The TRAM dam design: a new method for treatment of an enterocele.

A new method for the treatment of an enterocele is described and illustrated with a case report. In a patient with Ehlers Danlos syndrome, a pedicled muscle sparing transverse rectus abdominis myocutaneous flap was used to fill the pelvic inlet and rectovaginal space. The flap prevents descend of bowel into the pelvic inlet and rectovaginal space. The patient's defecation problems and pelvic discomfort were resolved. The technique does not require the use of a synthetic mesh and causes little donor site morbidity.

Methylprednisolone attenuates airway and vascular responses induced by reactive oxygen species in isolated, plasma-perfused rat lungs.

The effects of methylprednisolone (MP) on the acute airway and pulmonary vascular responses induced by reactive oxygen species (ROS) were investigated in isolated, plasma-perfused rat lungs. ROS were generated by adding xanthine oxidase and hypoxanthine to the perfusate. MP was administered in 3 different ways: 1. Added to the perfusate (1 mg*ml-1) 5 min prior to xanthine oxidase and hypoxanthine, 2. Given as intraperitoneal injections (40 mg*kg-1) to lung donor rats 12 and 2 hours prior to the experiments, or 3. Combining 1 and 2. The lungs were perfused at constant volume inflow (15 ml*min-1). Pulmonary arterial pressure and transpulmonary pressure were followed for 30 min after addition of xanthine oxidase and hypoxanthine. ROS induced a powerful, acute broncho- and vasoconstriction, which was inhibited by addition of MP to the perfusate. Pretreatment with MP also inhibited the vascular and airway responses. Adding MP to the perfusate of pretreated lungs further reduced the ROS-induced smooth muscle constriction. In conclusion, MP inhibits vasoconstriction and bronchoconstriction induced by ROS in isolated rat lungs.

Haematological disorders and lung alveolar macrophage function following total parenteral nutrition in rats.

Alterations in haematological parameters have been reported both clinically and experimentally following administration of total parenteral nutrition (TPN). Fat emulsions also affect function of the mononuclear phagocytic system. We have examined haematological parameters and pulmonary alveolar macrophages in rats fed intravenously with the individual components of TPN; a 20 % fat emulsion (Intralipid) and an amino acid solution (Vamin-Glucos), for 1, 3 and 7 days as a continuous infusion. The control groups were given saline infusion for the same periods of time. Haemoglobin, haematocrit, red blood cells, leukocytes, leukocyte superoxide anion production, leukocyte distribution, platelets and platelet aggregation were measured. Lung lavage fluid was examined for alveolar macrophage concentration and procoagulant activity of macrophages. Several of the animals in the experimental groups developed superior caval vein thrombosis. Both experimental groups developed anaemia after 7 days of infusion. Thrombocytopaenia occurred in both experimental groups after 3 and 7 days of infusion. Platelet aggregation decreased already after 1 day of infusion. We did not observe any alteration in counts, distribution in peripheral blood, or superoxide production of leukocytes. The concentration of alveolar macrophages in the lung lavage fluid increased in the experimental groups. The tissue factor activity of the alveolar macrophages increased in the group receiving Intralipid. Our observations are consistent with a granulomatous inflammation reaction.

Mortality and survival rates after elective hepatic surgery in a low-volume centre are comparable to those of high-volume centres.

Background. Over the last decades, liver resection has become a frequently performed procedure in western countries because of its acceptance as the most effective treatment for patients with selected cases of metastatic tumours. The purpose of this study was to evaluate the results after hepatic resections performed electively in our centre since 1979 and compare the results to those of larger high-volume centres. Methods. Medical records of all patients who underwent liver resection from January 1979 to December 2011 were reviewed. Disease-free survival and overall survival were determined by Kaplan-Meier analysis. Risk factors for complications were tested with the log-rank test and the Cox proportional hazard model. Complications were classified according to the modified Clavien classification system. Results. 290 elective liver resections were performed between January 1979 and December 2011. There were 171 males (59.0%) and 119 females (41.0%). Median age was 63 years, range 1-87. Overall survival ranged from 0 to 383 months, with a median of 31 months. Five-year survival rate for patients who underwent liver resection for colorectal metastases was 35.8% (34/95). Discussion. Hepatic resections are safely performed at a low-volume centre, with regard to perioperative- and in-house mortality and 5-year survival rates.

A large abdominal intercostal hernia in a patient with vascular type Ehlers-Danlos syndrome: a surgical challenge.

A patient with vascular type Ehlers-Danlos syndrome developed a large abdominal intercostal hernia secondary to coughing. The tissue friability and associated risks for arterial ruptures and visceral perforations in these patients make hernia repair challenging. The hernia was successfully treated using a novel approach.

Impact of radiotherapy on local recurrence of rectal cancer in Norway.

BACKGROUND: The purpose of this study was to analyse the impact of radiotherapy on local recurrence of rectal cancer in Norway after the national implementation of total mesorectal excision (TME). METHODS: This was a prospective national cohort study of 4113 patients undergoing major resection of rectal carcinoma between November 1993 and December 2001. RESULTS: The proportion of patients who had radiotherapy before or after operation increased from 4.6 per cent in 1994 to 23.0 per cent in 2001. The cumulative 5-year local recurrence rate decreased from 16.2 to 10.7 per cent. Multivariable analysis showed that preoperative radiotherapy significantly reduced local recurrence (hazard ratio 0.59 (95 per cent confidence interval 0.39 to 0.87)). The use of preoperative radiotherapy in patients from a local hospital offering radiotherapy was 50 per cent higher than that for patients from a hospital without such services (P = 0.003); cumulative 5-year local recurrence rates for these patients were 10.6 and 15.8 per cent respectively (P < 0.001). CONCLUSION: Following national implementation of TME for rectal cancer, increased use of preoperative radiotherapy appeared to reduce recurrence rates further.

Pulmonary function in rats dying from long-term parenteral nutrition.

Infusion of Vamin or Intralipid causes death in a rat model of continuous parenteral nutrition. Morphological investigations have shown vascular injury and thrombus formation in the lungs. In this study, lung function in rats was examined before death due to parenteral nutrition. The rats were fed saline intravenously (group I); 100 mL kg(-1) day(-1) (controls); a 7% amino acid-glucose solution (Vamin-Glukos) (group II); 100 mL kg(-1) day(-1), or 20% fat emulsion (Intralipid) (group III); 40 mL kg(-1) day(-1). The infusion was stopped when the condition of the rats deteriorated. In a saline-perfused, isolated lung model, pulmonary arterial pressure (Ppa), transpulmonary pressure (Ptp), endothelial function, measured as inactivation of serotonin (bioassay), and the capillary filtration coefficient (CFC) were determined. Haematological parameters were also evaluated. Constant findings in group II and III were central thrombus formation, anaemia and thrombocytopenia. Ppa increased from 0.7 (0.04) kPa in group I to 1.4 (0.1) kPa and 1.7 (0.1) kPa in groups II and III, respectively (p<0.001). Inactivation of serotonin was reduced to 36% (2) in group II and 37% (2) in group III compared with 74% (5) in group I (p<0.002). CFC increased to 25 mg min(-1) (5) (group II) and 30 mg min(-1) (6) (group III) compared with 13 mg min(-1) (2) in controls (p=0.01). The study shows that major pulmonary hypertension and severe reduction of the endothelial function are present when rats deteriorate after infusion of parenteral nutrition substrates.

Pulmonary hypertension and microvascular injury in rats given parenteral nutrition.

Clinical reports have suggested that parenteral nutrition may damage the lungs. We studied the pathophysiologic pulmonary changes in rats receiving a fat emulsion (Intralipid), an amino acid solution (Vamin-glucose) or saline solution. Control rats were not infused. The pulmonary arterial pressure, capillary filtration coefficient and inactivation of serotonin were determined in isolated, perfused lungs following the in vivo perfusion with the respective solutions. After 12 days of Intralipid infusion the rats showed pulmonary hypertension, increased capillary filtration coefficient and reduced inactivation of serotonin compared with control lungs. Reduction of serotonin inactivation was found after only 3 days. Vamin-glucose infusion altered only serotonin clearance. Saline infusion did not change lung function compared with controls. The study suggests that parenteral nutrition in rats may lead to severe and possibly lethal pulmonary changes.

Increased microvascular permeability caused by toxic oxygen metabolites is partly reversed by exchanging the perfusate in isolated rat lungs.

Toxic oxygen metabolites (TOM) released from stimulated phagocytes and lung tissue have been shown to injure the pulmonary microcirculation. In the present study we evaluated microvascular injury caused by TOM in rat lungs perfused with plasma. The injury, as indicated by an increase in vascular permeability, was assessed by determining the fluid filtration rate (FFR) after paralysing the pulmonary vascular bed with papaverine (0.1 mg/ml). TOM were generated by adding xanthine oxidase (XO) (0.05-0.125 U/ml) and hypoxanthine (HX) (1 mmol/l) to the perfusate. FFR was measured before, 30 and 60 min after addition of XO and HX. The following interventions were done: 1. the H2O2-scavenger catalase, 2. substitution of the perfusate after 30 min, 3. BW 755 C, a combined lipoxygenase and cyclooxygenase inhibitor, and 4. indomethacin, a cyclooxygenase inhibitor. Addition of XO and HX caused FFR to increase from 14 +/- 4 mg/min (mean +/- s.e. mean) at the onset to 56 +/- 7 mg/min and 86 +/- 10 mg/min after 30 and 60 min, respectively. Replacing the perfusate with fresh plasma after 30 min caused a significant reduction in FFR at 60 min, from 86 +/- 11 mg/min to 58 +/- 10 mg/min. Catalase prevented the increase in FFR. Indomethacin and BW 755 C had no effect on the increase in FFR. We conclude that TOM induced a partly reversible increase in microvascular permeability of isolated rat lungs. From previous studies, the activity of XO was expected to cease after 30 min. Therefore it is suggested that secondary products of TOM propagate the lung injury. The increase in permeability was not mediated by arachidonic acid metabolites.

Toxic oxygen metabolites reduce inactivation of prostaglandin E2 in isolated perfused rat lungs.

The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.

Allopurinol inhibits hypoxic pulmonary vasoconstriction. Role of toxic oxygen metabolites.

The exact mechanism whereby hypoxic pulmonary vasoconstriction (HPV) is elicited is still unsettled. We have evaluated a possible role for toxic oxygen metabolites (TOM), employing a set-up of blood-perfused isolated rat lungs. HPV reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/- 0.2 kPa to 3.2 +/- 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase (XO), allopurinol (AP) reduced the subsequent response to 2.5 +/- 0.2 kPa (P less than 0.001). By contrast, AP did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of XO). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on HPV; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that AP inhibition of XO depresses HPV. This could be due either to reduced production of TOM or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of TOM refutes a role for these metabolites in the elicitation of HPV. More likely, AP inhibits HPV by interfering with the purine metabolism.

The function of granulocytes and alveolar macrophages following a single dose of endotoxin in rabbits. Effects of methylprednisolone.

It is a generally held opinion that steroids attenuate the activation of phagocytes. However, this statement has its limitations; in rabbit endotoxemia, for instance, steroids enhance the procoagulant activity of monocytes. The present study aimed to investigate the release of toxic oxygen metabolites (TOM) from granulocytes and alveolar macrophages 24 h after endotoxin injection in rabbits, and the effect of concomitant injection of methylprednisolone (MP). Release of TOM was assessed by peak chemiluminescence (CLP). Expression of thromboplastin activity by alveolar macrophages was determined as well, employing a recognized method for assessment of activity. In terms of mean +/- s.e.mean, endotoxin increased granulocyte count from a baseline value of 1.8 +/- 0.2 X 10(6) cells/ml to 3.7 +/- 1 X 10(6) cells/ml, which increased further to 9.8 +/- 2.5 X 10(6) cells/ml following administration of MP. Whereas endotoxin given alone caused no significant change in granulocyte CLP, additional administration of MP increased CLP from 1723 +/- 389 to 16610 +/- 8428 counts. On the other hand, MP attenuated an endotoxin-induced increase in both CLP and thromboplastin activity of alveolar macrophages. Thus, MP appears to have a proinflammatory effect on circulating granulocytes in rabbit endotoxemia, simultaneously depressing the function of stationary macrophages. This may suggest an injurious effect of MP in rabbit endotoxemia.

Toxic oxygen metabolites induce vasoconstriction and bronchoconstriction in isolated, plasma-perfused rat lungs.

Effects of toxic oxygen metabolites (TOM) on the pulmonary vascular bed and airways were studied in isolated, plasma-perfused rat lungs. TOM were generated by xanthine oxidase (XO) (0.1 or 0.25 unit.ml-1) and hypoxanthine (HX) (1 mol.l-1). In vitro measurements by chemiluminescence indicated that the major oxygen metabolite generated by XO and HX was H2O2. Measurements of PO2 in the perfusate as an indicator of O2-consumption suggested that production of TOM by XO and HX was finished within 30 min. XO and HX induced an early dose-dependent bronchoconstriction and a late increase in transpulmonary pressure (Ptp). Pulmonary arterial pressure (Ppa) increased gradually and levelled off within 30 min with low-dose XO, but not with high-dose XO. As judged by weight increase of the lungs, interstitial edema occurred regularly. Allopurinol, an inhibitor of XO, blocked the lung responses caused by XO and HX. Catalase attenuated all lung responses induced by XO and HX, while superoxide dismutase had no effect. The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development. This study shows that TOM induce vasoconstriction, bronchoconstriction and lung edema in plasma-perfused rat lungs, mainly due to generation of H2O2 and the hydroxyl radical.

Reactive oxygen intermediates reduce inactivation of serotonin in isolated, perfused rat lungs.

Reactive oxygen intermediates such as free radicals have been proposed to mediate lung injury. The present work examined whether or not enzymatically generated oxygen metabolites altered serotonin clearance. Isolated, plasma-perfused rat lungs were exposed to xanthine oxidase (XO) and hypoxanthine (HX). Pulmonary arterial pressure (Ppa) and lung weight were recorded. Fulminant edema was defined as a spontaneous weight increase exceeding 500 mg. Inactivation of serotonin was determined by superfusion bioassay. XO and HX reduced serotonin inactivation from 74 +/- 3% (mean +/- SEM) to 62 +/- 2%. This reduction was inhibited by the scavenger enzymes superoxide dismutase (SOD) and catalase and by allopurinol, an inhibitor of XO. Hydrostatic edema and perfusion per se did not decrease the pulmonary clearance of serotonin. XO and HX did not significantly alter Ppa. Fulminant edema developed in four of six lungs after exposure to XO and HX compared with none in the other groups. It was concluded that reactive oxygen intermediates inhibited serotonin inactivation in isolated rat lungs.

Interaction of verapamil and halogenated inhalation anesthetics on hypoxic pulmonary vasoconstriction.

Calcium channel blockers and halogenated inhalation anesthetics reduce hypoxic pulmonary vasoconstriction (HPV) when administered separately to isolated rat lungs. This study was undertaken to investigate the effect of combining the calcium channel blocker verapamil with halothane or isoflurane. HPV was elicited in three groups of experiments. First, we studied the effect of halothane 1.3 MAC and varying concentrations of verapamil. Halothane reduced HPV as a mean by 34.7%, and a dose-dependent reduction was seen with verapamil. The depressant effect of the combination of halothane and verapamil was significantly greater than when the drugs were administered alone. We further investigated in separate groups the effects of varying concentrations of halothane and isoflurane, administered both separately and in combination with a constant dose of verapamil (1.02 nmol). Both anesthetics depressed HPV in a dose-dependent fashion. Verapamil reduced HPV as a mean by 34.2% and 39.3% in the halothane and isoflurane groups, respectively. The inhibition caused by combining verapamil with an anesthetic was significantly greater than when administered separately. We conclude that verapamil in combination with halothane or isoflurane has an additive dampening effect on HPV.

Endothelin-1-induced increases in microvascular permeability in isolated, perfused rat lungs requires leukocytes and plasma.

Effect of endothelin-1 (ET-1) (10(-8) M) on pulmonary microvascular permeability was examined in isolated rat lungs perfused with blood or various blood components. Microvascular permeability was assessed by measuring fluid filtration rate (FFR) in lungs pretreated with papaverine in order to prevent changes in vascular smooth muscle tone. ET-1 significantly increased FFR (131.0 +/- 10.1 mg/min, P < 0.01) after perfusion with blood for 60 min. In lungs perfused with leukocytes resuspended in plasma, ET-1 increased FFR significantly both 30 min (40.4 +/- 11.4 mg/min, P < 0.01) and 60 min (97.4 +/- 14.5 mg/min, P < 0.01) after it was added to the perfusate. Heat inactivation (56 degrees C; 1 hr) of plasma did not attenuate this effect of ET-1 (94.4 +/- 25.1 mg/min, P < 0.01). When lungs were perfused with leukocytes resuspended in Krebs Ringer albumin instead of plasma, or with plasma only, ET-1 did not cause any change in FFR. In conclusion, ET-1 increases microvascular permeability in isolated blood-perfused rat lungs. The effect is critically dependent on the presence of leukocytes and plasma components other than complement.

Pharmacokinetics of 7-hydroxy-methotrexate and methotrexate in the rat.

To investigate the pharmacokinetics of the active metabolite of methotrexate (MTX), 7-hydroxy-methotrexate (7-OH-MTX), 1 mg/kg of the compound was administered as single intravenous bolus injections to 6 unanaesthetized rats. For comparison, 1 mg/kg of the parent drug MTX was given to the same number of animals. Venous blood samples were drawn at intervals for a total of 120 min., and thereafter the rats were sacrificed and tissue samples were obtained from the brain, lungs, liver, kidneys, testes, fat, and muscle. Pharmacokinetics of 7-OH-MTX and MTX were biphasic, with a significantly (P less than 0.05) smaller central compartment of distribution (Vc) and a longer second phase half-life (t1/2(beta)) for 7-OH-MTX. MTX tissue concentrations exceeded those of 7-OH-MTX in all tissues examined. The highest 7-OH-MTX concentrations were found in renal tissue. It is implied that 7-OH-MTX is less extensively distributed than the parent compound.

[Alcohol and head injuries]. / Alkohol og hodeskader.

42 patients with epidural haematoma were operated upon in the surgical department of the regional hospital, Tromsø, in the years 1967-1985. Clinical evaluation showed that 17 of these patients (40.5%) were intoxicated by alcohol at the time of trauma. 14 of the intoxicated (82.4%) but only 7 (28%) of the sober patients, had been injured either in the evening or at night. 13 in the intoxicated group (76.5%) and 10 in the sober group (40%) were hurt by falling or as a result of violence. 15 of the sober group (60%) and 4 intoxicated patients (23.5%) arrived less than 4 hours after the accident. We found a significant difference between the two groups as regards the time lag between accident and arrival at Tromsø hospital.

Effects on leukocyte function by arthroplasty. Thromboplastin activity and oxygen-derived free radicals studied in rheumatoid arthritis and arthrosis.

We examined thromboplastin activity (TA) of monocytes and release of oxygen-derived free radicals (ODRFs) from monocytes and granulocytes before and after implantation of a hip or a knee prosthesis in 7 patients with rheumatoid arthritis and in 8 patients with arthrosis. Monocyte TA rose threefold on the first postoperative day in the rheumatoid patients, but was unaltered postoperatively in the arthrosis patients. Granulocyte chemiluminescence doubled in the arthrosis group on the second postoperative day, but was unaltered in the rheumatoid patients. Monocyte chemiluminescence was not influenced by the operation. Thus, leukocytes from the rheumatoid patients responded differently from surgical trauma when compared with leukocytes from the arthrosis patients. This difference may have an impact postoperatively.

[Laparoscopic hernia repair. A useful method for surgical treatment of inguinal hernia?]. / Laparoskopisk brokkreparasjon. Brukbar metode i kirurgisk behandling av lyskebrokk?

Between September 1992 and May 1993 14 groin hernias in 13 patients were treated with laparoscopic transabdominal preperitoneal repair using a polypropylene mesh to reinforce the abdominal wall. There were two indirect and 12 direct hernias. Five hernias were recurrent. There were no perioperative complications. In the follow up period 14-24 months after the operations, two patients developed recurrent hernias after four and ten months respectively, one patient presented with a new hernia on the contralateral side, and one patient died from cardiac disease. Laparoscopic hernia repair is technically demanding and in our setting is more time- and resource consuming than an open, tension-free repair. Thus it is questionable whether this method should be used in primary hernia repair. It may, however, have a place in the treatment of recurrent hernias and bilateral hernias.