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Biomedical subjects

K Sack

Publications and source records attributed to K Sack.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Diagnostic value of lymphocyte differentiation in the early phase following kidney transplantation].

In 50 patients who had a renal transplantation, treated with ciclosporin, regular monitoring of lymphocyte subpopulations was undertaken prospectively to assess its value with respect to cellular rejection, herpes virus infection, and ciclosporin overdosage. Herpes virus infection was characterized by inversion of the T4/T8 ratio below 1.0 (sensitivity 90%, specificity 88%), caused by proliferation of the T8 subpopulation, which--compared with the findings in patients with rejection crises--was significantly raised (P less than 0.001). But such rejection crises could not be predicted from the T4/T8 ratio. Ciclosporin had no effect on the ratio, total lymphocyte count in this group being higher (P less than 0.002) than in patients with rejection.

Creatinine↗
PubMed1988

[Therapy of amyloid nephrosis in Crohn disease: plasmapheresis plus azathioprine?].

A 38-year old woman with serious nephrotic syndrome due to kidney amyloidosis in consequence of Crohn's disease was observed. The long-term prognosis of this illness is serious, but since in the literature several good results have been mentioned under treatment with immunosuppressives, in the present case an aggressive immunosuppression was carried out, which was started under the conception that, in consequence of elimination of preamyloid substances from the serum by plasmapheresis in combination with an additional inhibition of the reproduction of these substances by azathioprine, the clinical picture could be favourably influenced. During therapy with long-term intermittent plasmapheresis in combination with azathioprine a complete remission of the nephrotic syndrome was achieved.

Adult↗
PubMed1987

Fosfomycin protects against tubulotoxicity induced by cis-diaminedichloroplatin and cyclosporin A in the rat.

The nephroprotective effect of fosfomycin against tubulotoxicity induced by cis-diaminedichloroplatin (DDP) and cyclosporin A (Cs) was studied in the rat. The parameter of nephrotoxicity was urinary tubular cell excretion. The experiments revealed that fosfomycin, given either concomitantly or in advance was able to reduce the nephrotoxic effect of DDP and Cs significantly. We conclude from these studies that fosfomycin is a broad-spectrum nephroprotective agent.

Animals↗
PubMed1987

[Experimental studies of the nephroprotective effect of fosfomycin].

We studied in an experimental rat model, if fosfomycin reduces the tubulotoxicity induced by tobramycin, teicoplanin, cisplatin or ciclosporine A and is thus a nephroprotective agent. 10 female wistar rats per dose and compound were used, measures of tubulotoxicity were urinary excretion rates of tubular cells and malate dehydrogenase on 5 successive days. Fosfomycin proved to be a potent nephroprotector against all 4 nephrotoxins. Its activity was not based on pharmacokinetic interactions but on a pharmacodynamic effect. Presumably, fosfomycin stabilises the membranes of lysosomes in tubular cells.

Acute Kidney Injury↗
PubMed1987

Teicoplanin: renal tolerance and pharmacokinetics in rats.

The nephrotoxicity and pharmacokinetics of teicoplanin were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary excretion of tubular cells and malate dehydrogenase. The experiments revealed that 1 mg/kg or more of teicoplanin daily resulted in an increase of excretion rates of tubular cells. Similarly to vancomycin, teicoplanin is accumulated in the kidneys. Nephrotoxicity induced by teicoplanin can be reduced by coadministration of fosfomycin and D-glucaro-1.5-lactam, and enhanced by administration of tobramycin. We conclude that renal function should be monitored closely during teicoplanin therapy.

Animals↗
PubMed1985

Influence of immunosuppressive therapy with azathioprine and prednisolone on serum-immunoglobulin concentration in renal transplanted patients.

Serological diagnosis of infectious diseases are based on the assumption that a change in virus-specific antibody - titer reflects the response to a certain viral infection due to changes in the concentration of the respective virus - specific antibodies. On the other hand immunosuppressive medication interacts with that system responsible in producing antigen-specific antibodies. This study was outlined therefore to follow the variation of the concentration of serum immunoglobulins of classes IgG and IgM with regard to a better evaluation of virus-specific antibody titers especially for those viruses that remain persistent after a primary infection and an reactivate. The study followed ten patients after allogenic cadaver kidney transplantation under immunosuppressive medication with azathioprine and corticosteroids. Concentration of serum-IgG and -IgM protein was continuously measured for 6 months after transplantation along with measurement of virus-specific antibody-titers with enzyme immunoassay (Elisa) especially for cytomegalovirus. The results show a drastic decrease in serum immunoglobulins IgG and IgM - the lowest concentration being reached 25-50 days after transplantation. The concentration of IgG increased thereafter if no severe infectious diseases occurred during the post-transplant period. The concentration of IgM seems to react more sensitively upon infectious processes. In general, virus-specific antibody-titers (IgG) follow the sometimes drastic variation in the respective immunoglobulin class. It therefore reveals that antigen-specific antibody-titers in those patients should be controlled continuously during the time after transplantation for better evaluation of titer variations that eventually occur in correlation to the absolute concentration of the immunoglobulin class.

Adult↗
PubMed1985

[Herpes simplex infection after kidney transplantation under immunosuppression by cyclosporin. Diagnostic and therapeutic experiences].

Incidence and course of herpes simplex infections was determined prospectively in 22 patients who had a kidney transplant and were treated with cyclosporin. In addition to clinical findings, serial studies were undertaken of throat washings for herpes simplex virus in cell culture, as well as of patient sera for herpes-specific IgG and IgM antibodies. There were 13 clinically manifest infections, 12 of them localized, while one had dissemination with necrotizing retinitis. Virus demonstration was successful in all cases in which virostatic drugs had not yet been used. Asymptomatic virus excretion was noted in three cases. Significant IgG titre rise occurred in six of the 13 cases, but a positive IgM titre in only two. Acyclovir proved to be an effective virostatic drug with few side effects. The outcome in the localized infections was favourable, but in the disseminated one residual defects remained.

Acyclovir↗
PubMed1985

Renal tolerance of imipenem/cilastatin and other beta-lactam antibiotics in rats.

Imipenem is inactivated by the renal dehydropeptidase I, which can be inhibited by cilastatin. Therefore, both compounds are administered in combination. According to the manufacturers, they are not nephrotoxic in rats. 70 female Wistar rats (n = 10/test series) were treated over five days at dosage intervals of 12 hours with intraperitoneal injections (injection volume: 10 ml/200 g body weight) of isotonic 0.9% NaCl, cilastatin (1000 mg/kg/day), imipenem (500 and 1000 mg/kg/day), cilastatin + imipenem (500 or 1000 mg/kg/day each) and cefsulodin (1000 mg/kg/day). The nocturnal excretion of renal tubular cells was determined. Furthermore, three rats in each test were treated intraperitoneally with 150 mg/kg imipenem or with the combination of imipenem and cilastatin (150 mg/kg each). Imipenem concentrations were measured over four hours in the blood of the tail vein. Commencing on the second day of study, cilastatin, imipenem and the combination of both substances induced significant surplus excretion of tubular cells compared to the control group. The tubulotoxic effects of imipenem and imipenem + cilastatin in combination were dose-dependent. The toxic effects of imipenem, imipenem + cilastatin and cefsulodin did not significantly differ. Cilastatin prolonged the half-life of imipenem in the blood from 0.4 to 0.9 h and increased the AUC of imipenem from 156 to 325 mg/l/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The therapeutic response of cephalosporin-treated E. coli pyelonephritis of the rat, in relation to variations of the infection model.

In the E. coli pyelonephritis, induced in female Wistar rats by retrograde infection (high pressure reflux), we investigated the influence of 1) the time of commencement of therapy, 2) the renal bacterial counts, i.e. the inflammatory activity of the pyelonephritis after endovesical instillation of cultures with different bacterial concentrations, and 3) the level of infection resistance of the experimental animal strain on the therapeutic response of the model infection with single doses of cefoxitin (150 mg/ml) and cefotaxime (5 mg/ml). Early commencement of therapy post inoculation was therapeutically advantageous provided the intrarenal multiplication of the infective organisms was not delayed or the initial bacterial concentrations were not too high. The mild form of pyelonephritis with lower renal bacterial concentrations and poor inflammatory activity after endovesical instillation of a low inoculum (10(4) cfu/ml) was less amenable to treatment than the inflammatory active pyelonephritis with high renal bacterial counts, using a high inoculum (10(7) cfu/ml). High renal bacterial counts after retrograde inoculation of an E. coli culture of 10(8) cfu/ml resulted in significant reduction of bacterial counts 48, 72 and 96 h post infectionem, with i.m. application of cefoxitin 12 h prior. For Wistar rat strain Bor:WIST, which showed a stronger infection resistance with lower renal bacterial concentrations and a stronger tendency to spontaneous healing, application of a single dose of cefotaxime (5 mg/ml) was therapeutically ineffective, whereas, in contrast, with Han: WIST rats the acute phase of E. coli pyelonephritis could be treated effectively.

Animals↗
PubMed1985

Bactericidal activity and induction of cell volume alterations of cephalosporins in Escherichia coli.

The bactericidal efficacy of cefuroxime and cephacetril on Escherichia coli cultures was measured by killing curves. Simultaneously bacterial cell volumes were analysed by electronic particle counting using a Coulter Counter Channelanalyser system in order to study the relationship between bactericidal activity and bacterial cell volume alterations. Various concentrations (2-120 mg/l cefuroxime and 16-120 mg/l cephacetril) and different exposure times (over a time period of 12 h) were used. Growth medium was human plasma ultrafiltrate. The bactericidal activity of cefuroxime, as measured by the rate of killing of the E. coli culture, was independent of the concentration and constant in the range 4-120 mg/l. The characteristic cefuroxime-induced change in bacterial cell volume was a marked volume increase up to a maximum of 5-fold after 160-200 min exposure with a low-grade bacteriolysis following. The cefuroxime-induced bacterial volume changes were, in accordance with the bactericidal testing, almost independent of the concentration. In contrast, the killing curves for cephacetril strongly depended on the drug concentration. However, this effect was short-lived and regrowth of the E. coli culture followed. The typical cephacetril-induced volume distribution curves were also highly concentration-dependent. With increasing drug levels bacterial cell volume increased up to 20-fold, and regrowth of a persisting bacterial population occurred at lower antibiotic concentrations. Bacteriolysis started earlier than with cefuroxime. The relationship between loss of viability and cell volume increase was more marked with cefuroxime than with cephacetril.

Autoanalysis↗
PubMed1985

Habekacin: nephrotoxicity, pharmacokinetics and prophylactic efficacy in rats.

1-N[(S)-4-amino-2-hydroxybutyryl]-kanamycin B (habekacin), a new aminoglycoside antibiotic found in 1973 was tested for its nephrotoxicity, pharmacokinetics and prophylactic efficacy in 351 female rats. Increased urinary elimination of tubule cells and malate dehydrogenase (MDH) demonstrated tubulotoxicity even at the minimal dosage of 2.5 mg/kg/d. At high dosages (100 or 50 mg/kg/d) habekacin produced more tubule damage than dibekacin. At lower dosages (20, 10 or 5 mg/kg/d) both aminoglycosides showed similar effects. Additionally, possible glomerular lesions were found at high dosages (100 mg/kg/d) as indicated by proteinuria, CAF (cellulose acetate foil)-electrophoresis of the urinary protein and raised albumin/globulin ratio. - Pharmacological studies revealed serum concentrations similar to dibekacin, in renal tissue, however, the concentrations of habekacin were much higher than those of dibekacin. - In experimental E. coli pyelonephritis, 9 single doses of habekacin or dibekacin (5 mg/kg) given prophylactically reduced the bacterial counts significantly; a single dose of the antibiotics (5 mg/kg) was slightly effective.

Aminoglycosides↗
PubMed1985

Nocardial infection in a renal transplant recipient--a case report.

Report is given about a 50 year old renal transplant recipient who developed signs of a severe pneumonia 37 days post transplantation. The diagnosis following chest X-ray and physical examination was multifocal nodular pneumonia of unknown origin in an immunosuppressed patient. Although a varying antibiotic chemotherapy was administered at high doses he died 4 weeks later without identification of the infective agent. Post-mortem and microbiological examinations revealed a systemic suppurative infection caused by Nocardia asteroides. Percutaneous or open lung biopsy within the first 10 days after onset of clinical symptoms has to be recommended to secure the diagnosis and treatment with sulphonamides.

Abscess↗
PubMed1984

[Serologic diagnosis of cytomegalic inclusion disease using the Elisa technic in kidney transplant patients].

During the first six months after transplantation cytomegalovirus-(CMV-)specific serum IgM and IgG antibody titres were determined regularly with the Elisa technique in 25 renal transplant recipients and compared with results of the complement binding reaction (CBR). Active CMV infection was diagnosed in six patients: two primary infections and four reactivations. Titres of 1 : greater than 40 were considered positive. IgG titre increases of up to 1 : 20 000 and of 1 : 4000 for IgM were observed. IgM titres of 1 : greater than 200 are suspicious of active CMV infection, four-fold titre increases establish the diagnosis. Such IgM titres were accompanied by clinical symptoms of active CMV infection. The Elisa technique is a reliable method from the first week of disease for early demonstration of CMV infection. The prognostically relevant differentiation between primary CMV infection and reactivation of latent disease is possible using the IgG/IgM antibody titre relations. IgM titres indicate cure or persistence of infection. CBR with CMV antigen is of no use for diagnosis.

Adult↗
PubMed1984

Standardization of a model of E. coli-pyelonephritis in rats.

The validity of preclinical testing of antibiotics in animal experiments is highly dependent on the quality and, especially, the standardizability of the infection model. Some of the factors associated with standardization of the acute phases of infection are demonstrated for experimental pyelonephritis in female albino Wistar rats after transuretheral infection. The renal bacterial count and infection rate are correlated to the volume and bacterial concentration of the instilled E. coli suspension. Strains of albino Wistar rats from different breeding institutions show differing resistance to the infection. E. coli pyelonephritis establishes more easily in female Wistar rats of strain Han: WIST than in strain Bor: WIST. Following dissection of the animals, the infected kidneys can be stored for at least 4 weeks at -30 degrees C or in liquid nitrogen, because the bacterial counts remain constant. However, in frozen renal homogenates the bacterial counts fall rapidly. During the first 4 post-infection days the bacterial content of the kidneys is relatively constant. The period 30-72 h post infection is especially suitable for therapeutic studies.

Animals↗
PubMed1984

Analysis of cephalosporin-induced changes in the volume distribution of Escherichia coli cultures by an electronic counter-channelanalyser.

The demonstration of morphological alterations of the bacterial cell together with bactericidal kinetics are of value for the description of the antibacterial activity of beta-lactam antibiotics. One of the indicators of antibiotic effect on bacterial morphology is the change in bacterial cell volume. This can be demonstrated graphically and numerically by means of electronic cell counting and volume distribution analysis using the Coulter Counter-Channelanalyser system connected to a computer. After registration of the distribution of the relative volume of the Escherichia coli population, the mean cell volume was calculated. The latter parameter increased more than 6 fold with increasing cefotaxim-exposure times. The onset of the delayed (2 h after cefotaxim administration) bacteriolytic effect was reorganized by the appearance of small cell breakdown particles and quantified by counting. In order to demonstrate the therapeutic process graphically the distribution curves were transformed to a common scale. Since a complete storage of the data per sample is performed normally within one minute, the Coulter Counter-Channelanalyser technique can be carried out simultaneously with the bactericidal kinetic experiment. The data demonstrate the speed and intensity of the morphological cell alterations induced by the beta-lactam antibiotic.

Bacteriological Techniques↗