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.

Circulating endothelial cells are elevated in patients with type 2 diabetes mellitus independently of HbA(1)c.

AIMS/HYPOTHESIS: Patients with diabetes mellitus are well known to be at high risk for vascular disease. Circulating endothelial cells (CECs) have been reported to be an ex vivo indicator of vascular injury. We investigated the presence of CECs in the peripheral blood of 25 patients with diabetes mellitus and in nine non-diabetic control donors. METHODS: Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads, and were stained with acridine orange dye and counted by fluorescence microscopy. The cells were also stained for von Willebrand factor and Ulex europaeus lectin 1. RESULTS: Patients with diabetes mellitus had an elevated number of CECs (mean 69+/-30 cells/ml, range 35-126) compared with healthy controls (mean 10+/-5 cells/ml, range 3-18) (p<0.001). The increase in CECs did not correlate with the levels of HbA(1)c. Circulating endothelial cell numbers were elevated regardless of glucose levels, suggesting that, even with control of glucose levels, there is increased endothelial cell sloughing. CONCLUSIONS: Our study suggests that the higher number of CECs in patients with type 2 diabetes may reflect ongoing vascular injury that is not directly dependent on glucose control.

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.

A fatal case of sclerosing mesenteritis.

A 22-year-old patient was admitted because of abdominal pain and vomiting. Computed tomography diagnosed small intestinal malignancy. Ileal resection was performed, and the histological findings were consistent with sclerosing mesenteritis. The patient was treated with enteral nutrition, corticosteroids, azathioprine and methotrexate, but died 2 years later.

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.

Human heme oxygenase: cell cycle-dependent expression and DNA microarray identification of multiple gene responses after transduction of endothelial cells.

The purpose of the present study was to examine the role of human heme oxygenase (human HO-1) in cell cycle progression following exposure to heme or human HO-1 gene transfer and to identify target genes associated with human HO-1-meditated increases in cell cycle progression using cDNA microarray technology. Heme-induced robust human HO-1 expression in quiescent human microvessel endothelial cells cultured in 1% FBS and the levels of human HO-1 expression progressively declined without a change in the cell cyclin. To identify genes regulated by human HO-1 in the cell cycle, human endothelial cells were transduced with a retroviral vector encoded with human HO-1 gene or an empty vector. Transgene expression and functionality of the recombinant protein were assessed by Western blotting, enzyme activity, carbon monoxide, cGMP production, and cell cycle analysis. Human cDNA gene array and quantitative real-time RT-PCR were used to identify both known and novel differentially expressed genes in cells overexpressing human HO-1. Major findings were upregulation of several genes associated with cell cycle progression, including cyclin E and D; downregulation of cyclin-dependent kinase inhibitors p21 and p27, cyclin-dependent kinases 2, 5, and 6, and monocyte chemoattractant protein-1; and upregulation of growth factors, including vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor I (VEGFRI), endothelial growth factor (EGF) and hepatic-derived growth factor (HDGF). These findings identify an array of gene responses to overexpression of human HO-1 and elucidate new aspects of human HO-1 signaling involved in cell growth.

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.

Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah's Witness newborns as an alternative to exchange transfusion.

OBJECTIVE: The religious convictions of parents who are Jehovah's Witness adherents lead them to reject the use of exchange transfusions as therapy for severe hyperbilirubinemia in newborns in whom intensive phototherapy has failed to control this problem. Consequently, physicians caring for such infants may be obliged to initiate legal action to compel use of the procedure when severe hyperbilirubinemia not sufficiently responsive to phototherapy warrants an exchange transfusion. Our goal was to determine if we could use the potent inhibitor of bilirubin production, Sn-Mesoporphyrin (SnMP), to resolve the troubling medical-legal issues in such situations in 2 infants with hemolytic disease of the newborn who required exchange transfusions for severe hyperbilirubinemia but whose Jehovah's Witness parents rejected the procedure. SnMP was administered in a single dose, as in previous studies, at the time when exchange transfusion would have been initiated and plasma bilirubin levels were monitored at close intervals thereafter. METHODS: SnMP is a potent inhibitor of heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin. We found in earlier studies that in single doses of 6 micromol/kg birth weight, SnMP is extremely effective in moderating the course of hyperbilirubinemia and in eliminating the need for supplemental phototherapy in jaundiced newborns. In the 2 cases described, a single dose of SnMP (6 micromol/kg birth weight) was administered intramuscularly to severely jaundiced infants with immune hemolysis at a time when clinical circumstances dictated the need for exchange transfusion. CASE 1: This patient was a preterm male infant (gestational age: 35 5/7 weeks; birth weight: 2790 g) whose plasma bilirubin concentration (PBC) at 1 hour after birth was 5.0 mg/dL. Despite intensive phototherapy with 3 banks of lights and 1 biliblanket, the PBC increased steadily with no diminution in the rate of increase for 75 hours. In view of the problems of immune hemolysis, and prematurity, and the inability of phototherapy to stop progression of hyperbilirubinemia, a decision to carry out an exchange transfusion was made; the decision was, however, rejected by the Jehovah's Witness parents. Pending legal action to compel use of the procedure, a request to this (Rockefeller) laboratory for SnMP was made; its use was approved by the Food and Drug Administration; and the inhibitor was delivered to the physician-in-charge (D.P.M.) in Sioux Falls, South Dakota. The single dose of SnMP was administered to the infant at 75 hours after birth; the course of hyperbilirubinemia before and after the use of the inhibitor is shown in Fig 1. [figure: see text]. CASE 2: This female term infant (gestational age: 38-39 weeks; birth weight: 4140 g) with immune hemolysis was delivered by cesarean section and because of problems related to meconium aspiration required helicopter transfer to the Special Care Nursery in Abilene, Texas, where 10 hours after birth the first PBC was determined to be 18.0 mg/dL. Double-bank phototherapy plus a biliblanket was initiated; a third bank of lights was later ordered. The PBC fluctuated in the ensuing 2 days between 13.8 to 25.8 mg/dL during which suggestive clinical signs of possible bilirubin encephalopathy became manifest. In view of the clinical circumstances and the continued severe hyperbilirubinemia, permission for a double-exchange transfusion was requested. The parents, who were Jehovah's Witness adherents, refused the procedure. While preparing legal action to compel use of the exchange, a request was made to this (Rockefeller) laboratory for use of SnMP to attempt control of hyperbilirubinemia. With FDA approval, the SnMP was delivered to the attending neonatologist (J. R. M.) in Abilene and administered in a single dose (6 micromol/kg birth weight) at 56 hours after birth when the PBC was 19.5 mg/dL. The course of bilirubinemia before and after SnMP use is shown in Fig 2. [figure: see text]. RESULTS AND CONCLUSIONS: The use of SnMP to moderate or prevent the development of severe hyperbilirubinemia in newborns (preterm, near-term, term with high PBCs [15-18 mg/dL], ABO-incompatibility; glucose-6-phosphate dehydrogenase deficiency) has been extensively studied in carefully conducted clinical trials the results of which have been reported earlier. This inhibitor of bilirubin production has demonstrated marked efficacy in moderating the course of hyperbilirubinemia in all diagnostic groups of unconjugated neonatal jaundice. The 2 cases described in this report confirmed the efficacy of SnMP in terminating progression of hyperbilirubinemia in infants in whom phototherapy had failed to sufficiently control the problem and whose parents, for religious reasons, would not permit exchange transfusions. Interdiction of severe hyperbilirubinemia by inhibiting the production of bilirubin with SnMP can be an effective alternative to the use of exchange transfusion in the management of severe newborn jaundice that has not responded sufficiently to light treatment to ease concern about the development of bilirubin encephalopathy.

Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs.

Our objective was to determine whether overexpression and underexpression of human heme oxygenase (HHO)-1 could be controlled on a long-term basis by introduction of the HO-1 gene in sense (S) and antisense (AS) orientation with an appropriate vector into endothelial cells. Retroviral vector (LXSN) containing viral long terminal repeat promoter-driven human HO-1 S (LSN-HHO-1) and LXSN vectors containing HHO-1 promoter (HOP)-controlled HHO-1 S and AS (LSN-HOP-HHO-1 and LSN-HOP-HHO-1-AS) sequences were constructed and used to transfect rat lung microvessel endothelial cells (RLMV cells) and human dermal microvessel endothelial cells (HMEC-1 cells). RLMV cells transduced with HHO-1 S expressed human HO-1 mRNA and HO-1 protein associated with elevation in total HO activity compared with nontransduced cells. Vector-mediated expression of HHO-1 S or AS under control of HOP resulted in effective production of HO-1 or blocked induction of endogenous human HO-1 in HMEC-1 cells, respectively. Overexpression of HO-1 AS was associated with a long-term decrease (45%) of endogenous HO-1 protein and an increase (167%) in unmetabolized exogenous heme in HMEC-1 cells. Carbon monoxide (CO) production in HO-1 S- or AS-transduced HMEC-1 cells after heme treatment was increased (159%) or decreased (50%), respectively, compared with nontransduced cells. HO-2 protein levels did not change. These findings demonstrate that HHO-1 S and AS retroviral constructs are functional in enhancing and reducing HO activity, respectively, and thus can be used to regulate cellular heme levels, the activity of heme-dependent enzymes, and the rate of heme catabolism to CO and bilirubin.

Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats.

A single dose of Sn-mesoporphyrin prevents development of severe hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns.

OBJECTIVES: Severe neonatal jaundice is a common clinical manifestation of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and the most difficult to manage; kernicterus is not an uncommon outcome. We assessed in healthy, direct Coombs test-negative Greek newborns of >/=38 weeks' gestational age 1) the current burden of G-6-PD deficiency-associated severe jaundice, and 2) the efficacy of preventive use of Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase activity and thus of bilirubin production, in ameliorating jaundice in G-6-PD-deficient neonates. METHODS: The studies were conducted at Metera Maternity Hospital in Athens, Greece. Enrolled newborns had the plasma bilirubin concentration (PBC) determined in cord blood and daily thereafter until a declining level was obtained and the case was closed. Intervention with phototherapy was dictated at exact, age-specific PBC levels. In our initial study, we enrolled consecutive mature healthy G-6-PD-deficient newborns as well as a threefold excess of G-6-PD-normal neonates born at approximately the same time (control group). For the SnMP trial, G-6-PD-deficient neonates were administered SnMP as a single intramuscular dose of 6 micromol/kg birth weight within 24 +/- 12 hours of age. RESULTS: SnMP was administered at 26.7 +/- 6.1 hours of age to 172 G-6-PD-deficient newborns (group A); 168 G-6-PD-normal (group B) and 58 G-6-PD-deficient (group C) newborns who were enrolled earlier provided the comparison groups. Except for the expected excess of males in the G-6-PD-deficient groups (A and C), there were no differences in the demographic characteristics among the 3 groups. The incremental changes in PBC from cord blood to 24 hours of age also were similar (group A: 4.13 +/- 1.32 mg/dL; group B: 4.05 +/- 1.34 mg/dL; group C: 4.39 +/- 1.07 mg/dL), but there were significant differences in the next period, 24 to 48 hours of age (group A: 0.63 +/- 1.44 mg/dL; group B: 1.69 +/- 1.5 mg/dL; group C: 2.45 +/- 1.72 mg/dL). Peak PBC was significantly different (group A: 7.81 +/- 3.04 mg/dL; group B: 8.68 +/- 3.1 mg/dL; group C: 11.24 +/- 3.76 mg/dL) as was the age at which peak PBC was recorded (group A: 56 +/- 29 hours of age; group B: 69 +/- 26 hours of age; group C: 83 +/- 29 hours of age). These differences in favor of group A were observed despite the fact that phototherapy was used in 15% of the newborns in group B and 31% of those in group C, whereas none of those treated with SnMP required phototherapy. Finally, in one female, who was heterozygous for G-6-PD deficiency, in group C phototherapy failed and 2 exchange transfusions were performed. CONCLUSIONS: In comparison with normal neonates, G-6-PD-deficient neonates experienced a twofold increase in the prevalence of significant hyperbilirubinemia requiring phototherapy. A single dose of SnMP administered in the 1st day of life to the G-6-PD-deficient newborns shifted the peak PBC distribution to the left (lower values) even in relation to normal neonates and entirely eliminated the need for phototherapy. Interdiction of bilirubin production by use of a heme oxygenase inhibitor such as SnMP represents a simple and highly effective means for the preventive management of jaundice in G-6-PD-deficient newborns.

Manometric study in Kearns-Sayre syndrome.

Although swallowing difficulties have been described in patients with Kearns-Sayre syndrome (KSS), the spectrum of manometric characteristics of dysphagia is not yet well known. Moreover, it is conceivable that a combination of various degrees of swallowing difficulties with different patterns in manometric studies exist, each playing a major role in the prognosis, natural history, and quality of life of KSS patients. An 18-year-old girl diagnosed at the age of 5 years with KSS (muscle biopsy) was admitted to our department with an upper respiratory tract infection and dysphagia. Clinical examination revealed growth retardation, external ophthalmoplegia, pigmentary retinopathy, impaired hearing, and ataxia. An electrocardiogram revealed cardiac conduction defects (long Q-T), and brain magnetic resonance imaging showed abnormalities in the cerebellar hemispheres. A manometric and motility study for dysphagia was conducted and the pharynx and upper esophageal sphincter (UES) resting pressures were similar to control group values, but the swallowing peak contraction pressure of the pharynx and the closing pressure of the UES were very low and could not promote effective peristaltic waves. Relaxation and coordination of the UES were not affected although pharyngeal and upper esophagus peristaltic waves proved to be very low and, consequently, were practically ineffective. The patient was started on treatment comprising a diet rich in potassium, magnesium, and calcium, and oral administration of vitamin D and co-enzyme Q10 100 mg daily; she was discharged 6 days later with apparent clinical improvement.

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.

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

A comparative experimental study of the effects of diclofenac and ketoprofen on the small-bowel mucosa of canines.

The aim of this experimental study was to investigate the effect of diclofenac sodium and ketoprofen, two non-steroidal anti-inflammatory drugs (NSAIDs) with different excretion pathways, and the role of other enteric factors during simultaneous administration of these drugs on the development of mucosal lesions of the small intestine in canines. Twenty-five animals were divided into three groups. Group I included 10 canines, 5 with diclofenac sodium (group Ia) and 5 with ketoprofen administration (group Ib). Group II included 5 animals in which a segment of ileum was surgically isolated from the rest of the small intestine. Group III included 10 animals in two subgroups of 5; a segment of ileum was surgically isolated in both subgroups; groups IIIa received diclofenac and group IIIb ketoprofen. Histological examination of the specimens taken revealed macroscopic and microscopic mucosal lesions in 5/5 animals in group Ia, whereas none of the 5 animals in group Ib had any lesions. Group II did not reveal any mucosal lesions. Three out of 5 animals (60%) administered diclofenac in group IIIa had intestinal mucosal lesions, but none of the 5 revealed lesions in the isolated loop of ileum. No lesions were observed in the isolated loop or in the rest of the intestinal mucosa in the animals in group IIIb. Our results suggest that NSAIDs produce intestinal mucosal lesions not only when administered per mouth but also after intramuscular administration. Diclofenac, unlike ketoprofen, was responsible for the development of lesions in the intestinal mucosa. The role of drugs and/or their metabolites in the intestine and certain other factors must still be determined.

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.