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Biomedical subjects

S H Jacobson

Publications and source records attributed to S H Jacobson.

89 records · Page 5Linked to original sources

P-fimbriae receptors in patients with chronic pyelonephritis.

The adherence of fluorescein isothiocyanate-labeled P-fimbriated Escherichia coli to uroepithelial cells from 19 women with chronic pyelonephritis was determined with the fluorescence-activated cell sorting technique. The application of this method has made it possible to study bacterial binding to a large number of cells. Renal function was determined in all patients and the recurrences of P-fimbriated Escherichia coli bacteriuria, cystitis and acute pyelonephritis during a 3-year followup were studied. We found a significant correlation between the P-fimbriae receptor accessibility on uroepithelial cells and glomerular filtration rate (r equals -0.75, p less than 0.001). Uroepithelial cells from the patients with chronic pyelonephritis and renal insufficiency had a higher binding capacity of P-fimbriated Escherichia coli than uroepithelial cells from patients with a normal glomerular filtration rate. There was no correlation between kidney function and the availability of P-fimbriae receptors in a control group of patients with polycystic kidney disease.

Adult↗

Aerobactin-mediated uptake of iron by strains of Escherichia coli causing acute pyelonephritis and bacteraemia.

A total of 285 strains of Escherichia coli isolated from children and women with acute non-obstructive pyelonephritis and from patients with bacteraemia as well as 120 faecal strains of E. coli from healthy children and adults were examined for aerobactin-mediated uptake of iron. The incidence of aerobactin-positive strains was significantly more in isolates from children with acute pyelonephritis (81%) than in faecal isolates from healthy children (50%, P less than 0.01). It was also higher in isolates of E. coli from women with acute pyelonephritis (72%) compared with faecal isolates from healthy adults (42%, P less than 0.001). Of the E. coli strains causing bacteraemia, 55% were aerobactin-positive. A significant correlation was found between the presence of aerobactin and expression of P-fimbriae in strains of E. coli isolated from children with acute pyelonephritis (P less than 0.01) and in isolates from bacteraemic patients (P less than 0.001). These results indicate that the presence of an aerobactin-mediated system of iron uptake may be an important virulence factor in strains of E. coli that cause ascending pyelonephritis.

Acute Disease↗

Renal hemodynamics and blood pressure control in patients with pyelonephritic renal scarring.

Pyelonephritic renal scarring is a common cause of renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), total renal area (TRA), systolic (SBP) and diastolic (DBP) blood pressure in 22 female patients with verified renal scarring and a history of febrile urinary tract infection (UTI) and in 9 healthy age-matched women with normal urograms and no history of symptomatic UTI. The patients with renal scarring had significantly lower GFR, smaller TRA and higher SBP than the healthy controls, but not significantly different RPF or FF. A decrease in GFR and RPF was associated with higher SBP and DBP in the patients with renal scarring. RPF/TRA, representing an approximation of the perfusion of renal tissue and GFR/TRA, were similar in patients with renal scarring and healthy controls. A reduction of renal parenchyma was accompanied by a proportional decrease in GFR and RPF, resulting in unchanged FF. These findings do not support the concept of hyperfiltration as a main cause of renal insufficiency in patients with pyelonephritis renal scarring. An increase in FF and a decrease in GFR/TRA and RPF/TRA was associated with higher DBP and a decrease in GFR/TRA and RPF/TRA with an increase in the urinary albumin excretion. We conclude that renal hemodynamics play an important part in the blood pressure control of patients with renal scarring and that in these patients with various degrees of renal failure there was no evidence of hyperfiltration or hyperperfusion by remnant glomeruli.

Adult↗

Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring.

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.

Adult↗

Symptomatic recurrent urinary tract infections in patients with renal scarring in relation to fecal colonization with P-fimbriated Escherichia coli.

We evaluated prospectively 49 women with renal scarring and a history of febrile urinary tract infections in regard to the incidence of recurrent symptomatic urinary tract infection and fecal colonization with P-fimbriated Escherichia coli. During a 3-year followup 26 patients (53 per cent) had symptomatic urinary tract infection (0.036 infections per patient-month), including 8 (16 per cent) who had 9 new episodes of febrile urinary tract infection, while 33 (67 per cent) had Escherichia coli bacteriuria (10(5) bacteria per ml. urine in pure culture). Thus, patients with previous febrile urinary tract infections and renal scarring have a high risk for recurrent infections. For comparison, the incidence of symptomatic urinary tract infection also was determined in 35 women with a recent episode of acute nonobstructive pyelonephritis and with normal kidneys on excretory urography. These patients had 0.031 symptomatic infections per patient-month. The fecal flora were examined twice a year for P-fimbriated Escherichia coli in 48 patients with renal scarring. Of these patients 21 (44 per cent) had at least 1 fecal colonization with a P-fimbriated Escherichia coli strain. However, in only 1 instance was a relationship detected between the presence of P-fimbriated Escherichia coli in the fecal flora and the development of subsequent febrile urinary tract infection. The findings indicate that fecal sampling twice a year is not of value to predict future urinary tract infections in adults with renal scarring.

Adult↗

The use of biochemical markers, serotype and fimbriation in the detection of Escherichia coli clones.

Biochemical reactions, O and K serotypes and presence of P-fimbriae were analysed in 116 Escherichia coli strains isolated in blood cultures from patients with bacteraemia and in 99 faecal strains isolated from healthy individuals. By using biochemical typing, the strains could be grouped into six main clusters with similarity index less than 0.8 (Gower, 1971) and altogether 16 subclusters with similarity index 0.82-0.89. The most discriminating tests between the clusters were fermentation of D-tagatose, saccharose, salicin and sorbose. No single biochemical property could differentiate bacteraemic isolates from faecal strains, although strains isolated from blood were significantly more often found in certain subclusters, whereas other subclusters contained mainly control strains. Bacteraemic strains possessed P-fimbriae more often, especially strains isolated from patients with E. coli in the urine concomitantly with bacteraemia. Equally, no single reaction could separate P-fimbriated from non-P-fimbriated strains. D-Tagatose was fermented more often by the P-fimbriated strains; on the other hand, melibiose and lactose fermentation tests were less often positive. Certain O serotypes (O1, O4, O6, O7, O18 and O25) were more common among bacteraemic isolates than controls. K serotypes such as K1, K5 and K52 were also more frequent among blood isolates. We conclude that a combination of biochemical tests, fimbriation and serotyping might be used to identify potentially pathogenic clusters of E. coli.

Adolescent↗

Renal size, glomerular function and urinary excretion of albumin and beta 2-microglobulin in patients with renal scarring due to pyelonephritis.

We have determined glomerular filtration rate (GFR), renal plasma flow (RPF), urinary excretion of albumin and beta 2-microglobulin, urinary osmolality and total renal area in 22 female patients with renal scarring and a history of febrile urinary tract infections (UTI) and in nine healthy age-matched controls with normal i.v. urography. The aim of the study was to compare different methods of determining glomerular function in patients with renal scarring due to previous pyelonephritis and to determine the urinary excretion of beta 2-microglobulin in these patients. All individuals were investigated in hydropenia. The patients with renal scarring had significantly lower GFR, smaller kidneys and lower urinary osmolality than the controls. A significant positive correlation between GFR and total renal area (r = 0.70, p less than 0.001) and between GFR and urinary albumin excretion (r = -0.69, p less than 0.001) was demonstrated. This indicates that determinations of total renal area from an i.v. urography and the urinary albumin excretion can be used for estimating GFR. Increased urinary excretion of beta 2-microglobulin does not occur in patients with renal scarring until the glomerular function is severely deteriorated.

Adult↗

Blood pressure regulation, peripheral renin activity and aldosterone in patients with pyelonephritic renal scarring.

Patients with renal scarring due to previous upper urinary tract infections (UTI) are at risk of developing hypertension and renal insufficiency. In this study glomerular filtration rate (GFR), systolic (SBP) and diastolic (DBP) blood pressure, peripheral renin activity (PRA), plasma (p-Aldo) and urine aldosterone (u-Aldo), the urinary excretion of sodium (UNa) and potassium (UK) and the fractional sodium (CNa/CIn) and potassium (CK/CIn) excretion were determined in 22 female patients with verified renal scarring and a history of febrile UTI and in nine age-matched healthy women with normal i.v. urograms. The patients had significantly lower GFR, higher SBP, higher PRA and higher CK/CIn than the healthy controls. A significant correlation between CNa/CIn and SBP (r = 0.51, P less than 0.05), DBP (r = 0.50, P less than 0.05) and PRA (r = -0.47, P less than 0.05) was found. The ratio of UK/UNa was significantly correlated to SBP (r = -0.43, P less than 0.05), DBP (r = -0.44, P less than 0.05), PRA (r = 0.65, P less than 0.01) and p-Aldo (r = 0.68, P less than 0.01). It is concluded that the renin-aldosterone system probably is involved in the pathogenesis of hypertension in patients with pyelonephritic renal scarring and that screening determinations of UNa and UK may prove useful for detection of individuals with increased PRA and p-Aldo.

Adult↗

P-fimbriated Escherichia coli in adults with renal scarring and pyelonephritis.

The commonest organism in urinary tract infections (UTI) is Escherichia coli. Pyelonephritogenic E.coli strains possess P-fimbriae which firmly attach to uroepithelial cells by recognition of a carbohydrate structure, alpha-D-Galp-(1-4)-beta-D-Galp, which is confined within all glycosphingolipids related to the human P-blood group antigens. Several investigators have studied virulence properties of E.coli and host resistance in relation to UTI. Uroepithelial cells from children and women with recurrent UTI have an increased capacity to bind E.coli. In contrast to previous studies the present one deals with patients with renal scarring, who constitute the major risk group among patients with UTI. P-fimbriae mediated binding to uroepithelial cells was studied and the risk of recurrent UTI in patients with renal scarring was determined. Ninety per cent of the E.coli isolates from female patients with acute non-obstructive pyelonephritis in this study possess P-fimbriae (I). The fecal E.coli colonies obtained from these patients were P-fimbriated in 55% compared to 11% of the fecal E.coli colonies from healthy controls. The P-blood group distribution in 56 female patients with renal scarring and a history of febrile UTI was the same as in a control group of 39 healthy subjects (II). A history of recurrent and/or early infections did not increase the percentage of the P1 blood group phenotype. Forty-nine female patients with renal scarring were prospectively investigated for the incidence of symptomatic UTI in relation to fecal colonization with P-fimbriated E.coli (III). Fifty-three per cent of the patients had altogether 65 episodes of symptomatic UTI during the three-year follow-up (0.036 infections per month). Eight patients (16%) had nine attacks of acute pyelonephritis and 4/5 of the tested E.coli strains from these patients were P-fimbriated. No relationship was demonstrated between the presence of P-fimbriated E.coli in the fecal flora and the development of subsequent acute pyelonephritis. The binding of P-fimbriated E.coli to uroepithelial cells from 19 female patients with renal scarring was studied with the fluorescence-activated cell sorting (FACS) analysis (IV). The uroepithelial cells from the patients with renal scarring exhibited a significantly higher binding capacity (p less than 0.01) than uroepithelial cells from healthy controls. Furthermore, uroepithelial cells from the patients with renal scarring and kidney insufficiency had a higher availability of P-fimbriae receptors on their uroepithelial cells than cells obtained from patients with renal scarring and normal renal function (r = -0.75, p less than 0.001) (V).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

P-fimbriae studies on the diagnosis and prevention of acute pyelonephritis.

Theoretically there are several ways to prevent pyelonephritis and renal scarring caused by P-fimbriated Escherichia coli. Screening for individuals at risk, e.g. those carrying P-fimbriated pyelonephritogenic E. coli or those with high receptor density on their uroepithelial cells, could perhaps define a population where prophylaxis with a receptor analogue or vaccination with P-fimbriae may be relevant. Epidemiological measures in neonatal and maternity wards may prevent the nosocomial spread of virulent bacteria and reduce the number of colonized infants. However, no such methods have so far had any proven clinical relevance, and today, the important concern is still to try by conventional means-as we have always done-to get an early diagnosis and to treat the patient without delay.

Adult↗

Lack of correlation of P blood group phenotype and renal scarring.

Renal scarring is in most instances caused by infection in the young child. The most commonly occurring etiological agent in urinary tract infections is Escherichia coli. An important virulence factor for these nephropathogenic E. coli is the ability to adhere to urinary tract epithelium. This adhesion is often mediated by P-fimbriae, which recognize and specifically bind to the receptor structure (alpha-D-Galp-(1-4)beta-D-Galp) present on the cell membranes of human urinary tract epithelium. This carbohydrate structure occurs as an entity of the glycosphingolipids that correspond to the antigens of the human P blood group system. It has been proposed recently that children with recurrent acute pyelonephritis have a higher frequency of the P1 blood group phenotype than the expected 75%. We have studied 56 adult female patients with a history of febrile urinary tract infection and signs of renal scarring on urogram. The P blood group phenotype was determined in all patients. There was no increase of the P1 blood group phenotype in the patients with verified renal scarring. In conclusion, our results do not support a role of the P1 blood group phenotype in the pathogenesis of renal scarring due to previous febrile urinary tract infection.

Adult↗

P-fimbriae studies on the diagnosis and prevention of acute pyelonephritis.

Theoretically there are several ways to prevent pyelonephritis and renal scarring caused by P-fimbriated Escherichia coli. Screening for individuals at risk, e.g. those carrying P-fimbriated pyelonephritogenic E. coli or those with high receptor density on their uroepithelial cells, could perhaps define a population where prophylaxis with a receptor analogue or vaccination with P-fimbriae may be relevant. Epidemiological measures in neonatal and maternity wards may prevent the nosocomial spread of virulent bacteria and reduce the number of colonized infants. However, no such methods have so far had any proven clinical relevance, and today, the important concern is still to try by conventional means--as we have always done--to get an early diagnosis and to treat the patient without delay.

Animals↗

Monocyte-related determinants of inflammation in patients on peritoneal dialysis.

AIMS: We studied markers of monocyte activation, i.e., the cell surface expression of CD11b and CD62L, and the serum concentrations of monocyte chemotactic protein 1 (MCP-1; a monocyte-specific chemoattractant) and soluble vascular cell adhesion molecule 1 (sVCAM-1; an adhesion molecule involved in monocyte recruitment) in 20 patients on peritoneal dialysis (PD), in 25 patients with chronic renal insufficiency, and in 27 healthy subjects. RESULTS: Monocytes obtained from the peripheral blood of PD patients had a significantly higher expression of CD62L (p = 0.02) as compared with monocytes from healthy subjects and a lower CD11b/CD18 expression as compared with monocytes collected from healthy subjects (p < 0.001) and from patients with renal insufficiency (p < 0.001). Monocytes from PD patients had, however, the capacity to increase the expression of CD11b following stimulation with a potent chemotactic factor. The serum concentrations of MCP-1 and sVCAM-1 were higher in PD patients (575 +/- 51 and 1,517 +/- 89 ng/ml) than in healthy subjects (225 +/- 17 and 668 +/- 64 ng/ml, respectively; p < 0.001 for both comparisons). There was a correlation between the levels of sVCAM-1 and MCP-1 (r = 0.48, p < 0.05) in patients on PD, but neither correlated with the monocyte expression of CD11b/CD18 or CD62L. The concentration of C-reactive protein was higher in patients on PD as compared with healthy subjects and correlated significantly with the concentration of sVCAM-1 (r = 0.63, p < 0.01). CONCLUSIONS: Monocytes in the peripheral circulation of patients on PD have a CD62L(high)/CD11b(low) phenotype, indicating that they have not undergone complete differentiation. Patients also have an increase in the systemic chemotactic activity for monocytes in combination with increased levels of sVCAM-1 and C-reactive protein. These inflammatory aberrations may play a pathophysiological role in the response to inflammatory and infectious diseases in patients on PD.

Adult↗

Leukocyte overshoot: a new sign of bioincompatibility in fast hemodialysis.

A high blood flow of 400 ml/min induces leukocytosis after 2 hr of dialysis with leukocyte concentrations of 110-150% of predialysis values. The leukocytosis occurs with both low and high biocompatible membranes, such as Cuprophan, Hemophan, and Polyamide. Cuprophan induces the most profound leukopenia, and also induces the most pronounced leukocytosis. For treatments with a given membrane there was, however, no correlation between leukopenia and leukocytosis. Leukopenia was independent of blood flow, while leukocytosis was strongly influenced by this factor. These observations indicate that different factors cause leukopenia and leukocytosis. Although a larger area induced more leukopenia, the effect was small. Membrane area had no effect on leukocytosis. There were no acute clinical side effects during dialysis that could be related to the leukocyte overshoot. The cause and chronic clinical consequences of leukocyte overshoot are unknown.

Adult↗

Biocompatibility of dialysis membranes is of no importance for objective or subjective symptoms during or after hemodialysis.

The clinical importance of biocompatibility of hemodialysis membranes is a matter of controversy. The authors studied the relationship between biocompatibility and acute symptoms during hemodialysis (HD). Twenty-three patients underwent 12 different bicarbonate HD using Cuprophan, Hemophan, or Polyamide membranes for short (2 hr) and long (4 hr) treatments, with small or large membrane areas. Subjective and objective symptoms were registered during HD and 12 and 36 hours thereafter. Type of membrane, membrane area, or Kt/V were of no importance for the occurrence of subjective or objective symptoms. The patients registered fewer symptoms during 2 hr HD with high blood flow than during 4 hr HD with slow blood flow (p = 0.04). Headache was particularly more frequent during the 4 hr HD. Blood pressure, and to some extent subjective symptoms, were influenced by ultrafiltration volume but not by type of membrane. Biocompatibility is not a determinant of acute side effects of hemodialysis.

Biocompatible Materials↗