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Biomedical subjects

B Rippe

Publications and source records attributed to B Rippe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Computer simulations of ultrafiltration profiles for an icodextrin-based peritoneal fluid in CAPD.

BACKGROUND: The three-pore model of peritoneal transport has the ability to predict ultrafiltration (UF) profiles rather accurately, even when high molecular weight (MW) solutes are employed as osmotic agents in continuous ambulatory peritoneal dialysis (CAPD). In the present simulations, we wanted to assess, for various theoretical perturbations, the UF properties of a peritoneal dialysis (PD) solution with an osmotic agent having an average MW of 20 kD and a "number average MW" of 6.2 kD, which is similar to that of icodextrin (ICO). METHODS: For a PD solution containing a completely monodispersed 20 kD MW osmotic agent, the degree of UF modeled is much higher than that reported for ICO. Hence, to model the behavior of ICO, we subdivided the ICO molecules into eight or more different MW size fractions. For simulations using six or eight subfractions, we obtained an excellent fit of simulated to reported UF data. More dispersed solutions produced UF profiles similar to that with eight fractions. RESULTS: A 2.05 L 7.5% ICO PD solution, despite being slightly hypotonic, yielded a UF volume of nearly 600 mL in 12 hours, modeled for patients not previously exposed for ICO. After nine hours, the UF volume exceeded that produced by 3.86% glucose. The UF rate and volumes increased in proportion to (1) the ICO concentration, (2) the peritoneal surface area, and (3) the peritoneal UF coefficient, but was almost insensitive to increases in the instilled fluid volume. Simulated for patients previously exposed to ICO, having steady-state plasma concentrations of ICO degradation products, the predicted UF volume at 12 hours was reduced to approximately 400 mL. CONCLUSION: Employing the three-pore model of peritoneal transport and taking into account the polydispersed nature of ICO, it was possible to accurately computer simulate the UF profiles of ICO in accordance with reported data. The simulations suggest an advantage of using ICO in patients with type I UF failure, where UF with a high-MW osmotic agent will exceed that seen in patients not showing UF failure who are on glucose-based PD solutions.

Absorption↗
PubMed2000

Leukocyte sequestration in isolated guinea pig lungs during extracorporeal circulation: effects on microvascular function.

Neutrophils accumulate in patient lungs during clinical hemodialysis and in isolated blood-perfused guinea pig lungs due to the contact between blood and extracorporeal system. However, it is unclear how these sequestered and partly activated neutrophils affect the lung microvasculature. We, therefore, studied pulmonary vascular resistance, vascular permeability, gas exchange, and oxygen free radical production in isolated guinea pig lungs during perfusion with whole blood containing partly 'activated' neutrophils in comparison with perfusions using leukopenic blood. We also connected a Cuprophan hemodialysis membrane to the whole-blood perfusion system in order to investigate whether a dialyzer, which may further activate leukocytes, affects lung microvascular permeability, vascular resistances, and reactive oxygen species production. The sequestered neutrophils did not seem to markedly affect the lung microvascular function, since neither the leukocyte-free perfusion nor the hemodialysis membrane altered any of the measured variables as compared with whole-blood perfusion in a system without a dialyzer. We conclude that neutrophils, whether activated by a perfusion system or by a dialysis membrane, can accumulate in isolated lungs without adversely affecting the microvascular function.

Animals↗
PubMed1999

Urine IgG2/IgG4-ratio indicates the significance of the charge selective properties of the glomerular capillary wall for the macromolecular transport in glomerular diseases.

BACKGROUND: Alterations of the charge-selective properties of the glomerular capillary wall are important constituents of the pathogenesis of many glomerular diseases. Thus, differences in the degree of such changes could be of help in understanding the mechanisms governing the transport of macromolecules across the glomerular capillary wall. METHODS: The ratio between urine concentrations of neutral IgG2 and negatively charged IgG4 (IgG2/IgG4-ratio) was measured in 150 proteinuric patients and 21 healthy controls. The patients were subdivided into seven biopsy verified diagnostic groups. RESULTS: The study revealed decreased IgG2/ IgG4-ratio in membranous glomerulonephritis (0.57) compared to healthy controls (2.09) and to all other diagnosis groups; crescentic necrotizing glomerulonephritis (1.28), diffuse proliferative glomerulonephritis (1.10), IgA nephropathy (1.11), mesangial proliferative glomerulonephritis (1.55), minimal change nephropathy (1.00), and nephrosclerosis secondary to hypertension (1.06). Although not statistically significant, there was a tendency towards lower IgG2/IgG4-ratio values in all the studied glomerular diseases compared to healthy controls. CONCLUSIONS: Since IgG is transported entirely through the large pores of the glomerular basement membrane decreased IgG2/IgG4-ratio implies that this pathway is strongly influenced by the charge-selective properties of the glomerular capillary wall. The conclusion that could be drawn from that is that the large pore radius must be discrete, in the order of 80-90 A, and thus not non-discriminatory to macromolecules as previously thought.

Adolescent↗
PubMed1999

In vivo microvascular clearance of albumin in renal and extrarenal tissues in puromycin aminonucleoside (PAN) induced nephrotic syndrome.

BACKGROUND: The nephrotic syndrome is characterized by generalized oedema considered to be due to the fall in serum albumin and to sodium retention. The aim of the present study was to investigate whether a generalized disturbance in vascular integrity contributes to the oedema formation. METHODS: We used the PAN-(puromycin aminonucleoside) nephritis model in order to induce the nephrotic syndrome in female Wistar rats. Eight rats were given PAN, 15 mg/100 g body weight, intraperitoneally 10 days prior to the study, whereas 21 rats served as controls. Albumin clearance to tissues was measured using a dual isotope technique. Repeated blood samples as well as samples from various muscles, kidney, liver, lung, heart, abdominal wall and from ascites fluid were taken to determine radioactivity and tissue dry-to-wet weights. Clearance of albumin (Clalb) from plasma to interstitium was calculated from the (linear) increment in 'plasma equivalent tissue albumin space' as a function of time, corrected for intravascular volume and oedema. The plasma and urine concentrations of albumin were determined in a parallel study by single radial diffusion using monospecific rabbit anti-rat antiserum in seven PAN animals and 13 controls. RESULTS: A marked fall in dry-to-wet weight ratios together with pronounced proteinuria, oedema and ascites were found in the PAN animals. Haematocrit decreased from 45% (32-51) to 30% (28-38) and serum albumin from 22.0 g/l (16.3-25.2) to 4.94 g/l (3.20-6.72) in control and PAN animals, respectively. However, Clalb apparently remained unchanged in the PAN animals in comparison to controls in most tissues examined. Thus, in these in vivo experiments there was no direct evidence of an increased extravasation of albumin in extrarenal tissues. CONCLUSIONS: There was no strong support for the contention that a generalized disturbance of capillary integrity outside the renal vasculature would contribute to the oedema formation in the PAN nephrotic syndrome.

Animals↗
PubMed1999

Peritoneal lymphatic absorption and solute exchange during zymosan-induced peritonitis in the rat.

Lymph flow is elevated in most inflammatory conditions. However, a few previous studies have indicated that peritoneal lymph flow may actually fall during acute peritonitis. This study was performed to explore this issue further and to study the pathophysiology of peritoneal exchange during peritonitis. Therefore, we wanted to assess the total peritoneal clearance (Cl) and the clearance from peritoneum to plasma (Cl --> P) of 125I-labeled albumin (125I-albumin) as well as plasma-to-dialysate clearance (Cl --> D) of Evans blue-labeled albumin together with peritoneal ultrafiltration (UF) profiles and mass transfer area coefficients of 51Cr-EDTA and glucose in rats after acute peritonitis induced by zymosan. Zymosan incubation of the peritoneal cavity (120 mg) for 4 h generally led to a 4- to 10-fold increase in peritoneal fluid white blood cell count, indicating that acute peritonitis had been induced. Then 16 ml of 3.86% Dianeal and 125I-albumin were instilled intraperitoneally, whereas Evans blue-labeled albumin and 51Cr-EDTA were given as infusions intravenously. Compared with control, mass transfer area coefficients for glucose and 51Cr-EDTA increased markedly from 0.43 +/- 0.06 and 0.25 +/- 0.04 to 0.91 +/- 0.06 and 0.59 +/- 0.05 (SE) ml/min, respectively, during peritonitis, whereas Cl and Cl --> D increased from 32.8 +/- 5.6 and 8.6 +/- 1.6 to 74.5 +/- 7.3 and 12.9 +/- 1.0 microl/min, respectively. The UF profile in peritonitis indicated type I loss of UF (resulting from the increases in permeability-surface area product for glucose). However, the Cl --> P declined to 5.9 +/- 1.0 microl/min from 7.9 +/- 0.8 microl/min (P < 0.05) in control. In conclusion, despite marked effects on peritoneal solute transport and on UF, conceivably resulting from vasodilatation and increases in capillary permeability, zymosan-induced peritonitis did not cause any acute increases in direct peritoneal lymphatic absorption.

Animals↗
PubMed1999

Size and charge selectivity of the glomerular filter in patients with insulin-dependent diabetes mellitus: urinary immunoglobulins and glycosaminoglycans.

BACKGROUND: In diabetic nephropathy, a reduction in negative membrane charge in the glomerular filter, i.e., the number of sulphated groups of glycosaminoglycans, has been argued to lead to increases in excretion of negatively charged molecules, such as albumin and IgG4. However, albuminuria and an increased excretion rate of IgG may also be caused by an increase in radius or number of glomerular large pores. METHODS: Timed urinary excretion rates of sulphated glycosaminoglycans, albumin, and IgG2, IgG4, and IgM were analyzed in 94 patients with insulin-dependent diabetes mellitus with different degrees of nephropathy and compared with the excretion rates in 26 control subjects. Sulphated glycosaminoglycans were measured spectrophotometrically after addition of 1, 9-dimethylmethylene blue. Albumin and immunoglobulins were measured by immunoassays. RESULTS: With increases in the albumin excretion rate the excretion of IgG2, IgG4, and IgM also increased, in contrast to a decrease in glycosaminoglycans and the ratio between IgG2 and IgG4 (selectivity index). This index decreased from 6.2 to 0.7 (median; p < 0.01). However, with linear regression analysis the excretion rates of albumin and immunoglobulins were not associated with those of glycosaminoglycans. CONCLUSION: In diabetic nephropathy changes in both large-pore number and in charge selectivity may be pathogenic mechanisms for albuminuria.

Adult↗
PubMed1998

Proteinuria selectivity index based upon alpha 2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases. Technical note.

BACKGROUND: The proteinuria selectivity index (SI) may be used to describe changes of the glomerular permeability for macromolecules in glomerular diseases. Proteins the size of alpha 2-macroglobulin (alpha 2 M) or IgM cannot normally pass the glomerular barrier, whereas IgG can pass through the large pores of glomerular basement membrane. Comparison of the clearance of the three high-molecular-weight proteins to that of albumin may be useful in characterization and diagnosis of different glomerular diseases as well as in understanding of the permeability characteristics of the glomerular filter. METHODS: Three types of SI, each calculated as a ratio of clearance of either IgG, alpha 2M or IgM to that of albumin, were measured in 199 proteinuric patients. The patients were subdivided into eight different biopsy-verified glomerular diseases. RESULTS: Two diagnoses could be clearly distinguished using SI based on alpha 2M (alpha 2 M SI) or IgM (IgM SI). Both alpha 2M SI and IgM SI were significantly lower in minimal change nephropathy and higher in crescentic necrotizing glomerulonephritis than in all the other diagnoses. The SI based on IgG (IgG SI) was less useful in determining specific diagnoses, since patients with minimal change nephropathy could not be distinguished from those with other types of primary glomerulonephritis and patients with crescentic necrotizing glomerulonephritis did not differ from those with diabetic nephropathy. CONCLUSIONS: The findings of this study indicate that alpha 2M SI and IgM SI are superior to IgG SI in characterization of glomerular disorders and might replace the IgG SI for this purpose.

Adolescent↗
PubMed1998

Size-selectivity of the glomerular barrier to high molecular weight proteins: upper size limitations of shunt pathways.

To evaluate the large pore radius of the glomerular capillary filter, plasma-to-urine fractional clearances of a number of endogenous proteins were assessed in normal and in nephrotic Wistar rats in which proximal tubular reabsorption had been inhibited using lysine. The proteins studied varied in radius from 16.2 A (Beta 2-microglobulin) to 90 A (alpha 2-macroglobulin). The nephrotic syndrome was induced by puromycin aminonucleoside (PAN). A marked restriction of the transport of large proteins across the glomerular capillary wall was found, indicating that there are no non-discriminatory 'shunt pathways' in the glomerular barrier. Rather, there seems to be large pores of radius 110 to 115 A accounting for the clearance of large proteins into the primary urine. This protein excretion pattern was almost the same for control and nephrotic rats, except that in the latter, the number of large pores was increased 170 times. The ratio between the number of large and small pores was calculated to be approximately equal to 7 x 10(-7) in normal rats and to 1.2 x 10(-4) in PAN nephrotic rats, assuming no classic shunt pathways. If classic shunt pathways had still existed, they would normally contribute to no more than approximately equal to 10(-5) of the total glomerular filtration rate. We postulate that very large macromolecules like IgM will not pass the glomerular filter at all under normal conditions, whereas the urine concentration of alpha2-macroglobulin will normally be extremely low.

Animals↗
PubMed1998

Capillary diffusion capacity and tissue distribution of pancreatic procolipase in rat.

The permeability-surface area product of procolipase and its apparent distribution volume in rat tissues were assessed using a tissue uptake technique. Procolipase was investigated together with 51Cr-EDTA, used as an inert extracellular marker, and 131I-albumin, used as a plasma volume marker. The tissue uptake of procolipase seemed to occur by passive transport in most of the organs studied, such as in muscle, liver, lung, adipose tissue, adrenal glands, colon, and skin. However, throughout the gastrointestinal tract, except in the colon, there was a high uptake of procolipase, greatly exceeding that of 51Cr-EDTA. This was especially evident in the stomach, in which the procolipase uptake was nonsaturable within the experimental period. Also, in the central nervous system (CNS), there was evidence of specific, possibly carrier-mediated, transport. These results suggest that procolipase may have specific, conceivably receptor-mediated, transport pathways across the microvascular endothelium in the stomach, pancreas, duodenum, ileum, and the CNS.

Animals↗
PubMed1998

Enhanced peritoneal diffusion capacity of 51Cr-EDTA during the initial phase of peritoneal dialysis dwells: role of vasodilatation, dialysate 'stirring', and of interstitial factors.

Mass transfer area coefficients (PS) to small solutes are usually markedly increased during the first 0-15 min of peritoneal dialysis (PD) dwells. This phenomenon may be due to, for example, initial arteriolar vasodilatation and, hence, recruitment of capillary surface area. Other possibilities are an initial discharge (or saturation) of solutes from (in) the interstitium or an increased mixing, i.e., 'macrostirring' caused by the exchange procedure per se. We have investigated these possibilities during acute PD in rats, by assessing PS for 51Cr-EDTA as a function of time [PS(t)]. The discharge effect was studied by saturating the peritoneal interstitium with 51Cr-EDTA by intravenous tracer infusion prior to each dwell and the results compared to those obtained in rats when tracer infusion and dwells were started simultaneously. The potential effect of initial vasodilatation was studied by adding isoproterenol to the dialysis fluid. Finally, the potential influence of an increased interstitial 'microstirring', induced by high glucose concentrations, was investigated by comparison of results for 1.36% Dianeal with those for 3.86% Dianeal. In nonvasodilated rats there was a significant drop in PS(t) between 2.5 and 15 min regardless of whether the rats were preloaded with tracer or not. However, there were no significant changes in PS(t) within the isoproterenol-treated group, indicating that vasodilatation plays a crucial role for the high PS initially. Furthermore, there was no difference in overall PS for 51Cr-EDTA among 1.36 and 3.86% Dianeal dwells. In conclusion, we have found that vasodilatation, but not interstitial discharge (or loading), may explain the inflation of PS occurring during the initial part of PD dwells. In addition, 'macrostirring', induced by the exchange procedure per se, may also be important.

Animals↗
PubMed1997

An isolated blood-perfused guinea-pig lung model for simultaneous registration of haemodynamic, microvascular and respiratory variables.

We have developed an optimized isolated lung perfusion system, which possesses several advantages. Firstly, studies of microvascular, respiratory, haematological and biochemical variables are combined in one model. Secondly, blood perfusion resulted in less oedema formation than buffer-perfused lungs, and high PO2 through ventilation with room air. Finally, data for the variables can be displayed, controlled and recorded in real time using a computerized system permitting subsequent processing (e.g. filtering without destroying original data). In this paper we discuss the basic behaviour of the model in terms of vascular resistance, vascular permeability, respiration and neutrophil sequestration. In addition, the effects of oleic acid, histamine and histamine receptor blockers were tested, and two methods of calculating vascular permeability are discussed. The way in which different anaesthetics affect the neutrophil content of lung tissue and blood was also investigated. In the model, oleic acid increased pulmonary vascular resistance and permeability, whereas histamine did not affect either permeability or the pre/postcapillary vascular resistance ratio. However, histamine receptor blockers increased this ratio, indicating that there was endogenous histamine release. The neutrophil content of the isolated lungs was increased, but this did not affect the variables measured. There was also accumulation of neutrophils in the lungs of blood donor animals, due to CO2 sedation. However, CO2 sedation proved to be superior to pentobarbital or ketamine anaesthesia in maintaining the levels of neutrophils circulating in the blood. In conclusion, this model seems to be sensitive and to yield reproducible results regarding the physiology or pathophysiology of the lung.

Animals↗
PubMed1997

Decreased excretion of urine glycosaminoglycans as marker in renal amyloidosis.

BACKGROUND: The diagnosis of renal amyloidosis is normally established by kidney biopsy. In order to advance the determination of the diagnosis and the initiation of the therapy, fast and cheap, non-invasive diagnostic techniques are required. METHODS: Urine excretion of glycosaminoglycans (GAG) was measured in 10 patients with AA amyloidosis and 5 patients with AL amyloidosis and compared to 25 controls with primary glomerular diseases and 22 healthy controls. The subjects with primary glomerular disease were matched with regard to their renal function and the degree of albuminuria. RESULTS: The median urine GAG to creatinine ratio and the median fractional GAG excretion were significantly decreased (P < 0.05) in both AA amyloidosis (0.21 mg/mmol and 0.053 respectively) and AL amyloidosis (0.33 mg/mmol and 0.077 respectively) compared to control patients with primary glomerular disease (1.73 mg/mmol and 0.336 respectively) and healthy controls (2.67 mg/mmol and 0.226 respectively). The urine GAG to creatinine ratio did not correlate to age, sex, serum creatinine, urine albumin, or to the plasma levels of acute phase proteins. CONCLUSIONS: The decreased GAG excretion in renal amyloidosis is probably caused both by diminished number of functioning nephrons, decreased GAG synthesis in functioning glomeruli, and the trapping of GAG by amyloid fibrils. Urinary GAG excretion may serve as an independent marker of renal amyloidosis. It may be used in diagnostic work-up of renal amyloidosis in patients with glomerular diseases and in screening of amyloidosis in patients with chronic inflammatory disorders, with or without signs of renal disease.

Adult↗
PubMed1997

Decreased excretion of glycosaminoglycans in patients with primary glomerular diseases.

Urine glycosaminoglycans (GAG) concentrations were measured in 150 patients with primary glomerulonephritides: endocapillary glomerulonephritis, mesangial proliferative glomerulonephritis, IgA nephropathy, membranous glomerulonephritis and minimal change nephropathy, and in 63 healthy controls and 19 patients with diabetes nephropathy. The urine GAG to creatinine ratios (GCR) were significantly reduced (p < 0.01) in all the glomerulonephritides investigated (0.20 mg/mmol in endocapillary glomerulonephritis, 1.60 mg/mmol in mesangial proliferative glomerulonephritis, 1.74 mg/mmol in IgA nephropathy, 1.09 mg/mmol in membranous nephropathy, and 1.16 mg/mmol in minimal change nephropathy) compared to healthy controls (2.87 mg/mmol) but not compared to diabetes patients (1.17 mg/mmol). Also, the GCR in a group of 23 non-albuminuric glomerulonephritis patients (1.98 mg/mmol) was shown to be significantly decreased (p < 0.01) compared to healthy controls. Moreover, the GCR was significantly lower (p < 0.01) in endocapillary glomerulonephritis than in any of the other diseases studied. The GAG excretion per functioning glomerular area, calculated as fractional GAG excretion (FGE), was decreased in all the glomerulonephritides investigated compared to both healthy controls and diabetes nephropathy. The decreased GAG excretion in glomerulonephritides, obtained in the present study, might be a consequence of decreased synthesis or turnover of GAG in the functioning nephrons whereas the mechanisms for the reduced GAG excretion in diabetes nephropathy might be of a different nature. Urinary GAG excretion in this group of glomerular disorders and particularly in endocapillary glomerulonephritis, may lead to new approaches in non-invasive renal diagnostics and, particularly with regard to the differentiation of acute and chronic forms of glomerulonephritides.

Adolescent↗
PubMed1996

Liver is not essential for solute transport during peritoneal dialysis.

Based on theoretical calculations on solute exchange capacities of various peritoneal tissues, the liver has been predicted to account for up to 43% of the permeability-surface area product (PS) of the entire peritoneal "membrane" for a small solute (sucrose) during peritoneal dialysis (PD). In these calculations, the abdominal wall and the diaphragm were found to contribute only approximately 10 to 15% of the total PS. However, evisceration has in previous studies been shown to affect the PS characteristics during PD only marginally (10 to 30%). In such evisceration experiments the liver was usually not removed, and therefore it has been suggested that an intact liver might have significantly contributed to the solute exchange under these premises. We assessed the peritoneal PS of 51Cr-EDTA (constantly infused intravenously) and the plasma-to-peritoneal clearance (ClB-->P) of 125I-human serum albumin (RISA) (given as an i.v. bolus) in Wistar rats during acute PD. In one group of rats the liver surface was sealed off using Histoacrylate glue (N = 6) and in another group a 90% hepatectomy was performed, the remaining portion of the liver, usually the right lower lobe, being sealed off by glue (N = 6). A third group was sham operated to serve as control (N = 12). The PS for 51Cr-EDTA was 0.32 +/- 0.03(+/- SE) ml. min-1 (N = 12) during control, 0.32 +/- 0.04 ml.min-1 after "sealing" of the liver surface (N = 6, P > 0.1) and 0.40 +/- 0.03 after hepatectomy (N = 6, P > 0.1), that is, remained unchanged after experimental intervention. The CIB-->P of RISA during control was 5.88 +/- 1.0 microliter.min-1 (N = 10), and was not altered after hepatectomy, 6.17 +/- 0.48 microliters.min-1 (N = 5, P > 0.1), but slightly increased after liver surface sealing (9.69 +/- 1.09 microliters.min-1, N = 5, P < 0.05). In conclusion, the present experiments indicate that the liver does not play an essential role in the overall solute exchange between the plasma and the peritoneal cavity (PC) during PD.

Animals↗