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J O Stadaas

Publications and source records attributed to J O Stadaas.

At least 37 records · Page 2Linked to original sources

Methylprednisolone in high doses gives different effects on the early and the late part of complement.

The effects of methylprednisolone (MP) on endotoxin-induced activation of complement were studied in citrated pool plasma. Complement activation was tested in two immunoassays: one evaluating C3 activation fragments (C3act) and the other the terminal complement complex (TCC). These components are indicators of initial and terminal complement activation, respectively. Plasma samples were obtained at 1, 2, 4 and 6 h of incubation. Plasma containing endotoxin (2.10(9) ng/l) without MP revealed a marked increase of both C3act and TCC after 1 h. MP in high doses (10 mg/ml) gave an additive effect on activation of the initial part of the complement cascade compared to test plasma containing only endotoxin. In contrast, endotoxin-induced activation of the terminal part of the complement cascade was inhibited by the same dose of MP. The influence of lower doses of MP (0.1 and 1 mg/ml) on endotoxin-induced activation of complement was insignificant. Interestingly, MP without endotoxin induced activation of the initial part of complement. In test plasmas containing 5 and 10 mg/ml of MP (without endotoxin) marked increases of C3act values were seen. Despite this obvious activation of the early part of complement, only insignificant changes were found in TCC values. Test plasmas containing 0.1 and 1 mg/ml of MP revealed only minor changes in both C3act and TCC. In conclusion, the present study shows that high doses of MP activate the initial part of complement and that the endotoxin-induced activation of this cascade system was facilitated by MP. The terminal part of complement was, on the other hand, inhibited by high doses of MP.

Complement Activation↗

Combined drug therapy in porcine endotoxemia. Hemodynamic and proteolytic effects of antagonists against histamine, serotonin and endorphin.

In order to investigate the importance of potential mediators of pathophysiologic derangements in endotoxemia, we have examined the effects of the combined administration of antagonists against histamine, serotonin and endorphins in a porcine model of endotoxemia. The treatment regimen significantly reduced the increase in pulmonary artery pressure, pulmonary vascular resistance and systemic arterial pressure seen in the early stages of endotoxemia. Also, cardiac output was better maintained. However, the hemodynamic performance after an observation period of 5 h was not statistically different from untreated animals. The treatment regimen did not hinder the activation of the kallikreinkinin and fibrinolytic systems of plasma, which was evident in both treated and untreated animals, and could not counteract the increase in hematocrit or leukopenia seen in this model. This study shows that the combined blocking of histamine, serotonin and endorphines is not enough to abrogate the detrimental effects of endotoxin in a porcine model.

Animals↗

Pulmonary function and energy expenditure after marked weight loss in obese women: observations before and one year after gastric banding.

Pulmonary function and pulmonary gas exchange at rest, and during and after a standard exercise load of 500 kpm in 1 min on bicycle ergometer were studied in 34 women with severe, uncomplicated obesity, aged 37.8 (20-59) years, before and 1 year after gastric banding, resulting in a weight loss from 113.2 (84-156) to 81.7 (60-110) kg. Following the weight loss, TLC and VC rose from 93 and 94 per cent of expected to 98 and 101 per cent, respectively. FRC, ERV and FRC/TLC rose more markedly from 77, 64 and 83 per cent to 98, 109 and 99 per cent. IC fell from 108 to 99 per cent. RV and RV/TLV remained unchanged. FEV1.0 rose from 97 to 103 per cent, while MVV rose from 102 to 112 per cent, i.e. above normal. TLCO and PaCO2 remained unchanged, at 90 and 95 per cent, whereas PaO2 rose from 86 to 91 per cent. Resting O2 intake (VO2) decreased from 147 to 115 per cent of the expected for normal weight women, while VO2/BSA decreased from 113 to 99 per cent, the changes being greater than expected from commonly used formulas for prediction of metabolic rate. O2 cost of work (EO2) decreased from 142 to 105 per cent. Resting ventilation (V) declined from 136 to 113 per cent, while ventilatory cost of work (EV) decreased from 142 to 105 per cent. CO2 recovery time after work (CO2RT) decreased from 121 to 100 per cent, while the ratios CO2RT to EO2 and to extra CO2 output of work (ECO2) rose slightly. Thus, the loss of weight led to increased filling of the lungs, improved dynamic function, reduced ventilation/perfusion disturbances and greater than expected reduction of energy expenditure, both at rest and exercise. In the obese state there was no evidence of alveolar hypoventilation or impaired ventilatory control. The beneficial effect of weight reduction on the exertional dyspnea included a combination of marked reduction of ventilatory demands and moderate rise in ventilatory capacity.

Adult↗

Methylprednisolone affects inhibitors of the complement and the contact systems; functional and immunochemical studies on alpha 2-macroglobulin and C1 inhibitor.

The effects of methylprednisolone sodium succinate (MP) on main inhibitors of the classical pathway of complement and on the contact system were studied in citrated pool plasma. Endotoxin (2.10(9) ng/l, lipopolysaccharide B, E. coli 026: B6 Difco Laboratories, Detroit, Michigan, USA) and/or MP in doses of 0.1, 1, 5 and 10 mg/ml were incubated with plasma at 37 degrees C. Plasma samples were obtained at timed intervals up to 24 hours for determination of C1 inhibitor (C1inh) and alpha 2-macroglobulin (alpha 2M) values using both functional and immunochemical assays. Plasma containing endotoxin without MP revealed decreases of C1inh and alpha 2M values after 12 hours. Addition of MP in high doses (10 mg/ml) gave an additive effect on the endotoxin-induced decreases of C1inh and alpha 2M values, evident 1 and 12 hours after the beginning of incubation, respectively. When MP alone was added to plasma (5 and 10 mg/ml) also significant decreases in C1inh and alpha 2M values were seen. MP in low doses (0.1 and 1 mg/ml) did not either influence the endotoxin-induced changes in the protease inhibitor functions, or induce significant changes in C1inh and alpha 2M values when incubated in plasma without endotoxin. This study demonstrates that MP in high doses induces marked decreases in plasma C1inh and alpha 2M inhibitory functions and that MP has an additive effect on the endotoxin-induced decreases of these inhibitors.

Blood↗

[Surgical treatment of necrotizing fasciitis].

We present nine patients with necrotizing fasciitis. Two of them had Fourniers gangrene. Predisposing factors included diabetes mellitus, alcohol and drug abuse. Local signs were redness, swelling and pain rapidly followed by fever and deterioration in the patient's general condition. Soft tissue-gas was observed in all patients. It was found either clinically, on roentgenograms or by CT. Bacteria were found in blood cultures and/or necrotic tissues in all patients. The dominating treatment was radical surgical excision and early reexplorations. Antibiotics, intensive care support and early parenteral nutrition were given. Four patients were given hyperbaric oxygen treatment. The overall mortality rate was 11%. Amputation of one lower extremity became necessary in three patients. In these cases 4-8 days had elapsed between the onset and the first surgical excision. We find it important to underline early diagnosis and radical surgical excision in patients with necrotizing fasciitis.

Adult↗

[Duodenal injuries due to blunt trauma].

UNLABELLED: During the last ten years we have seen fourteen patients with duodenal injury after blunt trauma. Five patients with intramural hematomas received no treatment. Nine patients had a perforated duodenal wall, and in four of these the diagnosis was delayed for more than 24 hours. Revision and primary suture were carried out in seven patients, with no complications. In one patient, where the diagnosis was delayed for three days, the perforation was closed around a Pezzer catheter for external drainage. She developed an intraabdominal abscess which required reoperation. One patient died from liver injury with profuse bleeding; the others survived without sequelae from the duodenal injury. CONCLUSIONS: Duodenal injuries are rare and early diagnosis is difficult. We think that frequently repeated physical examinations, liberal use of diagnostic peritoneal lavage, and careful peroperative exploration of the entire duodenum when performing laparotomy after abdominal injuries, are important for early diagnosis and treatment.

Abdominal Injuries↗

[New therapeutic alternatives for patients with gallstones].

Calculi in the bile ducts are usually removed by surgery or endoscopic papillotomy. When these methods are contraindicated or fail, new and non-surgical alternatives can now be used. Percutaneous transhepatic balloon dilatation of the papilla of Vater enables expulsion of stones in the bile duct. Large stones in the bile ducts can be reduced in size using extracorporeal shock waves or completely dissolved by instillations of Methyl-tertiary-butyl ether in the common bile duct. We report the cases of three patients who were treated successfully for stones in the bile duct using combinations of these techniques.

Aged↗

[Surgical treatment of pancreatic injuries].

Major pancreatic traumas are not frequent, and diagnosis often difficult. In a retrospective study we found 11 verified cases of pancreatic trauma treated in the period 1977-86. Three were penetrating and eight blunt trauma victims. Five patients suffered serious lesions in other organs. Laparotomy was performed in nine patients. One patient died, due to other lesions. The patients can be separated clinically into two groups. In the first group emergency laparotomy is indicated because of bleeding or peritonitis, most often due to lesions in other abdominal organs. In the other group the initial symptoms and clinical signs are sparse, and the diagnosis is based on repeated clinical examinations, ultrasound CT, peritoneal lavage and repeated amylase determinations. Contusions and minor lacerations without injury to the duct are treated with revision and canalization. Resection and pancreatico-jejunostomy should be considered when the pancreas is heavily lacerated with damage to the duct system.

Adolescent↗

Peritoneal lavage efficiently eliminates protease-alpha-2-macroglobulin complexes and components of the contact system from the peritoneal cavity in patients with severe acute pancreatitis.

Trypsin (Try), plasma kallikrein (KK) and plasmin activities together with coagulation factor XII (F XII, Hageman factor), high-molecular-weight kininogen (HMWK), plasma prekallikrein (PKK), alpha 2-macroglobulin (alpha 2-M), C1 inhibitor (C1Inh), and functional plasma kallikrein inhibition (KKI) values were studied in peritoneal fluid and lavage taps of 9 patients with severe acute pancreatitis treated with peritoneal lavage. Both immunochemical methods and functional techniques based on chromogenic peptide substrate assays were used. In the exudate obtained before peritoneal lavage was performed, F XII was 52%, HMWK was 30%, PKK was 40%, alpha 2-M was 29% and C1Inh was 57% of standard plasma pool values, determined by immunochemical technique. Functional plasma KKI values were zero, whereas Try activities determined by chromogenic peptide substrate technique were markedly elevated in the exudate. Using a prepacked HR 10/30 Superose Tm 12 column (Pharmacia, Uppsala, Sweden) and chromogenic peptide substrate assays, Try and KK activities were detected in the alpha 2-M containing fractions of the peritoneal exudate demonstrating KK-alpha 2-M and Try-alpha 2-M complex formation. The peritoneal lavage procedure efficiently eliminated components of the contact system and protease activities. In the first lavage tap, Try activities were markedly reduced compared to values found in the exudate and concentrations of F XII, HMWK, PKK, alpha 2-M and C1Inh were all zero. In consecutive lavage taps Try values were also zero. The study shows that the lavage procedures efficiently clears the peritoneal cavity for protease-alpha 2-M complexes generated during acute pancreatitis. Also, components of the contact system found in peritoneal exudate, and which might serve as substrates for the protease-alpha 2-M complexes, are rapidly eliminated by the procedure.

Acute Disease↗

Plasma proteolysis and circulating cells in relation to varying endotoxin concentrations in porcine endotoxemia.

Ten juvenile pigs receiving a continuous infusion of 0.01 mg/kg of endotoxin over 3 hr and seven animals infused with sterile saline (serving as controls) were studied for 5 hr. Endotoxin concentrations in plasma as determined with a chromogenic Limulus amoebocyte lysate (LAL) test reached a steady state of about 1,000 ng/liter after 1 hr and declined rapidly as the infusion was discontinued. Preinfusion values were reached at the end of the observation period. Endotoxin concentrations found during the infusion period were comparable with those seen in humans with septicemia. The endotoxin infusion was followed by hemoconcentration, leukocytopenia, and thrombocytopenia. Using chromogenic peptide substrate assays, activation of the plasma kallikrein-kinin, fibrinolytic, and coagulation systems was detected. Although the endotoxin concentrations reached preinfusion values within the last 2 hr of the observation period, changes found in circulating cells and components of the plasma cascade systems did not normalize, and the hemodynamic situation did not change.

Animals↗

Dose dependence of endotoxin-induced activation of the plasma contact system: an in vitro study.

The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.

Chromogenic Compounds↗