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Biomedical subjects

D F Thomas

Publications and source records attributed to D F Thomas.

At least 37 records · Page 2Linked to original sources

Failure of pre-natal ultrasonography to prevent urinary infection associated with underlying urological abnormalities.

OBJECTIVES: To analyse the reasons underlying the failure of routine pre-natal ultrasonography to prevent the subsequent development of urinary tract infection (UTI) in children with predisposing urological abnormalities. PATIENTS AND METHODS: This retrospective study comprised 39 children (22 females and 17 males) who had at least one documented UTI, the presence of an anatomical anomaly of the urinary tract recognized as predisposing to UTI and had undergone ultrasonography of the urinary tract undertaken in fetal life as part of routine maternal ante-natal ultrasonography. Four categories of patients were defined: Group A, those with normal findings on pre-natal ultrasonography and no urological abnormality detected; Group B, those with a urological abnormality detected but where there was a subsequent failure of communication among clinicians; Group C, those with a urological abnormality but who received inappropriate or sub-optimal post-natal management and; Group D, those with a urological abnormality but who had a UTI despite appropriate post-natal management. In each case, the most severe documented episode of UTI was categorized as: Grade I, asymptomatic bacteriuria; Grade II, mild/moderate symptomatic UTI and; Grade III, severe symptomatic UTI necessitating hospital admission. RESULTS: Group A comprised 22 (56%), Group B three (9%), Group C two (5%) and Group D 12 children (31%). Of the 22 children in Group A, nine experienced a UTI of sufficient severity to necessitate hospital admission. Of the 12 children in Group D only one required hospital admission. CONCLUSIONS: The failure of pre-natal ultrasonography to identify the underlying predisposing urological abnormality was the most important factor contributing to subsequent UTI in post-natal life. Failure of communication and inappropriate post-natal management were numerically unimportant. In some children, UTI occurred despite pre-natal detection of their underlying anomaly and appropriate post-natal management. However, in this group the UTI was less severe than in those children whose urological anomalies had not been detected by pre-natal ultrasonography.

Child, Preschool↗

Fetal pelvi-ureteric junction obstruction: predictors of outcome.

OBJECTIVE: To examine the relationship between pre-natal ultrasonographic findings typical of pelvi-ureteric junction (PUJ) obstruction and post-natal renal function in the affected kidney. PATIENTS AND METHODS: This retrospective study comprised 35 infants in whom pre-natal ultrasonography had identified a unilateral pattern of dilatation of the renal pelvis and calices typical of PUJ obstruction. In each case, the presence of unilateral hydronephrosis had been confirmed post-natally by ultrasonography, and differential function and drainage evaluated by isotope renography. The results of isotope renography were compared with the severity and timing of onset of the fetal hydronephrosis. RESULTS: Eleven kidneys (31%) appeared normal in the second trimester and dilatation only became apparent during the third trimester. Mean differential function in these kidneys was 48%. However, mean differential function was reduced (mean 38%) in those kidneys noted to be dilated between 16 and 24 weeks gestation. Differential function was loosely correlated with the severity of dilatation in early onset cases, i.e. the mean differential function was 42% for mild, 37% for moderate and 27% for severe dilatation. A considerable variation in differential function values was present in each group except for those with severe dilatation, which was a significant predictor of poor functional outcome when compared with mild and moderate dilatation combined (P < 0.01). CONCLUSION: Fetal PUJ obstruction is a heterogeneous condition permitting only broad predictions of functional outcome. Severe dilatation detected on second trimester imaging predicted significant loss of function. Mild and moderate degrees of dilatation were associated with a one in three risk of functional impairment in the obstructed kidney.

Dilatation, Pathologic↗

Prenatally detected posterior urethral valves: is gestational age at detection a predictor of outcome?

Between 1982 and 1992, 67 boys with posterior urethral valves were managed at our hospital, including 32 (48%) in whom the condition was detected prenatally. We examined the relationship between gestational age at detection and outcome at a median followup of 3.9 years (range 4 months to 10 years). Detection at or before 24 weeks of gestation predicted a poor outcome with 9 of 17 patients (53%) dead or in chronic renal failure at followup. Of the cases detected later in pregnancy only 1 had a poor outcome (p = 0.01). All of the cases detected after 24 weeks of gestation had had normal second trimester scans. Growth parameters for boys in the early and late detection groups were not statistically different. However, there was a significant association between renal failure and growth with 67% versus 14% having heights less than the 3rd percentile (p = 0.05). Respiratory distress at birth predicted a poor outcome, while the presence of palpable abdominal abnormalities or vesicoureteral reflux failed to predict outcome.

Female↗

Cantwell-Ransley epispadias repair in male epispadias and bladder exstrophy.

A total of 16 boys (8 with primary epispadias and 8 with bladder exstrophy) underwent epispadias reconstruction as a 1-stage procedure. Reverse meatal advancement of MAGPI, ventral transposition of the neourethra and chordee correction by corporeal rotation or "cavernocavernostomy" were performed as primary (13 boys) or secondary/salvage (3 boys) procedures. At a mean followup of 27 months all children had a horizontal or downward angled penis while standing. Catheterization in 10 children revealed an easily negotiable neourethral channel. Minor revision surgery was necessary in the area of previous paraexstrophy flaps in 2 cases, and 1 child required neourethral tapering and proximal anastomotic revision. The Cantwell-Ransley epispadias repair produces a good functional and cosmetic result.

Adolescent↗

Mild dilatation of the fetal kidney: a follow-up study.

OBJECTIVE: To assess morbidity in children with mild prenatally detected pelvicalyceal dilatation and to document the natural history of this ultrasound finding in post-natal life. PATIENTS AND METHODS: A retrospective (on-going) study was carried out in 29 children (39 kidneys) with mild dilatation confined to the pelvis and/or calices confirmed on initial post-natal ultrasound scan. Re-evaluation was carried out at a mean age of 4.2 years (range 1.5-7.8). Clinically, each patient's history, height, weight and blood pressure were recorded. On ultrasound examination the renal length, collecting system appearances and dimensions were recorded. RESULTS: Vesico-ureteric reflux was demonstrated in 1 of 14 infants who underwent neonatal micturating cystourethrography. During cumulative follow-up totaling 122 years, there were only two documented episodes of urological morbidity, i.e. one episode of unexplained haematuria and one of urinary tract infection. By a mean age of 4.2 years the ultrasound appearances had reverted to normal in 69% of kidneys. In 31% dilatation persisted and was unchanged or diminished in severity. No case of increasing dilatation was seen. Renal growth was normal in 97% of kidneys. CONCLUSIONS: Mild dilatation of the fetal urinary tract is a common prenatal ultrasound finding. When confined to the renal pelvis and/or calices it is of doubtful clinical significance and is associated with a low level of morbidity in infancy and early childhood. Invasive investigation in post-natal life is not justified.

Child↗

Normal human urothelial cells in vitro: proliferation and induction of stratification.

BACKGROUND: The purpose of the work was to establish urothelium as an in vitro model for the study of proliferation, stratification, and differentiation in "complex" epithelia. EXPERIMENTAL DESIGN: Normal human urothelial cells were cultured in a serum-free medium. The effects of epidermal growth factor (EGF), cholera toxin (CT), extracellular calcium and 13-cis-retinoic acid on cell growth, morphology, phenotype, and cytodifferentiation were studied using phase-contrast microscopy and indirect immunofluorescence. Stratification-related changes were additionally analyzed by transmission electron microscopy. RESULTS: Under optimized conditions, long-term cultures were successful in 44 (74.5%) out of 59 specimens. Bacterial infection was the most common cause of failure (9 cases). Primary urothelial cells required an initial plating density of > or = 10(4) cells/cm2 for survival; passaged cells survived much lower plating densities (> or = 2.5 x 10(2) cells/cm2). CT significantly improved cell attachment, but neither CT nor EGF were essential for growth. By contrast, cells failed to proliferate without bovine pituitary extract. In media containing bovine pituitary extract, CT, and EGF, cultures had a mean population doubling time of 14.7 +/- 1.8 hours, maintained a nonstratified phenotype, and expressed the cytokeratin (CK) profile of basal/intermediate urothelium: CK7, CK8, CK17, CK18 and CK19, with variable expression of CK13. CK20 was not expressed in vitro. CK14 and CK16 were also expressed, suggestive of squamous metaplasia in culture, which could be inhibited with 13-cis-retinoic acid. Increasing extracellular calcium from 0.09 to 0.9-4.0 mM slowed cell proliferation, induced stratification and desmosome formation, and increased expression of E-cadherin. High calcium, EGF, CT, and retinoic acid did not induce markers of late/terminal urothelial cytodifferentiation. CONCLUSIONS: We describe a simplified technique for the isolation and long-term culture of human urothelial cells. Urothelial cells in vitro are capable of rapid proliferation and can be induced to form integrated stratifying cell layers in high calcium medium. Stratification-related changes are not necessarily accompanied by urothelial cell maturation and differentiation.

Adolescent↗

Urothelial tissue culture for bladder reconstruction: an experimental study.

An in vitro system for the growth of normal human urothelial cells has been developed. Urothelial cells were isolated from tissue samples in 38 patients and cultured in a defined serum-free medium. Confluent cell monolayers of 25 cm.2 were produced after 7 days in 32 cases. Subsequent subcultures at a 1:20 split ratio achieved confluency within another 7 days and a consistently high rate of growth was sustained for at least 7 passages. Characterization by immunofluorescence with a panel of antibodies demonstrated that the cultured cells were exclusively epithelial and retained the characteristic antigenic profile of normal urothelium, even after extended periods in culture. The only consistent cause of failure (6 of 38 cases) was bacterial contamination secondary to an underlying urinary tract infection in these patients.

Adolescent↗

Novel inhibitors of prolyl 4-hydroxylase. 2. 5-Amide substituted pyridine-2-carboxylic acids.

A series of 5-[(arylcarbonyl)amino]- and 5-(arylcarbamoyl)pyridine-2-carboxylic acids has been prepared and tested for activity as inhibitors of the enzyme prolyl 4-hydroxylase (EC 1.14.11.2). All the analogues prepared were inhibitors of the enzyme in vitro, the best compounds being equipotent with the known inhibitor pyridine-2,5-dicarboxylic acid (9). Like 9 these amidic analogues were not active in a cultured embryonic chick tendon cell model, considered to be a predictor of in vivo activity. The activity of the amides is not consistent with the model described for the mode of action of 9 with the enzyme and aspects of this are discussed.

Amides↗

Use of 99mtechnetium-dimercaptosuccinic acid to study patterns of renal damage associated with prenatally detected vesicoureteral reflux.

Static isotope imaging with 99mtechnetium-dimercaptosuccinic acid was performed at a mean age of 34 days in 32 children (50 kidneys) whose vesicoureteral reflux had been identified as a result of prenatal ultrasound scanning. Three patterns of isotope uptake were observed: 1) noninfected primary vesicoureteral reflux (15 children, 24 kidneys), 2) noninfected secondary (obstructed) vesicoureteral reflux (9 patients, 11 kidneys) and 3) infected primary reflux (8 infants, 15 kidneys). In 20 pattern 1 kidneys (83%) renal morphology and differential isotope were normal. In the 4 kidneys (17%) that showed evidence of impaired function this took the form of global parenchymal loss, that is small kidneys rather than focal scarring. In pattern 2 the combination of fetal vesicoureteral reflux and obstruction was a potent cause of renal damage with total or near total loss of function in 7 of 9 refluxing units associated with posterior urethral valves and in 2 kidneys with secondary ureteropelvic junction obstruction. Appearances of focal scarring were confined in pattern 3 and were found in 4 kidneys (27%). This overall incidence of detectable renal damage was lower than expected. Even when infection occurs, prenatal diagnosis may lessen the risk of scarring by enabling treatment to be instituted promptly. The findings suggest that uncomplicated primary vesicoureteral reflux is a relatively benign insult to the fetal kidney and that reflux nephropathy found in children presenting clinically is the result of infected vesicoureteral reflux in postnatal life. Any comparison of published studies will prove difficult until there is a more standardized approach to imaging technique and patient selection.

Female↗

Experience with the Fowler Stephens and microvascular procedures in the management of intraabdominal testes.

The Fowler Stephens operation and microvascular procedures were compared for the management of 23 intra-abdominal testes in 15 boys, 7 of whom had the prune belly syndrome. The Fowler Stephens operation was used for 15 testes (4 single-stage and 11 two-stage) and microvascular transfer was used for 8 testes. Eleven testes treated by the Fowler Stephens procedure (73%) and 7 treated by microvascular procedures (88%) were viable and intrascrotal after an average follow-up of 3.0 years, giving an overall success rate of 78%. Eight of 9 post-pubertal testes were biopsied. Severe maturational arrest was evident in all and carcinoma in situ was present in one.

Abdomen↗

Antenatally detected pelviureteric junction obstruction. Is non-operation safe?

We report follow-up data (minimum of 1 year) on 63 kidneys with antenatally detected pelviureteric junction obstruction, as defined by renographic criteria. The condition was bilateral in 10 patients (i.e. 20 kidneys), 2 patients had unilateral obstruction with contralateral multicystic dysplastic kidneys, and 41 patients had unilateral obstruction with a normal contralateral kidney. In the latter group, 29 (71%) had good function (greater than 40%) at initial assessment. Of the 63 kidneys, 24 (38%) were operated upon following initial assessment, mainly for impaired function. Of 39 patients, initially managed non-operatively, 8 (21%) were operated upon subsequently: 3 for deteriorating function (2 of whom have been reassessed and both have regained their lost function) and 5 for other renographic or ultrasonic indications). Of the original 63 kidneys, 31 (49%) continue to be managed non-operatively; 16 of these (52%) show improving ultrasound appearances, 8 of 17 studied show improved drainage, and all unilateral cases have stable good function. It is concluded that non-operative management of selected cases of antenatally detected pelviureteric junction obstruction is safe.

Female↗

Prenatally diagnosed reflux: a follow-up study.

This report analyses the characteristics and outcome of 25 infants with vesicoureteric reflux detected prenatally on the basis of dilatation of the fetal urinary tract. Sixteen infants had bilateral reflux--a total of 41 refluxing units. The high proportion of males (84%) contrasts with clinically presenting reflux, which is dominated by females. Prenatally diagnosed reflux is generally of a higher grade--usually grade IV. Eight children (32%) had coexistent congenital abnormalities. Chemoprophylaxis was completely effective in 17 children (68%), who remained infection-free; 3 children (12%) had a single urinary infection and were managed conservatively whilst 5 (20%) experienced 2 or more infections and required reimplantation or vesicostomy. Spontaneous cessation of reflux was observed in 6 (35%) of 17 refluxing ureters reassessed after a mean interval of 2.1 years. The significance of isotope findings was sometimes difficult to assess but results in 30 refluxing units support the concept that focal renal scarring is usually a consequence of infected reflux in postnatal life.

Female↗

Fetal uropathy.

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Female↗

Bilateral fetal uropathy: what is the outlook?

OBJECTIVE: To assess the morbidity and mortality associated with a prenatal diagnosis of bilateral fetal uropathy. DESIGN: Retrospective study. SETTING: Departments of radiology, paediatric surgery, obstetrics, and pathology in two teaching hospitals that serve as referral centres for the Yorkshire region. PATIENTS: 126 Cases of fetal uropathy were referred either prenatally or postnatally from hospitals in Yorkshire between August 1982 and December 1987. The disease was bilateral in 54 cases and unilateral in 72 cases. In 14 cases bilateral fetal uropathy was associated with coexistent disease. INTERVENTIONS: All cases were managed individually by an obstetrician after discussion with the radiologists and paediatric surgeons. Babies who survived were treated prophylactically with antibiotics after delivery and were operated on if appropriate. END POINT: Assessment of prognosis for long term renal function for each baby referred between August 1982 and December 1987: follow up ranged from six months to five years. MEASUREMENTS AND MAIN RESULTS: Of the 54 fetuses with bilateral fetal uropathy, 13 were terminated as the prenatal findings of ultrasonography were considered to be incompatible with long term survival. Ten of the liveborn babies died, five of renal or pulmonary insufficiency, or both, and five of associated congenital anomalies. Thirty one infants survived to follow up; four of these had serious coexistent disease and two had impaired renal function. Thus the overall mortality was 43% and the morbidity rate 19%. The renal anomaly was associated with other serious disease in 14 cases (26%) compared with two (3%) of the 72 cases of unilateral fetal uropathy. All but two of the 27 infants with isolated bilateral urinary tract disease had excellent prospects for survival. CONCLUSION: Although bilateral fetal uropathy is associated with a high morbidity rate and mortality, careful prenatal assessment can help to identify fetuses with a poor prognosis. The outlook for a fetus with isolated renal disease if treated promptly after delivery is excellent and compares favourably with that reported after prenatal surgical intervention.

Abnormalities, Multiple↗

Cloacal malformations: embryology, anatomy and principles of management.

The cloacal anomaly is characterised by the persistence of a common channel draining the urinary, genital and alimentary tracts via a single orifice. It results from abnormal compartmentalisation of features that are normal in the primitive female embryo. Abnormal embryology and cloacal anatomy are described in detail. Cloacal abnormalities are usually diagnosed promptly in the neonatal period. Management can be divided into three phases: (1) investigating and defining the anatomy, (2) neonatal intervention with relief of obstruction and (3) definitive surgical reconstruction. Successful management of the child with a cloacal abnormality remains one of the greatest challenges to the pediatric surgeon.

Cloaca↗