Elevated serum levels of pancreatic secretory proteins in cigarette smokers after secretin stimulation.

The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.

Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.

Demonstration of pancreatic protease-antiprotease complexes in the peritoneal fluid of patients with acute pancreatitis.

During a 4 year period (1972 to 1975), 69 patients with acute severe pancreatitis, of whom 58 had hemorrhagic pancreatitis, were treated with peritoneal lavage at the intensive care ward of Malmö General Hospital. The mortality rates in these four years were 27%, 28%, 17%, and 14%, respectively. Peritoneal exudates were analyzed from 10 patients with hemorrhagic pancreatitis, four of whom died. About 65% of alpha 2-macroglobulin was in complexed form, as was 15% of alpha 1-antitrypsin. Immunochemical analyses of the alpha 1-antitrypsin revealed the presence of trypsin, chymotrypsin, and elastase complexed with alpha 1-antitrypsin. This means that the pancreatic proteases had been activated, as only active proteases are bound by plasma protease inhibitors.

Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden.

AIM: This study investigates the potential relation between breast cancer location and axillary lymph node involvement (ALNI). METHODS: Out of all cases with unilateral first-time diagnosis of invasive breast cancer in Malmö, Sweden, between 1961 and 1991, 3472 underwent axillary dissection. The association between tumour location and ALNI was investigated using logistic regression analysis (adjusted for potential confounders) yielding odds ratios (OR), with a 95% confidence interval. All analyses were repeated in different birth-year cohorts. RESULTS: Outer tumours (upper outer or lower outer quadrants), as compared to inner (upper inner and lower inner quadrants), were associated with a statistically significant risk of ALNI, OR: 1.31 (1.11-1.55). Central tumours were also associated with ALNI, OR: 2.61 (2.08-3.27). Among women born before 1909, corresponding OR:s for outer tumours was 1.61 (1.19-2.18), and for central tumours 3.50 (2.32-5.28). CONCLUSIONS: Outer and central breast tumours are associated with a high risk of axillary lymph node involvement.

Early diagnosis of a pancreatic abscess in acute pancreatitis.

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated on crossed immunoelectrophoresis of the peritoneal fluid in 4 patients, who developed a pancreatic abscess during an attack of acute pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important.

Parity in relation to risk of axillary lymph node involvement in women with breast cancer. Results from Swedish population-based series of 3,472 consecutive cases.

OBJECTIVE: To investigate the association between parity and axillary lymph node involvement (ALNI) at breast cancer diagnosis. METHODS: One surgeon has reviewed all breast cancer cases in Malmo, Sweden, diagnosed 1961-1991. This study includes the 3,472 women who had a first-time diagnosis of unilateral invasive breast cancer, and who had undergone axillary dissection. Information was collected regarding date of birth, date of diagnosis, age at diagnosis, menopausal status, tumour size, histological type, tumour location, type of surgery, stage (ALNI), and parity. Parity was investigated in relation to ALNI using logistic regression analysis, adjusted for potential confounders, yielding odds ratios (OR) with 95% confidence intervals (CI). The analyses were repeated in different strata with regard to birth-years cohort, age at diagnosis, and period of diagnosis. RESULTS: High parity was associated with ALNI, the adjusted OR for ALNI among women with 4 or more children was 1.56 (1.13-2.15). This association was stronger in comparatively old women (> or = 67.45 years), OR 1.78 (1.10-2.88). Considering parity a continuous variable, the OR for ALNI among all women was 1.06 (1.01-1.12). CONCLUSIONS: We conclude that women with 4 or more children had an increased risk of ALNI at breast cancer diagnosis.

Trasylol prevents trypsin-induced shock in dogs.

The effect of simultaneous intravenous administration in the dog of bovine trypsin and Trasylol followed by continued infusion of Trasylol was studied. Special attention was paid to the interchange between the dominating plasma protease inhibitors alpha1-antitrypsin and a-macroglobulins and to the disappearance of Trasylol and its trypsin complexes from the circulation. The following results were obtained: 1) Trypsin was preferentially bound by the alpha-macroglobulins, though Trasylol is a strong trypsin inhibitor. 2) On saturation of the alpha-macroglobulins, a considerable amount of trypsin was bound by alpha1-antitrypsin. 3) Trasylol was bound to the trypsin-alpha-macroglobulin complexes and then rapidly eliminated from the circulation. 4) On saturation of the alpha-macroglobulins, Trasylol was identified in a free form but increasing amounts of Trasylol were also bound to trypsin. This could be explained not only by direct complexation of Trasylol and trypsin but also by a transfer of trypsin from unstable trypsin-alpha1-antitrypsin complexes to free Trasylol.

Studies on the influence of heparin on trypsin-induced shock in dog.

Intravenous infusion of bovine trypsin in dogs can induce intravascular coagulation, which is claimed to be one of the causes of the shock accompanying such infusions. Treatment with heparin prior to trypsin administration prevents the usual decrease of fibrinogen but apparently does not influence the trypsin-induced shock seen upon trypsin saturation of alpha 2-macroglobulin. The prompt appearance of fibrinogen fragments following trypsin saturation of alpha 2-macroglobulin is probably a consequence of plasminogen activation. Under similar conditions alpha 1-antitrypsin (alpha 1-protease inhibitor) seems to be acting as plasma inhibitor in the absence of free alpha 2-macroglobulin and the fast reacting plasmin inhibitor, antiplasmin. Thus, trypsin-induced shock in dogs is apparently not caused by intravascular coagulation to any significant degree.

Malignant cystosarcoma phyllodes in a man treated with polyestradiolphosphate. Case report.

Cystosarcoma phyllodes is a rare breast tumor and only five cases have been previously reported in males. A case of cystosarcoma phyllodes in a man treated with polyestradiolphosphate for prostatic carcinoma and by radiation because of breast tenderness is presented. The tumor showed a malignant stroma histologically and the epithelial component was similar to a ductal carcinoma in situ. Electron microscopy revealed several cell types. The possible relationship to radiation and estrogen therapy is discussed.

Bleeding birth of a gallstone from a hanging papilla of Vater.

A case of major gastrointestinal hemorrhage due to the passage of a gallstone from a 20 mm long, hanging papilla of Vater is presented. An upper digestive endoscopy revealed the stone in the very process of expulsion from the papilla into the duodenum in which fresh blood was seen. Bleeding stopped a few days afterwards. Follow-up endoscopic and radiological examinations of the gastrointestinal tract disclosed no other potential source of bleeding.

Crohn's disease and small bowel diverticulosis in two sisters.

Small bowel diverticula may cause abdominal pain, diarrhoea, malabsorption and weight loss. The same symptoms are also seen in Crohn's disease. Two elderly sisters with simultaneous small bowel diverticulosis and Crohn's disease are presented.

Studies on the role of the plasma protease inhibitors on in vitro C3 activation and in acute pancreatitis.

Plasma samples from 32 patients with severe acute pancreatitis contained cleavage products of C3, and the C3 levels were significantly lower than those of control subjects. Peritoneal exudate from all patients showed complete degradation of C3 on crossed immunoelectrophoresis. Alpha 1-Antitrypsin and alpha 2-macroglobulin showed no signs of complex formation in plasma. However, in the peritoneal exudate, 5%-25% of the alpha 1-antitrypsin and 45%-100% of the alpha 2-macroglobulin were in complex. Trypsin-alpha 1-antitrypsin complexes were demonstrated in all peritoneal exudates. All patients showed significantly decreased levels of alpha 2-macroglobulin in their plasma. Alpha 1-Antitrypsin levels varied greatly, but the mean value was not significantly increased compared with those of normal controls. Orosomucoid, another acute-phase reactant, was present in increased concentration in the plasma of all patients. The addition of increasing amounts of human trypsin to serum in vitro resulted in the appearance of cleavage products of C3 upon saturation of alpha 2-macroglobulin, when the alpha 1-antitrypsin was found to be only about 40% saturated. Taken together, these data are evidence of complement catabolism in acute pancreatitis and suggest that this process takes place mainly in the abdominal cavity as a result of a protease-antiprotease imbalance. Alpha 2-Macroglobulin, but not alpha 1-antitrypsin, can protect against C3 degradation caused by trypsin in vitro.

Leukocyte elastase alpha 1-proteinase inhibitor complexes may diagnose pancreatic abscesses early.

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated by crossed immunoelectrophoresis of the peritoneal fluid from four patients who developed a pancreatic abscess during an attack of pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important. The appearance of these complexes denotes the liberation of large amounts of leukocyte elastase. This may help explain the pathophysiology and high mortality of the pancreatic abscess, since leukocyte elastase is known to cause degradation of all components of connective tissue and also degradation and activation of many components within the different cascade systems.

Gabexate mesilate (FOY) and aprotinin. A comparative study of the effects on trypsin-induced activation of the kinin and complement systems in vivo and in vitro.

The effect of gabexate mesilate (FOY) was studied in vitro in human and canine serum upon the addition of trypsin, and in vivo in dogs during intravenous trypsin infusion. The effect of FOY was compared with the effect of aprotinin. FOY did not show any protection against trypsin-induced activation of the complement and kinin systems in vitro or in vivo, while aprotinin did. All dogs exhibited signs of circulatory shock together with a consumption of the two main proteinase inhibitors, alpha-macroglobulin and alpha 1-proteinase inhibitor, when intravenous infusions of FOY and trypsin were performed simultaneously. However, all dogs survived without signs of shock if aprotinin was given instead of FOY. The ineffectiveness of FOY in serum is explained by the complete dissociation of FOY trypsin complexes together with a rapid degradation of FOY to inactive metabolites. Although FOY is an effective proteinase inhibitor in defined buffer systems in vitro, the results of the present study indicate that it is not an effective proteinase inhibitor in vivo. Aprotinin protects against trypsin-induced activation reactions, although much higher concentrations are needed in human than in canine serum.

Aprotinin turn-over studies in dog and in man with severe acute pancreatitis.

The elimination of aprotinin after intravenous infusion was exponential until 95% of the dose was cleared from the plasma after 1 h in dogs with bile-induced pancreatitis. The half-life of this part of the elimination was 10 min. The concentration of aprotinin in the peritoneal fluid reached a maximum plateau after 1 h. Direct intra-abdominal infusion of aprotinin was followed by a relatively slow elimination of the inhibitor from the cavity. One hour after the infusion the concentration of aprotinin in the peritoneal exudate was about 50% of the initial value. Four hours later the concentration of inhibitor with unchanged immunoreactivity and inhibiting capacity was still about 25% of the initial value. Based on the results of this experimental study an intraperitoneal dosage schedule for aprotinin was tested in three patients with haemorrhagic pancreatitis. A total amount of 14 X 10(6) KIU was given in repeated dosages during 18 h. This resulted in a minimum level of aprotinin in the peritoneal exudate of about 10 mumol/l. According to our earlier published data this level should largely block trypsin-induced effects relevant in pancreatitis. In conclusion; due to the rapid elimination of aprotinin from plasma, after i.v. application a therapeutically useful concentration is never reached in the peritoneum, while the elimination from the peritoneum is relatively slow, thus providing therapeutically useful concentrations which can be maintained for some time after i.p. application.

Peritoneal lavage in severe acute pancreatitis.

An analysis is presented of 73 attacks of acute pancreatitis treated with non-operative peritoneal lavage, classified according to Ranson's 11 signs and followed up for on average four years. None of the 21 moderate attacks was associated with complications or mortality. In the 52 severe attacks, four patients (7.7%) died, new pseudocyst developed in five patients (9.6%) and abscess in four (7.7%), and diabetes was found in 12 patients (23%) at follow-up. In all these respects the severe attacks showed statistically significant difference from the moderate attacks, as did the need for assisted ventilation, the volume of gastric retention and the length of hospital stay. The authors conclude that non-operative peritoneal lavage is beneficial, probably by removing toxic substances from the peritoneal cavity.

Influence of plasma protease inhibitors and Trasylol on trypsin-induced bradykinin-release in vitro and in vivo. Protease inhibitors and trypsin-induced bradykinin release.

The release in dog plasma of bradykinin in an experimental model in vitro and in vivo secondary to the addition of increasing amounts of trypsin was studied. The release was correlated with the degree of saturation of the plasma protease inhibitors, alpha 2-macroglobulin and alpha 1-antitrypsin, without and in the presence of Trasylol. There was a good correlation between the saturation of alpha 2-macroglobulin with trypsin and the release of bradykinin. A simultaneous fall in blood pressure was seen in the in vivo experiments. alpha 1-Antitrypsin was unable to block this tryptic activity in the absence of free alpha 2-macroglobulin. In the presence of Trasylol, the saturation of alpha 2-macroglobulin was not followed by any significant kinin liberation and the blood pressure remained stable.

Diagnostic accuracy of lightscanning and mammography in women with dense breasts.

The diagnostic accuracy of lightscanning and mammography in 610 breasts with mammographically dense parenchymal patterns was investigated. Lightscanning identified 31 out of 36 cancers and mammography 32. Lightscanning and mammography were in agreement in 28 cases of cancer. One noninvasive lobular carcinoma was not identified by either modality. Four cancers were not correctly identified with lightscanning alone and 3 cancers with mammography alone. Of the 574 breasts without cancer, lightscanning falsely denoted 101 (18%) as possibly being cancerous (false-positives). The corresponding figure for mammography was 25 (4%). Thus, lightscanning, as performed in this study, has the same sensitivity as mammography in detecting cancer in mammographically dense breasts. However, its usefulness is limited by a low predictive value of a positive test (high rate of false-positives).