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Biomedical subjects

M B Kaack

Publications and source records attributed to M B Kaack.

30 records · Page 2Linked to original sources

Treatment of experimental pyelonephritis in the monkey.

Previous studies show that chronic pyelonephritis and end stage renal disease may follow acute pyelonephritis in children and adolescents when improperly or inadequately treated. Our study shows that there is a significant decrease in renal function following untreated acute bacterial pyelonephritis due to nephron loss. The acute inflammatory response is responsible for much of the renal damage, although damage from renal ischemia is an additional significant factor. The present study used a combination of an antibiotic and a xanthine oxidase inhibitor (allopurinol) as compared to antibiotic therapy alone begun 72 hours after infection. Both were successful in eradicating the infection rapidly, but did not entirely prevent renal damage. Treatment prior to 72 hours thus is important. It appears that the combined treatment, designed to eradicate the bacteria as well as reduce the post-ischemic reperfusion damage and the phagocytic burst of phagocytosis is ideal, as this combined treatment was effective in preventing almost all renal damage and loss of renal function.

Allopurinol↗

P-fimbriae vaccines. I. Cross reactive antibodies to heterologous P-fimbriae.

To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P-fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme-linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity.

Animals↗

P-fimbriae vaccines. II. Cross reactive protection against pyelonephritis.

Protection against acute pyelonephritis was induced by immunization of baboons with purified P-fimbriae of Escherichia coli as vaccines. To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with P-fimbriae purified from either E. coli strain ER2 or strain JR1 and subsequently challenged the animals with E. coli strain JR1. All vaccinated animals showed elevated antibody titers to P-fimbriae from both of the E. coli strains used. Both vaccines tended to reduce the time of bacteriuria. They partially prevented pyelonephritis and protected against loss of renal function.

Animals↗

Adherence of bacteria to human foreskins.

The mucosal surface of the human foreskin from newborns shows a propensity to be colonized by pathogenic bacteria. Bacteria with P fimbriae and type 1 fimbriae adhere. However, hydrophobic interaction as well as electrostatic charge appear to be as important in this adherence as are fimbriae. Since bacterial adherence has been shown to precede urinary tract infection in female patients it is assumed that this adherence to the foreskin in male patients also may be necessary before initiation of the disease. The high incidence of urinary tract infection in uncircumcised male patients combined with these findings of adherence of pathogenic bacteria to the mucosal surface of the foreskin, thus, would seem to be related. Prevention of urinary tract infection and acute pyelonephritis in male neonates then may require either circumcision or the prevention of bacterial adherence to the human foreskin.

Bacterial Adhesion↗

Maternal immunization with P fimbriae for the prevention of neonatal pyelonephritis.

Rhesus monkeys (Macaca mulatta) were immunized with purified P fimbriae from Escherichia coli during the last trimester of pregnancy. Infants born of these mothers were compared with those from nonimmunized rhesus mothers. A delay in the onset of renal disease after bladder infection showed protection from passive immunization. This was associated with a high antibody titer in serum. In addition to delayed onset of renal infection, a decreased number of immunized monkeys developed pyelonephritis.

Animals↗

Vesicoureteral reflux in the primate. IV. Infection as cause of prolonged high-grade reflux.

High-grade reflux commonly lasts longer than moderate reflux, which disappears with maturation of the ureterovesical junction. It is known that ureteral function is affected by urinary tract infection from studies in experimental animals, as well as through clinical findings in patients with upper tract infection. Whether infection might affect the ability of the ureter to prolong high-grade reflux was questioned. This observation might explain why high-grade reflux does not disappear as rapidly as moderate reflux in children with recurrent urinary tract infections. Vesicoureteral reflux was produced surgically in combination with bladder neck obstruction using infant monkeys. The reflux thus produced was high grade with ureteral dilation and caliectasis. In the group of animals in which the bladder neck obstruction was relieved surgically, the reflux rapidly disappeared. In the other group, a bladder infection was produced with Escherichia coli at the time of release of the bladder neck obstruction. The reflux lasted significantly longer, an average of 18 months. Therefore, it appears that treatment of urinary tract infection rather than vesicoureteral reflux is the most important therapy.

Animals↗

P-fimbriated Escherichia coli urinary tract infection: a clinical correlation.

We designed a retrospective study to determine the incidence of P-fimbriated Escherichia coli in patients with asymptomatic bacteriuria, acute urethral syndrome, bacterial cystitis, acute pyelonephritis, possible acute pyelonephritis, and acute and chronic prostatitis. In addition, we compared the incidence in uncompromised vs compromised hosts, inpatients vs outpatients, and children vs adults. P-fimbriated E coli were isolated in more than 80% of uncompromised patients with either acute pyelonephritis or acute prostatitis. In clinically compromised patients having these disorders, the incidence dropped to approximately 30% (P less than .025). Neither age nor inpatient/outpatient status was a significant factor. We stress the importance of P-fimbriation as a virulence factor in acute pyelonephritis and acute prostatitis caused by E coli, though these diseases may be caused by less virulent organisms in compromised patients. Thus, patients with acute pyelonephritis or acute prostatitis caused by E coli negative for P-fimbriae probably should be considered compromised; the compromising factor should be determined as a guide to subsequent treatment.

Acute Disease↗

Dynamic corpus cavernosography: effect of papaverine injection.

A study was done in 21 men to identify individuals with venous leakage as a cause of impotence. Combined pressure flow measurement and cinecavernosography were performed before and after the injection of papaverine into the corpora. After papaverine injection, erections and/or higher pressures occurred at lower flow rates in all the men. The venous drainage of the corpora decreased or disappeared in most subjects while the corpora became larger and contained more contrast material. The findings suggest that an active venous obstructive mechanism is important during erection, can be induced by the administration of papaverine, and should be evaluated in impotent men.

Adult↗

Immunology of pyelonephritis. VII. Effect of allopurinol.

The inflammatory response and the respiratory burst of bacterial phagocytosis have been shown to be at least partially responsible for the renal damage from infection. In addition, we have shown that renal blood flow decreases following infection. Hypoxanthine is produced in ischemic tissue during the anaerobic metabolism of adenosine monophosphate (AMP). During reperfusion hypoxanthine is metabolized to uric acid and superoxide in the presence of xanthine oxidase. The toxicity of this oxygen radical was prevented by preventing its formation with pretreatment with allopurinol, an xanthine oxidase inhibitor. The data suggest that xanthine oxidase may be the enzyme responsible for the respiratory burst of phagocytosis, as well as preventing reperfusion damage which occurs after ischemia.

Adenosine Monophosphate↗

Immunology of pyelonephritis. VIII. E. coli causes granulocytic aggregation and renal ischemia.

We studied renal venous blood after renal infection for its concentrations of leukocytes, complement and renin. In addition, we evaluated this blood for granulocytic aggregation and chemiluminescence of granulocytes. We found that very rapid activation of serum complement occurred with associated granulocytic aggregation and evident vascular occlusion and ischemia since renin rose rapidly. It appears that this early sequence of events will cause renal damage by ischemic change, as well as that known to occur from the inflammatory reaction.

Animals↗

Effect of prenatal ionizing radiation on the visual cortex and hippocampus of newborn squirrel monkeys.

Five squirrel monkeys were exposed to 200 rads whole-body ionizing irradiation (60Co) at 0.4 rads per second on approximately the seventy-fifth day of gestation, and six squirrel monkeys were sham-irradiated. The mean cortical depth and the mean number of neurons per mm3 in the visual cortex was less in irradiated animals than in controls, but the differences were not statistically significant. The mean number of glial cells in this cortical region was significantly lower in the irradiated animals. An analysis of variance of the combined spine count data from apical, basal, and oblique dendrites revealed a significantly lower number of dendritic spines on basal dendrites in irradiated than in control animals in Meynert neurons in the visual cortex of irradiated offspring. In the hippocampus, the depth of the stratum oriens and the combined depth of the strata radiatum, lacunosum, and moleculare were significantly less in irradiated than in control animals, although the difference in the depth of the pyramidal layer, considered individually, was not statistically significant. The mediolateral width of the CA-1, CA-2, and CA-3 zones, as seen in transverse section, was significantly less in irradiated animals than in controls. The number of dendritic spines per unit length of pyramidal cell dendrite in the CA-1 zone and the total number of pyramidal neurons in the CA-1, Ca-2 and CA-3 zones, per transverse section, were significantly lower in irradiated than in control brains. Canonical correlations provided statistical evidence for greater radiation vulnerability of the hippocampus compared to motor and visual areas of the cerebral cortex.

Animals↗

Bacterial adherence in urinary tract infections: preliminary studies in a primate model.

Escherichia coli with both P and type 1 fimbriae caused vaginal colonization in the female green monkey, while only the P-fimbriated bacteria frequently caused ascending bladder infection. Bladder inoculation caused only short-lived bladder infection from type 1 fimbriated E. coli, but those with P-fimbriae caused acute pyelonephritis even in the absence of vesicoureteral reflux. Thus, type 1 fimbriae of E. coli, while causing vaginal colonization, did not often cause ascending infection in the non-compromised host as did P-fimbriated bacteria.

Animals↗