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Biomedical subjects

K Andrassy

Publications and source records attributed to K Andrassy.

At least 145 records · Page 8Linked to original sources

Dialysis membranes and coagulation system.

Artificial membranes used for hemodialysis differ from endogenous membranes, i.e. endothelial cells, by their variable thrombogenicity. The key step in activation of the coagulation system by dialysis membranes is thrombocyte activation which is preceded by formation of a protein layer of critical thickness. Crucial questions concerning the quality of this protein membrane as a determinant of thrombocyte activation are not well understood. Activation of the contact phase of the intrinsic plasmatic coagulation system by dialysis membranes is well documented. Local action of thrombin in the membrane microenvironment is documented by release of fibrinopeptide A and deposition of fibrin on the membrane. Apart from thrombin, other mechanisms, e.g. PMN elastase, plasma-independent activation of blood cells, facilitatory action of erythrocytes etc., may play a contributory role. With respect to the polycarbonate membrane, some authors find less platelet extraction and unchanged platelet release reaction. In our own studies, polycarbonate membranes were not superior to cuprophane membranes with respect to thrombogenicity.

Animals↗

Different in vitro generation of C3d by cuprammonium and polycarbonate capillary hemodialyzers.

Cellulosic membranes have been shown to activate C3 via the alternative pathway. Generation of the stable product C3d was compared in polycarbonate (PC) and cuprammonium (CU) hollow-fiber minidialyzers with identical geometry, using an in vitro recirculation system with platelet-poor plasma (recirculation rate 20 ml/min; 1,600 fibers; 0.115 m2; 40 ml system priming volume; recirculation time 120 min). After extensive washing, residual protein was removed by reverse transmembrane pressure (1.5 bar) from the air-filled dialysate compartment. Such protein fraction, functionally defined as 'secondary membrane', was similar in quantity for PC and CU fibers. Plasma proteins were present in the membrane without selective adsorption (flat-bed polyacrylamide gel electrophoresis and rocket immunoelectrophoresis using monospecific antibodies). C3d, measured by immunoelectrophoresis, increased with time in the fluid phase compartment of both dialysers, but C3d generation was consistently and significantly (p less than 0.05) less in PC than in CU dialysers. The observation documents an activation of C3 with PC, in contrast to previous reports of no activation. However, C3 activation with PC was less intense than with CU.

Adsorption↗

Pharmacokinetics of erythromycin in patients with different degrees of renal impairment.

The kinetics of erythromycin (E.) was studied in 16 patients with different degrees of impairment of renal function after a single intravenous dose. Renal clearance of E. was found to be significantly correlated to the creatinine clearance. Total recovery in urine did not exceed 7.5%. As expected from the small fraction excreted via the kidneys, the elimination half-life and the total clearance of E. did not depend on renal function. We conclude that impairment of renal function does not justify a dose adjustment of E. Hearing acuity should, however, be monitored during treatment since transient deafness predominantly in patients with renal failure has been reported by various authors.

Adult↗

[Drug treatment of chronic glomerulonephritis: contra].

It is controversial whether the pathomechanisms involved in chronic idiopathic glomerulonephritis are susceptible to therapeutic intervention. Etiological therapy, i.e. elimination of the responsible antigen, is possible only in exceptional cases, e.g. tropical diseases, infected ventriculoatrial shunt etc. Antiinflammatory therapy directed against pathomechanisms initiating or maintaining glomerular inflammation has an uncertain theoretical foundation because of lack of knowledge relating to the exact steps mediating tissue injury. Recent studies suggest keyroles for terminal components of complement system, products of lipoxygenase pathway of arachidonic acid and oxygen radicals-all of which are not readily influenced by available therapeutic modulaties. Finally, progression of glomerular inflammation to renal failure is usually not the cause of cumulative acute inflammatory glomerular lesions but rather the consequence of progressive sclerosis of glomeruli, arterioles and interstitium. As examples of controlled intervention trials, studies on extramembranous and membranoproliferative glomerulonephritis are discussed. The studies show limited and not always statistically significant influence on renal function, however, at the expense of considerable side effects. It is concluded that it is highly questionable whether inflammatory pathomechanisms are influenced by currently available drugs. However, therapeutic nihilism is not appropriate given modalities to influence mechanisms of nonspecific damage, e.g. by antihypertensive medication or dietary intervention.

Azathioprine↗

Antimicrobial therapy in dialysis patients. I. Penicillins and cephalosporins.

Antibiotic therapy, using penicillins or cephalosporins, is frequently required in patients on maintenance hemodialysis. Points to consider are dose adjustment for drugs which are excreted via the kidney, drug dialysability, and cumulation with frequent occurrence of side reactions, neurotoxicity and bleeding being the clinically most important ones. For third-generation cephalosporins with N-methylthiotetrazole side chain, impaired intrahepatic vitamin K metabolism may cause problems of hemostasis which can be avoided by dose adjustment and prophylactic administration of vitamin K1.

Bacterial Infections↗

Hypertension in mesangial IgA glomerulonephritis.

Blood pressure in 75 patients with IgA nephropathy (IgA-GN), confirmed by renal biopsy, was related to clinical, immunological and morphological findings. The findings were compared with an age-matched control group of patients with non-IgA-GN. Overall prevalence of hypertension (HT) was similar in IgA-GN and non-IgA-GN (38.7% vs 38.2%). The presence of HT in IgA-GN was related to age, renal function, immunohistological pattern and degree of glomerular sclerosis or vascular lesions respectively. No correlation was found between HT and elevated serum IgA, circulating IgA immune complexes and IgA skin deposits. The current observations underline the value of hypertension for predicting development of renal failure. Vascular lesions are not only strongly correlated with, but may even precede development of, hypertension as confirmed by longitudinal observations.

Adolescent↗

Sicca syndrome in mesangial IgA glomerulonephritis.

Schirmer-test, history of conjunctivitis, salivary gland scintigraphy and SSA/SSB (Ro/La) antibodies were evaluated in 24 patients with mesangial IgA glomerulonephritis (IgA-GN), 58 patients with non-IgA-GN and 100 healthy controls. A sicca syndrome (positive Schirmer-test) was found in 46% of patients with IgA-GN and 17% of non-IgA-GN and 8% of controls (p less than 0.001). Only one of the IgA-GN patients volunteered a history of xerosis of the conjunctiva, but upon questioning 17% reported a history of ophthalmological treatment for recurrent conjunctivitis. The observation adds another extrarenal facet to the syndrome of mesangial IgA-GN. Diminished tear production may be another (immune?) abnormality of the oropharyngeal system.

Adolescent↗

Possible coumarin-like mechanism of action for cephalosporins.

In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K1 was injected to investigate whether this was followed by an increase in vitamin K1 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K1-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K1-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K1-epoxide plasma concentrations following injection of 10 mg vitamin K1, whereas in normal subjects only traces of K1-epoxide could be detected (less than 0.030 micrograms/ml). The K1-epoxide concentrations found in our three patients treated with cephalosporins were 0.12, 0.16 and 0.19 micrograms/ml, respectively. This indicates that latamoxef or cefazedone might reduce clotting factor synthesis by a coumarin-like mechanism of action in these patients. Although the effect of cephalosporins in enhancing vitamin K1-epoxide plasma concentrations is less than that of coumarins, it might cause severe hypoprothrombinaemia in the presence of latent vitamin K deficiency.

Aged↗

Evidence for impaired hepatic vitamin K1 metabolism in patients treated with N-methyl-thiotetrazole cephalosporins.

In 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin K1 was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause of bleeding complications and depression of vitamin K1-dependent procoagulants in patients treated with the new class of cephalosporins.

Aged↗

[Vaccination of uremic patients against hepatitis B].

Hepatitis B vaccine (Merck, Sharp & Dohm) was administered according to various vaccination schedules to 12 patients in preterminal renal failure without haemodialysis treatment, 81 patients on a chronic haemodialysis programme and 43 staff of a nephrological centre. After three-times vaccination (at 0, 1, 6 months) with 20 micrograms HBs antigen, seroconversion occurred in 91% of persons without kidney disease. A double dose (40 micrograms) was given, at the same time intervals, to 29 dialysis patients, with a seroconversion rate of 55% and titre levels less than in those without renal disease. Of 26 dialysis patients given the same dose (40 micrograms) five times (at 0, 1, 2, 4, 6 months), 63% achieved seroconversion with a definitely higher anti-HBs titre than those dialysis patients vaccinated only three times. Passive-active vaccination with 40 micrograms HBs antigen (at 0, 1, 2, 4, 6 months) as well as 3 ml hepatitis B immunoglobulin (at 0, 2 months) was given to 26 dialysis patients. There was a comparable frequency of seroconversion (58%) and a comparable titre rise to those obtained with active vaccination alone. Twelve pre-uraemic patients not requiring dialysis (serum creatinine 753 +/- 184 mumol/l) also were actively vaccinated three times, the results not differing from those in dialysis patients. The findings indicate that patients with renal disease potentially needing dialysis should, in the early stages of renal failure (serum creatinine less than 500 mumol/l) be vaccinated with hepatitis B vaccine.

Antibody Formation↗

Deposition of polymeric IgA1 in idiopathic mesangial IgA-glomerulonephritis.

IgA deposits in kidney and skin biopsies from patients with idiopathic mesangial IgA-glomerulonephritis were characterized with immunofluorescence microscopy using monoclonal antibodies against the IgA subclasses IgA1 and IgA2. IgA1 was the major constituent in all biopsy specimens. Double immunofluorescence microscopy showed that IgA deposits were constantly associated with J-chain. Secretory component was never found in the deposited material. In vitro fixation of free secretory component, however, was observed in some biopsies. These findings indicate that most if not all of the deposited IgA in patients with idiopathic IgA-glomerulonephritis is polymeric in nature.

Adolescent↗