[Thrombosis of the inferior vena cava in Behçet disease]. / Thrombose der Vena cava inferior bei Morbus Behçet.

Behçet's disease is considered to be a systemic process caused by a nonspecific vasculitis with a diversity of symptoms. It is defined by the coexistence of aphthous stomatitis, genital ulcerations, inflammatory conditions of the eye such as iritis and dermatological changes. Cardiovascular involvement includes both arteries and veins. We report an unusual case of thrombosis of the inferior vena cava with extensive collateral circulation of the superficial abdominal and paravertebral veins due to Behçet's disease diagnosed by phlebography and magnetic resonance imaging.

Renal tolerance of fleroxacin in healthy volunteers.

In order to evaluate kidney tolerance of fleroxacin, a new fluoroquinolone, we performed a volunteer study with 16 healthy males, 20-27 years old. On three consecutive days 800 mg of fleroxacin was administered orally. Alanine-aminopeptidase and distal- and pan-tubular antigens were determined in 24 h urine collections with specific monoclonal antibodies. Routine haematological and biochemical parameters were determined daily and were in the normal range during the follow-up. No significant changes in excretion of alanine-aminopeptidase and of the urinary antigens were observed during the three days of fleroxacin administration and on the following three days. The results obtained in this volunteer study indicate that fleroxacin has no nephrotoxic side effects.

Investigation on renal tolerability of ciprofloxacin with tests based on monoclonal antibodies.

The results obtained during the investigation on the excretion of nine urinary antigens originating in the kidney and characterized by monoclonal antibodies and of the brush-border marker-enzyme alanine aminopeptidase in the urine of 12 volunteers before and during the administration of therapeutic doses of ciprofloxacin on seven consecutive days gave no indication that this drug exerts tubulo-toxic side effects. The mean excretion curves showed no significant increases during ciprofloxacin treatment for any of the nine kidney-derived antigens. The measured antigen-excretion courses correlated with the curve of the excretion of AAP, which was measured as a marker for the brush border of the proximal tubule, and also with the course of the fluid elimination. There was no indication of selective damage to the distal section of the tubular apparatus resulting from possible crystalluria. These results, as well as the fact that all the other laboratory parameters were within the normal range, indicate that the kidney function of the volunteers was normal during the observation period and that ciprofloxacin is tolerated by the kidney.

Identification of fragments of proximal and distal tubular cells in the urine of patients under cytostatic treatment by immunoelectron microscopy with monoclonal antibodies.

In an attempt to identify the origin of cellular fragments released in the urine of patients treated with potentially nephrotoxic drugs such as cytostatics, two monoclonal antibodies were applied: monoclonal antibody PM II 9 C2, directed against an antigen in distal tubular cells; and monoclonal antibody PM II 39 H11 specific for an antigen in proximal tubular cells. The specificities of both monoclonal antibodies were elaborated in the indirect as well as in the direct immunofluorescence technique. Both antibodies were then used to identify cellular fragments obtained from the urine of patients treated with cytostatic drugs by ultracentrifugation. By application of the indirect immunogold method, it was shown that material of proximal as well as distal tubular origin was shed by the damaged cells. Whereas the proximal tubular antigenic epitope recognized by PM II 39 H11 was always found in large irregular complexes of debris-containing vesicles, the distal tubular antigenic epitope recognized by PM II 9 C2 was always found associated with filament-like regular structures. This is the first report in which excretion of components of distal tubular cells is demonstrated as a consequence of the nephrotoxic side effects of cytostatic treatment. With the help of monoclonal antibodies, it has now become possible to identify and to investigate the damage inflicted on the distal part of the tubule system in addition to the well-documented proximal tubular damage.

Kidney-derived urinary antigens assayed with monoclonal antibodies for the detection of renal damage.

For the quantitation of kidney-derived Urinary Antigens (UA) monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron were applied in sandwich ELISA. Antigen excretion was measured in the urine of healthy individuals, patients suffering from various diseases, kidney transplant recipients, and healthy volunteers receiving therapeutic doses of antibiotic drugs. In healthy individuals, in patients with diseases primarily affecting the glomerulus, and in inactive phases of chronic diseases antigen excretion was low. Toxic drug effects enhanced antigenuria. Excretion of some or all of the antigens always indicated tubular alterations. The tests thus provide information on location and extent of acute primary tubular damage.

Urinary kidney-derived antigens determined by tests built on monoclonal antibodies: new markers for kidney damage.

We have developed a series of sandwich ELISA for the quantitation of kidney derived urinary antigens (UA) utilizing monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron of human kidney. Antigens derived from the distal and proximal parts of the tubular system as well as antigens localized over its entire length can be detected and quantified in urine samples. Antigen excretion was measured in the urine of healthy individuals, patients with various diseases with and without kidney involvement, kidney transplant recipients, and healthy volunteers after receiving antibiotics. Low antigen excretion values were found in healthy individuals, patients with diseases primarily affecting the glomerulus, and inactive phases of chronic diseases. Toxic side effects of drugs were reflected by slightly (antibiotic drugs) or strongly (cytostatic drugs) enhanced antigenuria. Excretion of some or all of the antigens was always indicative of massive alteration of tubular structures, such as in acute phases of tubulointerstitial disease or during rejection episodes in kidney transplant recipients. The results obtained indicate that it is possible to obtain information on the location and extent of acute primary processes in the kidney with these tests.

[Immunodiagnosis of kidney tubular cell injuries using specific anti-membrane antibodies]. / Immundiagnostik tubulärer Zellschäden der Niere mit Hilfe spezifischer Antimembran-Antikörper.

In contrast to healthy persons, microvillous antigens of the proximal tubule were excreted at an increased rate in patients with kidney diseases as could be shown using specific antisera against brush border (BB) fragments (tissue-proteinuria, histuria). These urinary membrane components were immunologically completely identical with those antigens prepared from isolated kidney cell membranes. A glycoprotein of 240 000 dalton, containing mannose and N-acetylglucosamine was identified as a major immunoreactive constituent of the brush border surface and found to be part of a multienzyme complex. BB-antigens were excreted in urine of patients with glomerulonephritis, hypertension, pyelonephritis, multiple myeloma, after operations, after kidney transplantation, under cytostatic treatment, and after administration of radiopaque agents. Histuria of BB-antigens was significantly higher in patients with multiple myeloma and Bence-Jones-proteinuria compared to those patients where no Bence-Jones L-chains in urine became apparent. Selective kidney angiography and intravenous urography caused a significantly higher output of BB-antigens as compared to the control period (2 p less than 0,005). In a volunteer model, on the basis of BB-histuria, a different nephrotoxic potency of cephalosporins and aminoglycosides arose. In addition, beside soluble BB-antigens, also high molecular weight membrane vesicles were discovered in urine of patients after cytostatic treatment (cis-platinum), after x-ray contrast media, and after kidney transplantation. Both, soluble as well as supramolecular membrane vesicles were isolated from urine applying immunospecific affinity chromatography (anti-BS-agarose beads). Labeled antisera directed against the vesicle material of urine revealed a specific immunofluorescence of cortical tubule only.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of subtotal nephrectomy on the excretion of urinary alanine aminopeptidase and gamma glutamyltransferase in the male Wistar rat. A long-term study.

The study of alanine aminopeptidase (AAP) and gamma glutamyltransferase (GGT), two integral components of the brush border membrane of the proximal kidney tubule, has generated considerable interest for research on the nephrotoxicity of drugs. AAP and GGT activity in urine correlate strongly. The three phases after a subtotal nephrectomy can be described as follows: the first phase, lasting 1 month, is characterized by an abrupt decrease of 70% in AAP and GGT activity, corresponding to the excised kidney mass. During the second phase, a partial recovery occurs representing nearly 50% of the AAP and GGT activity in the control group (30th to the 75th day after nephrectomy). These activities begin to decrease slightly in the third phase until the end of the experiment. In terms of remaining kidney mass, the results demonstrate a twofold increase of the AAP and GGT activity. The same phenomenon can be seen in the excretion of creatinine, except that the compensatory activity is multiplied by four in the remaining kidney. Good correlations between AAP activity, GGT activity, urinary creatinine, 24-hour urine volume, and 24-hour creatinine output are found in both experimental and control groups.

Enzymuria: a parameter for the assessment of potential nephrotoxicity of cephalosporins.

Ten informed healthy volunteers with normal renal function received 2 X 3.0 g ceftazidime on three consecutive days. The combination of the same dose of ceftazidime together with tobramycin (3 mg/kg/d) was administered four weeks later to the same group of volunteers. In the first trial with ceftazidime alone no changes in the elimination of brush-border membrane enzyme AAP were found. In contrast, the administration of ceftazidime together with tobramycin produced the expected response to tobramycin with the cumulative pattern of enzyme elimination into urine. Functional parameters remained unchanged.

Hepatitis B vaccine: safety study in anti-HBs seropositive human volunteers.

HBsAg, which has been purified from HBsAg and HBeAg positive plasma, was repeatedly applied to human volunteers, who were seropositive for anti-HBs. The intramuscular or subcutaneous injections caused a clear booster effect on anti-HBs concentrations in serum. The injections were well tolerated. Only minor local side effects occurred. Vaccination left serum transaminase activities unaffected. None of the volunteers developed serologic or clinical signs related to viral hepatitis.

Hepatitis B vaccine: safety study in anti-HBs seronegative human volunteers.

A hepatitis B vaccine which has been prepared from HBsAg and HBeAg positive human plasma and which consists of purified HBsAg in an alum suspension was investigated for safety and immunogenicity in a clinical trial. Twenty-three anti-HBs seronegative volunteers received three injections each of 40 micrograms HBsAg intramuscularly. No rise in serum transaminase activities occurred during the follow-up period, and none of the volunteers developed clinical signs related to viral hepatitis. Only minor side reactions like burning or reddening at the site of injection were reported by the volunteers. 100% seroconversion occurred within 150 days after first vaccination. The subsequent two vaccinations caused a strong booster effect.

Assessment of the nephrotoxic potential of ceftazidime and a ceftazidime/tobramycin combination in volunteers.

Ten informed healthy volunteers with normal renal function received 2 X 3.0 g ceftazidime intravenously for three consecutive days. Four weeks later, ceftazidime was combined with 1 X 3 mg/kg body weight tobramycin, administered intramuscularly, for three consecutive days. The effect of the two treatments on parameters used to assess renal function was examined prior to administration, during administration for three days and for a follow-up period. Alanine-aminopeptidase (AAP) levels in 24 h urine samples were measured in addition to kidney function parameters. The urine from the volunteer who had shown the highest AAP levels in each series was examined by ultracentrifugation for the presence of membrane particles with AAP activity. Ceftazidime showed no effect on the proximal tubular membrane. No increased elimination of AAP could be demonstrated. The kidney function parameters remained unchanged. The combination of ceftazidime with tobramycin led to a cumulative increase in AAP activity which was not significantly different from the increase observed when the same dose of tobramycin is administered alone. No additive effects could be demonstrated. Ultracentrifugation showed no indication of an impairment of the membrane integrity when ceftazidime was administered alone or in combination with tobramycin.

[Kidney tolerance of fosfomycin in humans with normal kidney function (author's transl)]. / Untersuchungen zur Nierenverträglichkeit von Fosfomycin bei normaler Nierenfunktion.

In a study with informed healthy volunteers Fosfomycin and their renal tolerance was under investigation. 6 volunteers received 15 g Fosfomycin on three consecutive days. The activity of the brush border enzyme alanine-aminopeptidase (AAP) in 24-hour urine has been measured. It could be demonstrated that these high dosages of Fosfomycin have been without any influence on the membrane integrity. Functional parameters as creatinine-clearance remained unchanged as well.

Development of a radioimmunoassay for a high molecular mass tubular antigen in urine--its application for early detection of tubular damage.

In order to isolate urinary kidney antigens, the gammaglobulins fraction of an antiserum against human kidney cortex plasma membranes was coupled to Sepharose 4B. By immunospecific affinity chromatography an antigen fraction was obtained from the urine of a patient suffering from severe kidney disease. After gel filtration, the main fraction, eluted with the exclusion volume of a Sephadex G-200 column and enriched 16 000-fold, was labelled with 131I and used in a radioimmunoassay system. Soluble kidney antigens, presumably of proximal tubular origin, could be detected and quantified by the assay system in urine samples of patients with various diseases. The samples did not need to be treated, either concentrated or dialyzed, before application. The results of our experiments show a correlation between antigen excretion and kidney damage. Rejection episodes in patients with kidney transplants could be recognized early by enhanced antigen excretion. Potentially nephrotoxic drugs caused antigen excretion as well. In normal, healthy subjects output of the antigen was very low. The assay system might be of value for monitoring renal diseases.