Colon perforation in an adolescent after short-term diclofenac intake.

Chronic intake of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to cause side-effects distal to the duodenum. These include strictures, diaphragm-like lesions and perforations of the small and large intestines. This is the first case report on colon perforation occurring in an adolescent (16-year-old girl) after short-term diclofenac intake.

Pulmonary microcirculation in mild and severe experimental pancreatitis.

BACKGROUND: Research aimed at elucidating the pathogenesis of pancreatitis-associated lung injury and evaluating novel strategies for preventing respiratory complications in acute pancreatitis (AP) has not yet involved intravital microscopic (IVM) studies of pulmonary microcirculation in animals with severe disease. OBJECTIVE: To characterize and compare pulmonary microcirculation in severe/necrotizing (NP) and mild/edematous pancreatitis (EP) in the rat. METHODS: EP was induced by intravenous cerulein infusion (n = 10) and NP by a standardized intraductal infusion of glycodeoxycholic acid followed by intravenous cerulein (n = 10). After 24 h a left-sided thoracotomy was performed for IVM examination of pulmonary capillary blood flow, permeability, leukocyte sticking and the thickness of alveolar septi. Further measurements included monitoring of arterial blood gases and histological evaluation of lung injury. RESULTS: In animals with NP, histology revealed severe pulmonary edema together with clustering of polymorphonuclear leukocytes in pulmonary microvessels and alveoli. IVM showed a greater number (n) of leukocytes sticking on the endothelium of pulmonary capillaries (9.4 +/- 0.7 vs. 1.8 +/- 0.2 in healthy control animals) and increased capillary permeability (260 +/- 14 vs. 136 +/- 6% relative fluorescein intensity) while capillary blood flow was decreased (0.41 +/- 0.05 vs. 0.57 +/- 0.03 mm/s). In comparison, changes in EP were significantly less pronounced (flow 0.5 +/- 0.04 mm/s, permeability 156 +/- 4%, leukocyte sticking n = 4.6 +/- 0.7). CONCLUSIONS: These findings suggest that deterioration of pulmonary microcirculation in AP correlates with disease severity and that a model featuring NP may therefore be more suitable to further study pancreatitis-associated pulmonary injury.

RES function and liver microcirculation in the early stage of acute experimental pancreatitis.

BACKGROUND/AIMS: The reticuloendothelial system and in particular the Kupffer cells in the liver are important for eliminating antigens and toxic substances in many diseases including acute pancreatitis. Optimal Kupffer cell function is believed to depend on numerous factors including intact hepatic blood supply and microcirculation. The aim of the study was to evaluate whether hepatic microcirculation and Kupffer cell function are impaired in acute pancreatitis and whether enhancement of hepatic capillary blood flow leads to improved reticuloendothelial system function. METHODOLOGY: Acute pancreatitis was induced in rats by intraductal infusion of bile salt followed by i.v. cerulein hyperstimulation. Animals were randomized to receive either a selective endothelin-A receptor antagonist (ET-RA; LU-135252; 50 mg/kg) or saline. Sham-operated animals (intraductal and i.v. saline infusion) treated according to the same protocol served as controls. Liver phagocytic function was evaluated in 6 animals per group 6 and 24 hrs after acute pancreatitis induction and treatment using 99mTc-labeled Nanocoll and a scintillation camera technique. Another 6 animals of each group were used for intravital microscopic determination of hepatic capillary blood flow using fluorescein-labeled erythrocytes. RESULTS: Six hours after acute pancreatitis induction, hepatic capillary blood flow and nanocoll clearance were significantly decreased in saline-treated animals (compared to saline-treated healthy controls). Endothelin-A receptor antagonist significantly improved hepatic capillary blood flow and nanocoll clearance. This beneficial effect was no longer seen after 24 hrs when these parameters had spontaneously returned to values not significantly different from normal. CONCLUSIONS: Reticuloendothelial system function and hepatic capillary blood flow are impaired (only) in the early stage of this acute pancreatitis model. Endothelin-A receptor antagonist improves hepatic capillary blood flow at this stage. Enhancement of hepatic capillary blood flow is accompanied by normalization of nanocoll clearance, suggesting that hepatic microcirculation influences phagocytic Kupffer cell function early in acute pancreatitis.

Persistent multiple organ microcirculatory disorders in severe acute pancreatitis: experimental findings and clinical implications.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

An experimental rat model for studying pulmonary microcirculation by in vivo videomicroscopy.

It is unclear what role pulmonary microcirculatory disorders play in the pathogenesis of adult respiratory distress syndrome. The aim of this study was to establish a rat model for the direct visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. The pulmonary terminal vascular bed was visualized and the microcirculatory parameters of leukocyte sticking, erythrocyte velocity, capillary permeability, and interalveolar septal diameter were quantified. These parameters were examined simultaneously. The preparation was stable for 120 min. Under hyperthermia, there was increased permeability with a relative fluorescence of 0.39 +/- 0.19 compared to 0.16 +/- 0.13 in the control group, and interalveolar septal diameters were wider (30.7 +/- 2.9 microm) than in control animals (17.3 +/- 3 microm). Under hypothermia and hypovolemia, the erythrocyte velocity was lower (0.351 +/- 0.063 and 0.378 +/- 0.044 mm/s) than in control groups (0.527 +/- 0.07 mm/s). Under hypoventilation, we observed a higher amount of leukocyte sticking (3.1 +/- 1.1 vs 1.8 +/- 0.8 cells/alveolus) and increased permeability (relative fluorescence 1.03 +/- 0.37 vs 0.16 +/- 0.13 in the control group). The model of rat lung exposure for direct examination of microvascular structures in living animals was valuable because it remained stable for 2 h under baseline conditions and demonstrated distinct changes in microcirculatory parameters following specific pathophysiological interventions.

Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis.

BACKGROUND: Intravascular fluid loss contributes to pancreatitis-associated multiple organ dysfunction and is thus a major target for therapy in this life-threatening disease. AIM: To evaluate intravascular fluid loss and extravascular fluid sequestration together with cardiorespiratory and renal function in a well-established rat model of severe acute pancreatitis (AP) and to investigate the effect of fluid resuscitation with and without endothelin receptor A blockade on these parameters. METHOD: Induction of AP in rats by a standardized bile salt infusion into the pancreatic duct and intravenous cerulein hyperstimulation. Six hours after AP induction, animals were randomized into 4 groups to receive (1) no therapy; (2) 4 ml/kg/h Ringer's lactate (RL) i.v.; (3) 8 ml/kg/h RL i.v., or (4) 4 ml/kg/h RL plus an endothelin receptor antagonist. Target parameters measured before and after AP induction and during the 24-hour observation period included: mean arterial blood pressure, heart rate, hematocrit, arterial blood gases, urine production, ascites and pleural effusions. RESULTS: After 6 h, all animals presented with severe hemoconcentration (hematocrit >57%) and oliguria (<0.5 ml/6 h). Cardiorespiratory parameters were within the normal range. Up to 12 h after AP induction, animals without therapy had an increased hematocrit and oliguria and developed metabolic acidosis. Animals receiving fluid resuscitation had a significant drop in hematocrit and maintained compensated blood gas values. A significant increase in urine production was only observed in animals given 8 mg/kg/h RL. Between 12 and 24 h, urine production significantly increased with fluid resuscitation and respiratory parameters stabilized except for animals treated with 8 ml/kg/h RL which developed arterial hypoxia and hypercapnia. CONCLUSIONS: Intravascular fluid loss and extravascular fluid sequestration together with decreased urine production characterize the early phase of this model of severe AP. Massive fluid resuscitation necessary for increasing urine output may lead to respiratory distress. Reduction of intravascular fluid loss by endothelin receptor blockade is associated with improved renal and respiratory function.

[Acute appendicitis. Analysis of surgical indications]. / Die akute Appendizitis. Analyse der Operationsindikation.

We analyzed 276 patients operated on for acute appendicitis between January 1995 and June 1997. In 26 patients intraoperative assessment revealed a pathological finding other than appendicitis. Fifty-nine patients (24%) had a perforated appendix, 116 acute appendicitis verified by histological examination, 75 (30%) chronic fibroplastic appendicitis or no signs of appendicitis. Patients with histologically acute inflammation fulfilled more clinical criteria of appendicitis than those without (5.1 vs. 3.7). Negative histological findings were most common in younger females admitted on Mondays and Tuesdays. Clinical observation rather than immediate operation and laparoscopy rather than laparotomy appear appropriate for the latter group and may lower the rate of negative appendectomy.