D F Thomas

St. James University, Сент-Джеймс, New York, United States

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Publications (12)42.24 Total impact

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    ABSTRACT: Reconstruction of the urinary bladder with bowel to restore storage capacity is associated with significant complications arising from substituting an absorptive, mucus-producing intestinal epithelium for the barrier urothelium of the bladder. To overcome these problems, we are developing a "composite enterocystoplasty" procedure to replace the epithelium of the bowel with autologous in vitro-propagated normal urothelial cells. The aims of this study were to evaluate synthetic biomaterials as delivery vehicles for the cultured urothelial cells and provide support during transfer and cell adherence to the de-epithelialized bowel wall. The surgical compliance of 12 biomaterials was evaluated, along with their ability to support urothelial cell attachment. Transfer of urothelial cells onto biomaterials as single cell suspensions or intact cell sheets was investigated. Seeding of a single cell suspension on to non-woven mesh resulted in poor cell attachment. Seeding onto woven mesh was more efficient, but the most effective transfer method involved producing an intact cell sheet that could be combined with woven, knitted and non-woven biomaterials. Transfer of the cell sheet : mesh complexes onto a de-epithelialized bladder stroma produced a stratified epithelium incorporating the strands of the mesh and expressing urothelial-associated antigens after 48 h in organ culture. Thus, we have developed and evaluated a suitable transfer method for in vitro propagated urothelial cells to be used in "composite enterocystoplasty".
    Journal of Materials Science Materials in Medicine 01/2001; 12(10-12):991-6. DOI:10.1023/A:1012869318205 · 2.38 Impact Factor
  • Advances in Experimental Medicine and Biology 02/1999; 462:43-7. · 2.01 Impact Factor
  • Advances in Experimental Medicine and Biology 02/1999; 462:19-30. · 2.01 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Laboratory Investigation 10/1994; 71(4):583-94. · 3.83 Impact Factor
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    ABSTRACT: 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.
    The Journal of Urology 09/1994; 152(2 Pt 2):698-701. · 3.75 Impact Factor
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    ABSTRACT: 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.
    The Journal of Urology 09/1993; 150(2 Pt 2):721-5. · 3.75 Impact Factor
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    ABSTRACT: 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.
    The Journal of Urology 11/1992; 148(4):1229-31. · 3.75 Impact Factor
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    ABSTRACT: 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.
    British Journal of Urology 09/1991; 68(2):199-202.
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    ABSTRACT: To assess the morbidity and mortality associated with a prenatal diagnosis of bilateral fetal uropathy. Retrospective study. Departments of radiology, paediatric surgery, obstetrics, and pathology in two teaching hospitals that serve as referral centres for the Yorkshire region. 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. 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. 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. 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. 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.
    BMJ Clinical Research 06/1989; 298(6685):1419-20. DOI:10.1136/bmj.298.6685.1419 · 14.09 Impact Factor
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    D F Thomas, A C Gordon
    Archives of Disease in Childhood 02/1989; 64(1 Spec No):58-63. DOI:10.1136/adc.64.1_Spec_No.58 · 2.91 Impact Factor
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    ABSTRACT: We analyzed 25 cases of multicystic kidney to assess the impact of prenatal diagnosis on the management of this condition. The incidence of unilateral multicystic kidney was 1 in 4,300 live births. Of the 23 children with unilateral multicystic kidneys only 3 (13 per cent) had a readily palpable lesion. These findings suggest that multicystic kidney is a more common renal anomaly than was previously recognized and that the majority of cases remained undiagnosed before the advent of prenatal diagnosis. Ultrasound re-evaluation in 11 children suggests that the natural history of multicystic kidneys is towards spontaneous involution. Two kidneys were not identifiable by followup ultrasound. Hypertension and malignancy complicating multicystic kidney are reported infrequently. The literature on hypertension does not generally support the view that multicystic kidney poses a significant risk of hypertension in later childhood or adult life. We believe that the routine removal of multicystic kidneys in infancy is no longer appropriate.
    The Journal of Urology 12/1988; 140(5 Pt 2):1231-4. · 3.75 Impact Factor
  • D F Thomas, H C Irving, R J Arthur
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    ABSTRACT: Dilatation of the fetal urinary tract can now be detected by ultrasound imaging in pregnancy. Forty-six cases of pre-natally diagnosed dilatation were analysed to assess the contribution of this information to subsequent urological management. Positive pre-natal scans proved accurate. Dilatation was confirmed by neonatal ultrasound imaging or by autopsy in 24 of 25 consecutive inborn neonates and two aborted fetuses. Forty-four live births were studied. Twelve neonates had physical signs at birth which rendered the pre-natal diagnosis unnecessary. In 32 neonates (73%) the urinary tract anomaly was identified solely as a result of pre-natal imaging and would otherwise have remained undetected. However, in seven neonates the information was of doubtful value (mild unilateral dilatation), in 16 it was of probable value (confirmed unilateral PUJ obstruction, multicystic kidney, etc.) and in only nine neonates (20%) was it of definite value (treatable conditions affecting both kidneys or a solitary kidney, e.g. urethral valves, PUJ obstruction in a solitary kidney, etc.). Pre-natally detected bilateral dilatation (18 infants) carried a poor prognosis--33% mortality and 56% incidence of coexistent abnormalities. No infants in our series had undergone intra-uterine drainage, but the numbers of survivors and their renal function was comparable to the published results for fetal intervention.
    British Journal of Urology 01/1986; 57(6):784-7.