[An interactive national symposium with mentometer voting. Experienced specialists learned more about SLE with renal involvement].
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Adult↗
Biomedical subjects
S H Jacobson
Publications and source records attributed to S H Jacobson.
Prevalence of antibodies to hepatitis E virus among hemodialysis patients in Sweden.
In order to study the prevalence of antibody to hepatitis E virus (HEV) among hemodialysis patients and to evaluate whether chronic hemodialysis is associated with an increased risk of exposure to HEV in developed countries, the IgG anti-HEV was determined in serum samples obtained from 182 patients on chronic hemodialysis and 349 statistically selected, healthy Swedish control subjects. Serum specimens from 11 of the 182 (6.0%) hemodialysis patients and from 18 of the 349 (5.2%) control subjects were repeatedly positive for HEV antibodies (the difference was not significant: P = .67). Analysis of serial serum samples obtained at the initiation of hemodialysis and consecutively during follow-up periods of several years demonstrated no IgG anti-HEV seroconversion during chronic hemodialysis. The seroprevalence of anti-HEV antibody in the adult Swedish population was associated significantly with age. In persons younger than 40 years, the percentage of seropositive individuals was 2.5%, whereas the seroprevalence rate of anti-HEV was 7.4% in subjects older than 40 years (P < .05). This study indicates that nosocomial transmission of HEV to patients on maintenance hemodialysis was non-existent in three dialysis centers in Sweden (a developed country) and that chronic hemodialysis is not associated with an increased risk of exposure to HEV infection in this region.
Adult↗
Addressing the challenges to immunization practice with an economic algorithm for vaccine selection.
The biotechnology revolution is producing a growing bounty of new vaccines which pose difficult choices in selecting among many products. Some major public and private purchasers of vaccine may offer individual physicians and clinics their choice in assembling vaccine inventories. Others might purchase only a limited stock of products that would satisfactorily immunize a typical child. In either case, current vaccine selection decisions are based principally on purchase price alone without systematic consideration of other factors of fiscal consequence. As a potential tool for decision making, we developed an economic algorithm for vaccine selection that would minimize the overall costs of disease control through immunization by considering: (1) purchase price, (2) number of doses needed, (3) preparation time, (4) route of administration, (5) cold storage needs, (6) shelf life, (7) earliest age of full immunity, (8) adverse events frequency, and (9) efficacy of protection. To demonstrate the algorithm, variables (1) to (4) above were incorporated into a pilot binary-integer linear programming model that satisfied the recommended immunization schedule for diphtheria, tetanus, pertussis, Haemophilus influenzae b, and hepatitis B, using eleven vaccines (DTaP, DTaP-Hib, Hib, HepB and Hib-HepB) from four manufacturers. Five (or six) opportunities to vaccinate were modeled at (1), 2, 4, 6, 12-18, and 60 months of life, assuming US$40 per clinic visit, $15 per injection, and $0.50 per minute of nurse preparation time. Vaccine costs were varied using actual March and September 1997 US Federal vaccine prices, as well as estimates for unpriced new vaccines. Over 16,000 distinct vaccine stocking lists by vaccine type and brand were possible. Including a 1-month visit, the lowest-cost 'solution' of the algorithm was $529.41 per child in the March cost-assumption case, and $490.32 in the September one (both included four doses of DTaP-Hib, three HepB, and one DTaP). Without a 1-month visit, the lowest-cost solution in the March case cost $486.67 (four DTaP, two Hib-HepB, one DTaP-Hib, and one HepB), while the September case cost $450.32 (four DTaP-Hib, three HepB, and one DTaP). Ensuring at least one product was selected from each of the four manufacturers increased costs about $13.00, and the needed injections rose from eight to nine. The most economical selection of vaccines to use cannot be intuitively predicted, as permutations are large and solutions are sensitive to minor changes in costs and constraints. A transparent, objective selection method that weighs the economic value of distinguishing features among competing vaccines might offer the 'best value' to vaccine purchasers, while also creating strong market incentives for continuing innovation and competition in the vaccine industry.
Adolescent↗
Soluble interleukin-6 receptor, interleukin-10 and granulocyte colony-stimulating factor in acute pyelonephritis: relationship to markers of bacterial virulence and renal function.
BACKGROUND: Cytokines and cytokine receptors are involved in the systemic and local inflammatory response in patients with urinary tract infections. METHODS: We examined urine and serum concentrations of soluble IL-6 receptor (sIL-6R), IL-10 and granulocyte colony-stimulating factor (G-CSF) in 29 women with acute pyelonephritis caused by Escherichia coli 2 weeks after the infection, during the subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sIL-6R, IL-10 and G-CSF were related to the expression of five virulence markers of E. coli and to glomerular filtration rate (GFR) after pyelonephritis. RESULTS: On admission because of acute pyelonephritis the serum concentration of sIL-6R was similar to that of 12 healthy controls. Two weeks after the infection when all patients had received antibiotic treatment, the serum concentration of sIL-6R was significantly higher compared to that on admission (p < 0.001) and also higher compared to healthy controls (p = 0.001). Patients with increased concentrations of sIL-6R in serum 2 weeks after infection had significantly lower GFR at follow-up (p < 0.05). Patients with acute pyelonephritis had higher concentrations of G-CSF and IL-10 in serum compared to healthy subjects (p < 0.001 and p = 0.06, respectively). G-CSF in serum was higher in patients infected by E. coli producing cytotoxic necrotizing factor (p < 0.05). Patients infected by strains producing hemolysin had lower concentrations of sIL-6R (p < 0.001). Patients with detectable levels of the anti-inflammatory cytokine IL-10 in serum had significantly higher concentrations of IL-6 and the soluble tumor necrosis factor receptors I and II in serum as compared to patients in whom IL-10 was not detectable (p < 0.001, p = 0.001 and p < 0.05, respectively. CONCLUSION: These investigations, together with our previous findings summarized in this paper, contribute to an increased understanding of the local and systemic inflammatory response arising in response to acute pyelonephritis.
Acute Disease↗
Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring.
Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130+/-4 versus 107+/-1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.
Animals↗
Dialysis-induced serum factors inhibit adherence of monocytes and granulocytes to adult human endothelial cells.
In patients on hemodialysis, the sequences of events required for adhesion molecule-mediated adherence of monocytes and granulocytes to endothelial cells are pathophysiologically disrupted because activation of the cells with subsequent alterations in adhesion molecule phenotypes takes place in the extracorporeal circuit far away from the respective endothelial cell ligand. As a consequence, the host defense to infections may be affected. We analyzed the expression of CD62L and CD11b/CD18 on monocytes and granulocytes and the adherence of these cells, collected before, during, and after cuprophan hemodialysis, to resting and interleukin-1 beta (IL-1 beta)-stimulated adult human saphenous vein endothelial cells (HSVECs). Monocytes collected before dialysis adhered more avidly to HSVECs than did granulocytes. Adherence of both cell types increased to IL-1 beta-stimulated HSVECs (P < 0.05). Granulocytes obtained at 180 minutes adhered less to resting HSVECs than granulocytes harvested before hemodialysis (P < 0.05), despite an increase in CD11b/CD18 expression. To study if serum factors inhibiting adherence accumulate during hemodialysis, we incubated leukocytes harvested before hemodialysis in the same patients' serum collected before, during, and after dialysis. Serum collected at 180 minutes of cuprophan hemodialysis exerted inhibitory effects on both monocyte and granulocyte adhesion to HSVECs (P < 0.05). By contrast, serum collected during polysulfone hemodialysis of the same patients did not have any significant impact on the adherence of inflammatory cells to HSVECs. These findings contribute to an increased understanding of the factors involved in the impaired immune response observed in dialysis patients.
Adult↗
Impaired leucocyte rolling, adhesion and transendothelial migration following cuprophane haemodialysis.
In this study, we investigated how different steps in the extravasation process of leucocytes, i.e. rolling, adhesion and transendothelial migration, are affected by haemodialysis with cuprophane membranes. Human leucocytes obtained from whole blood prior to clinical haemodialysis and from the afferent blood line (post-dialyser) 15 min after the initiation of dialysis were injected into the mesenteric microcirculation of urethane anaesthetized rabbits and analysed for their ability to roll in the microvessels by use of intravital fluorescence microscopy. Moreover, neutrophils from the two leucocyte populations were compared with respect to chemoattractant-induced adhesion and transmigration across confluent monolayers of bovine aortic endothelial cells. Our results show that, as compared with pre-dialysis leucocytes, 15 min of cuprophane haemodialysis impaired leucocyte rolling by 78 +/- 7%, reduced N-formyl-methionyl-leucyl-phenylalanin (fMLP)-induced adhesion by 34 +/- 9%, and abolished transendothelial migration. These findings demonstrate that intradialytical activation of leucocytes during cuprophane haemodialysis severely affects leucocyte functions that are critical in the extravasation process of these cells at inflammatory tissue sites, and thus may help explain the increased susceptibility to infections observed in patients on chronic haemodialysis.
Animals↗
Patients infected with the same hepatitis C virus strain display different kinetics of the isolate-specific antibody response.
The antibody response to the hypervariable region of the E2 protein (HVR1) of hepatitis C virus (HCV) was studied in 5 patients who were infected by a common virus strain during an outbreak in a hemodialysis unit. Two patients resolved the infection, while 3 developed chronic HCV infection. For studying the antibody response to HVR1 during the early phase of infection, a Western blot assay using recombinant phage displaying HVR1 was developed. The 2 patients with resolving infection had a more rapid antibody response to HVR1 than did the patients developing chronic infection. Anti-HVR1 antibodies were repeatedly absent in 1 of the chronically infected patients. Antibodies to recombinant E2 protein occurred later than the anti-HVR1 antibodies and did not correlate with resolution of the infection. Thus, the present results suggest that early appearance of antibodies to the HVR1 may predict clearance of HCV infection.
Amino Acid Sequence↗
Occurrence of anti-C1q antibodies in IgA nephropathy.
BACKGROUND: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. METHODS: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n = 36) and SLE nephritis (n = 37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulonephritis (n = 7) and minimal change disease (n = 2), in which circulating immune complexes are usually not present, and in 40 healthy controls. RESULTS: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P < 0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P < 0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. CONCLUSIONS: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.
Adolescent↗
Molecular evidence for pap-G specific adhesion of Escherichia coli to human renal cells.
PURPOSE: To study the interaction between class II G-adhesin of Escherichia coli and human urogenital cells. MATERIAL AND METHODS: The adherence of two wild type P-fimbriated E. coli strains, both carrying a class II G-adhesion, and two constructed mutants (one class II G-adhesion knock-out mutant and one class switch mutant in which the papG gene was exchanged with a prsJ96 allele which is a representative of the class III G-adhesin) to human urogenital cells were examined by light microscopy and flow cytometry. RESULTS: The wild type E. coli strains adhered avidly to proximal tubular cells, but the isogenic mutant strains did only adhere in one of the experiments. A soluble receptor analogue inhibited bacterial attachment. CONCLUSIONS: These experiments strongly suggest that the papG class II tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.
Adhesins, Bacterial↗
Renal fibrosis in cyclosporin A-treated renal allograft recipients: morphological findings in relation to renal hemodynamics.
Nineteen nondiabetic kidney graft patients treated with cyclosporin A for 2 years underwent percutaneous renal allograft biopsy as well as renal hemodynamic examination. Renal allograft fibrosis was quantitatively evaluated as the relative volume of the renal cortical interstitium (VV %) and as the interstitium/tubuli ratio (I/T ratio). The histological changes were then classified into four groups, depending on the degree of interstitial fibrosis. The glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), filtration fraction (FF), and fractional clearance of sodium, potassium, phosphate, chloride, osmoles, and free water clearance were determined in all patients and in 13 healthy controls. Kidney graft recipients had significantly lower GFR, lower RPF, and lower RBF than the healthy controls (P < 0.001 for all comparisons) while FF was similar in patients and controls. Transplant recipients had a significantly higher fractional excretion of sodium, potassium, chloride, and phosphate than controls. All except one patient had clearly increased VV values, indicating increased interstitial fibrosis. The mean VV in renal allograft patients was 35% +/- 10% (normal < 16% +/- 5%) and the I/T ratio was 1.07 +/- 0.60 (normal < 0.24 +/- 0.08). No correlation was found between the quantitative or semiquantitative biopsy analysis and any renal hemodynamic parameter measured. We conclude that renal function is significantly decreased in kidney graft recipients, but that adaptive tubular changes occur in the graft. Interstitial renal fibrosis was common but did not correlate to any renal functional parameter.
Adolescent↗
Genotypic and phenotypic characterization of two newly established renal cell carcinoma cell lines.
Two new cell lines from human renal cell carcinoma are reported. Primary cell cultures from 75 consecutive cases of nephrectomy and metastatic surgery due to different stages of RCC during 4 years were studied. Two cell cultures could be propagated for more than 50 passages in vitro. HN4 was derived from a grade III clear cell carcinoma. HN51 originated from a metastatic brain lesion of a clear cell carcinoma grade III. Karyotype analysis of HN4 revealed triploidy with a clonal aberration, der(10)t(3;10)(q13;p12). HN51 also had a triploid pattern with different marker chromosomes but without any clonal aberration. Loss of heterozygosity studies revealed no loss of heterozygosity on 3p or other chromosomal markers in HN4 but LOH was found on one 3p marker and one 14q marker in addition to all 17 p and q markers in HN51. In vitro light microscopy showed distinctly different morphology in the two cell lines although they both had a typical epithelial growth pattern. Doubling times in vitro were low but slightly higher for HN51. Repeated tumorigenenic experiments in athymic mice only gave rise to subcutaneous tumors with HN51. On characterization by 2-dimensional gel electrophoresis, the two cell lines exhibited different polypeptide patterns with higher expression of proliferating cell nuclear antigen in HN51 and higher expression of glutathione-S-transferase in HN4 constituting the most prominent differences.
Aged↗
Tumour necrosis factor soluble receptors I and II and interleukin-1 receptor antagonist in acute pyelonephritis in relation to bacterial virulence-associated traits and renal function.
Urinary tract infections activate both mucosal and systemic inflammatory responses reflected by elevation of cytokine concentrations in serum and urine. We determined urine and serum concentrations of tumour necrosis factor soluble receptors I and II (sTNFR I and sTNFR II) and interleukin-1 receptor antagonist (IL-1ra) in 41 women with acute pyelonephritis caused by Escherichia coli, 2 weeks after the infection, during a subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sTNFR I, sTNFR II and IL-1ra were related to the expression of five virulence markers of E. coli, glomerular filtration rate (GFR) and to the concentration of C-reactive protein (CRP) in serum. Patients with acute pyelonephritis had elevated serum concentrations of sTNFR I and sTNFR II compared to healthy women (P < 0.001 for both comparisons). The concentrations of sTNFR I and sTNFR II in urine were significantly higher in patients with acute pyelonephritis compared to controls (P < 0.001 in both cases). The concentration of sTNFR II in urine was higher in patients infected by E. coli producing haemolysin (P = 0.05) and in patients infected by E. coli expressing hydrophobic properties (P = 0.05) compared to patients infected by strains without these virulence traits. Patients who had high concentrations of sTNFR II in serum during acute pyelonephritis had lower GFR at follow-up (r = -0.48, P = 0.05). Patients who responded with a marked increase in CRP had higher sTNFR I and sTNFR II in urine (r = 0.58, P < 0.01 and r = 0.48, P < 0.01, respectively). The concentrations of sTNFR I and sTNFR II in serum and urine decreased during follow-up and were lower 2 weeks after the infection when all patients were free from bacteriuria. IL-1ra in serum was elevated during pyelonephritis (P < 0.001) while that in urine was significantly lower compared to controls (P < 0.001). It is concluded that the increased concentrations of TNF receptors may block the cytotoxic and inflammatory actions and reduce the sensibility of renal cells to TNF alpha-mediated effects.
Acute Disease↗
Subclinical pulmonary oedema and intermittent haemodialysis.
It has been postulated that patients with chronic renal failure, even in the absence of cardiopulmonary symptoms, accumulate interstitial pulmonary fluid, which is removed by haemodialysis. To test this hypothesis we used the indocyanine green (ICG)-heavy water double indicator dilution method to measure lung water, cardiac output, and central blood volume in relation to haemodialysis. Ten uraemic patients, without cardiopulmonary symptoms, were investigated at the beginning and end, and 2 h after, a regular dialysis session. A group of 18 surgical patients about to undergo elective abdominal surgery served as controls. Despite normal gas exchange, central blood volume, and cardiac output at the start of dialysis the mean (SD) lung water was significantly higher than in the control group [4.8 (0.9) compared with 3.6 (0.7) ml/kg, P < 0.001]. There was no correlation between weight gain between sessions of dialysis and the magnitude of lung water at the start of dialysis. Lung water decreased (P < 0.001) to the level of the control group in response to dialysis. There was no correlation between weight loss and reduction in lung water induced by dialysis. In conclusion, we have verified the presence of subclinical pulmonary oedema which was removed by dialysis in a group of patients with established renal failure. The variations in lung water cannot be explained by hydrostatic mechanisms alone.
Blood Volume↗
Increased amounts of C3a and the terminal complement complex at high dialysis blood-flow: the relation with dialysis efficiency.
To estimate the influence of blood-flow on complement generation and the relation with dialysis efficacy (KT/V) 10 patients underwent cuprophan hemodialyses for 6 h using low (200 ml/min) or high (400 ml/min) blood-flow (n = 40). Dialysis with high blood-flow compared to low induced a more rapid drop in leukocyte count and a more pronounced leukocyte rebound. Net generation of C3a (microgram/min) was also larger at all 15 measuring points during high blood-flow dialysis and there was significantly larger total generation of C3a (after 3 h p < 0.05, after 6 h p < 0.05) as compared to low blood-flow. Reaching a KT/V of 1.2-1.4 with high blood-flow induced a 40% larger total net generation of C3a and 21% more of TCC than with low blood-flow. Net generation of TCC (AU/min) was higher during the first and last parts of high blood-flow dialysis compared to low. In conclusion, increased blood-flow in order to increase dialysis efficiency (KT/V 1.2-1.4) results in larger net infusion of complement products with possible impact on immune response and complement-associated pathophysiological mechanisms.
Complement C3a↗
Transmission of hepatitis C virus by transfer of an infected individual to a new dialysis unit.
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Amino Acid Sequence↗
Monocyte and granulocyte CD11b/CD18, CD62L expression and sICAM-1 concentration in the interdialytic period.
We studied cell surface modulation of CD11b/CD18 and CD62L on monocytes and granulocytes, sICAM-1 concentrations and the responsiveness of cells to exogenous fMLP in patients in the intra- (0-4 h Cuprophan dialysis) and interdialytic period (5-28 h) and in healthy subjects (0-24 h). The high CD11b/CD18, low CD62L granulocyte phenotype occurred rapidly during dialysis. By contrast, CD62L increased on the subpopulation of monocytes in circulation initially during dialysis and CD11b/CD18 was mobilized much slower. In the interdialytic period, the CD62L/(CD11b/CD18) ratio was reduced up to 12 h after start of treatment on both monocytes and granulocytes. This ratio was significantly lower than in healthy subjects up to 8 h after start of treatment. The responsiveness of granulocytes to exogenous fMLP, in terms of CD11b/CD18 mobilization, was significantly reduced in patients during and after hemodialysis as compared to that on granulocytes obtained from healthy controls. Monocytes were more refractory to fMLP up to 4 h after dialysis. sICAM-1 was significantly increased in patients before dialysis as compared to controls and remained elevated and fairly stable throughout treatment and in the interdialytic period. The variation in the expression of adhesion molecules on monocytes and on granulocytes in the interdialytic period was not related to the presence of activating serum factors remaining in the circulation after treatment. Our findings emphasize the importance of including the interdialytic period in the evaluation of dialysis membrane biocompatibility, especially when effects on monocytes are of interest.
Adult↗
Modulation of CD11b/CD18 on monocytes and granulocytes following hemodialysis membrane interaction in vitro.
We studied the generation of CD11b/CD18 mobilizing factors in serum after incubation with dialysis membrane fragments of different chemical composition. We also evaluated the relative importance of the alternative and classical pathways of the complement system in the generation of such factors. Monocytes and granulocytes from healthy blood donors were incubated in normal human serum (NHS) and in NHS that had been preincubated with Cuprophan (CU) membrane (NHS-CU), Hemophan (HE) (NHS-HE) or polysulfone (PS) (NHS-PS). NHS-CU caused the highest up-regulation of the CD11b/CD18 receptor on monocytes and granulocytes. The rank in capacity to mobilize CD11b/CD18 on granulocytes was CU > HE > PS (p < 0.001), CU > HE (p < 0.05) and HE > PS (p < 0.001). The rank in capacity to mobilize CD11b/CD18 on monocytes was CU > HE > PS (p < 0.001), CU > HE (p < 0.05) and HE > PS (p < 0.01). NHS-PS induced a lower up-regulation of CD11b/CD18 compared to NHS which indicates that serum factors with the ability to mobilize the CD11b/CD18 receptor on monocytes and granulocytes are deposited on or absorbed by PS. In order to study the relative contribution of the alternative and classical pathways of the complement system in the generation of CD11b/CD18 mobilizing factors in serum, three different serum preparations (1. both pathways intact. 2. only the alternative intact and 3. only the classical pathway intact) were used. The CU membrane activated the classical pathway to a larger extent than the PS membrane (p < 0.01). When only the alternative pathway was intact no difference in the generation of CD11b/CD18 mobilizing factors between the CU and PS membranes was observed. These studies show that CD11b/CD18 mobilizing serum factors are generated after incubation with CU membranes and that such factors are probably adsorbed by PS. The classical pathway of complement activation seems to contribute to the generation of CD11b/CD18 mobilizing factors in serum.
Biocompatible Materials↗