Kidney disease in hypomelanosis of Ito.
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Adolescent↗
Biomedical subjects
R A Risdon
Publications and source records attributed to R A Risdon.
Congenital maxillary sinus cholesteatoma.
Cholesteatoma of the paranasal sinuses is a rare condition. The purpose of this paper is to present a child with a congenital maxillary sinus cholesteatoma. An 18-month-old girl presented with a 4-week history of right cheek and intraoral swelling. Examination revealed a smooth swelling of the right hard palate in association with the facial swelling in the maxillary region. An inferior meatal antrostomy revealed pultaceous debris in the right maxillary antrum and biopsy confirmed a maxillary sinus cholesteatoma. The inferior meatal antrostomy was enlarged to allow exteriorisation of the disease. Recurrence of the disease has not presented on follow-up. An exteriorisation procedure as performed, in child of this age, allows normal facial growth. If recurrence develops then further treatment may be instituted in a more mature facial skeleton.
Cholesteatoma↗
Potential biological role of transforming growth factor-beta1 in human congenital kidney malformations.
Transformations between epithelial and mesenchymal cells are widespread during normal development and adult disease, and transforming growth factor-beta1 (TGF-beta1) has been implicated in some of these phenotypic switches. Dysplastic kidneys are a common cause of chronic kidney failure in young children and result from perturbed epithelial-mesenchymal interactions. In this study, we found that components of the TGF-beta1 axis were expressed in these malformations: TGF-beta1 mRNA and protein were up-regulated in dysplastic epithelia and surrounding mesenchymal cells, whereas TGF-beta receptors I and II were expressed in aberrant epithelia. We generated a dysplastic kidney epithelial-like cell line that expressed cytokeratin, ZO1, and MET, and found that exogenous TGF-beta1 inhibited proliferation and decreased expression of PAX2 and BCL2, molecules characterizing dysplastic tubules in vivo. Furthermore, addition of TGF-beta1 specifically induced morphological changes compatible with a shift to a mesenchymal phenotype, accompanied by loss of ZO1 at cell borders and up-regulation of the mesenchymal markers alpha-smooth muscle actin and fibronectin. The descriptive and functional data presented in this report potentially implicate TGF-beta1 in the pathobiology of dysplastic kidneys and our results provide preliminary evidence that an epithelial-to-mesenchymal phenotypic switch may be implicated in a clinically important developmental aberration.
Child, Preschool↗
Quantitative 99mTc-DMSA uptake in experimental pyelonephritis.
UNLABELLED: Quantitative 99mTc-dimercaptosuccinic acid (DMSA) renal uptake was studied in unilateral reflux-related pyelonephritis in pigs. The changes to absolute % dose uptake and differential uptake occurring with induction and after treatment of pyelonephritis were correlated with the DMSA images and renal pathology. METHODS: Quantitative uptake in 53 young pigs was obtained from planar images acquired 6 h after injecting the dose. Baseline studies were made (Q1), and studies were made again after urinary infection was established (Q2), when 8 pigs had normal (no defect) renal images (group A), 23 had photon-deficient (reversible) focal defects (group B) and 22 had photon absent (irreversible) focal defects (group C). Q3 studies were made in 21 animals from groups B and C after 3-wk antimicrobial treatment. RESULTS: At Q2 the affected kidney differential uptake was unchanged for group A and reduced for groups B and C (respective mean changes -1.7%, P < 0.01; and -5.5%, P < 0.01). The absolute % dose uptake was unchanged in pyelonephritic kidneys, but increased in the contralateral nondiseased kidneys in groups B and C (respective mean increases +1.4%, P < 0.05; and +5.4%, P < 0.01), while remaining unchanged for group A. In group C, global renal accumulation was actually increased above the Q1 values. After treatment (Q3) the reduced pyelonephritic kidney differential uptake persisted in groups B and C. In group C, however, the increased absolute % dose uptake by the contralateral kidney was less marked and not significantly different from Q1 values in this small group. CONCLUSION: Induction of unilateral pyelonephritis produced a small reduction in diseased kidney differential uptake that was greatest in the group with irreversible imaging defects. The method did not discriminate individuals with reversible and irreversible imaging defects. The decrease in pyelonephritic kidney differential uptake resulted from increased DMSA accumulation (absolute % dose uptake) by the nondiseased contralateral kidney, while that in pyelonephritic kidneys remained unchanged. After treatment, the reduced pyelonephritic kidney differential uptake persisted, but the elevated global DMSA accumulation seen for group C (with irreversible imaging defects) was not sustained and was variable.
Animals↗
Five-year study of medical or surgical treatment in children with severe vesico-ureteral reflux dimercaptosuccinic acid findings. International Reflux Study Group in Europe.
UNLABELLED: The results of serial dimercaptosuccinic acid (DMSA) imaging over 5 years are reported in 287 children with severe vesico-ureteral reflux entered into the European Branch of the International Reflux Study in Children. The children were randomly allocated to medical (n=147) or surgical (n=140) management and DMSA studies were performed during the follow up period at least 6 months after any urinary tract infection. Abnormal images were classified into four types: (1) large polar hypodensity with normal renal outline; (2) peripheral photon deficient defect(s) in a non-deformed kidney; (3) small renal image with normal contour; and (4) peripheral defect(s) with resultant irregularity of the renal outline. The DMSA findings were abnormal at entry in 235 (82%) with no difference in incidence or severity between the two treatment groups. During follow up, deterioration was observed in 25 medically and 23 surgically treated patients and comprised image deterioration alone in 17, image deterioration with corresponding reduction in differential function in 16 and reduction in relative function without image change in 15, with similar distribution between the two treatment groups. Deterioration was more frequent in children entering the study under the age of 2 years and in those with grade IV rather than grade III reflux. These findings, showing no difference in outcome between children managed surgically or medically, are consistent with the radiological results already published. CONCLUSION: In the International Reflux Study the DMSA scintigraphic data showed no difference in outcome between children managed surgically or medically.
Child↗
Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults.
To ascertain the outcome of childhood vesicoureteric reflux (VUR), 226 adults (37 males), mean age 27 years, were studied after 10-35 years, extended to 41 years by postal questionnaire in 161. At presentation (mean age 5 years) all had VUR (grade III-V in 68) and urinary tract infection (UTI); there was renal scarring in 85 (acquired before referral in 11 and during follow-up in 1), hypertension in 6 and impaired renal function in 5. They were managed and followed prospectively by one paediatrician; 63% of these children remained free from UTI; VUR persisted in 63 and had resolved in 69% of 193 children managed medically. At follow-up, 61% of adults had remained free from infection; 17 adults had hypertension and/or raised plasma creatinine, 16 with scarred kidneys. Their deterioration was predictable because of scar type, blood pressure or plasma creatinine levels in childhood. No new scars developed after puberty. Renal growth rates were unaffected by initial severity or persistence of VUR. On the later questionnaire, 9 further adults, mean age 38 years, had moderate hypertension. The adults with complications were those with extensive renal scarring and/or at least borderline hypertension in childhood. Those with VUR, but no scarring, and managed carefully in childhood, did not suffer serious consequences as adults. There is a need for early recognition and treatment of children with VUR and UTI to limit scar development.
Adolescent↗
An evaluation of the role of suction rectal biopsy in the diagnosis of intestinal neuronal dysplasia.
BACKGROUND: German pathologists have developed a consensus for histological features of intestinal neuronal dysplasia. METHODS: A blind reevaluation of ganglionic suction rectal biopsies from infants and children who initially presented with symptoms of intestinal dysmotility was made. RESULTS: 84 of 411 specimens had sufficient depth of submucosa for adequate assessment. Questionnaires or clinical interviews were employed 3-5 years after biopsy in these 84 patients to assess the relationship between histological changes and persistent symptomology. Eighteen children were lost to follow-up, 4 others had Hirschsprung's disease the study biopsy specimen having been taken from the pulled-through bowel after surgical resection of the aganglionic segment. The remaining 62 patients were divided into three groups. There were six patients in group A (both obligatory criteria) and 28 in group B (nonessential, or just one of the obligatory criteria), and 28 in group C (normal appearances). On follow-up, two of the 28 (7%) in group B, and six of the 28 (21%) in group C had persistent dysmotility symptoms. CONCLUSIONS: Histological criteria of the consensus of German Pathologists for intestinal neuronal dysplasia was unhelpful in predicting the clinical outcome and therefore, should not influence clinical management. As one of the obligatory criteria, hyperplasia of the submucosal plexus was significantly more common in neonates (< 4 weeks), it is concluded that this is an age-related variation.
Acetylcholinesterase↗
Long-term renal function in the posterior urethral valves, unilateral reflux and renal dysplasia syndrome.
PURPOSE: The syndrome of posterior urethral valves, persistent unilateral reflux and renal dysplasia (VURD) is said to be protective of the contralateral nonrefluxing kidney and the outcome for renal function is reported to be excellent. We tested this hypothesis in our patients by replicating previous studies but with longer followup and glomerular filtration rate data. MATERIALS AND METHODS: We retrospectively reviewed the records of 183 boys presenting with posterior urethral valves between 1980 and 1989, including 12 who underwent nephrectomy for ipsilateral nonfunction and fulfilled all criteria for the VURD syndrome. Mean age at the most recent followup was 8.5 years. Serial serum creatinine levels and glomerular filtration rates were analyzed and compared to age matched normal values. RESULTS: Histological evaluation revealed dysplasia in all kidneys, confirming the VURD syndrome. Followup plasma creatinine was normal 67% of the patients during year 2 of life, 50% between ages 4 and 5 years, and only 30% between ages 8 and 10 years. Glomerular filtration rate was within the normal range in 25% of boys tested in year 2 of life, and between ages 5 and 8 years. CONCLUSIONS: Our data do not support the protective effect of the VURD syndrome on long-term renal function. All patients with posterior urethral valves require diligent long-term followup.
Abnormalities, Multiple↗
The PAX2 tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations.
Human dysplastic kidneys are developmental aberrations which are responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent in undifferentiated cells around dysplastic tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining the tendency of some of these organs to regress. In contrast, apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud malformations. On occasion, these tubules form cysts which distend the abdominal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubules maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epithelia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to epithelia] conversion, is expressed ectopically in dysplastic kidney epithelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes which are tightly regulated in the normal program of human nephrogenesis.
Child↗
Congenital enterocyte heparan sulphate deficiency with massive albumin loss, secretory diarrhoea, and malnutrition.
BACKGROUND: The molecular basis of protein-losing enteropathy is unknown. However it has been shown that sulphated glycosaminoglycans may be important in regulating vascular and renal albumin loss. METHODS: We describe three baby boys who presented within the first weeks of life with massive enteric protein loss, secretory diarrhoea, and intolerance of enteral feeds. All required total parenteral nutrition and repeated albumin infusions. No cause could be found in any case despite extensive investigations, including small intestinal biopsy sampling, which were repeatedly normal. FINDINGS: By specific histochemistry, we detected gross abnormality in the distribution of small intestinal glycosaminoglycans in all three infants, with complete absence of enterocyte heparan sulphate. The distribution of vascular and lamina propria glycosaminoglycans was, however, normal. INTERPRETATION: The presentation of these infants suggests that enterocyte heparan sulphate is important in normal small intestinal function.
Albumins↗
Deregulation of cell survival in cystic and dysplastic renal development.
Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.
Animals↗
Endocrine cells of the human gastrointestinal tract have no proliferative capacity.
There is compelling evidence that the epithelial cell lineage of the gastrointestinal tract are derived from a common stem cell precursor, but the details of the subsequent cellular hierarchies remain uncertain. In this context, it is important to know the arrangement of cell proliferation that gives rise to the final cell populations. In rodents, a number of studies have been performed examining the possible proliferative capacity of endocrine cells, but a wide range of technical problems makes interpretation of these data difficult. Continuous labelling studies suggest there is potential for proliferation in endocrine cells but flash labelling studies have not been conclusive. In man there are no data on this issue. We have taken advantage of the ability to perform double immunostaining for operational markers of proliferation (Ki67 antigen) and endocrine cell phenotype (chromogranin expression). We demonstrate that there are no double-labelled cells in the normal stomach, small intestine or colon of fetal, neonatal or adult humans. Moreover, no double-labelled cells are found in pathological states associated with endocrine cell hyperplasia (gastritis, ulcerative colitis). These data indicate that the normal endocrine cells of the human gut have no proliferative capacity and that, in this cell lineage, population expansion precedes differentiation.
Adult↗
Renal pathology and the 99mTc-DMSA image before and after treatment of the evolving pyelonephritic scar: an experimental study.
This study reports the effects of 3-weeks' antimicrobial treatment on the pathology and appearance of the 99mTc-DMSA renal image in piglets with pyelonephritis induced by a combination of vesicoureteral reflux (VUR) and urinary infection. Before treatment, either photon-deficient (B1, B2) or photon-absent (C) scintigraphic abnormalities were present in the refluxing kidney in all 22 animals examined. All (100%) of the initially B1 and the majority (71%) of B2 photon deficient defects resolved with treatment, leaving only insignificant residual pathologic lesions. Conversely almost all (93%) of the C photon-absent scintigraphic abnormalities persisted after treatment and were always associated with significant scarred or cratered pathologic lesions in the refluxing kidney at sacrifice.
Animals↗
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.
Acute Disease↗
The small scarred kidney in childhood.
Reflux nephropathy is now a generally accepted term to describe small scarred kidneys discovered during childhood; it recognises the close association between this renal lesion and vesicoureteric reflux (VUR). This paper briefly reviews the pathogenic factors involved in reflux nephropathy and suggests that at least two main mechanisms operate: acquired segmental scarring due to intrarenal reflux and congenital maldevelopment (renal dysplasia). The spectrum of renal changes associated with VUR can be usefully divided on this basis and the opportunity to recognise by fetal ultrasound those renal lesions acquired in utero may further enhance our understanding of the congenital maldevelopment group.
Child, Preschool↗
The diagnosis of Hirschsprung's disease.
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Fluorescent Antibody Technique↗
Reflux nephropathy in children submitted to unilateral nephrectomy: a clinicopathological study.
The clinical findings and renal histopathology have been reviewed in children with gross primary vesicoureteric reflux (VUR) submitted to unilateral nephrectomy. Of the 42 children reviewed, sections of the nephrectomy specimens were available in 36. In this series, 34 patients were male and eight were female. The boys included seven in which hydronephrosis was identified by fetal ultrasound. The male patients tended to present earlier and had nephrectomies younger than the females. Segmental scarring was frequent in both males and females, but evidence of dysplastic renal development was confined to the male patients and occurred in the majority (63%). Acquired mechanisms for the induction of segmental renal scarring, involving VUR, intrarenal reflux (IRR) and urinary infection, shown to be important in older children, clearly operate in infancy. However, this study emphasizes that congenital malformation of the kidney is a crucial factor in the development of reflux nephropathy (RN) in this younger age group, particularly in males. Speculation on the significance of the association between renal dysplasia and RN is discussed in relation to observations on the embryological development of the male lower urinary tract.
Age of Onset↗
Urinary endothelin (ET1) in complete ureteric obstruction in the miniature pig.
Segmental renal scarring occurs in experimental obstructive uropathy in the multipapillary porcine kidney, and segmental abnormalities in renal perfusion are likely to be responsible. This preliminary study examines the urinary excretion of the potent locally active vasoconstrictor endothelin 1 (ET 1) in a pig model of renal obstruction and subsequent relief. Significant urinary excretion of ET 1 from the postobstructive kidney was found to occur after longstanding obstruction. Preglomerular arteriolar stenosis may be the cause of the renal ischaemia in obstruction that is at first reversible but later becomes irreversible if the stimulus persists. ET 1 may be implicated in the pathogenesis of this injury.
Animals↗