Tissue-type plasminogen activator (t-PA) and dilute blood clot lysis time in nephrotic patients.

When compared to normal weight normolipidemic control subjects, dilute blood clot lysis time was found to be obviously (p less than 0.001) prolonged in hypertriglyceridemic patients without proteinuria and slightly (p less than 0.05) accelerated in hyperlipidemic nephrotic patients in spite of their very high levels of plasma fibrinogen. As a result the ratio plasma fibrinogen (mg/dl) per clot lysis time (minutes) was 1.241 +/- 0.08 (X +/- SEM) in control subjects, 0.574 +/- 0.07 in hypertriglyceridemic patients and 2.69 +/- 0.172 in nephrotic patients. This finding suggesting that a larger amount of fibrin is rather readily dispersed from dilute blood clots of nephrotic patients was associated with higher levels of plasma t-PA:Ag (9.45 ng/ml +/- 1.18 in nephrotic patients versus 5.8 ng/ml +/- 1.23 in controls before venous occlusion and respectively 33.1 ng/ml +/- 3.83 versus 20.3 +/- 3.40 in controls after venous occlusion). Plasminogen activator activity of the euglobulins as assessed by the bovine fibrin-agarose plate was significantly higher in nephrotic patients only after venous occlusion. Plasma samples of nephrotic patients exerted a more potent inhibition of fibrinolysis in a urokinase activated system. This effect was, however, mainly due to the high levels of alpha 2 macroglobulin in nephrotic plasma which apparently have little influence on dilute blood clot lysis time.

Bioavailability of nifedipine from different oral dosage forms in healthy volunteers.

The absolute and relative bioavailability of nifedipine (1) from different formulations administered as single oral doses in healthy volunteers was determined. Serum concentrations of 1 were measured by GC. The absolute bioavailability of 1 was 53% because of presystemic metabolism. The bioavailability of Adalat (Bayer) tablets, Nifedipina (Terapia) and Corinfar (VEB Arzneimittelwerk Dresden) sugar-coated tablets was 93%, 92% and 86% (respectively) as compared with Adalat capsules. The AUC were not significantly different. The Cmax and tmax values were different, indicating that the absorption of 1 showed differences in first-order rate constants of dissolution in the above mentioned order. Despite the differences among the formulations studied, each preparation may have its merits. In a multiple dose regimen of 20 mg 1 (Nifedipina, Terapia) t.i.d., minimal therapeutic drug levels were achieved and maintained during steady state, from the 1st d of treatment.

Hemorrhagic fever with renal syndrome: report of 11 observations.

Based on the observation of 11 patients (10 males and 1 female), the occurrence of hemorrhagic fever with renal syndrome in two new geographic areas of Romania is reported. Two patients died within several hours after admission. The other nine recovered gradually. In four patients hemodialysis was necessary. A complete recovery of renal functions one year after onset could be proved in four patients. The clinical, laboratory, morphopathological (necroptic and bioptic), epidemiologic and evolutive characteristics of the disease, especially the main features supporting the diagnosis of hemorrhagic fever with renal syndrome, are discussed.

[Severe complications following intermittent administration of rifampicin]. / Accidente grave consecutive administrarii intermitente de rifampicina

In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.

Behaviour of fibrinolysis in the nephrotic syndrome.

When compared to 39 normal-weight normolipidemic control subjects, the dilute blood clot lysis time was found to be slightly (p less than 0.05) accelerated in the 49 investigated nephrotic patients, although their plasma fibrinogen, factor XIII as well as the inhibitors of fibrinolysis, are markedly increased. These findings indicate that the fibrinolytic system as a whole is not markedly depressed in the nephrotic syndrome. Although the fibrinolytic activity of euglobulins tested on agarose-fibrin plates was not significantly increased in nephrotic patients, one cannot definitely preclude an enhanced secretion of plasminogen activators in this pathological condition. A different quality of the inhibitors which may be less active in retarding dilute blood clot lysis time could also be considered.

Plasma von Willebrand factor antigen and activity and platelet aggregability in patients with proteinuria.

Using a complex stimulating mixture containing ADP, epinephrine and collagen, a significantly (p less than 0.002) enhanced platelet aggregability, expressed as platelet sensitivity factor (PSF) was noted in platelet rich plasma of patients with proteinuria (PSF = 472 +/- 125), as against normal weight normolipidemic control subjects (PSF = 32.76 +/- 2.67). A significantly negative correlation (r. -0.579; p less than 0.001) was found between serum albumin concentration and the logarithmic values of platelet sensitivity factor. Plasma von Willebrand factor activity expressed as a percentage of normal was also significantly (p less than 0.001) higher in proteinuric patients (287% +/- 25.8) than in control subjects (99% +/- 5.02), but this hemostatic variable did not correlate with the logarithm of platelet sensitivity factor. Platelet aggregability was higher in hyperlipidemic nephrotic patients than in proteinuric patients with normal serum lipids, while renal failure led to a decrease of platelet function. The raised plasma levels of von Willebrand factor noted in proteinuric patients were not influenced by either hyperlipidemia or by chronic renal failure. It is concluded that changes affecting platelet function in the nephrotic syndrome are produced by other mechanisms than these leading to an increase of endothelia-derived von Willebrand factor. Both changes may, however, contribute to the thrombotic tendency of nephrotic patients.

Plasma fibronectin and factor XIII in nephrotic syndrome.

When compared to control subjects plasma fibronectin and factor XIII as well as plasma fibrinogen, factor VIII-related antigen and serum cholinesterase were found to be significantly increased in nephrotic patients. Factor XIII activity was positively correlated with serum cholinesterase, while plasma fibronectin displayed weak correlations with plasma fibrinogen and factor VIII-related antigen. It is considered that increased levels of factor XIII and fibronectin should be related to the intensity of the liver's compensative response to proteinuria, although their turnover rates and the signals triggering this response may differ. It is however difficult to assess possible consequences of the above-mentioned changes for the evolution of the nephrotic syndrome.

Abortion prohibition and acute renal failure: the tragic Romanian experience.

During the period 1966-1989, pregnancy interruption was severely punished in Romania. However, natality rose only temporarily, while illegal abortions reached at least 3.36%/year and became the main etiology of ARF. From the 653 patients hemodialyzed for ARF during 1979-1989 in Cluj, 131 (20.07%) had abortions; during 1990-1993 only 3 (1.52%) had this diagnosis. Of the women with postabortion ARF, 71.64% were oligoanuric. The average duration of oligoanuria was 18.9 days, the longest reversible oligoanuria 89 days, the mean schedule of dialysis 1/2.98 days. Hysterectomy was performed in 44.3%; chronic renal failure occurred in 8.21% of the patients. Mortality rate averaged 14.92%, being greater in hysterectomized women (18.64%) and in those with a BUN over 150 mg% at admission. The survivors had to face the menace of imprisonment and the interrogation of prosecutors already in the hospital, regardless of their health problems.

Anatomo-pathologic observations on epidemic nephropathy.

Two cases of necropsy and 5 cases of renal biopuncture were studied on the occassion of an epidemic of "hemorrhagic fever with renal syndrome" identified in mountainous areas of Transylvania. The prevalent pathogenic process was capillary toxicosis which injured the renal tubules and vessels. The severity of the disease was determined by the phenomena of tubular failure, by the hemorrhagic syndrome and shock.

Calcitonin secretion in chronic renal patients treated with hemodialysis.

Calcitonin levels were studied in 18 patients with chronic renal insufficiency periodically hemodialysed, comparatively with 9 only drug-treated uremic patients. Calcitonin was radioimmunologically assayed before and after hemodialysis and repeated 5 months later in some of the patients. Serum calcitonin was increased in most of the studied patients, especially in the dialysed ones and with a creatinine clearance below 10 ml/min. Calcitonin concentration was all the more increased as the dialytic treatment lasted longer. Considering the increasing role of calcitonin as osteoprotector, these findings might be of interest in the treatment of renal osteopathy.

Hemostatic variables in nephrotic patients.

The paper reviews data in the literature as well as the authors' own investigations, performed during the last seven years, concerning the hemostatic balance in nephrotic patients. The obviously increased plasma levels of fibrinogen, fibronectin, fibrin-stabilizing factor XIII, clotting factors V and VIII, von Willebrand factor as well as the enhanced platelet aggregability of such patients, associated with a decreased plasma antithrombin III, are compatible with a thrombotic tendency. On the other hand the increased plasma protein C may provide a compensative antithrombotic mechanism. A rather complex behaviour of the fibrinolytic system was noted in the nephrotic syndrome. Actually the enhanced release of tissue plasminogen activator (t-PA) from the endothelia of nephrotic patients is accompanied by an accelerated lysis of dilute blood clots, although the inhibitors of fibrinolysis such as alpha 2-macroglobulin and alpha 2-antiplasmin are increased. Failure or exhaustion of the compensative antithrombotic mechanisms would accentuate the hemostatic imbalance and favour the occurrence of thrombotic events. It is considered that increased urinary loss of antithrombin III and the enhanced hepatic synthesis of clotting factors would represent the main mechanisms involved in the production of this precarious hemostatic balance of nephrotic patients.

[Amyloidosis associated with chronic hemodialysis. The prognostic significance of beta 2-microglobulin changes in patients with terminal chronic kidney failure treated by repeated hemodialysis]. / Amiloidoza asociata hemodializei cronice. Importanta predictiva a modificarilor beta 2 microglobulinei la bolnavii cu insuficienta renala cronica terminala tratati cu hemodializa iterativa.

In patients with chronic renal insufficiency (CRI) treated by programmed haemodialysis (HD) were detected, during the last years, amyloid stores at the level of carpal tunnel, of some joints, bones etc., finding which permitted to describe a new type of amyloid, the so-called "dialysis associated amyloid". The immunochemical structure of this amyloid is similar to that of the beta-2-microglobulin (beta-2m). Patients display various clinical manifestations. The variations of serum and urinary beta-2m were studied in 51 uraemic patients chronically dialyzed by means of dialyzers with cuprophan membrane, the average duration of the HD treatment being of 51.5 months. The pre- and postdialysis values of the beta-2-m were determined by Mancini radial immunodiffusion. A considerable increase--about 25 times--of serum beta-2-m was observed, which was more marked in anuric patients and those with a duration of more than 5 years of HD treatment. Among these, 15.7% show various articular manifestations (detected clinically and radiologically): a carpal tunnel syndrome (one patient required surgery) and arthropathies with various sites (scapulohumeral, knee). During a HD sitting with cuprophan membrane dialyzers, an increase of beta-Z-m was recorded, but it was statistically non-significant.(ABSTRACT TRUNCATED AT 250 WORDS)