Stability of amiodarone in serum samples under various storage conditions.

The present study was intended to examine the stability of amiodarone (Cordarex, CAS 1951-25-3) and its metabolite desethylamiodarone. For this purpose 20 ml of blood were taken from each of 12 patients treated with amiodarone and were stored, after centrifuging, at room temperature, +5 degrees C, -18 degrees C and -38 degrees C. The amiodarone and desethylamiodarone concentrations were determined by the HPLC method 30 min, 24 h, 48 h, 72 h, one and two weeks after blood-taking. It turned out that the serum levels decreased continuously as of the first day regardless of the storage temperature. Correction factors were therefore calculated for the amiodarone concentration: if the blood level determination takes place after 24 h one should add 8% to the obtained value, after 48 h 16%, after 72 h 19%, after one week 23% and after two weeks 32%.

Relation of intraperitoneal and intravascular coagulation and fibrinolysis related antigens in peritoneal dialysis.

Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition. We found an intraperitoneal fibrinogen cleavage and thrombin-antithrombin III-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 +/- 7.0 ng/ml) and thrombin-antithrombin III-complex (TAT: 4.7 +/- 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well. The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.

[Amyloidosis in Crohn disease. Case reports and review of the literature]. / Amyloidose bei Morbus Crohn. Fallvorstellung und Ubersicht über die Literatur.

A review of the literature on Crohn's disease with secondary amyloidosis and four own case reports are presented. At least 1% of patients with Crohn's disease develop amyloidosis. The extent of the inflammatory bowel disease seems to have an influence on the occurrence of amyloidosis. The survival time of 40 out of 72 patients was 2.1 years after the onset of diagnosis. The complications induced by the amyloidosis determine the fate of the patients. Therefore the periodical protein determination in urine and the Congo-red-colouring of rectal mucosa after rectoscopy are justified. After the diagnosis of amyloidosis in patients with Crohn's disease the inflammation should be treated consequently, according to the principles of the treatment of the underlying disease. But the resection of the inflammatory bowel should be avoided if the renal function is still sufficient, because frequently there occurs a postoperative renal failure. In the case of renal amyloidosis with a creatinin-clearance of more than 10 ml/min, a therapeutic attempt should be made with 1.0 to 1.5 mg/day of colchicin or 10 g/day dimethylsulphoxid (DMSO) for at least six months. During existing renal failure the proceeding of amyloidosis in other organs is to be expected. The secondary amyloidosis disposes the fate of the patients.

Intraperitoneal heparin in peritoneal dialysis and its effect on fibrinopeptide A in plasma and dialysate.

In 6 patients on continuous ambulatory peritoneal dialysis we investigated the inhibition of intraperitoneal fibrin formation by heparin. A continuous addition of 500 U of heparin per liter dialysate was used for 52 h. In plasma no heparin activity could be detected, even 52 h after intraperitoneal administration of heparin. The fibrin formation was determined by fibrinopeptide A, a thrombin-induced split product of fibrinogen. In patients under regular continuous ambulatory peritoneal dialysis we determined the fibrinopeptide A concentrations in plasma. The values were comparable with the fibrinopeptide A concentrations measured in disseminated intravascular coagulopathy. They decreased during intraperitoneal administration of heparin from 63.2 +/- 11.8 to 4.9 +/- 1.7 ng/ml. The fibrinopeptide A concentration in the 4-hour intraperitoneal dialysate (155.8 +/- 15.7 ng/ml) decreased after heparin administration to 8.5 +/- 2.0 ng/ml and was always higher than in plasma. We conclude that 500 U heparin per liter dialysate prevents the intraperitoneal fibrin formation. The low antithrombin III concentration (0.44 +/- 0.13 mg/dl) in protein-poor dialysate seems to be sufficient to inhibit the thrombin activity after acceleration by heparin.

Intraperitoneal fibrin-formation and its inhibition in CAPD.

The intraperitoneal fibrin formation and its inhibition by intraperitoneal heparin (5000 U) was investigated in six patients on CAPD. The intraperitoneal heparin concentration decreased linearily from 1.78 U/ml to 1.13 U/ml during a 4-hour dwell time. The antithrombin III-concentration increased to 0.56 +/- 0.1 mg/dl, reaching 1.87% of normal plasma values. The antithrombin III-portion of total protein was 0.62% in plasma and 0.79% in dialysate. The fibrinopeptide A-concentration, a specific product of thrombin action on fibrinogen was 37.1 +/- 11.8 ng/ml in plasma (normal range: less than 2.5 ng/ml) and 153.4 +/- 16.8 ng/ml in dialysate during regular CAPD. After the addition of 5000 U heparin the fibrinopeptide A-concentration in dialysate decreased to 11.6 +/- 2.6 ng/ml during a 4-hour dwell time. In vitro experiments showed no remarkable inhibition of fibrin formation by heparin without antithrombin III in dialysate. We suggest that the fibrinopeptide A is produced intraperitoneally and the antithrombin III-concentration in dialysate is sufficient to inhibit the fibrin formation after acceleration by heparin.

[Differential diagnosis in fever of unknown origin: significance of concomitant clinical symptoms]. / Differentialdiagnose bei bisher ungeklärtem Fieber: Bedeutung klinischer Begleitsymptome.

Between 1978 and 1984, 169 patients were admitted to the hospital for fever of unknown origin which was repeatedly above 38.3 degrees C. After a retrospective analysis of their records the patients were divided into two groups on the basis of the following new criteria. The first group (74 patients) was described as having "monosymptomatic fever", i.e. fever without any other physical signs, whereas the second group (95 patients) had "polysymptomatic fever", i.e. fever with additional physical signs. In 56 patients (76%) of the monosymptomatic group fever had lasted longer than 3 weeks prior to admission. In 86% of these patients case history, physical examination, microbiological tests, serological tests for microorganisms and outoimune antibodies, and microscopic inspections of tissue and/or bone marrow led to a diagnosis. Malignancies, factitious fever and fever of unknown origin were found only in this group. The patients with malignancies were generally older than the rest of the patients (p less than 0.05), and eight of ten patients suffering from connective tissue diseases also had monosymptomatic fever. The incidence of infections in this group was 42% (31 cases), in contrast to 88% (84 cases) in the polysymptomatic group (p less than 0.05). Whereas the latter had significantly more bacterial infections (p less than 0.05), viral infections prevailed in the monosymptomatic group (p less than 0.05). Thus, the etiology of polysymptomatic fever distinctly differed from that of monosymptomatic fever. Since the frequency distribution of etiologies in the monosymptomatic group corresponded to that of the cases of fever of unknown origin in the literature, differentiation into monosymptomatic and polysymptomatic fever might be helpful in determining further diagnostic workup of patients with fever of unknown origin.

Pancreatic exocrine secretion in response to intraduodenal infusion of different detergent agents in anesthetized cats.

Bile salts, when instilled into the intestine at pH 6, stimulate pancreatic exocrine secretion in man and cat. We investigated if the surface tension as a major physicochemical property of bile acids might be responsible for this effect. In anesthetized cats, either conjugated taurocholate (TC) or unconjugated ursodesoxycholate (UDC) as steroidal detergents or oleate as nonsteroidal detergent were perfused into the duodenum. The critical micellar concentration (CMC) and the surface tension (gamma) were as follows: for oleate 18.6 mmol/l and 27.7 dyn . cm-1, for UDC 10.75 mmol/l and 46.5 dyn . cm-1, for TC 14.5 mmol/l and 58.6 dyn . cm-1. The intraduodenal perfusion of the three solutions at 30 mmol/l and pH 8 evoked an equal pancreatic flow (about 300 mg/15 min) and bicarbonate secretion. It is suggested that the free ionized form of TC perfused intraduodenally is responsible for stimulation of the pancreatic exocrine secretion. We show that the stimulatory effect seems to be independent of the detergency of these molecules.

Intraperitoneal heparin in CAPD.

In six patients on CAPD (continuous ambulatory peritoneal dialysis) the systemic effects of intraperitoneally administered heparin (5000 U) were investigated. Using a modification of a plasma heparin determination serial measurements of heparin concentration in dialysate were performed. During a dwell time of 4 hours the intraperitoneal heparin level decreased by 1825 +/- 253 U (mean +/- S.E.M.). Simultaneously the plasma anti-IIa-activity of heparin after 4 hours and the anti-Xa-activity after 2 and 4 hours increased significantly (p less than or equal to 0.05). The maximum of heparin activity after 4 hours was 0.015 +/- 0.001 U/ml and 0.024 +/- 0.003 U/ml, respectively (mean +/- S.E.M.). An increase of activated partial thromboplastin time was not observed. The small increase of heparin activity in plasma is in contrast to reported activities measured after subcutaneous application of this dose of heparin. In CAPD the effect of heparin is largely restricted to the peritoneal cavity.