Uric acid and oxidative stress.

Uric acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzing the conversion of hypoxanthine to xanthine and the latter to uric acid are catalysed by the enzyme xanthine oxidoreductase, which may attain two inter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase. The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products. The role of uric acid in conditions associated with oxidative stress is not entirely clear. Evidence mainly based on epidemiological studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective effects in situations associated with oxidative stress (e.g. ischaemia-reperfusion injury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant. This review presents the current evidence regarding the antioxidant role of uric acid and suggests that it has an important role as an oxidative stress marker and a potential therapeutic role as an antioxidant. Further well designed clinical studies are needed to clarify the potential use of uric acid (or uric acid precursors) in diseases associated with oxidative stress.

Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb, bcl-2, c-erbB-2, epidermal growth factor receptor (EGFR), proliferation indices (Ki-67, proliferating cell nuclear antigen (PCNA)), and conventional clinicopathological variables. METHODS: The immunohistochemical expression of metallothionein was investigated in 23 cases of colorectal adenoma and 94 adenocarcinomas. Metallothionein expression was examined by the avidinbiotin peroxidase immunoperoxidase (ABC) using the monoclonal mouse antibody E9, on formalin fixed, paraffin embedded tissue. RESULTS: Positive metallothionein expression (> 5% of neoplastic cells) was observed in 30.4% of adenomas and 25.5% of adenocarcinomas, while 8.7% of adenomas and 14.9% carcinomas showed focal metallothionein positivity. In contrast, 60.9% of adenomas and 59.6% of carcinomas almost completely lacked metallothionein expression. In the series of adenocarcinomas, metallothionein expression was inversely correlated with CD44 in neoplastic cells (p = 0.01). There was no statistically significant difference of metallothionein expression, or the other variables examined, between adenocarcinomas and adenomas. CONCLUSIONS: Metallothionein expression does not seem to indicate aggressive biological behaviour in colorectal adenocarcinomas, in comparison with the other types of carcinoma. The inverse correlation with CD44 could suggest that the decreased metallothionein expression may contribute to the metastatic spread of the lymph node involvement in colorectal cancer. Metallothionein expression does not seem to represent an independent prognostic marker in colorectal cancer.

Immunohistochemical evaluation of cathepsin D expression in colorectal tumours: a correlation with extracellular matrix components, p53, pRb, bcl-2, c-erbB-2, EGFR and proliferation indices.

The immunohistochemical Cathepsin D (CD) expression of tumour and stromal cells was investigated in a series of 93 human colorectal adenocarcinomas and 22 adenomas with the intention to evaluate its prognostic significance and its contribution in the metastatic potential of colorectal cancer. CD expression was correlated with the expression of extracellular matrix components (collagen type IV, laminin and fibronectin), p53 protein, pRb, bcl-2, c-erbB-2, EGFR, proliferation indices (Ki-67, PCNA) as well as with other conventional clinicopathological features. CD expression (> 10% of positive tumour cells) was observed in 60.2% of carcinomas and in 72.7% of adenomas. Stromal CD expression was detected in all cases. A statistically significant positive correlation between neoplastic cells CD and stromal cells CD (SCCD) was observed in both carcinomas and adenomas. Cancer cells CD (CCCD) was positively correlated with collagen type IV and pRb expression as well as with PCNA score. In carcinomas, SCCD expression was statistically correlated with p53 protein and pRb expression and a trend for correlation with PCNA score was found. These data suggest that Cathepsin D of cancer and stromal cells, especially in combination with other markers, may provide more information about the biological behaviour of colorectal cancer.

Laparoscopic surgery-induced changes in oxidative stress markers in human plasma.

BACKGROUND: The induction of the pneumoperitoneum increases intraabdominal pressure (IAP), causing splanchnic ischemia, whereas its deflation normalizes IAP and splanchnic blood flow. This procedure appears to represent an ischemia-reperfusion model in humans. METHODS: Thirty laparoscopic cholecystectomies (LC) were performed in 30 patients with a mean age of 54.6 +/- 15.6 years. A group of 20 patients mean age, 57.3 +/- 9.65 who underwent open cholecystectomy (OC) was also studied. Vein plasma levels of thiobarbituric acid-reactive substances (TBARS), a marker of free radical production; plasma total antioxidant status (TAS); and uric acid (UA) levels were measured preoperatively, 5 min after deflation of the pneumoperitoneum or at the end of operation, and 24 h postoperatively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBL) levels were measured preoperatively and 24 h after the operation. RESULTS: In the LC group, significant elevations in the concentration of TBARS were observed in the early postoperative measurements in comparison with the preoperative measurements. TAS and UA levels were decreased significantly 24 h postoperatively compared to preoperative levels. The postoperative levels of AST, ALT, and TBL increased significantly in comparison with the preoperative levels. In the OC group, no alterations in the concentration of TBARS were observed in the postoperative period. The other parameters had changes similar to those recorded for the LC group. CONCLUSIONS: Free radical-induced lipid peroxidation associated with a decrease in plasma antioxidant capacity and UA levels as well as altered hepatic function is observed after deflation of the pneumoperitoneum. These results suggest that free radicals are generated at the end of a laparoscopic procedure, possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum.

Phosphatidylcholine and intraperitoneal adhesions.

Phosphatidylcholine (PC), which has successfully been used in the past to increase ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD) patients, has recently been found to prevent experimental adhesion formation after intraperitoneal irrigation with warm saline. The aim of this study was to determine the most effective route(s) of PC administration in the aforementioned model. Eighty Wistar rats underwent laparotomy and intraperitoneal irrigation with saline at 40 degrees C, which in 20 rats was followed by closure of the abdomen (control group, GC). In another 20 rats PC was given per os before and after irrigation (per os PC group, GOPC). In the third group PC was diluted in the irrigation fluid (intraperitoneal PC group, GIPC), and in the last group PC was given per os and intraperitoneally (combined PC group, GCPC). Assessment of adhesions was performed 2 weeks after the irrigation. Adhesions were found in 12 rats in the GC, 5 rats in the GOPC (p = 0.05, Fisher's test), 17 rats in the GIPC, and 3 rats in the GCPC (p = 0.007, Fisher's test). The difference between GOPC and GCPC was not statistically significant. The decreased adhesion formation after PC administration combined with the increased ultrafiltration may be of considerable importance in CAPD patients.

Submucosa of canine small intestine as an alternative medium-diameter autogenous arterial graft.

BACKGROUND: Small intestinal canine submucosa has been used in previous studies as a large diameter arterial graft and has shown acceptable patency rates. The aim of our experimental study was to assess its effectiveness when it is used as an autogenous medium-sized diameter arterial graft (5-7 mm). METHODS: Fifteen mongrel dogs were included and underwent laparotomy under general anaesthesia. The mucosa, tunica muscularis and serosa were removed from a resected intestinal segment. The remaining tube, which consisted of the submucosa and the basilar tunica mucosa, represented the experimental graft which was used to replace a proportional gap of the canine infrarenal aorta. Ascertainment of peripheral pulses, measurement of the intra-aortic pressures, aortography and in vivo/in situ observation before the sacrifice of the animals, were the procedures used for verification of the graft's patency. RESULTS: The resistance to thrombogenicity of the graft was considered satisfactory: nine out of 10 grafts remained patent for postoperative intervals ranging from one day to one year; one graft showed partial obstruction due to a technical perioperative error. The grafts showed also excellent physical characteristics (ease of handling and suturing, blood impermeability and durability), resistance to infection and showed no tendency to develop myointimal hyperplasia. CONCLUSIONS: Small intestinal canine submucosa showed satisfactory haemodynamic properties, long-term patency and resistance to infection, when used as a medium-diameter arterial substitute.

A renal artery aneurysm incidentally found at operation. Should it be resected?

A rare case of a patient with a ruptured abdominal aortic aneurysm (AAA) and an incidentally found left renal artery aneurysm (RAA) is presented. Successful repair of both aneurysms was simultaneously performed. The indications for such a surgical approach are also discussed.

The prevalence of factor V Leiden as a risk factor for venous thromboembolism in the population of North-Western Greece.

BACKGROUND: Many predisposing factors have been associated with the development of venous thromboembolism. Recently, Factor V Leiden has been described as a common genetic risk factor. The geographic distribution of this genetic abnormality in the general population greatly varies. The prevalence of the Factor V Leiden mutation in Europe is high, particularly in Greece, where according to some authors it is especially high. The purpose of this study was to estimate the prevalence of the Factor V Leiden mutation in patients presenting with at least one episode of venous thromboembolism and to compare it with that of the general population. METHODS: Blood samples were drawn from 388 subjects. 240 healthy blood donors (controls) and 148 unselected patients with a history of one or more episodes of venous thrombosis. DNA analysis was performed using the polymerase chain reaction to amplify the factor V gene exon 10, and to detect the Factor V Leiden point mutation. RESULTS: DNA analysis revealed Factor V Leiden mutations in eight (3.3%) control subjects (seven heterozygous and one homozygous) and in twenty-four (16.2%) patients, (twenty-two heterozygous and two homozygous). The difference between the two groups is statistically significant (p<0.0001; chi2 test). CONCLUSIONS: The prevalence of the Factor V Leiden mutation in the general population of North-Western Greece is 3.3%, which is within the same range as that reported for other European countries. The Factor V Leiden mutation is one of the most important predisposing genetic factors in the development of venous thrombosis and was present in 16.2% of our patients.

Intramural post-traumatic haematomas of the duodenum: are there any late sequelae of operative intervention?

The data of nine children with post-traumatic intramural haematoma of the duodenum treated in Aghia Sophia Children's Hospital of Athens from 1967 to 1980 were retrospectively analysed. Diagnosis was preoperative in all but two children, in whom diagnosis was made during laparotomy. All but one were managed by operative intervention which consisted of simple evacuation of the haematoma and closure of the serosal incision in two out of eight children. Six out of eight children operated on were followed up for 15 years, during which they were free of symptoms. Hypotonic duodenography performed in the above patients was negative for deformity or stricture of the duodenum.

Effect of intraperitoneal saline irrigation at different temperatures on adhesion formation.

This study was designed to examine the influence of saline irrigation at different temperatures on adhesion/formation in the rat. Saline irrigation through a laparotomy incision was performed at the following temperatures: 30 degrees C, 34 degrees C, 37 degrees C, 40 degrees C, 45 degrees C, 50 degrees C, 55 degrees C, and 60 degrees C. The control group (Gc, n = 20) underwent laparotomy without irrigation. Adhesions were found in: 5/20 animals of the Gc (all slight); 6/20 of the 30 degrees C group (all slight); 6/20 of the 34 degrees C group (all slight); 6/20 of the 37 degrees C group (all slight); 12/20 of the 40 degrees C group (all slight); 12/20 of the 45 degrees C group (11 slight, 1 moderate); 14/20 of the 50 degrees C group (12 slight, 2 moderate); 18/19 of the 55 degrees C group (2 slight, 6 moderate, 10 marked); and 18/18 of the 60 degrees C group (1 moderate, 8 marked, 9 massive). These results indicate that saline irrigation below body temperature does not prevent adhesions whereas warmed saline encourages adhesion formation in the rat.

Prevention of peritoneal adhesions in rats with verapamil, hydrocortisone sodium succinate, and phosphatidylcholine.

OBJECTIVE: To assess the effectiveness of verapamil, hydrocortisone sodium succinate, and phosphatidylcholine in the prevention of experimental adhesions. DESIGN: Randomized trial. MATERIAL: 80 rats. INTERVENTIONS: Laparotomy and intraperitoneal irrigation with saline 40 degrees C, then verapamil hydrochloride 1 mg/kg intravenously 15 min before, during, and after irrigation; or hydrocortisone sodium succinate 50 mg/kg intravenously half an hour before irrigation; or phosphatidylcholine 5.5 mg/kg orally eight days before and seven days after irrigation plus 0.5 mg/ml in the irrigation fluid; or no further intervention. MAIN OUTCOME MEASURES: Development of adhesions two weeks after irrigation, and completeness of wound healing. RESULTS: Adhesions developed in 13 of 19 control animals; 7 of 20 that were given verapamil; 6 of 20 that were given hydrocortisone; and 3 of 20 given phosphatidylcholine. CONCLUSION: Adhesions that developed in rats after laparotomy and intraperitoneal irrigation with saline at 40 degrees C can be significantly reduced by phosphatidylcholine.

Assessment of local stage in rectal cancer using endorectal ultrasonography (EUS).

BACKGROUND: Preoperative staging of rectal cancer is essential for the selection of the optimal treatment. This study aims to evaluate the accuracy of endorectal ultrasonography (EUS) in local staging of rectal cancer. PATIENTS AND METHODS: During a 4-year period, 33 patients with biopsy-proven rectal cancer underwent evaluation of the invasion of the rectal wall, the mesorectal lymph nodes status and the pelvic organs using EUS. We compared the EUS findings (uTN) to the histopathology examination of the resected specimens (pTN) according to TNM classification. RESULTS: Most patients had T3 tumours. Overall accuracy in assessing the depth of rectal wall invasion (T) and the lymph node status was 79% and 59% respectively. Two patients previously treated by preoperative chemoradiation were correctly staged only for N stage. CONCLUSIONS: EUS is a valuable diagnostic tool in local staging of rectal cancer. Progressively increasing experience will overcome the obstacles in accurate interpretation of ultrasound images.

Alterations in body weight, breaking strength, and wound healing in Wistar rats treated pre- and postoperatively with erythropoietin or granulocyte macrophage-colony stimulating factor: evidence of a previously unknown anabolic effect of erythropoietin?

Several growth factors, such as growth hormone and insulin-like growth factor-1, have been used to reverse the high rate of catabolism observed either after an operation or during serious illness. We conducted a pilot study in Wistar rats in an attempt to assess whether regulatory peptides widely used in clinical practice, such as erythropoietin (EPO) and granulocyte macrophage colony-stimulating factor (GM-CSF), alone or in combination, might influence the metabolism after surgery. Forty animals were randomly allocated into four groups (one control group and three experimental groups; 10 animals per group). The rats in the control group received isotonic NaCl; the rats in one experimental group received recombinant human EPO (rHuEPO) at a dose of 500 IU/kg (EPO group) and those in another received recombinant GM-CSF at a dose of 20 microg/kg (GM-CSF group); in the fourth group, each animal received the two drugs in combination (EPO/GM-CSF group). In all groups, rats were given the drug(s) or NaCl daily for 15 days before the operation and for 7 days after the operation until they were killed. We estimated the body weight (g) and the hematocrit (%) on the first day of the experiment (baseline values) and on the seventh day after the operation, and we estimated the rate of healing and the breaking strength of the intestinal anastomosis on the day the rats were killed. At the end of the study we found that the body weight (median 250 g, minimum 230 g, maximum 270 g) and the levels of hematocrit (median 64%, minimum 60%, maximum 65%) were significantly increased in the EPO group (P < .001 and P < .005, respectively) as compared with the baseline values (median 217.5 g, minimum 200 g, maximum 250 g; median 51.5%, minimum 45%, maximum 55%, respectively). A similar significant increase in body weight (median 230 g; minimum 200 g; maximum 250 g) and hematocrit (median 64%; minimum 59%; maximum 67%) was found at the end of the study in the EPO/GM-CSF group (P = .01 and P < .005, respectively) as compared with the baseline values (median 210 g; minimum 200 g; maximum 250 g; median 50%, minimum 48%, maximum 54%, respectively). The breaking strength (in newtons (N)) statistically differed in the four groups (Kruskal-Wallis, P = .0008). A comparison between groups showed that the breaking strength had been significantly increased in the animals in the EPO group (median 2.18 N, minimum 1.98 N, maximum 2.44 N) as compared with those in the control group (median 1.66 N, minimum 1.33 N, maximum 1.87 N; P = .004), GM-CSF group (median 1.73 N, minimum 1.25 N, maximum 2.07 N; P < .005), and EPO/GM-CSF group (median 1.71 N, minimum 1.37 N, maximum 1.91 N; P = .0005). In conclusion, this study demonstrated that the administration of rHuEPO appears to have a beneficial positive effect on the body weight, hematocrit, and healing rate and the breaking strength of large bowel anastomoses in rats. These observations provide evidence of an as-yet-unknown anabolic effect of EPO, and they may expand its usual applications. However, more studies are needed to confirm our findings and furthermore to define the optimal dose and timing of EPO administration.

Cellular neurilemoma (schwannoma) of the descending colon mimicking carcinoma: report of a case.

We report a rare case of a cellular neurilemoma (schwannoma) of the descending colon, mimicking carcinoma, not accompanied by von Recklinghausen's disease. The differential diagnostic problems are discussed and the possibility of a site-specific, modified Schwann cell of myenteric plexus origin is suggested.

Mesenteric injury after blunt abdominal trauma.

OBJECTIVE: To present our experience of mesenteric injuries after blunt abdominal trauma. DESIGN: Retrospective study. SETTING: University hospital, Greece. SUBJECTS: 31 patients with mesenteric injuries out of 333 who required operations for blunt abdominal trauma between March 1978 and March 1998. 21 were diagnosed within 6 hours (median 160 min, early group) and in 10 the diagnosis was delayed (median 21 hours, range 15 hours-7 days, delayed group). INTERVENTIONS: Emergency laparotomy. MAIN OUTCOME MEASURES: Mortality, morbidity, and hospital stay. RESULTS: There were no deaths. The diagnosis was confirmed by diagnostic peritoneal lavage in 17/21 patients in the early group whereas 7/10 in the delayed group were diagnosed by clinical examination alone. Most of the injuries (n = 23) were caused by road traffic accidents. 30 patients had injured the small bowel mesentery and 4 the large bowel mesentery. 25 of the 31 patients had associated injuries. There were no complications in the early group, compared with 6 wound infections and 1 case of small bowel obstruction in the delayed group (p < 0.0001). Median hospital stay in the early group was 11 days (range 3-24) compared with 23 days (range 10-61) in the delayed group (p = 0.004). CONCLUSION: Because delay in diagnosis is significantly associated with morbidity and duration of hospital stay we recommend that all patients admitted with blunt abdominal trauma should have a diagnostic peritoneal lavage as soon as possible

Quality of life of patients after surgical treatment of anal fistula; the role of anal manometry.

OBJECTIVE: This study was undertaken to assess the quality of life of patients after surgical treatment of anal fistula and to investigate whether anal manometry (AM) can guide the choice of the proper surgical intervention in these patients in order to protect the sphincter mechanism. PATIENTS AND METHODS: One hundred patients with anal fistula (AF) were studied prospectively (78 men; mean age 45 years; range 11-78). Cleveland Incontinence Score (CIS) was record pre-operatively and 1 and 3 months postoperatively for each patient in order to specify their quality of life (QOL) before and after the surgical treatment. Also, anal manometry (AM) was performed pre-operatively and 1 month postoperatively. The pre-operative anal pressures and the type of fistula determined the kind of the surgical treatment. 55 patients had an intersphincteric fistula, 42 trans-sphincteric and 3 suprasphincteric. 65 patients underwent laying open of the fistulous track, 7 fistulectomy and 28 were treated by seton fistulotomy. RESULTS: Three patients had defective gas control and 6 reported some degree of soiling. 3 patients developed recurrent fistula. CIS was significantly impaired (P=0.02) at the first postoperative month in these patients who were treated for trans-sphincteric fistula by fistulotomy; AM revealed significant decrease of anal pressures in these patients (resting and squeeze; P=0.007 and 0.0001 respectively); CIS and AM in the remaining cases revealed no significant deterioration of QOL and fall of anal pressures respectively. CIS was normal in the vast majority of patients at 3-months postoperatively. CONCLUSIONS: QOL of patients after surgical treatment of AF is unalterable on the understanding that the AF is simple and the treatment is not associated by incontinence or recurrence. Pre-operative AM is important regarding the choice of the proper surgical procedure.

Heterotopic gastric mucosa together with intestinal metaplasia and moderate dysplasia in the gall bladder: report of two clinically unusual cases with literature review.

We report the clinicopathological findings of two patients with ectopic gastric mucosa within the gall ladder. The first patient, a 78 year old man, was asymptomatic. He was admitted to hospital for a colon adenocarcinoma. Intraoperatively, a firm nodule was palpable in the gall bladder. Histological examination of the resected specimen revealed a body type gastric mucosa in the submucosa, adjacent to which were extensive pyloric gland and intestinal metaplasia with mild to moderate dysplasia. The remaining gall bladder mucosa demonstrated changes of chronic cholecystitis. The second patient was a 62 year old woman with symptoms of chronic cholecystitis. The preoperative diagnosis was consistent with this diagnosis with a "polyp" at the junction of the neck and cystic duct. Cholecystectomy was performed and the histological examination of the resected specimen showed that the "polyp" consisted of heterotopic gastric mucosa with glands of body and fundus type. In the remaining mucosa, chronic cholecystitis was evident. To the best of our knowledge, this is the first report of a clinicopathological presentation of heterotopic gastric mucosa, pyloric gland type, and intestinal metaplasia with dysplastic changes in the gall bladder. As heterotopic tissue may promote carcinogenesis of the gall bladder, close attention should be paid to any occurrence of such lesions in this anatomical region.