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.

Methylprednisolone induces activation of the contact system in a dose-dependent manner. An in vitro study.

The effect of methylprednisolone sodium succinate (MP) on the contact system of plasma was studied in human citrated pool plasma. Contact activation was demonstrated by the presence of plasma kallikrein (KK) activity and activated Hageman factor (FXIIa) and/or KK in complex with C1 inhibitor (C1inh), detected by chromogenic peptide substrates or radioimmunoassays, using monoclonal antibodies directed to neodeterminants exposed on complexed C1inh, respectively. When plasma and different doses of MP were incubated for a period of 24 hours, the highest dose of MP (10 mg/ml) gave rapid and marked increases in KK activities and concentrations of C1inh complexes. MP at 5 mg/ml plasma also induced activation of the contact system, although this activation was less pronounced. Even the lower dose of MP (1 mg/ml), which is equivalent to doses used in humans, increased plasma concentrations of KK-C1inh complexes. In conclusion, this in vitro study shows that MP in a dose-dependent way activates the contact system of plasma.

Effects of protease inhibitor pretreatment on hemodynamic performances and survival rate in experimental, acute pancreatitis.

Acute pancreatitis was induced in pigs by manual retrograde injection of Na-Taurocholate into the pancreatic duct. Using chromogenic peptide substrate assays, increased plasma kallikrein activity (KK), paralleled by a reduction in functional plasma kallikrein inhibition values (KKI) were found in the peritoneal exudate in untreated animals. Several of the untreated animals experienced an increased trypsin activity (TRY) in the same exudate. Five out of eight animals died during a 6 hour observation period. Pretreatment with either Cl-INH or aprotinin given intravenously, resulted in a significantly increase in KKI capacity paralleled by unchanged KK and TRY activities in the peritoneal exudate. Furthermore, inhibitor pretreatment significantly improved hemodynamic performances (AP and CO) and the survival rate. The study underlines the pathophysiological importance of trypsin and the plasma kallikrein-kinin system during acute, severe pancreatitis.

Studies on the kallikrein-kinin system in plasma and peritoneal fluid during experimental pancreatitis.

Using chromogenic peptide substrate assay technique, components of the plasma kallikrein-kinin system and trypsin activity were studied in plasma and peritoneal exudate during acute pancreatitis in pigs. In the plasma no significant changes occurred, but increased kallikrein activity was found in the peritoneal exudate. This finding was paralleled by a reduction in prekallikrein levels and functional kallikrein inhibition values. The trypsin activity in peritoneal exudate, however, increased inconstantly. These results emphasize the significance of peritoneal protease-antiprotease imbalance during acute pancreatitis.

Evaluation of patients with acute pancreatitis by means of chromogenic peptide substrate assays and the proenzyme functional inhibition index.

Using chromogenic peptide substrate assays the severity and clinical course were evaluated in 37 patients with acute pancreatitis. Retrospective clinical evaluation revealed that 20 patients had a severe disease, whereas 17 patients had mild acute pancreatitis. Seven of the patients with severe acute pancreatitis died. The proenzyme functional inhibition index (PFI index) is defined as the sum of deviations from the normal plasma pool values of plasma prekallikrein, functional kallikrein inhibition, plasminogen, antiplasmin, prothrombin and antithrombin III. Increased values are counted as positive, whereas reductions compared with the normal plasma pool values are recognized as negative. During the second day after admission the PFI index revealed significantly more negative values in severe cases than in patients with mild acute pancreatitis, -159 in severe case, -74 in mild cases (median values, P less than 0.05). The PFI index values were maintained strongly negative for the following 3 days in severe cases whereas the index was brought to positive values during the same period in patients with mild acute pancreatitis. The fatal cases revealed strongly negative PFI index values for the whole observation period. The patients with severe acute pancreatitis were earlier identified by means of the PFI index than by individual parameters also used for calculating the index. The results show that by means of the PFI index severity of acute pancreatitis can be recognized during early stages of the disease.

Effects on peritoneal proteolysis and hemodynamics by high doses of methyl-prednisolone in experimental acute pancreatitis.

Acute pancreatitis was induced in 15 anesthetized pigs by injection of Na-taurocholate into the pancreatic duct. Seven animals were pretreated with methyl-prednisolone sodium succinate 30 mg/kg intravenously. Using chromogenic peptide substrate assays, values of trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and arterial pressure (AP) were regularly monitored before and during a six hour observation period. In acute untreated pancreatitis a 40% reduction of PKK levels was found paralleled by an increased KK activity and a reduction of KKI capacity. High TRY levels were found in several animals. The mortality rate was 63%. The pretreated animals all survived. CO and AP were significantly less reduced than in the untreated animals. Components of the plasma kallikrein-kinin system and TRY in the exudate remained mainly unchanged. Methyl-prednisolone given as pretreatment significantly improves hemodynamic parameters and increases the survival rate. Methyl-prednisolone suppresses generation of trypsin activity and activation of the plasma kallikrein-kinin system in the peritoneal exudate which may be of significant importance to the outcome.

Incidence of malignancies of the Billroth II operated stomach. A prospective follow-up.

In 1976 endoscopy with at least 20 biopsies and cytology were performed in 108 patients 20-25 years after partial gastrectomy (Billroth II). In one patient advanced carcinoma and in three cases severe dysplasia or carcinoma in situ, were found. At the follow-study in 1979, 7 patients had died of causes other than gastric carcinoma. A re-examination with endoscopy, biopsies and cytology were performed in fifty-eight patients. The present study did not show a progress of dysplasia in the gastric remnant during the three years of follow-up. The observations may suggest that re-examinations with gastroscopy and multiple biopsies every 3-5 years may be satisfactory in detecting carcinoma of the gastric remnant.

Missed diagnosis and delayed laparotomy in blunt abdominal trauma.

Abdominal organ injuries caused by blunt trauma are notoriously difficult to diagnose and a vital operation may as a result be dangerously delayed. In a series of 331 patients admitted after blunt abdominal trauma, 426 abdominal organ injuries were registered. 152 of these patients had 199 abdominal organ injuries requiring surgical repair. In 31 of these patients (20%) with 44 organ injuries operation was delayed for more than 6 hours after admission, in most instances because the diagnosis had been missed. One of these patients died as a consequence. Hollow organ injuries were the most commonly missed. Peritoneal lavage, repeated if necessary, and diagnostic imaging must be used as valuable tools in addition to repeated clinical evaluation, especially in comatose patients, in patients with multiple injuries, and in intoxicated patients.

Intragastric pressure/volume relationship before and after proximal gastric vagotomy.

The examinations were performed before and after proximal gastric vagotomy (PGV) in 10 patients with duodenal ulcer. A flaccid plastic balloon located in the corpus-fundus region was stepwise filled with known volumes of water. Post-operative insulin tests were negative in 8 patients and late positive in two. Basal and pentagastrin-stimulated acid output were reduced by a mean of 88 and 62 percent, respectively. Intragastric pressure was significantly increased after PGV, whereas rhythmic contractions were reduced in all cases. It is concluded that PGV interferes with gastric motility and adaptation to volume variations.

Intragastric pressure/volume relationship in the normal human stomach.

Intragastric pressure/volume relationship was studied twice in 8 healthy volunteers. Basal pressure and rhythmic contractile activity in response to defined volume loads were recorded. Reproducibility and precision of the parameters were evaluated. It is concluded that recording of the intragastric pressure/volume relationship is a valuable method for the evaluation of gastric motility, and it is well suited for clinical application. It is harmless and easy to perfrom. The reproducibility of the method and the precision of the parameters used are satisfactory.

Gastric motility 1 year after proximal gastric vagotomy.

The intragastric pressure/volume relationship was recorded in six patients with duodenal ulcer to study gastric motility before and after proximal gastric vagotomy (PGV). Recordings were done preoperatively and 6 weeks and 1 year after surgery by means of a flaccid plastic bag in the stomach connected to a low-pressure transducer. The bag was filled and emptied stepwise with defined volumes to study responses in gastric basal pressure or tone and contractions. Significant increase in basal pressure and reduced strength of rhythmic contractions were found 6 weeks after the operation, indicating disturbance of the gastric reservoir in the corpus and fundus. These changes were still present 1 year later, but some reduction of the pressure/volume relation was seen. The study indicates that a small tendency to adaptation or a revere towards normal occurs with gastric motility responses to volume loads simulating a meal 1 year after PGV, but the changes are still significantly different from the preoperative recordings.

Actions of thyrotropin-releasing hormone on gastrointestinal functions in man. III. Inhibition of gastric motility in response to distension.

The intragastric pressure/volume relationship has been measured in six healthy volunteers. Increased gastric motility was achieved by gastric distension, by stepwise increasing the volume from 0--600 ml. When thyrotropin-releasing hormone (TRH), 0.04 mg/h, was infused concomitantly in the individuals, gastric motility was significantly inhibited (p less than 0.05) and, with 1 mh/h of TRH, nearly abolished compared with the saline control test. The basal pressure was unaffected at 0.04 mg/h, whereas a significant rise was seen after 1 mg/h of TRH (p less than 0.05) compared with the control test. In three of the subjects the effect of rapid injection of TRH (0.2 mg), followed by infusion of TRH (0.6 mg/h), on the stimulated gastric motility was analysed. After the injection of TRH, almost no motor activity was observed during the 15-min observation period. It is concluded that TRH has a potent inhibiting effect on gastric motility, and the possible physiological role of TRH in the gastric regulation in man is discussed.

Primary non-Hodgkin lymphoma treated with liver resection. Case report.

In a patient who underwent extended right hemihepatectomy for a mass in the right liver lobe, the lesion proved to be primary non-Hodgkin lymphoma. When recurrence was diagnosed 9 months later, chemotherapy was begun. Primary non-Hodgkin lymphoma of the liver is rare, with only c. 55 cases reported in the world literature.