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Biomedical subjects

T Bosch

Publications and source records attributed to T Bosch.

At least 55 records · Page 3Linked to original sources
PubMed1996

Current status in extracorporeal immunomodulation: immune disorders.

Today, clinicians can choose from a variety of extracorporeal immunomodulatory procedures such as plasma exchange, double filtration, immunoadsorption, chemoadsorption, photopheresis, and cytoapheresis. The mechanisms underlying extracorporeal immunomodulation (ECIM) comprise removal of pathogenic antibodies and circulating immune complexes as well as reticuloendothelial system deblockage; modification of immune complex structure and processing can be induced by changing the antigen/antibody ratio and by modulation of immune complex solubility via complement activation. Finally, cellular components like lymphocyte subsets, can be modified. Clinical examples of ECIM include lupus erythematosus, Goodpasture's syndrome, anti-neutrophil cytoplasmatic antibodies-mediated systemic vasculitis, myasthenia gravis, and, hypothetically, sepsis.

Adjuvants, Immunologic↗
PubMed1996

[Nephrotoxicity and fluoride from the viewpoint of the nephrologist].

Fluoride released from methoxyflurane (MOF) during its hepatic and extrahepatic metabolism has been regarded as the major culprit responsible for MOF-induced nephrotoxicity. In the isolated, perfused rat kidney model, admixture of 1500 mumol/l fluoride to the perfusate resulted in tubular and glomerular damage with concomitant anuria. Fluoride administration in Fischer 344 rats in vivo elicited a renal diabetes insipidus-like syndrome that had also been observed in patients after MOF anaesthesia. The renal concentrating defect is most probably due to both dissipation of the corticomedullary osmolality gradient in the interstitium and failure of water reabsorption due to ADH refractoriness of the distal tubular cells. Hypothetically, the underlying mechanism may be a fluoride-induced inhibition of enzymes involved in intracellular energy production such as ATPase or enolase. The degree of nephrotoxicity correlates loosely with maximal serum fluoride levels, but can probably be modulated by further factors like intrarenal in situ formation of fluoride, urinary pH and flow, and especially, the presence of other nephrotoxins. This mitigates the importance of maximal fluoride serum levels, especially the 50 mumol threshold, as predictors of clinically relevant nephrotoxicity. To date, no nephrotoxic effects of sevoflurane could be demonstrated.

Anesthetics, Inhalation↗
PubMed1995

[Internal medicine complications of ventriculoatrial shunt].

BACKGROUND: Ventriculo-atrial shunts (VASs) and ventriculo-peritoneal shunts (VPSs) are the symptomatic treatment of choice for hydrocephalus. Bacterial contamination of the atrial part of VASs (usually with Staphylococcus epidermidis) can result in further organ complications, in most instances immune complex mediated glomerulonephritis ("shunt-nephritis") or direct microbial heart valve destruction. PATIENTS AND METHODS: In a retrospective study, we analyzed clinical and laboratory data of 11 patients with VAS associated complications as well as the course of the disease. RESULTS: The following complications were observed: glomerulonephritis (n = 9), glomerulonephritis and aortic valve destruction (n = 1), pulmonary embolism, pulmonary hypertension and tricuspid valve insufficiency (n = 1). Out of the 11 patients, 8 suffered from unexplained fever. All 11 patients had elevated circulating immune complexes. In 3 of 4 patients initially requiring dialysis, renal function improved which allowed to stop hemodialysis. Renal function also improved in 3 of 5 patients who presented with elevated serum creatinine. Unfortunately, the patient with multiple pulmonary embolisms and tricuspid valve insufficiency died of progressive pulmonary hypertension. CONCLUSION: The prognosis for impaired renal function is good only if the VAS infection is diagnosed early and an immediate surgical and antibiotic treatment leads to an eradication of the underlying chronic infection.

Adult↗
PubMed1995

Efficacy of lipid apheresis: definitions and influencing factors.

The comparison of efficiency of currently available lipid apheresis systems has been hampered by different definitions of efficacy and poorly controlled apheresis conditions. This paper suggests definitions of efficacy and standardization of its determinants. The acute efficacy of risk factor reduction reflects the relative decrease of pathogen by a single treatment session compared to preapheresis levels. Standardization of treated plasma volume in relation to the patients plasma volume and correction of changes in plasma volume during the procedure are mandatory. Its determination is most useful in the technical evaluation of new systems. The long-term efficacy of risk factor reduction as compared to baseline is determined by mean interapheresis levels of e.g. LDL-C in the pseudo-steady-state after about 3 months of regular treatment. It is the major criterion for potential regression of coronary artery disease and absolute average plasma levels of 120 < or = mg/dl LDL-C should be attained. It is influenced by the acute efficacy of the system, apheresis frequency and rebound kinetics. The clinical efficacy is defined by apheresis induced reduction of coronary morbidity and mortality. It is influenced by long-term risk factor reduction, the selectivity of the system as well as the control of non-lipid risk factors. Apheresis related effects on coronary artery disease comprise functional improvements of hemorheology and vasomotion as well as morphological benefits like regression of luminal narrowing and plaque stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1994

Single polymerase chain reaction for the detection of tetracycline-resistant determinants Tet K and Tet L.

Oligonucleotide primers were used in polymerase chain reaction assays to detect tetracycline-resistant determinants Tet K and Tet L. Forty-three isolates representing 11 genera carrying Tet K and/or Tet L determinants gave appropriate PCR products. The PCR products hybridized with labelled Tet K or Tet L probes, and differentiated the Tet K from the Tet L PCR products. We confirmed that two Haemophilus aphrophilus carried the Tet K determinant and two Veillonella parvula carried the Tet L determinant. This is the first time that either of these two genes have been found in Gram-negative species. Four vaginal samples, previously positive with the Tet M/O PCR assay, were also positive with the Tet K/L assay. This is the first report of a PCR assay for the detection of Tet K and Tet L determinants in bacteria or clinical specimens.

Animals↗
PubMed1993

Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood.

To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood. In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-1 production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citrate/ml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca2+ is recommended. In conclusion, this new adsorber exhibited selective LDL-C adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.

Acrylic Resins↗
PubMed1993

Renal complications of infected ventriculoatrial shunts.

Contamination of a ventriculoatrial shunt (VAS) with skin organisms that are usually nonpathogenic may be followed by an immunologically mediated renal injury. The bacteria characteristically involved are coagulase-negative Staphylococci (e.g., Staphylococcus epidermidis), which strongly adhere to the plastic surface of the VAS. These bacteria are protected from the body's natural defense mechanisms and respond only poorly to antibiotics. As a result, their growth persists and produces a continuous antigenic stimulation. Circulating immune complexes (CIC) are an appropriate tool to screen for chronically infected VASs. We followed CIC in 138 VAS patients. An infected VAS was seen in 20 of the 24 patients with highly elevated CIC and in 1 of the 19 patients with moderately elevated CIC, but none of the 95 patients with normal CIC had evidence of shunt infection. Of the 21 patients with shunt infections, 8 had renal involvement (4 requiring dialysis, and 4 with proteinuria, hematuria, and/or elevated creatinine). Results from kidney biopsy specimens available from 4 patients confirmed glomerulonephritis. Of the 4 patients requiring dialysis at diagnosis, renal function recovered sufficiently to stop dialysis after successful VAS exchange in all but 1. In the other 4 patients, renal symptoms (proteinuria, creatinine) also improved after VAS revision. Chronic infection with S. epidermidis or other bacteria is a continuing problem in patients with VASs and can lead to an immune-mediated renal injury. However, the prognosis for reversal of the renal injury is relatively good if the VAS infection is treated promptly.

Adolescent↗
PubMed1993

Long-term efficiency, biocompatibility, and clinical safety of combined simultaneous LDL-apheresis and haemodialysis in patients with hypercholesterolaemia and end-stage renal failure.

Three hypercholesterolaemic patients on maintenance haemodialysis with angiographically proven coronary artery disease were treated in a once-a-week schedule by combined, synchronous lipid apheresis (using heparin-induced extracorporeal LDL precipitation) and haemodialysis (HELP/HD) for 65-104 weeks. Clinical side-effects were few and mostly related to high ultrafiltration rates in patients with low compliance regarding interdialytic fluid restriction. Biocompatibility of the procedure was shown to be good and blood cell losses, leukocyte (elastase release) and thrombocyte (beta-thromboglobulin extrusion) as well as complement (C3a formation) activation were minimal. Interestingly, most of the C3a generated in the extracorporeal HELP circuit was immediately removed again in the precipitate filter. In the pseudo-steady-state after 3 months of regular therapy, acute haematocrit-corrected reduction of plasma components after the session compared to pre values were about 55% for the risk factors LDL cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and fibrinogen (FIB) with good recovery of HDL-C and other proteins. Urea, creatinine, and phosphate elimination was similar to normal haemodialysis. Mean interapheresis values of risk factors after one (n = 2) and two (n = 1) years of treatment were crucially dependent upon ultrafiltration (UF); thus, in two patients with high UF LDL-C concentrations amounting to 185 and 220 mg/dl at baseline and were reduced to about 135 mg/dl LDL-C, while in the patient with low UF the reduction was from 231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C), was reduced from 6.4 and 5.1 to about 4.3 in patients with high UF, from 6.1 to 3.3 in the patient with low UF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Reverse flux filtration: a new mode of therapy improving the efficacy of heparin-induced extracorporeal LDL precipitation in hyperlipidemic hemodialysis patients.

In the steady state after a run-in phase of 3 months, the acute effects of 3 modifications of weekly heparin-induced extracorporeal LDL precipitation (HELP) were studied in 5 ESRD and 2 non-uremic hypercholesterolemic coronary patients. In ESRD patients (n = 29 sessions), HELP reduced LDL-cholesterol (LDL-C) (56 +/- 7%) and fibrinogen (FIB) (54 +/- 10%) by a similar percentage as compared to non-uremic controls (60 +/- 4% and 61 +/- 3%, resp.; n = 5). In order to eliminate the need for extra HELP sessions in addition to the normal dialysis regimen, newly developed hardware was then used to perform combined synchronous HELP/HD (n = 12). However, premature precipitate filter plugging probably due to hyperfibrinogenemia in ESRD patients, accentuated by ultrafiltration (UF), decreased the corresponding reductions to 26 +/- 9% (LDL-C) and 34 +/- 11% (FIB). Therefore, the procedure was modified by reversing the filtrate flux through the precipitate filter membrane after 900 ml of treated plasma ("reverse flux filtration", RFF; n = 11). Thus, in RFF-HELP/HD the LDL/FIB/heparin coprecipitate was deposited on both filter membrane sides which caused a significant enhancement of the filter capacity and improved reductions to 46 +/- 14% for LDL-C and 51 +/- 15% for FIB. Elution of the precipitate from the precipitate filter after the sessions showed that RFF-HELP/HD had trapped 1733 +/- 238 mg LDL-C and 8108 +/- 1876 mg FIB in ESRD patients, while HELP eliminated 1890 +/- 333 mg LDL-C and only 3663 +/- 369 mg FIB in non-uremics. Filter precipitate recoveries (relative to the mass removed from the patient plasma pool) amounted to 97 +/- 18% for LDL-C and 158 +/- 67% for FIB in the ESRD group treated by RFF-HELP/HD vs. 70 and 76% in the non-uremic HELP group. Probably, passive transport of lipoproteins and FIB from the interstitium into the vascular space caused repletion of this compartment during HELP/HD where an UF induced solvent drag is effective. In summary, the new RFF-HELP/HD procedure effectively reduced LDL-C and FIB in ESRD patients who could not be adequately treated by the conventional HELP/HD system.

Blood Component Removal↗
PubMed1992

Adsorption treatment in hyperlipidemia.

Clinical LDL- adsorption has made overwhelming progress in recent years. Thus, immunoadsorption with polyclonal anti-LDL-antibodies and chemoadsorption using the dextransulfate system have been applied successfully for selective LDL-removal in routine clinical plasma treatment of hypercholesterolemic patients suffering from coronary artery disease. Clinical pilot studies showed good results using immunoadsorption with anti-LDL-F(ab)-columns. Promising laboratory results have been achieved using immunoadsorption with monoclonal LDL-antibodies, polyacrylate/fractogel and macroporous cellulose. While these systems need a primary separation step for cells and plasma, the integrated plasma separation/adsorption device and the LDL-hemoperfusion module using E 280590 can even treat whole blood. Thus, these systems hold a great promise for the future.

Biocompatible Materials↗
PubMed1991

Overview: techniques and indications of LDL-apheresis.

In recent years, LDL-apheresis has emerged to be an efficient treatment of hyperlipidemia in patients who do not respond sufficiently to diet and lipid lowering drugs. A survey of LDL lowering extracorporeal procedures is presented. Among them, to date 5 procedures have been used clinically on a routine basis: unselective plasma exchange, semi-selective double filtration (including its modifications like thermofiltration and predilution/backflush) and three highly selective LDL-apheresis systems: LDL-adsorption on dextran sulfate coated cellulose beads or anti-apoprotein B-linked sepharose and heparin induced extracorporeal LDL and fibrinogen precipitation (the so-called HELP system). Advantages, limitations and special indications of these commercially available systems are discussed. If atherosclerosis can really be made regress by drastic reduction of elevated serum cholesterol levels as indicated by recent publications, lipid apheresis will no doubt play a major role in attaining this goal.

Adsorption↗
PubMed1990

[Maximal therapy of hypercholesterolemia in coronary heart disease].

Extracorporeal procedures to eliminate LDL from plasma now allow us to drastically lower the plasma LDL-concentrations to virtually every desired level. In a new therapeutic approach the combination of HMG-CoA reductase inhibitors with an LDL/fibrinogen apheresis procedure (the HELP-system) was evaluated in hypercholesterolemic CAD-patients. HELP treatment alone can lower the mean plasma LDL-cholesterol by about 50-60%, HMG-CoA reductase inhibitor therapy reduces the LDL-cholesterol by about 40%. The combination of both treatments resulted in a lowering of mean LDL-cholesterol to about 80% of baseline values. Improvement of blood rheology by lowering plasma viscosity and inhibiting erythrocyte aggregation became apparent. No relevant adverse effects were noted over a period of two years. This therapeutic strategy for maximal LDL-cholesterol lowering may be useful in secondary prevention of coronary heart disease in hypercholesterolemic patients if plasma LDL-C cannot be reduced by diet and drug treatment to desirable plasma levels (LDL-cholesterol less than 120 mg/dl). Preliminary data show an improvement in the symptoms of our CAD-patients treated with this combined therapy. Furthermore, within the near future a combined HELP and dialysis unit will be available for patients with terminal renal insufficiency and progressive atherosclerosis.

Adult↗
PubMed1987

Ex vivo biocompatibility evaluation of a new modified cellulose membrane.

To evaluate membrane biocompatibility, an open loop ex vivo model was designed simulating the hemodialysis procedure. Blood was withdrawn continuously from healthy nonuremic donors, heparinized, and pumped through a module containing the membrane to be studied. C3a generation in the module was determined at various time points comparing the cuprammonium cellulose (CC) membrane and four types of modified cellulose (MC) membrane, each with a different degree of hydroxyl (OH-) group substitution. In other studies, C3a generation in the ex vivo mode was compared with that during in vivo dialysis. In the ex vivo model, C3a generation with MC membranes was reduced by 70% compared with CC. However, within the MC group, the degree of C3a generation did not correlate with the degree of OH-group substitution. In vivo studies confirmed the reduced degree of C3a generation with the MC membrane compared with CC. Additionally, validation studies using the CC membrane showed excellent agreement between C3a generation during ex vivo perfusion and in vivo dialysis. The results suggest that a group of new MC membranes causes substantially less complement activation than the CC membrane but that the degree of complement activation with various subtypes of MC membranes is not related to the degree of OH-group substitution.

Anaphylaxis↗
PubMed1987

A clinical study on different cellulosic dialysis membranes.

A controlled clinical study was performed over a period of 8 weeks in two dialysis centres (Rostock, GDR, and Munich, FRG). The aim was to compare a dialysis membrane made of modified cellulose (Hemophan) with classical regenerated cellulose (Cuprophan). Dialysers containing these membranes, together with a cellulose acetate dialyser, were therefore incorporated in a cross-over programme and clinical and biochemical investigations undertaken. The efficacy of the modified cellulosic membrane with respect to urea and creatinine clearance was shown to be comparable to that of regenerated cellulose and cellulose acetate. However, modified cellulose showed an increased clearance for inorganic phosphate, significantly different from that demonstrated by both regenerated cellulose and cellulose acetate. Blood compatibility studies, which included the assessment of C3a activation and the reduction of white blood cell (WBC) and platelet count, clearly demonstrated that in comparison to regenerated cellulose, modified cellulose resulted in significantly less complement activation and WBC reduction. Similarly in comparison to cellulose acetate, modified cellulose showed reduced complement-activating and WBC-reducing properties. The reason for the improved blood compatibility of modified cellulose is not, as was originally assumed, related to binding of complement-inhibiting heparin, but appears instead to be due to the substitution of hydroxyl groups of regenerated cellulose.

Biocompatible Materials↗
PubMed1986

Biocompatibility and clinical performance of a new modified cellulose membrane.

A new modified cellulose dialysis membrane (MC, 1.2 m2) in which less than 5% of cellulosic OH-groups are substituted by tertiary amino groups was tested in a 6-week clinical trial for biocompatibility and clinical performance and compared to both regenerated cellulose (RC, 1.2 m2) and cellulose acetate (CA, 1.0 m2). Ten patients on maintenance hemodialysis took part in the study; all hollow fiber modules were equally well tolerated and no adverse reactions were observed. Using MC/RC/CA, mean clearances after 15 min of hemodialysis (HD) amounted to 162/169/150 ml/min for urea, to 143/143/124 ml/min for creatinine, and to 104/107/84 ml/min for phosphate (QB = 200 ml/min, QD = 500 ml/min, UFR = 0). Mean drop of systolic blood pressure was 6/10/8 mmHg and mean decrease of heart rate averaged 3/3/3 beats per minute, respectively, during the first hour of HD as compared to starting conditions. Residual blood volume in the modules after HD was low and heparin consumption identical for all 3 membranes (34 IU/kg X h). Mean peak C3a generation for MC/RC/CA amounted to 1312/3486/3099 ng/ml, respectively; leucocyte and platelet counts dropped to a minimum of 67/24/47% and 81/86/91%, respectively during the first hour of HD as compared to initial values. Elastase release from PMNL and platelet factor 4 from platelets showed no significant differences between the membranes. In conclusion, the new MC membrane showed a significantly better biocompatibility and equally good clinical performance as compared to RC and CA.

Biocompatible Materials↗