Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint.

Using duodenocolic fistula in rats, this study attempts to highlight the particular cytoprotection aspects of the healing of fistulas and therapy potential of the stable gastric pentadecapeptide BPC 157, a cytoprotection mediator (i.e. upgrading minor vessels to induce healing at both fistula's sides). Upon duodenocolic fistula creation (two 'perforated' lesions put together) (assessed at 3, 6, 9, 12, and 15 min), BPC 157, given locally at the fistula, or intragastrically (10 µg/kg, 10 ng/kg), rapidly induces vessel 'recruitment', 'running' toward the defect, simultaneously at duodenum and colon, providing numerous collaterals and branching. The mRNA expression studies done at that time provided strongly elevated (nitric oxide synthase 2) and decreased (cyclooxygenase-2, vascular endothelial growth factor A, nitric oxide synthase (NOS)-1, NOS-3, nuclear factor-kappa-B-activating protein) gene expression. As therapy, rats with duodenocolic fistulas, received BPC 157 10 µg/kg, 10 ng/kg, per-orally, in drinking water till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24 h before sacrifice, at day 1, 3, 7, 14, 21, and 28. Controls exhibited both defects persisting, continuous fistula leakage, diarrhea, continuous weight loss, advanced adhesion formation and intestinal obstruction. Contrary, all BPC 157-treated rats have closed both defects, duodenal and colonic, no fistula leakage (finally, maximal instilled volume corresponds to healthy rats), no cachexia, the same weight as before surgery, no diarrhea, markedly less adhesion formation and intestinal passage obstruction. Thus, BPC 157 regimens resolve the duodenal/colon lesions and duodenocolic fistulas in rats, and rapid vessels recovery appears as the essential point in the implementation of the cytoprotection concept in the fistula therapy.

[ACUTE PAIN MANAGEMENT IN PATIENT ON OPIOID SUBSTITUTION THERAPY WITH METHADONE OR BUPRENORPHINE].

The result of the increase in drug abuse is a growing number of patients receiving methadone or buprenorphine substitution therapy. Physicians are increasingly confronted with patients on substitution therapy at the time when they are developing acute pain conditions or when they need surgery. Although pain has sensory qualities, it is a very personal and complex experience. The intensity and duration of pain are influenced by numerous factors. Poorly controlled pain leads to unnecessary suffering of the patients with the possibility of permanent changes in behavior and reduced quality of life. Efficacious pain treatment is considered a basic right of every patient. Because of the complex mechanisms of the emergence and transmission of pain and the emotional components that are involved in the experience of pain, appropriate pain relief in patients on substitution therapy is a major challenge for both the physicians and the patients. The article gives an overview of issues related to the treatment of acute pain and perioperative treatment in patients on substitution therapy with methadone and buprenorphine. The article highlights the wrong common misconception about pain treatment in these patients, which also are the most common cause of their inadequate treatment.

BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 µg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure.

Ischemic preconditioning decreases laparoscopy induced oxidative stress in the liver.

Experimental studies indicate that oxidative stress during and after laparoscopic surgery may cause liver ischemia-reperfusion injury. The aim of the study was to assess the effect of ischemic preconditioning against liver damage during pneumoperitoneum on oxidative stress. Twenty one New Zealand rabbits were divided into three groups of seven animals. Control group (C) rabbits received anesthesia for 60 min alone; 15 mm Hg intra-abdominal pressure with CO2 for 60 min was used in the pneumoperitoneum group animals (PNP); and 15-min insufflation and 10-min desuflation followed by 60-min pneumoperitoneum were used in the ischemic preconditioning group animals (IP). Venous blood samples were obtained at different time points to measure lipid hydroperoxide, glutathione reductase and total antioxidant status as indicators of increased oxidative stress. Aspartate transaminase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were evaluated as indicators of hepatocellular injury. The Kruskal-Wallis and Mann-Whitney U tests were used on statistical analysis. Elevated intra-abdominal pressure was found to produce significant increase in lipid hydroperoxide at the end of pneumoperitoneum and 30 min after desuflation in comparison with pre-insufflation period, and with both C and IP groups at the same time points. Total antioxidant status level decreased significantly in the PNP group at 24 h of desuflation. At 24h of desuflation, the AST, ALT and LDH levels were significantly increased in the PNP group in comparison with the levels measured before induction of anesthesia, and with the C and IP groups. Study results demonstrated that ischemic preconditioning prevented hepatocyte injury and oxidative stress during CO2 pneumoperitoneum.

Comparison of the effects of low intra-abdominal pressure and pentoxifylline on oxidative stress during CO2 pneumoperitoneum in rabbits.

BACKGROUND: The aim of this study was to investigate the effect of low-pressure pneumoperitoneum and pentoxifylline, a methylxanthine derivative, in the prevention of injury caused by free oxygen radicals generated during CO(2 )pneumoperitoneum. METHODS: Twenty-eight rabbits were allocated randomly to 4 groups. Control group rabbits (group 1) were subjected to anesthesia for 60 min; group 2 and 3 animals were subjected to a CO(2) pneumoperitoneum (15 or 7 mm Hg); and group 4 rabbits received 50 mg/kg pentoxifylline, followed by a 15-mm-Hg pneumoperitoneum. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), lipid hydroperoxide, glutathione reductase and total antioxidant status were measured. RESULTS: Compared with group 1, a significant increase in lipid hydroperoxide levels at the end of the pneumoperitoneum and 30 min after deflation and a significant decrease in total antioxidant status 24 h after deflation were recorded in group 2. In addition, a significant increase was observed in ALT, AST and LDH levels. These changes were attenuated by low-pressure pneumoperitoneum, whereas pentoxifylline pretreatment appeared to attenuate only transaminase levels. CONCLUSION: Low-pressure pneumoperitoneum could attenuate ischemia/reperfusion injury induced by CO(2 )pneumoperitoneum in a rabbit model whereas pentoxifylline pretreatment appeared to attenuate only transaminase levels. Pentoxifylline did not prevent the development of oxidative stress.

Relationship between inflammatory cytokines and cardiorenal anemia syndrome: treatment with recombinant human erythropoietin (rhepo).

BACKGROUND AND AIM: Hemodialysis (HD) patients are exposed to persistent inflammatory state. Erythropoietin resistance is known to be strongly associated with chronic inflammation. Aim of the study was to analyze the effect of elevated inflammatory markers on hemoglobin levels and rhEPO requirements in stable patients of our hemodialysis center. PATIENTS AND METHODS: The study population consisted of 42 patients, 19F/23M, mean age 54.5+/-12.0 years. C-reactive protein (CRP), interleukin-6 (IL-6), hemoglobin (Hb), ferritin and left ventricular mass index (LVMi) were recorded. Group 1 consisted of 10 patients with Hbor=10 g/dl, mean 12.6+/-1.91 g/dl. None of these 20 patients had been previously treated with rhEPO. Group 3 consisted of 22 patients with mean Hb 10.1+/-1.5 g/dl after treatment with rhEPO. RESULTS: Group 1 patients had significantly higher IL-6 concentrations than Group 2 (5.21+/-3.94 vs 3.03+/-3.64, p<0.03). Group 3, treated with rhEPO had IL-6 concentrations significantly lower compared to Group 1 (1.15+/-3.81 vs 3.03+/-3.64, p<0.05). HD pts in Group 1 presented significantly higher CRP concentrations compated to pts of Group 2 and 3 (23.1+/-9.1 vs 7.02+/-8.7 and 7.89+/-9.6 respectively, p<0.05). A negative correlation was demonstrated between IL-6 and Hb level (r: 0.33 p<0.05). CONCLUSIONS: A better management of anemia might improve inflammatory state and survival in this population.

Comparison of dexamethasone, metoclopramide, and their combination in the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) are one of the most common complaints following anesthesia and surgery. This study was designed to evaluate the efficacy of dexamethasone, metoclopramide, and their combination to prevent PONV in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 160 ASA physical status I and II patients were included in this randomized, double blind, placebo-controlled study. Patients were randomly assigned to 4 groups (n = 40 each): group 1 consisting of control patients administered 0.9% NaCl; group 2 patients received metoclopramide 10 mg just before the end of anesthesia; group 3 patients received dexamethasone 8 mg after the induction of anesthesia; and group 4 patients received dexamethasone 8 mg after the induction of anesthesia and metoclopramide 10 mg before the end of anesthesia. The incidence of PONV, mean visual analog pain scores at rest and on movement, time to the first request for analgesia, side effects, and well-being score were recorded during the first 24 h postoperatively. RESULTS: Data were analyzed using one-way analysis of variance (ANOVA) and the chi2 test, with p < 0.05 considered statistically significant. The total incidence of PONV was 60% with placebo, 45% with metoclopramide, 23% with dexamethasone, and 13% with the combination of dexamethasone plus metoclopramide. None of the dexamethasone plus metoclopramide group patients (p < 0.05 versus groups 1 and 2) and one dexamethasone group patient (p < 0.05 versus group 1) required antiemetic rescue, as compared with four patients in the metoclopramide group and six patients in the placebo group. Pain scores, the time to the first request for analgesia, and side effects were similar across the study groups. CONCLUSIONS: Dexamethasone and the combination of dexamethasone plus metoclopramide were more effective in preventing PONV than metoclopramide and placebo.

Aminotransferases after experimental pneumoperitoneum in dogs.

BACKGROUND: Laparoscopic surgery has rapidly become a popular and widely used technique. Elevated intra abdominal pressure due to gas insufflation for laparoscopic surgery may result in a number of local and systemic effects on the organism. The effects of pneumoperitoneum on the cardiovascular and respiratory system are well known today, but very few studies have been carried out on the consequences of pneumoperitoneum on hepatic integrity. The aim of the present study was to assess changes in aminotransferases, bilirubin and prothrombin time after pneumoperitoneum in dogs. METHODS: The effects of different levels and duration of intra abdominal pressure and different gases on liver function test were investigated in dogs. The levels of aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin, and prothrombin time, according to the duration and the level of pneumoperitoneum and gas, were measured at 6, 12, 24 and 48 h of desufflation. RESULTS: The levels of total bilirubin, direct bilirubin and prothrombin time showed no significant alteration. A statistically significant (P < 0.01) elevation of aspartate aminotransferase and alanine aminotransferase was recorded in the group of animals with higher intra abdominal pressure and longer duration of pneumoperitoneum. They returned to normal values within 48 h. CONCLUSION: Transient elevation of hepatic transaminases occurred after laparoscopic surgery, but they returned to normal values within 48 h. These increases were more prominent with higher and longer intra abdominal pressures irrespective of the type of insufflated gas. Alteration in aminotransferases was not associated with any clinical signs of hepatic dysfunction in experimental animals.

[Lipid status in patients on a chronic hemodialysis program]. / Lipidni status bolesnika na hronicnom programu hemodijalize.

Dyslipidemia causes development of atherosclerosis in chronic hemodialysis patients. The goal of this study was to determine values of serum lipids in hemodialysis patients. The study comprised 45 patients, whereas the control group consisted of 45 healthy persons of corresponding age and sex. We determined triacyglycerols, total cholesterol, HDL (high density lipoprotein) and LDL (low density lipoprotein) cholesterol in the serum of patients on an empty stomach. There were 51% of patients with normal findings, and 49% with hyperlipoproteinemia type IV. In regard to the control group triacyglycerol was increased both in patients with hyperlipoproteinemia type IV and in patients with normolipemia. Levels of total cholesterol were higher in patients with hyperlipoproteinemia type IV, while values of HDL cholesterol were decreased in both subgroups of patients in regard to the control group. Values of total cholesterol in relation to HDL cholesterol > 4.5 occurred in 38% of patients. Lipid profile of hemodialysis patients, including those with normolipidemia, points to high risk of cardiovascular diseases.

Laparoscopic treatment of nonparasitic cysts of spleen and liver.

Laparoscopic treatments of nonparasitic splenic and liver cysts in the period between March 1993 and April 1995 have been reported: partial decapsulation-fenestration and evacuation of a splenic pseudocyst in one patient, fenestration of large congenital liver cysts with total excision of a few smaller liver cysts in two patients and two unsuccessful treatments of splenic cysts. After successful laparoscopic procedures the patients experienced immediate and complete relief of the symptoms. Two years after the splenic cyst procedure and 6 months after the liver cyst operation, the patients remained free of the symptoms, and complete absence of the cysts was confirmed by computerized tomography scans. Laparoscopic fenestration of nonparasitic splenic and liver cysts with total excision of smaller liver cysts is a simple and safe surgical method with lower morbidity and a quick return to normal activity.

[Comparison of open and laparoscopic appendectomy]. / Usporedba otvorene i laparoskopske apendektomije.

The first laparoscopic appendectomy was performed by Senn in 1982. Since then, the dilemmas about the validity of this operation in relation to open operation have persisted. Many authors presented the technique modifications and results that are very different. The retrospective results, cost, duration of hospital stay and postoperative recovery analyses for fifty patients in each group were done in this study. Laparoscopic operations were done by "two-handed" technique and in different ways of appendix and mesoappendix closing and cutting. Endoscopic linear cutters were used in the second part of the study. When comparing parameters, laparoscopic operation in relation to open operation is equally safe; quicker; with less postoperative pain; with less wound infections rate; with shorter hospital stay; with less staff time involved; with faster recovery and return to work; more expensive; with better cosmetic effect. In conclusion, laparoscopic appendectomy is better, although more expensive, than open operation, so it should be recommended.

[Serum phospholipids in patients in a chronic hemodialysis program]. / Fosfolipidi seruma u bolesnika na hronicnom programu hemodijalize.

The aim of this investigation was to determine concentrations of total and single phospholipids and to examine distribution of phospholipid fractions in serum of chronic hemodialysis patients. The investigation included 21 patients, 10 with normal lipid level in serum and 11 with hyperlipoproteinemia type IV. The control group consisted of 17 healthy normolipidemic persons. The gathered results show that in hemodyalisis patients the level of phospholipids (3.10 +/- 0.66 mmol/L) is higher than the level of phospholipids in the control group (2.25 +/- 0.35 mmol/L). Dialysis patients with hyperlipoproteinemia type IV have an increased level of serum phospholipids (3.51 +/- 0.43 mmol/L) in regard to dialysis patients with normolipidemia (2.46 +/- 0.57 mmol/L). The distribution of phospholipid fractions, that is proportional occurrence of lysophosphatidylcholine, sphingophospholipids and phosphatidylcholine is disturbed in dialysis patients no matter what their lipid status is.

Laparoscopic cholecystectomy following abdominal surgery of the lower part of abdomen.

In this prospective study, laparoscopic cholecystectomy was performed in patients with previous abdominal surgery of the lower part of abdomen. According to authors experience, the usual method of 'blind' beginning of the laparoscopic procedure, with safety tests, is a safe and reliable method to start the laparoscopic procedure, even in these patients. This method does not carry a higher risk of intra-abdominal injury.

Laparoscopic cholecystectomy: results after 1000 procedures.

From May 1992, when the first laparoscopic cholecystectomy was performed at University Department of Surgery, Sveti Duh General Hospital, till October 1994, the authors performed more than 1000 procedures. Laparoscopic approach was successfully used in 965 (96.5%) patients. Thirty-five (3.5%) cases were converted to open surgery. Dangerous anatomy, some technical problems and perioperative bleeding were the most often reasons for conversion. Further, liver metastases and perioperatively recognized common bile duct lesion necessitated conversion in one case each. In total, there were 18 (1.8%) abdominal complications. Common bile duct lesion, postoperative common bile duct stricture and duodenal perforation occurred in one patient each. Major bleeding was present in eight and bile leak in seven patients. The mean duration of hospitalization was 2.8 days. Analyses of the results show laparoscopic cholecystectomy to be safe procedure with low perioperative and postoperative complications.

[The role of color doppler sonography in the diagnosis of atherosclerotic changes in arteries of the lower extremities]. / Uloga obojene doplerske sonografije u dijagnostici aterosklerotskih promjena arterija donjih udova.

In this study doppler ultrasound methods were evaluated from the point diagnostical values, and were compared with the standard X-ray methods (angiography). One of the basic question was, whether noninvasive doppler ultrasonic methods could replace the invasive contrast angiography i. e. in what relations and volume. The investigations were done by CW Doppler and angiodynography, and the results obtained, were compared with the ones of angiography that was taken as the referent method. The 264 segments of blood vessels of lower extremities arterial three were analyzed, and then ranged into the advance defined categories, on the basis of the degree of obstruction. The evaluation of the data obtained was statistically accomplished by the means of "decision matrix" test, and results were displayed by positive predictive values. Positive predictive value for the CW Doppler was 94.07 (in groups varied from 93.10-100) and for angiodynography was 97.35 (in groups varied from 93.15 to 100). From the data obtained, it could be concluded that Doppler's methods are very accurate in a way of diagnostical interpretation (96.03%). The advantages of the Doppler's methods against the conventional standard radiological researches reflect in the following facts: they enable dynamic indicators in real time, they are noninvasive, very exact, and the possibility of verification of stenosis is enabling us to apply the adequate diagnosic (angiography) and therapeutic methods in time.