Chronic Pyelitis Research Articles

Spred‐2‐deficiency results in dwarfism and kidney failure

The impact of fibroblast growth factor receptor 3 (FGFR3)-mediated signaling on bone growth has been demonstrated by various genetic approaches. Overexpression of fibroblast growth factors (FGF), several gain-of-function mutations in the FGFR3 and constitutive active mitogen-activated protein kinase (MAPK) kinase (MEK1) in chondrocytes have been shown to cause dwarfism in mice by activation of the MAPK signaling pathway. To investigate the previously reported inhibitory role of Spred in this pathway, we generated mice with a trapped Spred-2 gene. Here we show that lack of functional Spred-2 protein caused proportional dwarfism. Spred-2(-/-) mice showed reduced growth and body weight (males: 18 g vs. 23 g at 60 dpn, p < 0.01; n = 10), they had a shorter tibia length (16.1 vs. 18.1 mm in adult mice, p < 0.01; n = 26), and showed narrower growth plates (493 μm ± 80 vs. 599 μm ± 41 at 7 dpn) as compared to wild-type mice. We detected promoter activity and protein expression of Spred-2 in chondrocytes, suggesting an important function of Spred-2 in chondrocyte differentiation and bone development. Stimulation of chondrocytes with different FGF concentrations showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes. Furthermore, we observed that adult Spred-2(-/-) mice showed an enhanced scratching behavior (pruritus) and pathologically altered kidneys with chronic pyelitis, cysts, and massive lymphocytic infiltration. The importance of Spred-2 in kidney function was underlined by strong Spred-2 promoter activity and immunoreactivity in the tubular system. We conclude that loss of Spred-2 leads to reduced inhibition of the MAPK pathway which results in pathologic chondrocyte differentiation and kidney failure.

O‐acetylated sialic acid variants in intestinal glandular metaplasia of the urinary tract

Two cases of chronic cystitis, two of chronic ureteritis, one of chronic pyelitis and two transitional cell carcinomas of the urinary tract showed glandular metaplasia or focal mucin production. Positive staining for O-acetylated sialic acid variants (sites 7 and 8) detected by the PB-KOH-PAS method was found in the two cases of cystitis, in one of chronic ureteritis and in one of chronic pyelitis. Positive staining was observed only in areas showing an intestinal type of metaplasia and in which goblet cells and argyrophil cells were also identified. These findings taken together with earlier studies on ovarian cystadenomas lead the authors to believe that O-acetylated variants are markers of an intestinal type of epithelium. Evaluation of O-acetylated sialomucins may be useful in further studies on the histogenesis of primary adenocarcinomas of the bladder.

Urothelial changes of the renal papillae in Sprague-Dawley rats induced by long term feeding of phenacetin.

Thirty female Sprague-Dawley rats were fed 0.535 per cent phenacetin in the diet for up to 110 weeks. Twenty-six of these rats developed urothelial hyperplasia, partly papillary, of the renal papillae. Twenty-eight rats showed dilatation of the vasa recta frequently associated with thrombus formation and calcification. One phenacetin fed rat had epithelial hyperplasia associated with chronic pyelitis. In 2 of the 30 control rats urothelial hyperplasia was found to be associated with chronic pyelitis. The hyperplastic urothelial changes and vascular changes were often, but not always, present simultaneously. One control rat developed a mammary carcinoma, as compared with 5 rats in the phenacetin group. Four phenacetin fed rats developed carcinoma of the ear duct. The results of the present investigation provide evidence that phenacetin can induce proliferative lesions of the urothelium of the rat renal pelvis with weak carcinogenic activity in the ear duct and mammary glands.

Urothelial hyperplasia of the renal papillae in female Sprague-Dawley rats induced by long term feeding of phenacetin.

Twenty-one of 40 rats fed phenacetin in the diet for up to 86 weeks developed urothelial hyperplasia of the renal papillae. Two of 30 rats in the control group had similar changes associated with chronic pyelitis. The difference is statistically significant (p less than 0.01).

Pyelitis, an important factor in the pathogenesis of retrograde pyelonephritis.

Pyelitis with acute and chronic pyelonephritis and also primary chronic pyelitis were easily initiated in female rats by a single non-traumatic retrograde infusion of bacteria into the urinary tract. The virulence of the bacterial species and the time of observation were related to the type and extent of lesions, but pyelitis regardless of the virulence appeared to be an important factor. The apex and fornix of the renal pelvic lumen were anatomic sites of persistent pyelitis which permitted local proliferation of bacteria for long periods. Cortical and medullary lesions were anatomically related to these areas of underlying pyelitis. Spread of infection followed a pattern of contiguity rather than ascending tubular infection. The experimental model has many of the features of chronic urinary infections in man and suggests that pyelitis is an important factor in the pathogenesis of chronic pyelonephritis initiated by retrograde infection.

Pyelographic Changes in Pregnancy

1. Fifteen primiparae, with no previous history of renal disease, were studied by intravenous pyelography; firstly when under three months pregnant, secondly within ten days of delivery and thirdly three months after the second pyelogram. 2. Only five subjects showed a recognisable change. Two of these were followed up with a fourth pyelogram. The results are tabulated. 3. It was concluded: (i) Changes in the calyces and pelves are not common in primiparae during pregnancy: such changes as do occur do not persist to a degree likely to give rise to chronic renal infection after delivery. (ii) The findings of dilatation of the renal pelves and calyces especially on the right side during pregnancy are not themselves pathological. (iii) The persistence of these changes is not necessarily pathological unless associated with both the clinical history and findings of chronic pyelitis. (iv) No useful information can be obtained from the study of the ureters in these cases by intravenous pyelography. 4. It is considered that pyelographic abnormalities are likely to be due to a preceding pregnancy when: (i) A history of renal symptoms and signs following a normal pregnancy and delivery, is obtained. (ii) An imbalance in the pyelographic findings on the two sides, the right being more severely affected than the left. (iii) No other findings to explain the discovered changes can be demonstrated.

Radiographic features of ureterocele.

Ureterocele, from the Greek (όυρητήρ and κήλη), literally means hernia of the ureter. It is the result of a congenital stenosis of the ureteral orifice and a concomitant weakness of the wall of the lower ureter so that there is a resultant ballooning of the terminal ureter into the bladder. This intracystic ballooning of the dilated ureter produces a characteristic defect on the cystogram, which is practically pathognomonic in the infant. The extent of the radiographic defect is proportional to the size of the ureterocele, which may vary from a centimeter in diameter to sizes which fill the bladder and may occasionally, in the female, prolapse through the urethra. Because of obstruction secondary to the ureterocele there is frequently an associated hydronephrosis on the affected side. Of the anomalies concomitant with ureterocele, double ureter is the most common. When this latter anomaly is present, the ureterocele usually affects the ureter draining the upper kidney. Ureteroceles may also contain calculi. The sex incidence of ureterocele is not proved, though some observers report a greater incidence in females. There is no predilection as to location on the right or left side. Radiographically ureterocele appears as a round, constant filling defect at the ureteral orifice. On occasion, with intravenous urography, the thickness of the ureterocele wall will form a non-opaque halo or cobra head, with contrast substance in the ureter, ureterocele, and bladder. When stones are present they lie within this halo. In the practice of the pediatric urologist ureterocele is not rare (Campbell reports 1 in 30 cases of chronic pyelitis) but in a general x-ray department the lesion is not often seen. Ureterocele should be suspected when the radiographic signs described above are present. Once the condition is suspected, it is in the province of the urologist to make the final diagnosis and to prescribe treatment. There are no cardinal signs or symptoms of ureterocele other than complaints referable to the genitourinary tract. Dysuria is most commonly the chief complaint on the part of the younger patients. In the adult the symptoms are those due to the secondary hydronephrosis. We present five proved cases of ureterocele demonstrating the typical radiographic findings. These findings are sufficiently pathognomonic that the diagnosis can be readily made by intravenous urography, especially in the infant, without the aid of cystoscopy or retrograde pyelography.

Gantrisin (sulfisoxazole)-induced granulocytopenia.

Gantrisin® (3,4-dimethyl-5-sulfanilamido-isoxazole, also known as sulfisoxazole, and NU-445) is a relatively new sulfonamide which is now being widely used in the treatment of various bacterial infections, particularly those of the urinary tract. Recently, a case of agranulocytosis following the administration of this drug was reported. 1 In a careful examination of the literature, the authors of this report were able to find only eight instances in which use of the drug had led to leucopenia. 2 Most of the other investigators have emphasized the low toxicity of the compound. We wish herewith to report another instance of bone marrow depression presumably caused by gantrisin,® in order to reemphasize the possible dangers inherent in its use. REPORT OF A CASE E. L., aged 74, was first seen at the Research and Educational Hospitals, University of Illinois, for surgical treatment of benign prostatic hypertrophy and chronic pyelitis. At the time of his

Vascular obstruction of the ureter in juveniles

Seven proved cases and one probable instance of vascular ureteral obstruction in juveniles are reported. Loin pain is a frequent symptom. When infection with pyuria exists, “chronic pyelitis” is the usual diagnosis. When infection is slight or absent, the clinical diagnosis, based on urinalysis, is likely to be chronic interstitial nephritis. The existent nephritis is regularly of the toxic variety in the unobstructed organ and of the compression or back-pressure type in the obstructed kidney. This nephritis may be expected to disappear following removal or adequate treatment of the seriously diseased mate. Only by complete urological examination with urography can the diagnosis accurately be made preoperatively. Conservative surgery, chiefly vessel resection or ureteroplasty, is urged; nephrectomy is demanded with far-advanced renal destruction, infection or calculus disease. By specific example these cases serve to emphasize the great importance and necessity of the employment of modern urological methods in the diagnosis and treatment of persistent urinary tract disease in young patients.

Hemipyonephrosis in infants and children treatment by heminephrectomy

Five cases of hemipyonephrosis in very young children are reported. Being anomalous, reduplicated kidneys are more prone to disease than are normal organs. The condition illustrates another lesion which may cause persistent urinary infections in juveniles and because of pyuria, commonly leads to the diagnosis of “chronic pyelitis.” The correct diagnosis of hemipyonephrosis is made by urologic examination. When half of the double kidney remains undiseased, and the operation is technically feasible and the condition of the patient permits, ureteroheminephrectomy is the treatment. With marked renal infection, especially acute, nephrectomy is often the wiser course. In the youngest patient of this series, ureteroheminephrectomy was successfully performed at the age of six months.

RENAL TUBERCULOSIS IN JUVENILES

Although renal tuberculosis is not common in children except as part of a generalized infection, the incidence of the lesion as manifested by so-called chronic pyelitis is sufficiently high to merit serious consideration. Four personal cases of surgical renal tuberculosis in children (3, 7, 8 and 11 years of age, respectively) who were treated by nephrectomy and a bilateral nonsurgical case (at 7 years) are here reported, together with one of calcified renal tuberculosis in a boy of 17 years. In the latter case, the urinary tuberculous history dated from the age of 3 years. These cases emphasize by specific illustration the great importance of complete urologic investigation when symptoms of disturbances of the urinary tract exist in the young. All of the patients were examined because of persistent pyuria; in 2 (cases 2 and 6), urinary frequency with incontinence had led to the diagnosis of enuresis. In case 5,

CHRONIC URINARY INFECTION IN INFANCY AND CHILDHOOD

Because infection of the urinary tract so frequently complicates bacterial processes elsewhere, it is one of the commonest diseases of children and, in patients under 2 years of age, probably outranks any other. When the urinary infection is neither self-limited nor therapeutically cured within a period of from four to six weeks, the persistent pyuria quite regularly leads to the erroneous or inadequate diagnosis of chronic pyelitis or chronic cystitis. In these cases the inadequacy of the diagnosis pyelitis or cystitis is comparable to that of laryngitis when the disease is chronic pulmonary tuberculosis. It is my purpose here to demonstrate that (1) chronic pyuria is seldom the sign of an uncomplicated disease, (2) demonstration of the associated etiologic factors regularly requires complete urologic examination and (3) frequently urologic surgical treatment is demanded to control the infection or to save life. The clinical data here recorded were obtained by personal

URINARY CALCULI IN INFANCY AND CHILDHOOD

Because persistent pyuria is the outstanding symptom when urinary stone is present in infants and children, chronic pyelitis is the usual diagnosis; the time honored urinary antiseptics are administered; the disease progresses. While it has been my good fortune to collect for study from one institution a series of thirty juvenile cases of urinary calculi, my purpose here is not only to present a clinical summary of this group but also and more particularly to emphasize that (1) chronic pyuria rarely means uncomplicated renal infection, and (2) pyuria that still persists after four weeks of intensive medical treatment clearly warrants a complete urologic examination. Failure to subject patients with chronic pyuria to complete urologic examination (or even to a plain roentgenogram of the urinary tract) accounts for the rarity with which, in the past, urinary stones have been disclosed during the early years of life. INCIDENCE AND ETIOLOGY The incidence

CONGENITAL ABNORMALITIES OF THE URINARY TRACT IN CHILDHOOD

In preparing a recent report on chronic pyelitis, I was impressed by the number of cases in which congenital anomalies of the urinary tract played a part in the infection. It seemed of interest, therefore, to review such abnormalities observed at the Mayo Clinic in the last six years. In 1924, Bugbee and Wollstein, 1 writing on the surgical pathology of the urinary tract in infants, stressed the frequency with which congenital anomalies of the urinary tract were encountered in a series of 4,903 necropsies. Lesions were found in 117 cases, 101 of which were probably congenital. A clinical diagnosis of disease of the urinary tract was made before death in only two cases; in one of these congenital cystic kidney was diagnosed, in the other hydronephrosis. It is difficult to estimate the number of cases in which death was caused by disease of the urinary tract and the number

URETERAL STRICTURE AND CHRONIC PYELITIS IN CHILDREN

Imperfect drainage is usually the basic cause of chronic pyelitis in the adult. I have not seen a sufficient number of cases in children to warrant a similar dogmatic statement. By far the most common cause of renal urinary stasis in adults is ureteral stricture. In most of the infants and children I have treated for chronic pyelitis, ureteral obstruction has been present, and the usual tests by urogram and wax bulb have led me to interpret the obstruction as due to ureteral stricture. At any rate, I have found that establishment of urinary drainage by dilatation of the narrow ureteral area has resulted in a high percentage of cures in children as well as in adults. Apparently, up to the present time, the concensus among general practitioners and pediatricians has been that for children with chronic pyelitis there is no therapy beyond medicinal and dietary measures, or in extreme

Neuromuscular dysfunction of the bladder as a cause of chronic pyelitis in childhood : Helmholz, Henry F.Am. J. Dis. Child., Nov., 1926, xxxii

Neuromuscular dysfunction of the bladder as a cause of chronic pyelitis in childhood : Helmholz, Henry F.Am. J. Dis. Child., Nov., 1926, xxxii

THE THERAPEUTIC VALUE OF HEXYLRESORCINOL IN CHRONIC PYELITIS OF CHILDHOOD

Through the courtesy of Leonard, we were able to obtain a supply of hexylresorcinol to try out in the treatment of chronic pyelitis in children. Our clinical material consisted largely of patients who had had urinary infections lasting for months and years, rather than for days and weeks. The group, therefore, is made up of patients very difficult to cure. In this series there were fourteen patients, four with definite anatomic lesions of the urinary tract complicating the pyelitis. The duration of the infection was less than one month in one case, between one and six months in two, one year in three, two years in two, between five and ten years in four, and between ten and fifteen years in two cases. Bacillus coli was the infecting organism in ten cases, streptococcus in two, staphylococcus in one case, and Bacillus proteus in one. Hexylresorcinol was administered in olive oil