Margaret L. Godley

Renal pathology and the 99mTc-DMSA image during the evolution of the early pyelonephritic scar : an experimental study

This study describes the pathologic changes underlying the appearances of the 99mTc-DMSA renal image during acute pyelonephritis induced in piglets by a combination of vesicoureteral reflux (VUR) and urinary infection. In a total of 42 animals examined, pathologic lesions were identified in 36 of the 46 kidneys subjected to VUR and urinary infection, but no lesions developed in the remaining 10 refluxing kidneys. While scintigraphic defects were invariably associated with pyelonephritic lesions (specificity 100%), some small lesions were not identified (sensitivity 80%). There was a significant association (p = < 0.001) between the degree of photon deficiency seen scintigraphically and the histologic changes (early and late lesions). However, the scintigraphic appearance of individual lesions was also influenced by factors such as their extent and density, so that consideration of the macroscopic characteristics was also important for precise correlation.

Effects of In Utero Bladder Outflow Obstruction on Fetal Sheep Detrusor Contractility, Compliance and Innervation

PURPOSE Congenital bladder outflow obstruction caused by posterior urethral valves is a common cause of end stage renal failure in boys. We hypothesized that fetal bladder outflow obstruction perturbs detrusor contractility and innervation and bladder storage volume-pressure relationships. MATERIALS AND METHODS Severe bladder outflow obstruction was induced in male fetal sheep by placing a urethral ring and urachal ligation midway through gestation at 75 days. Fetuses were examined 30 days after surgery, when urinary tract dilatation, enlarged bladders and histologically abnormal kidneys were documented. Isolated strips of bladder detrusor from sham operated and obstructed fetuses were subjected to electrical field stimulation, carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Whole bladder storage characteristics were determined by filling cystometry and bladder innervation was investigated by immunohistochemistry and Western blot. RESULTS Tension-frequency contractility studies showed that obstructed fetal bladder strips were significantly hypocontractile versus sham operated controls in response to electrical field stimulation and the specific agonists carbachol, KCl and alpha-beta methylene-adenosine triphosphate. Hypocontractility was greater with nerve mediated stimulation than with carbachol, suggesting relative denervation. Reduced innervation was confirmed by S100 and protein gene product 9.5 immunohistochemistry and by measuring a significant reduction in protein gene product 9.5 protein expression using Western blot. Filling cystometry showed that obstructed fetal bladders appeared more compliant (Delta V/Delta P, where Delta V is the change in volume and Delta P is the change in pressure) with larger capacity, more flaccidity and yet retained stress relaxation. CONCLUSIONS In response to severe experimental fetal bladder outflow obstruction the bladder becomes large and hypocontractile, and has aberrant innervation.

A preliminary study of natural‐fill radiotelemetered ovine fetal cystometry

To determine whether fetal cystometric studies by radiotelemetry are feasible in the fetal lamb, and potentially suitable for chronically monitoring fetal bladder pressures in an experimental fetal model of bladder outlet obstruction (BOO), as in utero BOO (e.g. caused by posterior urethral valves) results in significant postnatal bladder dysfunction but the pathophysiological progression of fetal bladder maldevelopment remains poorly understood.

Radiotelemetered urodynamics of obstructed ovine fetal bladders: correlations with ex vivo cystometry and renal histopathology

To test the hypothesis that fetal bladder outlet obstruction (BOO) in sheep causes abnormal urodynamics correlating with the initiation of renal pathology, as most boys with posterior urethral valves (PUV) have bladder dysfunction when assessed after birth.

Bladder wall tension during physiological voiding and in patients with an unstable detrusor or bladder outlet obstruction

Sir, Mr Clarke is to be congratulated on his excellent article on the management of hormone-relapsed prostate cancer [1] but we comment specifically on the area of skeletal dysfunction. Mr Clarke has, quite rightly, drawn attention to the importance of medical treatments, chemotherapy and radiotherapy for metastatic bone disease (MBD) from carcinoma of the prostate. He also correctly stated that pathological fractures should be treated with rapid fixation or joint replacement, and gives an example of a patient who has undergone bilateral hip replacement for sclerotic metastases in the pelvis. However, we draw attention to the importance of prophylactic fixation in patients who have MBD, as highlighted in a recent publication [2].

Effects of Vesicoureteric Reflux on Renal Growth and Function as Measured by GFR, Plasma Creatinine and Urinary Concentrating Ability: An Experimental Study in the Minipig

The influence of vesicoureteric reflux (VUR) on renal growth and function measured by glomerular filtration rate (GFR), plasma creatinine concentration and urinary concentrating ability has been examined in a simple one-kidney model in the growing minipig over a period of approximately 5 months. Animals with reflux in association with low voiding pressures and normal bladder function (n = 6), as well as those with raised voiding pressures and abnormal bladder function (n = 5), were investigated together with appropriate non-refluxing controls (n = 12). Urinary infection and renal scarring were avoided since these factors may affect kidney function and growth independently. Statistical tests of difference failed to demonstrate any effect of VUR on 51Cr EDTA GFR or renal growth even in the presence of elevated voiding pressures and abnormal detrusor function. However, a significant association between VUR and reduced urinary concentrating ability was shown.