PubMed Health⌕ Search

Biomedical subjects

S H Jacobson

Publications and source records attributed to S H Jacobson.

At least 55 records · Page 3Linked to original sources

On complement net generation in fast hemodialysis: are high blood flow rates bioincompatible?

Arterial and venous concentrations of complement (C3a) and leukocyte count were determined in 17 patients during 201 hemodialysis sessions by 12 different treatment modes executed in random order using cuprophan, hemophan, or polyamide membranes with small or large membrane areas and high blood flow (Qb) (400 mL/min) for 2 hours or low Qb (200 mL/min) for 4 hours. With all membrane types, the number of leukocytes was significantly higher after 120 minutes of dialysis and by the end of treatment at high Qb compared with low Qb. C3a concentrations (microgram/mL) in the arterial and venous blood lines were significantly higher during cuprophan dialysis compared with hemophan and polyamide dialyses (P < 0.001). In addition, the net generation of C3a (microgram/min) was significantly higher during hemodialysis with cuprophan compared with hemophan and polyamide (P < 0.001). After 2 hours at high Qb for each of the three membranes, the net generation of C3a was significantly higher compared with low Qb (P < 0.05 for all comparisons). Possible reasons for the increase in the net generation of C3a (microgram/min) at high Qb are less protein deposition on the membrane at high Qb or the fact that the protein coat is stripped off in the dialyzer, thereby recreating a less biocompatible surface. Hemodialysis at high Qb may thus be less biocompatible than dialysis at low Qb.

Biocompatible Materials↗

Cell surface receptor modulation on monocytes and granulocytes during clinical and experimental hemodialysis.

We studied the modulation of cell surface receptors related to cell adhesion (L-selectin and Mac-1) on monocytes and granulocytes during clinical (7 patients treated with cuprophan, Cu, and polysulfone, PS, membranes, n = 14) and experimental Cu and PS hemodialysis (n = 14). The objective was to compare cell surface receptor modulation in vivo when large subpopulations of cells are withdrawn from the circulating pool with the experimental model when cells are not sequestrated. The expression of Mac-1 and L-selectin on monocytes increased during clinical Cu dialysis (p = 0.024 and p = 0.0096, respectively) but remained stable during PS dialysis. On granulocytes, an inverse receptor modulation of Mac-1 and L-selectin was observed during clinical Cu dialysis but not during PS dialysis. Mac-1 was significantly higher and L-selectin lower on granulocytes after 15 min of clinical Cu as compared to PS dialysis (p = 0.001 and p = 0.0093, respectively). During experimental Cu dialysis, Mac-1 expression increased and L-selectin decreased markedly and continuously on both monocytes and granulocytes. The L-selectin/Mac-1 ratio on monocytes and granulocytes may be used as an index of the ability of leukocytes to adhere and to be recruited to an inflammatory focus. This ratio was significantly lower during clinical Cu as compared to PS dialysis (p = 0.0008 and p = 0.0015 respectively) indicating that the recruitment of leukocytes to infection foci may be precluded in patients on Cu membranes. Both monocytes and granulocytes showed significantly lower L-selectin/Mac-1 ratio during and after experimental Cu as compared to PS dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A 3-D method for delineation of activity distributions and assessment of functional organ volumes with SPECT.

The distribution volume of an organ may have a clinical impact in many cases and various methods have been designed to make volume assessments. In this paper, we describe a new method for delineation of the distribution outline and volume determination. The method is based on smoothing, differentiation, image relaxation and voxel counting of single photon emission computer tomography (SPECT) image sets with 3-D operators. A special routine corrects for the inherent thickness of the voxel-based outline. Phantom experiments, using a SPECT system with LEGP-collimator and a 64 x 64 acquisition matrix with 6.3 x 6.3 mm2 pixel size, demonstrated good correlation between the measured and the true volumes. For volumes larger than 120 cc the correlation coefficient was 0.9999 with SE 1.0 cc and an average relative deviation of 0.49%. For volumes below 120 cc, the accuracy was impaired due to low resolution power. By improving the system spatial resolution with an LEHR-collimator and a smaller pixel-size (4.1 x 4.1 mm2), good accuracy was achieved also for volumes in the range from 3 to 120 cc. Measurements of 15 differently shaped phantoms of volumes between 3 and 104 cc demonstrated high correlation between measured and true volumes: R = 0.9921 and SE = 0.74 cc (5.3%). For volumes as small as 3 and 5 cc, the difference between the true and the assessed volume was 0.6 cc. The reproducibility of the method was within 3% for volumes above 120 cc and within 7% for volumes below.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Hepatitis C transmission in a hemodialysis unit: molecular evidence for spread of virus among patients not sharing equipment.

Three cases of simultaneous seroconversion to hepatitis C virus (HCV) in a hemodialysis unit initiated the investigation of the viral strains of 14 seropositive patients in the unit by nucleotide sequencing. The results showed that five patients had been infected with the same viral strain, and indicated that two other patients were sharing a second strain. Transmission was not related to blood transfusions and not associated with the dialysis machines, but occurred between patients treated on the same shift. The number of cases was higher than expected from the serological data. Thus, spread of virus may occur at high frequencies in environments where parenteral routes are made accessible, in spite of rigorous preventive measures. This may raise concern that non-transfusion associated spread of HCV may be present and unnoticed in several hospital settings.

Base Sequence↗

Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis.

The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.

Acute Disease↗

Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial-virulence-associated traits and renal function.

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Acute Disease↗

Individual differences in biocompatibility responses to hemodialysis.

There are very few reports in the literature on individual differences in the response to dialysis treatment. We studied the influence of the individual patient, dialysis membrane quality, blood-flow (Qb) and surface area on leukocyte activation and complement generation (C3a) during 234 hemodialysis treatments using Cuprophan (CU), hemophane (HE) and polyamide (PA) dialyzers. The most common reaction was a decrease in leukocyte count and an increase in C3a after 15-minutes of treatment. Leukocyte overshoot by the end of dialysis was observed at high Qb for all three membranes but at low Qb only during CU treatments. The reaction patterns were influenced by the quality of the membrane, area and Qb. Analysis of each individual patient showed for a large number of treatments reaction patterns corresponding to those described in the literature. However, some patients reacted differently. In four patients (20%), the nadir in leukocyte count and maximum in C3a concentration was reached considerably later during CU-dialysis. Three patients were devoid of pronounced early leukocyte response but presented with the late overshoot during CU-dialysis. Three other patients reacted with an early drop in leukocyte count and a rapid increase in C3a generation during PA treatments but not during HE treatments. Three other patients reacted vice versa. A particular mode of dialysis treatment may thus be biocompatible for some patients but not necessarily for all. In the case biocompatibility is desired the individual response to the particular dialysis mode needs to be identified. The underlying mechanisms warrant further studies.

Adult↗

Whole blood-, plasma- and red blood cell glutathione and cysteine in patients with kidney disease and during hemodialysis.

There are conflicting results regarding the activity of glutathione (GSH) in patients with kidney disease. We examined whole blood-, plasma- and erythrocyte concentrations of GSH and cysteine in 12 patients with renal disease and in 14 patients on maintenance hemodialysis. Total plasma GSH concentrations were higher in patients with kidney disease than in patients maintained on hemodialysis (23.5 +/- 13.1 vs 9.1 +/- 7.5 mumol/l, p < 0.01) but erythrocyte concentrations of GSH were similar. Whole blood-, plasma and erythrocyte concentrations of GSH remained stable during hemodialysis. The total concentration of cysteine in plasma was significantly higher in patients on hemodialysis (556 +/- 258 mumol/l) as compared to patients with kidney disease (248 +/- 53 mumol/l, p < 0.001) but red blood cell concentrations were similar. Whole blood- and plasma concentrations of cysteine decreased significantly during hemodialysis. There were no significant correlations between serum creatinine and GSH or cysteine concentrations in patients on hemodialysis but when all patients were evaluated together, a significant correlation between serum creatinine and total plasma cysteine concentrations was observed (r = 0.52, p = 0.0017).

Aged↗

Beta 2-microglobulin generation and removal in long slow and short fast hemodialysis.

We studied the influence of different modes of hemodialysis (HD) on plasma levels of beta 2-microglobulin (P-beta 2-m) and its correlation to changes in leukocyte count, complement activation (C3a), and elastase generation. The influence of dialyzer membrane, membrane surface area, duration of treatment, and blood flow was analyzed with respect to post-HD levels of P-beta 2-m. Twenty patients underwent 12 modes of bicarbonate hemodialysis in random order (n = 252) using three different membranes (Cuprophan [CU], hemophan [HE], or polyamide [PA], two dialyzer areas, and fast (400 mL/min) or slow (200 mL/min) blood flow (Qb) for 2 or 4 hours, respectively. All dialysate was collected and beta 2-m was analyzed (D-beta 2-m). After correction for hemoconcentration, P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes (CU, 0.9 +/- 0.3 mg/L, P = 0.002; HE, 1.2 +/- 0.3 mg/L, P < 0.001; and PA, 8.3 +/- 0.3 mg/L, P < 0.001). Elimination of P-beta 2-m was influenced by type of membrane (P < 0.001) and ultrafiltration volume (P = 0.0019) but not by membrane area or Qb. The largest reduction in P-beta 2-m (-10.4 mg/L) was achieved by the following treatment combination: PA membrane, large dialyzer area, and low Qb for 4 hours. P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours (-9.9 +/- 0.5 mg/L) than during high Qb for 2 hours (-6.8 +/- 0.5 mg/L, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Seroconversion to hepatitis C virus in dialysis patients: a retrospective and prospective study.

The prevalence and incidence of hepatitis C virus (HCV) infections were studied in 236 dialysis patients and related to clinical data at two hospitals in Stockholm, Sweden. Patients were followed during 12 months and tested by 1st- and 2nd-generation anti-HCV assays. Time of seroconversion to HCV could be determined by retrospective analysis of stored serum samples. A total of 36 (15%) patients were anti-HCV positive. Time of seroconversion could be determined for 23 patients and was in the majority of cases associated with blood transfusions, but late seroconversion (more than 6 months after transfusion) as well as lack of transfusion in some cases implied that HCV might be transmitted through dialysis equipment. Persistence of elevated alanine amino-transferase levels for more than 6 months occurred in 17% of anti-HCV-positive patients. In conclusion, routes of transmission in dialysis units have to be further evaluated since routes other than transfusion may occur and diagnosis may be delayed in this group of patients probably due to a poor immunological response.

Alanine Transaminase↗

The influence of dialyzer geometry on blood coagulation and biocompatibility.

The influence of dialyzer geometry on blood coagulation, heparin requirement and complement activation was studied in fourteen chronic hemodialysis patients. Each patient was dialyzed with two different cuprophan dialyzers, hollow fiber GF 120M and parallel plate Lundia IC5N. Both dialyzers had a wall thickness of 11 microns, surface area of 1.2 m2 and both were sterilized with ethylene oxide. Heparin doses were individually titrated. The mean heparin dose was 6089 +/- 988 U. Platelet count decreased from 218 x 10(9)/l to 193 x 10(9)/l and from 235 x 10(9)/l to 197 x 10(9)/l respectively (hollow fiber/plate dialyzer, ns). The number of leucocytes decreased at 15 min after start of dialysis by 56% and 61% (hollow fiber/plate dialyzer, ns). The heparin requirement, measured as prolongation of whole blood activated coagulation time after identical doses of heparin, were the same in hollow fiber and plate dialysis sessions. The arterial fibrinopeptide A concentrations increased during dialysis from 5.4 to 7.1 nmol/l and 8.5 to 9.6 nmol/l respectively (hollow fiber/plate dialyzer, ns). The residual blood volume in the hollow fiber dialyzers was 1.3 +/- 1.1 ml and in the plate dialyzers 1.5 +/- 0.9 ml (ns). C3a activation, indicated by a marked arterio-venous difference, was observed at 15 min after start of dialysis with hollow fiber as well as plate dialyzers. The arterio-venous difference was less pronounced at the end of dialysis. There were no differences in C3a activation between hollow fiber and plate dialyzers at any timepoint. It is concluded that dialyzer geometry does not significantly influence platelet count, blood coagulation, heparin requirement or complement activation.

Aged↗

Long-term prognosis of post-infectious renal scarring in relation to radiological findings in childhood--a 27-year follow-up.

In a previous report the long-term prognosis of 30 patients with renal scarring after pyelonephritis in childhood was described. In this study, we have related the extent of renal scarring present in childhood to the conditions in early adulthood. A radiological progression of scarring from childhood to adulthood was seen in one-third of the kidneys. The 7 patients with bilateral scarring in childhood had a smaller renal area, lower glomerular filtration rate and higher plasma vasopressin at follow-up than 13 healthy controls. The 20 patients who had unilateral scarring in childhood had a smaller renal area, lower glomerular filtration rate, higher diastolic blood pressure and higher plasma renin at follow-up than controls; 4 had hypertension. The most important finding was that children with unilateral disease are at risk of serious long-term complications. Filtration fraction at follow-up was higher in patients with extensive renal scarring in childhood compared with those with a normal renal area or small scars in childhood (r = -0.43, P less than 0.05). This may indicate glomerular hyperfiltration by remnant glomeruli. This paper emphasizes t the potential seriousness of childhood urinary tract infections especially when early infantile infections are overlooked. A follow-up of more than 4 decades may be necessary before the ultimate prognosis can be established, especially in patients with unilateral renal disease. It is advised that most patients with post-infectious renal scars are followed as high-risk patients, and that treatment continuity is established between paediatricians, nephrologists and, when required, obstetricians.

Adolescent↗

Mobilization of an intracellular glycoprotein (Mac-1) on monocytes and granulocytes during hemodialysis.

We studied the upregulation of the intracellular glycoprotein Mac-1 (CD11b/CD18, CR3) on monocytes and granulocytes during 36 bicarbonate hemodialyses in 12 patients who were randomly treated with Cuprophan (Cu), Hemophan (He) or Polysulfone (PS; low-flux) membranes. The degree of mobilization of this adhesion protein was related to changes in granulocyte and monocyte count, generation of C3a and production of interleukin-1 beta in plasma. Mac-1 expression on granulocytes was significantly higher after 5 and 15 min of Cu hemodialysis as compared to He or PS dialyses (p < 0.001) and correlated to changes in granulocyte count at 15 min (r = 0.62 and r = 0.76, p < 0.001). No differences in early Mac-1 mobilization on circulating monocytes was observed despite a decrease in cell count. Mac-1 expression on monocytes and granulocytes in the venous blood line at 180 min of treatment was significantly higher during Cu dialysis as compared to He and PS dialyses (p < 0.02 and p < 0.001, respectively). Early generation of C3a was higher in patients on Cu dialysis than in He or PS dialysis (p < 0.001) and correlated both to granulocytopenia (r = 0.45, p < 0.01) and to the subsequent increase in Mac-1 expression on granulocytes (r = 0.63, p < 0.001). An early increase in Mac-1 expression on monocytes was accompanied by an increase in plasma interleukin-1 beta later during dialysis (p < 0.05). Studies of Mac-1 expression during hemodialysis increased the sensitivity of biocompatibility measurements and correlated better than complement generation to changes in granulocyte count as it mediates adhesion to endothelial cells.

Adult↗

Dialysis granulocytopenia is preceded by an increased surface expression of the adhesion-promoting glucoprotein Mac-1.

We studied the expression of Mac-1 on granulocytes (flow cytometry) from 9 patients (27 examinations) during hemodialysis with cuprophane membranes (CuM). Samples were drawn before dialysis and from the arterial and venous lines at 5, 15 and 180 min. Granulocytopenia was most pronounced after 15 min of treatment. Mac-1 expression on granulocytes increased during dialysis, and a pronounced enhancement occurred across the dialyzer. Mac-1 expression on granulocytes increased 116% across the dialyzer at 5 min, and the degree of Mac-1 mobilization at 5 min correlated with the degree of subsequent granulocytopenia at 15 min. In in vitro experiments, granulocytes from healthy blood donors were incubated with plasma drawn from the arterial and venous lines at 5 min. Plasma drawn from the venous line at 5 min had a greater ability to mobilize Mac-1 than plasma from the arterial line (p less than 0.002). This difference correlated with the degree of granulocytopenia at 15 min (r = 0.76, p = 0.01). Pieces of a washed CuM were incubated in normal human serum (NHS) preparations for different times. Inactivation of the alternative pathway of complement activation (NHS-50 degrees) did not alter the generation of Mac-1-mobilizating capacity compared to NHS. In contrast, inactivation of the classical pathway (NHS-EGTA) decreased the early but not the late generation of Mac-1-mobilizating capacity. Our results indicate that the early mobilization and not the absolute expression of Mac-1 correlates with granulocytopenia, and that sera in vitro attain Mac-1-mobilizating capacity more rapidly when the classical pathway of complement activation is intact.

Aged↗

Biochemical fingerprinting of urinary Escherichia coli causing recurrent infections in women with pyelonephritic renal scarring.

A biochemical fingerprinting system, especially designed for subtyping of Escherichia coli and suitable for screening large number of bacterial strains was used in a long-term follow-up study of 19 women with non-obstructive pyelonephritic renal scarring and recurrent urinary infections in order to examine whether recurrent infections mostly are relapses or reinfections in this group of patients. Seventy-six recurrent infections occurred during a 47-month follow-up (0.09 infections per observation month). The majority of the recurrences were reinfections (58/76, 76%) and 18 (24%) were relapses caused by E. coli. Approximately 50% of relapses and reinfections caused by E. coli were symptomatic while the majority of reinfections caused by other bacteria were asymptomatic (23/30, 77%). In one patient a relapse of E. coli infection occurred more than two years (745 days) after the initial infection. Reinfections may occur early (7 days) after cessation of antimicrobial therapy in this group of patients. Two patients had an episode of symptomatic bacteriuria 51 and 56 days after asymptomatic bacteriuria with the same E. coli strain was detected. Biochemical fingerprinting of the E. coli isolates revealed that they belong to a wide variety of biochemical phenotypes which indicates that they are not members of widespread uropathogenic clones.

Adult↗

Effective anticoagulation by a low molecular weight heparin (Fragmin) in hemodialysis with a highly permeable polysulfone membrane.

The efficacy and kinetics of a low molecular weight heparin fragment (LMWH-fragment, Fragmin) were studied during one hemodialysis session with a highly permeable polysulfone membrane and compared to a second dialysis session using a conventional cuprophane membrane. All patients received 5000 U of Fragmin given as an injection into the arterial line at start of dialysis. The anticoagulative efficacy was evaluated by measuring plasma fibrinopeptide A concentrations. LMWH-fragment concentrations in plasma and ultrafiltrate were determined by an amidolytic activity assay and by a radioimmunoassay using a monoclonal antibody. During hemodialysis with cuprophane and polysulfone membranes the fibrinopeptide A concentrations were low indicating adequate anticoagulation. LMWH concentrations in plasma did not differ in the two membranes at any time. The LMWH-fragment in the ultrafiltrate could neither be detected with the amidolytic assay nor with the radioimmunoassay. We conclude that a single injection of Fragmin effectively prevents clotting during hemodialysis with a highly polysulfone membrane. No significant amounts of the anticoagulant are lost over the dialysis membrane.

Aged↗

Determination of functional kidney volume by single-photon emission computed tomography in patients with insulin-dependent diabetes mellitus.

Functional parenchymal kidney volume was determined by single-photon emission computed tomography (SPECT) for 99mTc-dimercaptosuccinic acid (DMSA) using a rotating gamma camera in phantom experiments and in patients with insulin-dependent diabetes mellitus (IDDM). The results from the patient examinations were corrected according to the phantom studies and were thereafter set in relation to renal haemodynamics, blood pressure, and urinary albumin excretion. Functional parenchymal kidney volume was significantly greater in diabetic patients compared to that of 11 healthy controls (P < 0.003). Urinary albumin excretion was increased and glomerular filtration rate (GFR) per renal parenchymal volume significantly less in patients with a duration of diabetic disease of more than 15 years compared to patients with shorter duration of disease (P < 0.03 and P < 0.05 respectively). Diabetic patients with a GFR of more than 120 ml/min had greater renal parenchymal volume than patients with lower GFR (P < 0.02). Patients with increased GFR, renal plasma flow (RPF), renal blood flow, or filtration fraction had significantly greater functional parenchymal volume than the healthy subjects (P < 0.01 for all comparisons). We conclude that by application of SPECT for DMSA we were able to show that IDDM patients have greater renal parenchymal volumes than healthy subjects. GFR/kidney volume was increased in IDDM patients with a duration of disease of < 15 years compared to patients with long-standing diabetes. The SPECT technique seems suitable for prospective long-term follow-up studies of functional kidney volume in IDDM patients.

Adult↗

Urinary Escherichia coli causing recurrent infections--a prospective follow-up of biochemical phenotypes.

Twenty-three women with non-obstructive acute pyelonephritis due to Escherichia coli were prospectively studied during 880 patient months, mean observation time 38 months. Each patient had between 1 and 4 new episodes of E. coli bacteriuria during the study period (altogether 49 recurrencies). All E. coli isolates were typed by biochemical fingerprinting. Twenty-six of the recurrencies were caused by an E. coli strain identical to one of those that had previously appeared. Sixteen of these infections were caused by a strain identical to the one that gave rise to the original acute pyelonephritis. Ten further recurrencies were due to an E. coli strain that had previously caused symptomatic or asymptomatic bacteriuria during the observation period. Despite appropriate treatment and repeated negative urine cultures post-treatment, infections caused by identical E. coli strains occurred up to 35 months after the initial episode of acute pyelonephritis. We suggest that the infecting E. coli strain may survive in the fecal flora or is harboured in the patient's surroundings, and after recolonizing the patient, these strains may give rise to further urinary tract infections.

Adult↗