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Biomedical subjects

K M Koch

Publications and source records attributed to K M Koch.

At least 163 records · Page 9Linked to original sources
PubMed1990

Continuous arteriovenous hemofiltration: in vivo functional characteristics and its dependence on vascular access and filter design.

The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Renal elimination of beta-2-microglobulin and myoglobin in patients with normal and impaired renal function.

Since the demonstration that beta 2-microglobulin (beta 2M) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of beta 2M, polyfructosan (an inulin analogue), and a second low-molecular-weight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of beta 2M significantly exceeded that of polyfructosan (0.198 +/- 0.037 vs. 0.182 +/- 0.05; p = 0.04), while that of myoglobin (0.177 +/- 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the beta 2M extraction decreased to 0.110 +/- 0.060 (p less than 0.01 vs. extraction of polyfructosan or myoglobin). This decrease was significantly correlated with the decrease of the endogenous creatinine clearance or the total or unilateral 131I-hippuran clearance. These results indicate that in normal renal function the glomerular filtration of beta 2M may be supplemented by a peritubular mode of removal. The mechanism(s) underlying the selective decrease of beta 2M extraction in kidneys with reduced function remain speculative. However, this decrease will lead to a further augmentation of the retention of beta 2M in renal failure.

Female↗
PubMed1990

Urinary IgA, secretory IgA and secretory component in women with recurrent urinary tract infections.

Urinary secretory IgA (sIgA), consisting of free secretory component (FSC) and dimeric IgA, is involved in the defense against urinary tract infections (UTI). Recurrent UTIs (rUTI) have been suggested to be associated with a defective excretion of sIgA. Therefore urinary sIgA, FSC and serum-type IgA concentrations were measured by ELISA in 68 normal women, 10 asymptomatic women with rUTIs and no urological abnormality (group A), 8 asymptomatic women with rUTIs and a urological abnormality (B), 4 women with acute UTI (C) and 5 women with a selective serum IgA deficiency (D). Annual UTI rates were increased in groups A, B and C, but normal in group D. In no patient group urinary FSC concentration was different from the normals, while sIgA concentrations were increased in group C, markedly reduced in group D, but normal in groups A and B. Urinary serum-type IgA concentrations were significantly increased in group A and C, markedly reduced in group D and normal in group B. These results demonstrate that the urinary sIgA system participates in the immune response to bacterial infections, but that even a complete failure of the sIgA system does not lead to an increased UTI rate. Furthermore, no association of recurrent UTIs with disturbances of the urinary sIgA excretion could be demonstrated.

Adolescent↗
PubMed1990

Adverse cardiovascular effects of partial correction of renal anemia by recombinant human erythropoietin.

The analysis of the hemodynamic parameters involved in the regulation of blood pressure during correction of anemia shows - although peripheral resistance and cardiac output behave qualitatively as in the nonuremic patient - that the extent of change may be inadequate resulting in an increased blood pressure. The underlying mechanisms are not yet fully understood but to a greater part may be related to preexisting pathology due to a history of long-lasting hypertension. To avoid cardiovascular complications under rhEPO therapy the following should be considered: patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk for developing hypertension under rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. Further studies will demonstrate whether in addition to the benefit of a very low maintenance dose of rhEPO subcutaneous administration will also contribute to the reduction of the incidence of hypertension.

Anemia↗
PubMed1990

Calcium channel blockers for kidney protection.

Acute postischemic renal failure (ARF) is a major complication in surgery and in particular in renal transplantation. Calcium channel blockers (CCBs) are able to prevent or ameliorate ARF in different experimental models when given before ischemic injury. Because ARF, which is observed in 20-60% of graft recipients, carries the risk of undetected rejections and nephrotoxic injury and is also expensive, we tested the hypothesis, suggested by animal experiments, that there is also a beneficial effect of CCBs when given after ischemic injury. A total of 134 recipients of first or second cadaver grafts were randomly assigned to a diltiazem pretreatment (DZ) or control (C) group. Kidney grafts were pretreated immediately prior to transplantation by reperfusion with 500 ml Euro-Collins (preservation fluid), with or without DZ. The DZ patients also received a 74-h infusion of DZ (0.12 mg/kg/h), starting 2 h prior to surgery. DZ was continued (90 mg b.i.d. p.o.) until day 30. Immunosuppression consisted of low-dose steroids and cyclosporine A (CSA) (10 mg/kg p.o.). CSA was instituted 6 h after surgery and later adjusted to achieve whole-blood trough levels of 300-600 ng/ml [by polyclonal radioimmunoassay (RIA)]. A total of 129 patients were available for efficacy analysis. There were no significant differences concerning donor demographics, human lymphocyte antigen (HLA) match, or ischemic times. ARF was defined as a need for dialysis in the first week. Our data show a significant reduction in ARF in grafts pretreated with DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Differences in the synthesis and kinetics of release of interleukin 1 alpha, interleukin 1 beta and tumor necrosis factor from human mononuclear cells.

Cell-associated and secreted interleukin 1 alpha (IL 1 alpha), IL 1 beta and tumor necrosis factor alpha (TNF-alpha), produced by human mononuclear cells (MNC) in vitro in response to lipopolysaccharide, were measured by radioimmunoassay. After 18 h of incubation, total production of IL 1 alpha in medium containing 1% heat-inactivated serum was two-to-three times higher than IL 1 beta. However, in the presence of 1% serum and 5% fresh plasma, IL 1 alpha and IL 1 beta were produced in similar amounts. Independent of the culture conditions, 90% of the IL 1 alpha remained cell associated whereas 80% of IL 1 beta was extracellular. The kinetics of production and release of IL 1 alpha, beta and TNF-alpha were also studied. IL 1 alpha and TNF-alpha reached maximal levels within 6 h of stimulation, whereas IL 1 beta reached maximal levels between 12 and 16 h. IL 1 alpha remained primarily cell associated (80%) for the first 24 h. After 48 h, extracellular IL 1 alpha exceeded cell-associated levels. IL 1 beta was primarily secreted (80%), appearing in the extracellular fluid within 6 h. TNF-alpha appeared in the extracellular fluid within 1 h of incubation, with less than 10% cell associated at any time during the 48 h of incubation. Although the three cytokines share many biological activities, this study provides evidence that MNC IL 1 alpha is predominantly a cell-associated cytokine acting on a cell-cell basis, whereas IL 1 beta and TNF-alpha are secreted as paracrine mediators.

Cells, Cultured↗
PubMed1989

Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1-2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5-15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15-40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40-80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

An increase in the ratio of thromboxane A2 to prostacyclin in association with increased blood pressure in patients on cyclosporine A.

The aim of this study was to determine the effect of two years of treatment with cyclosporine A on blood pressure and the rates of secretion into the circulation of the vasoconstrictor thromboxane A2 and the vasodilator prostacyclin. Seven patient suffering from multiple sclerosis took part. Their blood pressures and urinary concentrations of 2,3-dinor-thromboxane A2 (a major urinary metabolite of thromboxane A2) and of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) were determined at the end of two years of treatment with cyclosporine A, and once again three months after cessation of this treatment. No other drugs were given during or after cyclosporine A. Mean arterial blood pressure was 113 +/- 5 mmHg (mean +/- SEM) during the cyclosporine A treatment, but fell to 94 +/- 4 mmHg after the three-month's wash-out period. Urinary excretion of the thromboxane metabolite decreased slightly from 674 +/- 150 pg.mg-1 creatinine during cyclosporine A therapy to 503 +/- 90 pg.mg-1-creatinine after the end of therapy. At the same time the prostacyclin metabolite increased significantly from 82 +/- 17 pg.mg-1 creatinine to 113 +/- 23 pg.mg-1 creatinine (P less than 0.05). The ratio of 2,3-dinor-thromboxane B2 to 2,3-dinor-6-keto-prostaglandin F1 alpha (taken as a measure of vasoconstrictor prostanoid activity) fell significantly from 8.4 +/- 0.8 4.7 +/- 0.6 (P less than 0.005). The shift in prostanoid production observed during cyclosporine A treatment could be one causal factor for the hypertensive and thromboembolic events associated with the use of this drug.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

LTB4 in nephrotoxic serum nephritis in rats.

We studied leukotriene B4 (LTB4) synthesis in isolated glomeruli of rats with nephrotoxic serum nephritis. This nephritis was induced in male Sprague Dawley rats by injecting one proteinuric dose of nephrotoxic serum (rabbit anti-rat-GBM serum) after prior immunization of the rats with rabbit IgG. Histological and analytical examinations were performed in kidneys perfused until free of blood 6, 12, 24, 48 and 72 hours after induction of the disease. To investigate LTB4 production, glomeruli were isolated and incubated for one hour in the presence of Ca++-ionophore A23187. The supernatants were analyzed for LTB4. The peak comigrating on reverse-phase high performance liquid chromatography (RP-HPLC) with reference LTB4 was isolated. The ethyl ester trimethylsilyl ether derivative of this peak was analyzed by gaschromatography-mass spectrometry (GC/MS). Identical spectra of the glomerular samples and of reference LTB4 in the positive and in the negative ion chemical ionization mode provided unequivocal evidence that the substance released from the nephritic glomeruli was indeed LTB4. Six hours after injection of nephrotoxic serum, glomerular LTB4 release was highest with 5.52 +/- 0.50, then declining to 2.20 +/- 0.10 ng/mg glomerular protein at 12 hours. At 24, 48 and 72 hours no statistically significant difference from control animals was found. No metabolism of LTB4 to 20-hydroxy- or 20-carboxy-LTB4 was detected during the incubation period. Albuminuria developed during the first 24 hours after nephrotoxic serum challenge and rose steadily throughout the observation period up to 277 +/- 25 mg/24 hr after 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1989

Is the rise in plasma beta-2-microglobulin seen during hemodialysis meaningful?

Beta 2-Microglobulin (beta 2M) plasma levels and levels of a second low-molecular-weight protein (myoglobin) were studied during a 2- to 4-hour sham dialysis period (no dialysate flow, no weight loss) and during a 4- to 5-hour hemodialysis (HD) with a Cuprophan capillary dialyzer. While no rise of the beta 2M or myoglobin levels occurred during sham dialysis, a rise of 22.1 +/- (SD) 8.5% (beta 2M) or 19.9 +/- 12.1% (myoglobin) was seen during regular HD. The increases of both molecules showed a significant correlation (r = 0.44; p less than 0.03). Both rises could not be completely abolished using correction factors for hemoconcentration. The rises occurred irrespectively of the dialysate buffer. The results suggest that neither the Cuprophan membrane nor the extracorporeal circuit were responsible for the rise of both molecules during HD. It seems more likely that changes of the extracellular volume and extra- to intracellular water shifts are involved and account for the majority of the rise. However, the possibility of minor increase in the extracellular mass of beta 2M or myoglobin cannot be excluded completely.

Adolescent↗
PubMed1989

Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay.

Using a specific and sensitive ELISA for C5a, the present study shows that predialysis levels of C5a in end-stage renal disease patients are not elevated and that all membranes studied (Cuprophan, Hemophan, Gambrane and hydrophilic polysulfone) cause significant increases of C5a plasma levels albeit to different degrees. Higher increases of C5a were accompanied by larger decreases of circulating granulocytes and monocytes. Dialyzers with a newly introduced modified regenerated cellulose membrane, Hemophan, showed lower C5a plasma levels during hemodialysis than Cuprophan. With Hemophan C5a plasma levels were comparable to those with polysulfone membranes.

Adult↗
PubMed1989

Specific imaging of dialysis-related amyloid deposits using 131I-beta-2-microglobulin.

Dialysis-related amyloidosis (DRA), characterized by its association with beta 2-microglobulin (beta 2m), has become a major concern in long-term hemodialysis patients. Hitherto the diagnosis was based on histological examinations of tissue obtained by biopsy or during surgery. In this preliminary study a new noninvasive diagnostic method was developed using the affinity of beta 2m for its derived fibrils. 3 patients on long-term hemodialysis for 10-16 years with biopsy-proven DRA and 1 patient on chronic hemodialysis for only 6 months were examined after intravenous injection of 131I-labelled beta 2m. Specific local accumulation of radioactivity was noted in the DRA patients after 48 h, persisting for further 96 h and corresponding to clinically or radiologically evident sites of amyloid deposition and to several other hitherto unsuspected sites. Examination of an excised amyloid tumor subsequent to in vivo labelling confirmed a highly specific accumulation of radioactivity in the amyloid tissue but not in control tissue. In the patient on chronic hemodialysis for only 6 months, no specific local accumulation was detected even after 1 week. These findings provide in vivo evidence in man that a specific uptake of circulating amyloid precursor molecules into deposits occurs and that this uptake may be used to radiolabel even small tissue infiltrates of amyloid. This method therefore may not only allow an objective, noninvasive detection of DRA but may also be used to obtain new pathophysiologic insights into amyloid formation in man, as well as permitting the evaluation of preventive therapeutic strategies in prospective studies on new patients.

Amyloidosis↗
PubMed1989

Subcutaneous amyloid-tumor of beta-2-microglobulin origin in a long-term hemodialysis patient.

beta 2-Microglobulin (beta 2M)-derived amyloidosis has become a major concern in long-term hemodialysis patients. Clinical symptomatology is largely restricted to the articular and periarticular sites and in rare cases systemic manifestations have been described. We present a long-term hemodialysis patient, who after 16 years of hemodialysis with regenerated cellulosic membranes not only had a bilateral carpal tunnel syndrome, cystic bone translucencies and humeroscapular periarthritis but also developed two subcutaneous tumors in both gluteal regions, causing discomfort when sitting. Histology, immunohistology and electron microscopy of the tumor from the right side showed that it consisted of beta 2M-derived amyloid with concurrent scattered amyloid infiltration of the overlying skin. This report therefore adds a new clinical manifestation to the symptomatology of this type of amyloid.

Amyloidosis↗
PubMed1989

Hemodialysis-related induction of beta-2-microglobulin and interleukin-1 synthesis and release by mononuclear phagocytes.

We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Recent interest in beta 2M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis and that these patients have greatly elevated levels of monomeric beta 2M in their circulation. Since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by freshly prepared leukocytes and monocyte-derived macrophages under a variety of conditions. We utilized a novel enzyme-linked immunoabsorbant assay to quantitate beta 2M concentrations, and monitored interleukin-1 and beta 2M synthesis by immunoprecipitation. Incubation of leukocytes with Cuprophan or Hemophan does not increase beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes induces neither interleukin-1 nor beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin-1 induces synthesis and release of beta 2 M, indicating that beta 2 M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of beta 2M and interleukin-1 into the cellular medium. These results suggest that during hemodialysis, beta 2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with Cuprophan membranes.

Cells, Cultured↗