subjects. Healthy mothers and VPI without diseases causing eating disabilities at discharge. RESULTS: A total of 478 VPI were registered. At discharge, 60% were exclusively breastfed, 35% were exclusively bottlefed, and 5% were both breast- and bottle-fed. Mothers of high social class (p = 0.000) and 'not smoking' (p = 0.003) were significantly more often breastfeeding their preterm infant(s) at discharge. Single births infants tended more often to be breastfed (p = 0.09). Infant age at discharge and duration of hospitalization did not influence breastfeeding at discharge. Increase in weight z-score from birth to discharge was largest in the bottlefeeding-group compared with the breastfeeding-group (p = 0.000) probably as a result of feeding practice the last week(s) of hospitalization. CONCLUSION: Breastfeeding can successfully be established in very preterm infants. Mothers of low social classes, smokers, multiple birth and very preterm infants with low weight for age may need extra attention in breastfeeding establishing policies.

Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized study with special reference to obesity.

BACKGROUND: Minilaparotomy cholecystectomy (MC) has recently challenged the role of the laparoscopic approach (LC) for cholecystectomies. However, the situation is far from clear when operating times and recovery are evaluated. METHODS: Altogether 157 patients with uncomplicated symptomatic gallstones were randomized into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of age, body mass index, American Society of Anesthesiology (ASA) physical fitness classification, and operating surgeon. RESULTS: The mean operating time was 55 +/- 19.5 min in the MC group and 79 +/- 27.0 min in the LC group (p < 0.0001). The postoperative hospital stay and length of sick leave did not differ between the two groups. There were no significant differences in postoperative pain, analgesic consumption, or postoperative pulmonary function between the groups. The body mass index did not influence operating time or patient recovery in either group. No major complications occurred in either groups. CONCLUSION: The MC procedure seems to be a faster technique than the LC approach for noncomplicated gallstone disease, with no difference in recovery times. The MC procedure also seems to be suitable for the obese patient.

Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats.

BACKGROUND: Galacto-oligosaccharides potentially attenuate colonic inflammation by two mechanisms: through beneficial effects on intestinal microflora and by increasing the colonic short-chain fatty acid concentration. The purpose of this study was to investigate the effects of galacto-oligosaccharides on the development of inflammation and on the growth of bifidobacteria in trinitrobenzene sulphonic acid (TNBS)-induced colitis, a model that has been shown to benefit from short-chain fatty acid administration and to be associated with alterations in the colonic microflora. METHODS: Rats were given daily either whey-derived or lactose-derived galacto-oligosaccharides (4 g kg(-1) day(-1), p.o.); starting 10 days before colitis induction, or dexamethasone (2 mg kg(-1) day(-1), s.c., a positive control), starting at colitis induction. Colon wet weight, macroscopic damage and myeloperoxidase activity were assessed 72 h after the induction of colitis. Faecal bifidobacteria were counted at the beginning of the study, and immediately before and 72 h after colitis induction. RESULTS: Galacto-oligosaccharides increased the colonic levels of bifidobacteria but also the levels of other bacterial species. Neither whey-derived nor lactose-derived galacto-oligosaccharides reduced the severity of inflammation. CONCLUSIONS: Galacto-oligosaccharides are able to modify gut microflora in severe TNBS-induced colitis, but unable to attenuate the inflammation.

Effects of fluid and dobutamine treatment on renal function during partial superior mesenteric artery occlusion and reperfusion.

OBJECTIVE: We compared the effects of dobutamine, fluid resuscitation and their combination on renal function during experimental intestinal ischaemia and reperfusion. MATERIALS AND METHODS: Superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The animals were further assigned into four treatment arms. In the control arms, the animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms, dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with fluids. At 120 minutes, the occluder was released in all study groups and the animals were followed for an additional 60 minutes. Renal function was evaluated by means of serum and urine creatinine. urine volume and creatinine clearance. Systemic and regional haemodynamics as well as intramucosal pH, intramucosal-arterial pCO2 gradient, and portal venous-arterial lactate gradient were measured. RESULTS: In the ischaemic groups, diuresis increased and serum and urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p < 0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001, respectively) treated groups during SMA ischaemia. After SMA reperfusion, diuresis decreased in control group (p < 0.05) and in animals treated with dobutamine alone (p < 0.01). In addition, urine creatinine increased in dobutamine treated group (p < 0.05), and creatinine clearance decreased in control group (p < 0.01). Renal function and diuresis during the SMA occlusion and reperfusion did not differ between ischaemic and sham groups. All fluid treated groups had lower serum creatinine during SMA occlusion than control groups (p < 0.001). CONCLUSIONS: Intestinal ischaemia caused by partial SMA occlusion did not influence renal function. On the contrary, SMA reperfusion resulted in a significant impairment of renal function both in ischaemic and sham operated animals. The impairment was most obvious in control groups and in animals treated with dobutamine alone.

Gastric tonometry in assessing splanchnic tissue perfusion in acute pancreatitis.

BACKGROUND: Hypovolemia is typical early in acute pancreatitis. Despite fluid resuscitation splanchnic hypoperfusion may be present and may have a role in the course of pancreatitis. To test this hypothesis, we assessed gastric mucosal pH (pHi) and P(CO)2 during the first 48 h of hospitalization for acute pancreatitis. METHODS: Thirty-three patients were studied. A gastric tonometer was inserted on admission, and gastric mucosal pH and P(CO)2 were measured on admission and then every 12 h during next 48 h. RESULTS: On the basis of the Atlanta classification there were 22 cases of mild and 8 of severe pancreatitis. Three patients were excluded because of consent withdrawal. The groups were similar with regard to age, sex ratio, and etiology of pancreatitis. Independently of disease severity the gastric pHi decreased, and the gastric mucosal-arterial P(CO)2 difference and pH difference both increased over time as compared with base line. No difference was seen in these values between mild and severe pancreatitis. CONCLUSIONS: Moderate gastric mucosal hypoperfusion was found early in acute pancreatitis. However, gastric pHi measurement with tonometry has no obvious value as a screening tool to assess the severity of pancreatitis.

Gut permeability in patients with acute pancreatitis.

BACKGROUND: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. Increased gut permeability may be the initial phenomenon in this process. To test the hypothesis that gut permeability is increased in acute pancreatitis a clinical study was made where gut absorption and permeability were assessed with multi-sugar probes in patients with acute pancreatitis within 2 days after admission to hospital and again after recovery of disease. METHODS AND RESULTS: Twenty-three patients with acute pancreatitis and 20 healthy controls were studied. According to Atlanta classification, 15 patients had mild and 8 patients severe pancreatitis. Gut absorption, assessed as the 5-h urine excretion of L-rhamnose, D-xylose and 3-O-methylglucose, was decreased in patients with acute pancreatitis and more pronounced in patients with severe pancreatitis (L-rhamnose and D-xylose: P < 0.001; 3-O-methylglucose: P < 0.05). Gut permeability, assessed as the ratio of lactulose/L-rhamnose, was increased in severe pancreatitis (0.16 +/- 0.13, 0.07 +/- 0.03, 0.04 +/- 0.04; severe pancreatitis, mild pancreatitis, controls, respectively; P < 0.001 between three groups, P < 0.05 between pancreatitis groups). CONCLUSIONS: Gut absorption capacity is decreased and gut permeability is increased in patients with acute pancreatitis. Patients with severe pancreatitis may be more exposed to impaired gut barrier function.

Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins.

The ingestion of food antigens usually results in the induction of oral tolerance, but the clinical and immunologic consequences of brief exposure to cow's milk proteins during the neonatal period are not well-documented. The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed. A group of 129 infants was randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF), or a casein hydrolysate formula (CHF), during the first three days of life. They were then all exclusively breast-fed for a varying period of time and followed for two years. Serum IgG and IgE antibodies to cow's milk proteins and ovalbumin (OVA) were analyzed in blood samples obtained at birth, at 4 days and at 2, 4, 8, 12 and 24 months of age. The levels of IgG antibodies to beta-lactoglobulin (IgG-BLG) and bovine serum albumin (IgG-BSA) were higher in the CMF and the HM groups than in the CHF group for up to two years. This was particularly obvious for IgG-BLG in infants who started weaning before two months. The levels of IgG antibodies to casein (IgG-CAS) were higher in the CMF group, as compared with the CHF group at 8 and 12 months. The levels of IgG antibodies to OVA were similar in all three feeding groups. The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups. Exposure to cow's milk during the first three days of life stimulated IgG antibody production to cow's milk proteins and this was still obvious at 2 years of age, while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow's milk proteins.

Individualized protein fortification of human milk for preterm infants: comparison of ultrafiltrated human milk protein and a bovine whey fortifier.

BACKGROUND: To improve the nutritional management of pre-term infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated. METHODS: In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920-1750 g) were enrolled at a mean of 21 days of age (range, 9-36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content. RESULTS: Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1+/-0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group). CONCLUSIONS: Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.

Splanchnic tissue perfusion in acute experimental pancreatitis.

BACKGROUND: Gut hypoperfusion may have a role in the pathogenesis of multiple organ failure, which is a the main cause of death in severe acute pancreatitis. We hypothesized that gut hypoperfusion is present early in acute pancreatitis and that supporting the systemic hemodynamics by fluid resuscitation would prevent this. METHODS: In a pig model of randomized, controlled experimental hemorrhagic pancreatitis induced by Na-taurocholate the animals were divided into four groups (n = 6 for each): 1) pancreatitis, 2) control, 3) pancreatitis and fluid resuscitation to keep the pulmonary capillary wedge pressure at 5 to 6 mmHg, and 4) control and fluid resuscitation as in group 3. Splanchnic perfusion was assessed by means of local PCO2 gap with intestinal tonometer, oxygen delivery and consumption, lactate production, and blood flow. The follow-up time was 6 h. RESULTS: The Pco2 gap increased in pancreatitis (1.72+/-0.17, 1.94+/-0.29, 1.75+/-0.22, 2.32+/-0.33; 9.40+/-2.16, 3.72+/-1.78, 0.84+/-0.39, 1.11+/-0.21 kPa, respectively; P < 0.05). Oxygen delivery in portal-drained organs decreased in pancreatitis (2.5+/-0.3, 2.6+/-0.2, 2.8+/-0.4, 2.3+/-0.2; 1.7+/-0.3, 2.3+/-0.3, 2.4+/-0.5, 2.3+/-0.3 ml/min x kg, respectively; P < 0.05). Regional oxygen consumption did not change. Arterial plasma lactate increased (1.20+/-0.19, 1.33+/-0.16, 1.14+/-0.15, 1.43+/-0.33; 3.81+/-1.31, 1.48+/-0.48, 1.12+/-0.18, 1.18+/-0.35 mmol/l, respectively; P < 0.05). The portal venous blood flow decreased 50% in pancreatitis, but with fluid resuscitation it increased 50%. CONCLUSIONS: Splanchnic hypoperfusion is present early in acute hemorrhagic pancreatitis. The signs of hypoperfusion can be prevented with fluid resuscitation.

Lipid peroxidation products and antioxidant capacity in portal venous and systemic arterial plasma during gradual intestinal ischemia and reperfusion in pigs.

Intestinal ischemia may evoke an inflammatory response and eventually multiple organ failure. We investigated whether intestinal ischemic injury induces systemic lipid peroxidation and changes in the plasma antioxidant capacity in a pig model. Together with cardiovascular parameters, arterial and portal venous blood of 7 pigs were measured for thiobarbituric acid-reactive material diene conjugates, fluorescent chromolipids and plasma antioxidant capacity during graded occlusion of superior mesenteric artery and reperfusion. Plasma levels of lipid peroxidation products did not change significantly during graded ischemia and reperfusion. Portal venous plasma antioxidant capacity increased slightly during reperfusion (from 96.16 +/- to 3.91 to 142.49 +/- 12.01 mumol/l, p < 0.05). Although elevated levels of free radical reaction products have been found in ischemia-reperfusion, we found no evidence of systemic lipid peroxidation in our intestinal ischemia model.

Allergy development and macromolecular absorption in infants with different feeding regimens during the first three days of life. A three-year prospective follow-up.

A group of 129 infants were randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF) or a casein hydrolysate formula (CHF) during the first 3 days of life. Blood samples were taken on at 4 days and at 2, 4, 8, 12 and 24 months of age. Macromolecular absorption was analysed by measuring the serum concentration of human alpha-lactalbumin (S-alpha-LA) with a competitive radioimmunoassay (RIA). Total serum IgE was measured by RIA. A family history of allergy correlated to the proportion of infants with allergic symptoms both at 24 and 36 months of age (p = 0.03 and p = 0.04 respectively). In none of the three groups did correlation exist between the duration of breastfeeding and serum alpha-LA, serum IgE, family history of allergy, frequency of allergic symptoms and proportion of infants with infections.

Does early diet have an effect on subsequent macromolecular absorption and serum IgE?

A group of 130 healthy term infants were randomly assigned at birth to one of three feeding regimens for the first 3 days of life: human milk (HM), cow-milk formula (CMF), or a casein hydrolysate formula (CHF). The formula-fed infants received no human milk during the study days. After day 3, all infants were exclusively breast-fed. Blood samples were taken at 4 days and at 2 and 4 months of age during outpatient visits. Macromolecular absorption was analyzed 60 min after a feed of human milk by measuring the serum alpha-lactalbumin (S-alpha LA) concentrations by a competitive radioimmunoassay. Total serum IgE (S-IgE) was assayed by radioimmunoassay. The median S-IgE value was significantly lower at 2 months of age in the CHF group than in the HM group. The values remained significantly lower, even at 4 months of age, in the CHF group than in either the HM or the CMF group. The median S-alpha LA concentration at 2 months of age was significantly higher in the CHF group than in either the HM group or the CMF group. No significant differences could be found between the CMF and HM groups at any time. One infant in the HM group and one infant in the CMF group developed infantile colic. Two infants in the CHF group developed symptoms of cow-milk allergy. All other infants were healthy at 4 months of age.

Macromolecular absorption and cows' milk allergy.

The absorption of macromolecules was analysed by measuring serum concentrations of human alpha-lactalbumin after feeding human milk, using a competitive radioimmunoassay. The control group consisted of 78 children fed by cows' milk formula; concentrations of alpha-lactalbumin in their serum were low. The median concentrations in the different age groups varied between 7-13 micrograms alpha-lactalbumin/1 serum/1 human milk/kg body weight. Twenty-eight children with cows' milk allergy were studied before introduction of a diet free of cows' milk. Nineteen had gastrointestinal and nine skin symptoms. High serum alpha-lactalbumin concentrations were found. Only two children had alpha-lactalbumin concentrations below 100 micrograms alpha-lactalbumin/1 serum/1 human milk/kg body weight. Altogether 76 children on a diet free of cows' milk were studied directly after a cows' milk challenge; 26 developed symptoms. They had significantly higher serum alpha-lactalbumin values than the 50 children with no symptoms upon challenge. Eighteen of the 26 children with symptoms had serum alpha-lactalbumin concentrations of more than 100 micrograms/1 serum/1 human milk/kg body weight in contrast with two of the 50 with no symptoms. Total serum IgE antibodies were analysed in 43 children. No correlation was found between concentrations of serum IgE and serum alpha-lactalbumin in the children with cows' milk allergy.