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Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 73 records · Page 4Linked to original sources
PubMed2000

In vivo effects of dialysate flow rate on Kt/V in maintenance hemodialysis patients.

It is generally assumed that hemodialysis adequacy is only minimally affected by increasing the dialysate flow rate (Qd). Recent in vitro studies showed that dialyzer urea clearance (Kd(urea)) may increase substantially more than expected in response to an increase in Qd. Because these studies implied that dialysis efficacy may benefit from greater Qds, we studied in vivo the effects of various Qds on the delivered dose of dialysis in 23 maintenance hemodialysis (MHD) patients. Hemodialysis was performed at Qds of 300, 500, and 800 mL/min for at least 3 weeks each, whereas specific dialysis prescriptions (treatment time, blood flow rate [Qb], ultrafiltration volume, and type and size of dialyzer) were kept constant. Delivered dose of dialysis, assessed by single-pool Kt/V (Kt/V(sp)) and double-pool Kt/V (Kt/ V(dp)), was measured at least three times for each Qd (218 measurements). Mean +/- SEM Kt/V(sp) was 1.19 +/- 0.03 at Qd of 300 mL/min, 1.32 +/- 0.04 at 500 mL/min, and 1.45 +/- 0.04 at 800 mL/min. The relative gains in Kt/V(sp) for increasing Qd from 300 to 500 mL/min and 500 to 800 mL/min were 11.7% +/- 8.7% and 9.9% +/- 5.1%, respectively. Kt/V(dp) increased at a similar percentage (11.2% +/- 8.9% and 10.3% +/- 5.1%, respectively). The observed gain in urea clearance by increasing Qd from 500 to 800 mL/min was significantly greater than the increase in Kd(urea) predicted from mathematical modeling (5.7% +/- 0.4%; P = 0.0008). Removal ratios for creatinine and the high-molecular-weight marker, beta(2)-microglobulin, were not affected by increasing Qd from 500 to 800 mL/min. The proportion of patients not achieving adequacy (Kt/V(sp) >/= 1.2) was reduced from 56% at Qd of 300 mL/min to 30% at 500 mL/min and further to 13% at 800 mL/min. It is concluded that increasing Qd from 500 to 800 mL/min is associated with a significant increase in Kt/V. Hemodialysis with Qd of 800 mL/min should be considered in selected patients not achieving adequacy despite extended treatment times and optimized Qbs.

Aged↗
PubMed2000

T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients.

BACKGROUND: Patients on chronic intermittent haemodialysis (HD) show an impaired cellular and humoral immune response that clinically appears with frequent infectious complications and low vaccination responses. This immune defect strongly correlates with reduced in vitro proliferative responses of T cells. The defect is localized in antigen presenting cells, which show a decreased co-stimulatory activity. Furthermore, the impaired immune response correlates with an increased production of pro-inflammatory cytokines. In response to primary activation, CD4 positive T helper (Th) cells mainly differentiate into either Th1 or Th2 cells. Th1 cells support cell mediated immunity whereas Th2 cells enhance humoral immune responses. Since both types of responses mutually inhibit each other, the impaired humoral immune response seen in HD patients could either be due to a reduced number of Th2 cells or to a predominant Th1 response. METHODS: We analysed the Th cell profile in HD patients using flow cytometry. Monocytic cytokine expression was analysed using both flow cytometry and enzyme linked immunoadsorbant assays. RESULTS: Our data demonstrate that the cytokine differentiation profile in circulating T cells from HD patients is dysregulated and characterized by an increase in Th1 cells, but a normal amount of Th2 cells. Moreover, the skewed helper cell responses correlate with a higher percentage of monocytes capable of secreting the Th1 promoting cytokine interleukin 12 (IL-12). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of impaired cellular immune functions in dialysis patients and, in particular, the decreased antibody production after vaccination. They provide a link between overproduction of pro-inflammatory cytokines (IL-12) and imbalanced T-cell activation.

Aged↗
PubMed2000

[Immunological methods for the diagnosis of bovine tuberculosis--state of the art].

An overview is given about the most common immunological methods for the diagnosis of bovine tuberculosis. These methods are based on cell mediated immune reactions on the one hand (intradermal skin test, interferon-gamma-test, lymphocyte transformation test) or on antibody production against Mycobacterium bovis on the other hand (ELISA). The advantages and disadvantages of the methods as well as their specificity and sensitivity are discussed.

Animals↗
PubMed1999

Immunoaffinity extraction of morphine, morphine-3-glucuronide and morphine-6-glucuronide from blood of heroin victims for simultaneous high-performance liquid chromatographic determination.

The development of an immunoaffinity-based extraction method for the determination of morphine and its glucuronides in human blood is described. For the preparation of an immunoadsorber, specific antisera (polyclonal, host: rabbit) against morphine, morphine-3-glucuronide and morphine-6-glucuronide were coupled to 1,1'-carbonyldiimidazole-activated tris-acrylgel and used for immunoaffinity extraction of morphine and its glucuronides from coronary blood. The resulting extracts were analysed by HPLC with native fluorescence detection. The mean recoveries from spiked blood samples were 71%, 76% and 88% for morphine, morphine-3-glucuronide and morphine-6-glucuronide, respectively. The limit of detection was 3 ng/g blood and the limit of quantitation was 10 ng/g blood for all three analytes. The results of the analysis of coronary blood samples from 23 fatalities due to heroin are presented.

Chromatography, Affinity↗
PubMed1999

Remodeling of peritoneal-like structures by mesothelial cells: its role in peritoneal healing.

BACKGROUND: Intraabdominal adhesions are a common complication following laparotomy. Since the exact mechanisms involved in this processes are unknown we have analyzed in vitro the role of mesothelial cells in peritoneal healing. MATERIAL AND METHODS: Human mesothelial cells from omental tissue were cultivated for 2 weeks in a three-dimensional culture either on or in a collagen type I matrix. The effects of blood and collagen matrix were analyzed by exposing mesothelial cells to an overlying blood clot, simulating intraperitoneal bleeding, or a second collagen layer. The production of collagen types III and IV, fibronectin, and laminin was analyzed with immunohistochemical methods. RESULTS: Mesothelial cells grown on a collagen matrix formed a monolayer of flat or cobblestone-like cells whereas those cultivated in a collagen matrix exhibited spindle-like morphology. Mesothelial cells failed to grow into an overlying collagen matrix, but did grow into a blood clot, emphasizing a potential role of blood clots in peritoneal adhesion formation. Independent of the culture systems mesothelial cells produced collagen type III, fibronectin, and laminin but not collagen type IV. CONCLUSIONS: Our experiments demonstrate remodeling of peritoneal-like structures by mesothelial cells in a three-dimensional culture reflecting their putative role in the reepithelialization after serosal defects, and also in the formation of peritoneal adhesions.

Cells, Cultured↗
PubMed1999

Divergent kinetics of hsp70 induction in Oniscus asellus (Isopoda) in response to four environmentally relevant organic chemicals (B[a]P, PCB52, gamma-HCH, PCP): suitability and limits of a biomarker.

Mature specimens of the isopod Oniscus asellus were maintained on soil and leaf litter to which was added different concentrations of either benzo[a]pyren (B[a]P), 2,2',5,5'-tetrachlorobiphenyl (PCB52), gamma-hexachlorocyclohexane (gamma-HCH), or pentachlorophenol (PCP) for a maximum of 14 days. Time-dependent investigation of the body level of the 70 kD stress protein group (hsp70) in the isopods revealed a significant but transient induction of the hsp70 response after about 24 h of exposure to PCB52 or B[a]P. Despite continuous exposure, the hsp70 level decreased subsequently and ended up close to or below the control level independent of the concentration of PCB52 or B[a]P in the substrate. All applied PCP or gamma-HCH concentrations also resulted in an initial peak of hsp70 response after 24 h of exposure and a second peak after several days of exposure, as well as an elevated hsp70 level throughout the period of exposure. Although acute stress conditions posed by all four organic chemicals were monitored by stress protein induction, hsp70 can act as a biomarker of chronic exposure and effect for PCP and gamma-HCH only.

Animals↗
PubMed1999

Leptomeningeal carcinomatosis and cranial nerve palsy as presenting symptoms of a clinically inapparent gallbladder carcinoma.

We present an occult metastatic signet-ring cell gallbladder carcinoma in a 78-year-old woman, who complained of recurrent headaches, dysarthria, and paresis of the tongue. Cranial imaging showed contrast enhancement of the basal leptomeninges, and the cerebrospinal fluid displayed clusters of adenocarcinoma cells proposed as leptomeningeal carcinomatosis of the breast, lung or gut. However, postmortem examination revealed the gallbladder as the site of the primary carcinoma with focal signet-ring cell differentiation. In patients with progressive neurologic deterioration due to leptomeningeal carcinomatosis, adenocarcinomas from the gastrointestinal and hepatic systems should be considered. It is likely that signet-ring cell carcinomas display an increased affinity to leptomeningeal spread.

Aged↗
PubMed1999

Studies on the influence of combined administration of ochratoxin A, fumonisin B1, deoxynivalenol and T2 toxin on immune and defence reactions in weaner pigs.

In weaners, combined administration of fumonisin, deoxynivalenol and T2 together with ochratoxin A in quantities expected to be present in feeds of central European origin resulted, as a rule, in changes identical to those observed after single administration of ochratoxin A. Such reactions were partly compensated. Synergistic amplification of immunosuppressive changes due to the simultaneous intake of these mycotoxins in low concentrations is not to be expected.

Animals↗
PubMed1999

Studies of the influence of ochratoxin A on immune and defence reactions in weaners.

Even in subtoxic amounts, the mycotoxin, ochratoxin A, produced immunomodulation in weaner pigs in a dose-dependent mode. In addition to increased counts of total leukocytes and neutrophils in the blood, reduced lymphocyte levels were observed. There was a striking increase in the counts of eosinophils and of apoptotic phagocytes. Functionally, there was a predominance of the production of reactive oxygen radicals in whole blood, reduced phagocytosis performance and reduced expression of a swine-specific surface marker (SWC1) on lymphocytes. In a few single experiments, clinical manifestations could be demonstrated. Lung clearance and the degree of severity of experimental pneumonia as well as cutaneous hypersensitization may be influenced by ochratoxin A.

Animals↗
PubMed1999

Gender-specific differences in dialysis quality (Kt/V): 'big men' are at risk of inadequate haemodialysis treatment.

BACKGROUND: Inadequate dialysis dose is closely related to mortality and morbidity of maintenance haemodialysis (MHD) patients. According to the DOQI guidelines a minimum prescribed dialysis dose of single-pool Kt/V (Kt/Vsp)=1.3, equivalent to equilibrated double pool Kt/V (e-Kt/Vdp)=1.1, is recommended. Knowledge of patient-related risk factors for inadequate delivery of hacmodialysis would be helpful to select patient subgroups for intensive control ofdialysis adequacy. METHODS: A retrospective survey was conducted to assess the prevalence of inadequate dialysis dose according to DOQI criteria during a 7-month period. A total of 320 e-Kt/Vdp measurements in 62 MHD patients were evaluated (mean effective dialysis time 222+/-32 min). Residual renal function (RRF) was expressed as renal weekly Kt/V (r-Kt/Vweek) and included into assessment of total weekly renal and dialytic Kt/V (t-Kt/Vweek). RESULTS: Inadequacy (e-Kt/Vdp<1.10) was prevalent in 37.2% of all measurements and in 22/62 patients (35.5%). In 54% of underdialysed patients r-Kt/Vweek compensated for insufficient dialytic urea removal. Mean weekly Kt/V was inadequate (t-Kt/Vweek<3.30) in 12/62 patients (19.4%) of whom 91.7% (11/12) were male. Body-weight, urea distribution volume (UDV). and body-surface area (BSA) were significantly higher in inadequately is adequately dialysed males. UDV>42.0 litres or BSA>2.0 m2 and a lack of RRF (r-Kt/Vweek<0.3) put 'big men' at increased risk to receive an inadequate dose of dialysis. CONCLUSION: Our data identify patients at risk for inadequate haemodialysis treatment. Special attention should be focused on 'big men' with UDV>42.0 litres or BSA>2.0 m2. In this subset of patients frequent measurements of t-Kt/Vweek and assessment of RRF should be mandatory.

Adult↗
PubMed1999

High prevalence of hepatitis G virus (HGV) infections in dialysis staff.

BACKGROUND: Patients on renal replacement therapy, haemodialysis (HD), or after kidney transplantation (TX), are known to be at risk of acquiring blood-borne infections (HBV, HCV). GBV-C/Hepatitis G virus (HGV) has been described recently and is considered to cause blood-borne infections. The aim of this study was to analyse the risk for the medical staff of HD and TX patients to acquire HGV infection. METHODS: Eighty-five HD patients and 86 TX recipients were compared with 49 health-care workers and 64 blood donors as controls. The HGV prevalence was determined by RT-PCR and antibodies to E2 protein. RESULTS: A high prevalence of HGV was found in the medical staff (24%) which nearly corresponded to the prevalence of the patients (TX 36%, HD 25%) but not to the controls (9%). In contrast, the prevalence of HCV was low in the medical staff (2%) and controls (0%) but high in HD (13%) and TX (13%). Age and duration of employment in the department did not significantly influence the HGV prevalence in staff. The number of viraemic subjects in staff was high, possibly indicating a more recent infection. CONCLUSION: An occupational risk for HGV exists in medical staff of dialysis and transplant patients. Further routes of transmission than only parenteral may play a role in this setting.

Aged↗
PubMed1999

Influence of dialysis with polyamide vs haemophan haemodialysers on monokines and complement activation during a 4-month long-term study.

BACKGROUND: Contact between blood and dialysis membranes activates mononuclear cells and the complement system. The extent of activation is dependent on the dialyser material used and is considered an index of biocompatibility. Polyamide dialysers consist of a synthetic membrane that claims high standards of biocompatibility. Haemophan dialysers represent membranes made of modified cellulose that are now broadly used for treatment in Europe and are already considered to be more biocompatible than the cuprophane membranes that were used as reference in most previous studies. METHODS: In a cross-over treatment study short-term as well as long-term effects of a polyamide dialyser with respect to monokine induction and complement activation were compared to a haemophan dialyser. RESULTS: Neither haemophan nor polyamide dialysers induced relevant changes in plasma monokine levels. However, in vitro challenge of mononuclear cells with lipopolysaccharide (LPS) unmasked a significantly stronger preactivation for the secretion of proinflammatory monokines during haemophan than polyamide dialysis. Unlike other monokines the production of the regulatory monokine IL-10 was mainly influenced by individual factors and correlated with the patient's immune status rather than the dialyser type used. Enhanced preactivation of monocytes in haemophan compared to polyamide dialysis was paralleled by an increased complement activation. Cellular preactivation and formation of terminal complement complex remained constant over the 4-month treatment period. CONCLUSIONS: Haemophan and polyamide dialysers do not induce changes in plasma cytokine levels both during short-term and long-term use. However, they significantly differ in complement activation as well as preactivation of monocytes. Preactivated monocytes are prone to secrete high amounts of proinflammatory cytokines when exposed to a second stimulus like endotoxin. Secretion of the regulatory cytokine IL-10 is not influenced by the dialyser type.

Adult↗
PubMed1999

Secretory immunoglobulin A is a component of the human milk fat globule membrane.

Secretory immunoglobulin A (sIgA), the predominant antibody fraction of human milk, represents a major protective factor against neonatal infection. Until now, sIgA had been identified only in the humoral fraction of human milk. The aim of this study was to assess whether in human milk sIgA is also associated with the milk fat globule (MFG). Using anti-sIgA-agglutinated human MFG and immune fluorescence microscopy, we could demonstrate that sIgA is, in fact, associated with human MFG. In human MFG membranes separated by Western blotting, sIgA bands were specifically stained, suggesting that sIgA is strongly associated with the human MFG membrane. This may be of physiologic relevance, inasmuch as earlier we could show that a quantity of undigested and functional human MFG are in fact found in the stools of the newborn. This would allow an additional extension of the protective mechanisms of sIgA throughout the whole intestine.

Agglutination Tests↗
PubMed1999

Hepatoactive substances eliminated by continuous venovenous hemofiltration in acute renal failure patients.

BACKGROUND: Acute renal failure (ARF) in critically ill patients is mostly part of a multi-organ failure. Therefore, the effects of renal replacement therapy on the liver are clinically important. We investigated the effects of ultrafiltrates of patients treated with continuous venovenous hemofiltration (CVVH) on liver cells in vitro. METHODS: Patients with ARF were consecutively treated with CVVH using Multiflow60 (group I) or FH66 filters (group II). They were comparable with respect to diagnosis, age, sex, laboratory parameters, and renal replacement treatment, but were different in daily diuresis, serum levels, and blood flow. Ultrafiltrates were collected within the first 10 minutes after change of hemofilter. Proliferation (bromodeoxyuridine), vitality (lactate dehydrogenase), and acute-phase protein secretion of HepG2 cells were measured. RESULTS: Ultrafiltrates changed liver cell function significantly compared with medium control. Proliferation (group I 29.8+/-5.2% vs. group II 48.4+/-6.6%, P < 0.05) and vitality (group I 78.7+/-2.0% vs. group II 87.6+/-1.7%, P < 0.01) of HepG2 cells were significantly different. On the one hand, the secretion of the negative acute-phase protein transferrin [group 13.1+/-0.2 (ng/microg protein) vs. group II 5.1+/-0.5 (ng/microg protein), P < 0.01] was significantly reduced by Multiflow60 ultrafiltrates. On the other hand, positive acute-phase protein alpha1-acid glycoprotein was significantly stimulated by Multiflow60 ultrafiltrates [group I 2.6+/-0.1 (ng/microg protein) vs. group II 1.7+/-0.1 (ng/microg protein), P < 0.001]. CONCLUSION: This study demonstrates hepatoactive mediators in the ultrafiltrates. They are hepatotoxic and influence acute-phase protein metabolism. Further studies have to elucidate the different effects in both groups and the analysis of the putative mediator(s). It remains a challenging task to consider therapeutic measures to optimize renal replacement therapy in critically ill patients.

Acute Kidney Injury↗
PubMed1998

Glucocorticoids inhibit activation-dependent expression of costimulatory molecule B7-1 in human monocytes.

BACKGROUND: Glucocorticoids act as immunosuppressive drugs mainly via their effects on antigen-presenting cells. They are known to influence production of cytokines as well as expression of cell surface molecules. B7 molecules belong to the most important costimulatory signals for T-cell activation during transplant rejection. They are expressed on antigen-presenting cells and up-regulated during the immune response. We studied the influence of glucocorticoids on the regulation of these accessory signals. METHODS: Human monocytes were purified from peripheral blood of healthy volunteers by centrifugal counterflow elutriation. Activation-dependent transcription and expression of B7-1 (CD80) and B7-2 (CD86) were detected by reverse transcription-polymerase chain reaction and flow cytometry in the absence or presence of glucocorticoids. RESULTS: The expression pattern of B7-1 and B7-2 on monocytes depends on the type of stimulation. Activation by interferon-gamma induces both B7-1 and B7-2, whereas cAMP exclusively up-regulates B7-2. Glucocorticoids selectively inhibit the expression of B7-1 while leaving B7-2 unaffected. The effect occurs at concentrations that are reached during therapeutical application of the substances in humans. It is mediated via the cytoplasmic glucocorticoid receptor, as it can be abrogated by the glucocorticoid receptor antagonist RU38486. Inhibition of B7-1 occurs at the transcriptional level. Up-regulation of the molecule can similarly be inhibited by hydrocortisone, prednisolone, and dexamethasone at equipotent doses. CONCLUSIONS: Inhibition of the up-regulation of B7-1 by glucocorticoids is a previously unknown mechanism of action of these substances and may relevantly contribute to their effects as immunosuppressive drugs.

Antigen-Presenting Cells↗