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Biomedical subjects

D R Roth

Publications and source records attributed to D R Roth.

At least 19 recordsLinked to original sources
PubMed2006

Design and evaluation of immunotoxicity studies.

The evaluation of potential adverse effects of pharmaceuticals on the immune system is part of the standard drug development procedures and needs to be available prior to the start of phase III clinical trials. Although the histopathological assessment of lymphoid organs/tissues is considered fundamental for the identification and characterization of immunotoxic reactions, additional investigations are now recommended by the European guidelines for repeated-dose toxicity testing of medicinal products in order to achieve an accurate assessment of immune system functionality with regard to immunomodulation. In the present paper, we describe and discuss a study design which permits the investigation of the immune function in a 4-week study in rats following immunization by subcutaneous administration of the T-dependent antigen Keyhole Limpet Hemocynin (KLH). This includes assessment of hematology parameters, titration of KLH-specific antibodies in serum, lymphocyte immunophenotyping in blood, thymus, spleen and lymph nodes, macroscopic pathology and histopathological evaluation of the lymphatic organs/tissues and of the injection sites.

Adjuvants, Immunologic↗
PubMed2001

Neutron production from polyethylene and common spacecraft materials.

We report experimental measurements of neutron production from collisions of neutron beams with polyethylene blocks simulating tissue at the Los Alamos National Laboratory Neutron Science Center and 1 GeV/amu iron nuclei with spacecraft shielding materials at the Brookhaven National Laboratory AGS.

Elementary Particle Interactions↗
PubMed2000

Upper urinary tract manifestations of the VACTERL association.

PURPOSE: In patients suspected to have the vertebral, anal, tracheoesophageal, renal, radial, cardiac and limb abnormalities (VACTERL) association we studied the frequency of upper urinary tract anomalies, prevalence of these features, predictability of upper tract pathology and proper screening evaluation. MATERIALS AND METHODS: From 1991 to 1998 we identified 55 patients with the VACTERL association. Upper urinary tract assessment, including initial renal ultrasound and voiding cystourethrography, and followup data were available for 29 boys and 15 girls. Patients were considered to have the VACTERL association when 3 or more organ systems were involved. RESULTS: Average followup was 5.4 years. Upper urinary tract involvement was noted in 41 of the 44 patients (93.2%) and vesicoureteral reflux in 17 (25 renal units). Of the kidneys 21 were hydronephrotic without reflux or obstruction, 10 were solitary, 3 were multicystic dysplastic, 8 were obstructed and only 17 were normal. A total of 27 patients (61%) underwent at least 1 genitourinary procedure, primarily ureteroneocystotomy. All children were alive at the last followup. CONCLUSIONS: The VACTERL association involves multiple serious anomalies. However, these infants generally have a good outcome. Since the upper urinary system is the most common organ system involved, patients should receive prophylactic antibiotics until an initial urological assessment with renal ultrasound and voiding cystourethrography is performed. It is essential for physicians to know that most children with the VACTERL association have urological involvement that requires treatment and long-term management.

Abnormalities, Multiple↗
PubMed1999

Bilateral posterior pelvic resection osteotomies in patients with exstrophy of the bladder.

This paper describes a modification of bilateral posterior iliac osteotomies for bladder exstrophy, in which a strip of ilium is resected subperiosteally lateral to the sacroiliac joints, allowing easier anterior closure with less breakdown compared with traditional osteotomies. Thirty-one children underwent repair of bladder exstrophy between 1974 and 1994. Orthopaedic procedures included: closed reduction and cast application in the newborn period (four patients), classic bilateral posterior iliac osteotomies (12 patients), and bilateral posterior resection osteotomies (15 patients). Dehiscence occurred after one closed reduction, five classic osteotomies, and one resection osteotomy. Urinary continence was obtained in four patients who underwent closed reduction, nine patients who underwent classic posterior osteotomies, and nine patients who underwent posterior resection osteotomies.

Bladder Exstrophy↗
PubMed1999

Analysis of homeobox gene HOXA10 mutations in cryptorchidism.

PURPOSE: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations. RESULTS: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion. CONCLUSIONS: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.

Child↗
PubMed1998

Androgen receptor gene alterations are not associated with isolated cryptorchidism.

PURPOSE: Multiple theories of testicular descent exist but there is no consensus. Cryptorchidism is a component of the androgen insensitivity syndrome, suggesting that testicular descent may be at least partially under the control of androgenic stimulation. To determine whether isolated cryptorchidism may be caused by androgen insensitivity, we screened a population of boys with isolated cryptorchidism for the presence of androgen receptor gene alterations. MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) was isolated from tissue collected from 21 patients with isolated cryptorchidism during orchiopexy. Patient selection was biased to maximize the likelihood of detection of a genetic etiology of cryptorchidism. The DNA was screened for androgen receptor gene alterations in exons 2 to 8 using single strand conformational polymorphism analysis. RESULTS: No abnormalities in the androgen receptor gene were detected by single strand conformational polymorphism analysis in any patient. CONCLUSIONS: Mutations of the androgen receptor gene in the hormone and DNA binding domains of the protein appear to be an unlikely cause of isolated cryptorchidism.

Child↗
PubMed1998

Outcome based comparison of surgical approaches for pediatric pyeloplasty: dorsal lumbar versus flank incision.

PURPOSE: Dismembered pyeloplasty for the correction of ureteropelvic junction obstruction can be performed through a flank or dorsal lumbar incision. We compared the records of children who had undergone pyeloplasty by each approach to determine if 1 technique was more advantageous. MATERIALS AND METHODS: We retrospectively reviewed the records of 33 consecutive children undergoing simple dismembered pyeloplasty by a single pediatric urologist from 1992 to 1996. The flank approach was used exclusively in the first group of patients who underwent repair in 1992 to 1993 and the dorsal lumbar incision was used exclusively in the second group after 1993. Data were obtained from hospital and clinic records, and both groups were compared with the 2-tailed t test. RESULTS: Pyeloplasty was done by dorsal lumbar incision in 16 cases and via the flank approach in 17. One patient in each group had undergone simultaneous bilateral pyeloplasties. Although overall comparison of both groups revealed no differences in operative time, in children older than 1 year pyeloplasty through a dorsal lumbar incision (108.5 minutes) was statistically significantly faster than the flank approach (144.4 minutes). Hospital stay was approximately 2 days shorter in infants who had a dorsal lumbar (25.7 hours) versus a flank incision (73 hours), and this difference did reach statistical significance if the bilateral pyeloplasty patients were excluded. Hospital costs were less for the dorsal lumbar group but the difference was not statistically significant. Success and complication rates were similar between groups with 2 patients in each group requiring additional procedures. Review of other series of repair of ureteropelvic junction obstruction demonstrated that the dorsal lumbar repair had equivalent or shorter operative times and lengths of hospitalization compared to newer endoscopic methods, and the outcomes were superior. CONCLUSIONS: The dorsal lumbar incision is a safe and efficacious approach to pyeloplasty and may be more cost-effective. In our series it was significantly faster in patients older than 1 year and resulted in shorter hospital stays in those younger than 1 year old.

Child↗
PubMed1998

Long-term adjustment issues in patients with exstrophy.

PURPOSE: We explored the psychological adjustment of children with bladder or cloacal exstrophy. MATERIALS AND METHODS: We assessed 29 subjects with a mean age plus or minus standard deviation of 7.8 +/- 3.97 years using age appropriate standard psychological instruments. Psychological adjustment scores in the exstrophy group were compared to the norms of the various instruments. Subjects were divided into dichotomous groups according to several medical and demographic factors. For each factor the differences between the means of the 2 groups on the outcome variables were calculated using a t test. RESULTS: Children with exstrophy perceived their appearance more positively than the norm. Older children performed more poorly than younger children in adaptive behavior, specifically in skills related to functioning in school. Children who achieved continence after age 4 years were more likely to have problems with acting out behavior. There were no differences in adjustment in boys versus girls, bladder versus cloacal exstrophy, type of continence strategy or gender reassignment versus no reassignment. CONCLUSIONS: Children with exstrophy did not have clinical psychopathology. Differences existed in adaptive and acting out behavior rather than depression or anxiety, suggesting that improved outcomes may be achieved through a focus on normal adaptation rather than on potential psychological distress.

Adaptation, Psychological↗
PubMed1997

Distal hypospadias repair with meatal-based flaps on an outpatient basis.

We report the results of primary repairs that were performed on 52 consecutive patients with distal hypospadias as an outpatient procedure. A modified Mathieu repair with meatal-based vascularized flap was performed under 2.5 optical magnification using Scottring retractors, traction sutures, micro instruments and fine suture material. A total of 3 patients had complications that required reoperation (5.8%). One of these 3 complications was a urethrocutaneous fistula (1.9%). We found that the repair of distal hypospadias was successful with meatal-based flap using contemporary finer approaches and equipment.

Ambulatory Surgical Procedures↗
PubMed1997

Pediatric pyeloplasty: outcome analysis based on patient age and surgical technique.

OBJECTIVES: To analyze our experience with open pyeloplasty, with specific emphasis on procedural outcome on the basis of patient age, surgical technique, complication rate, and complication management. METHODS: All patients from 1974 to 1994 who underwent pyeloplasty at our institution were included in our review. Charts were analyzed for age at presentation, presenting signs and symptoms, type of surgical reconstruction, complications and treatment, and final outcome. RESULTS: From 1974 to 1994, 234 pyeloplasties were performed in 227 patients (108 less than 1 year old, 119 more than 1 year old). The percentage of children less than 1 year old increased throughout: 24% for 1975 to 1980, 37% for 1981 to 1990, and 69% for 1991 to 1994. Presenting signs and symptoms varied according to the age of the child at pyeloplasty. For children less than 1 year old, these were prenatal ultrasound in 86 (79%), urinary tract infection (UTI) in 9 (8%), and abdominal mass in 5 (4.6%). For children more than 1 year old, these were pain in 57 (48%), UTI in 29 (24%), hematuria in 12 (10%), and prenatal ultrasound in 3 (2.5%). Reconstruction was a dismembered pyeloplasty in all cases. The majority of patients in both age groups underwent a nonintubated repair (less than 1 year old, 99 of 114; more than 1 year old, 102 of 120). Postoperative results were evaluated by ultrasound or intravenous urography, with improvement or stable results in 95% of children less than 1 year old and in 96% of children more than 1 year old. Complications included UTI in 18 patients (7.7%), recurrent obstruction in 5 (2.1%), and persistent leak in 4 (1.7%). The complication rate was not related to age. CONCLUSIONS: The nonintubated, dismembered pyeloplasty is an excellent technique for all age groups and has a low complication rate.

Age Factors↗
PubMed1997

Comparison of onlay and tubularized island flaps of inner preputial skin for the repair of proximal hypospadias.

PURPOSE: Transverse island flaps of inner preputial skin have provided a reliable technique for the repair of proximal hypospadias. The flap may be used to create a neourethra by tubularizing the flap after urethral transection or applying the flap as an onlay patch onto an intact urethral plate. We retrospectively analyzed our experience with these 2 techniques to compare outcomes. MATERIALS AND METHODS: During 11 years 132 patients underwent hypospadias repair by a single surgeon using an onlay (58) or tubularized (74) island flap technique. Surgical results were reviewed retrospectively. RESULTS: At a mean followup of 20.3 months the overall complication rate was 36% for tubularized and 31% for onlay repair, and fistula rates were 14 and 17%, respectively. Despite similar fistula rates tubularized repairs tended to have larger fistulas that required more complex repair (p = 0.0147). In 9 patients who underwent tubularize repair diverticula developed, whereas no diverticula developed after onlay repair (p = 0.0162). The rates of urethral stricture, wound infection, residual chordee and cosmetic complications were not statistically significantly different between repairs. The use of double faced repair in 30 patients provided no difference in outcome in comparison to the overall study cohort. CONCLUSIONS: Hypospadias repair using transverse island flaps offers reliable and durable outcomes. While overall complication rates were not greatly different between tubularized and onlay flap repairs, onlay repair tended to result in fistulas of smaller size and diverticula did not develop.

Follow-Up Studies↗
PubMed1997

A renal size nomogram for the patient with myelomeningocele.

PURPOSE: Renal anatomy and function are usually monitored in the myelomeningocele population using routine ultrasound as the child grows. Clinical questions arise when a renal unit is of marginal size when evaluated with nomograms derived from normal patient populations. Our goal was to construct a renal size nomogram using ultrasound for the myelomeningocele population to help the clinician identify abnormal growth. MATERIALS AND METHODS: We reviewed the charts and radiological files of 96 patients with myelomeningocele followed at our institution. Images of 930 renal units were included to construct the nomogram. Patients were excluded from study due to hydronephrosis or hydroureter, solitary kidney, recurrent symptomatic urinary tract infection, vesicoureteral reflux, reconstructive surgery or known high bladder storage pressure. RESULTS: A renal size nomogram was constructed by plotting patient age against maximal renal length on real-time ultrasound. Expected mean and standard deviations were calculated for each age group. CONCLUSIONS: Previous studies using excretory urography have shown that kidneys in the myelomeningocele population are smaller than in a healthy control population. Ultrasound is now the modality most commonly used to monitor renal anatomy. The creation of a renal nomogram based on ultrasound should help the clinician identify abnormal renal growth more accurately.

Adolescent↗
PubMed1997

Molecular biology and function of the androgen receptor in genital development.

PURPOSE: The rapidly growing field of molecular biology has caused exponential growth in our knowledge of the processes of embryogenesis. Since the cloning of the androgen receptor gene in 1988, investigators have been able to clarify many of the molecular events of male sexual differentiation that are mediated through the androgen receptor. We reviewed the current state of knowledge of the androgen receptor and its role in male genital development. MATERIALS AND METHODS: An intensive literature search was conducted to review reports on the androgen receptor and sexual differentiation since 1988. This review also includes ongoing research from our laboratory on the role of the androgen receptor in human genital development, as well as collaboration with other investigators. RESULTS: We reviewed the basic molecular biology of androgenic action mediated through the androgen receptor. This information has been integrated into the current understanding of human male sexual differentiation to clarify how androgens virilize the undifferentiated embryo. Defects in function of the androgen receptor may be manifested as a spectrum of phenotypes of the androgen insensitivity syndrome, and these phenotypes of male pseudohermaphroditism have been reviewed on a clinical and molecular basis. New molecular techniques have augmented the evaluation and diagnosis of the androgen insensitivity syndrome, and some groups have successfully diagnosed the condition prenatally. CONCLUSIONS: Basic scientific research of androgen receptor function and its role in male sexual development has provided a clearer understanding of the mechanisms responsible for the spectrum of defects secondary to the androgen insensitivity syndrome. This knowledge will enable clinicians to offer more accurate diagnosis and insightful counseling to affected patients and their families.

Disorders of Sex Development↗
PubMed1996

Androgen receptor gene mutations are rarely associated with isolated penile hypospadias.

PURPOSE: Hypospadias has no known single etiology but it has been linked to androgen insensitivity caused by mutations of the androgen receptor gene. The purpose of this study was to search for such mutations in cases of various degrees of isolated hypospadias to determine whether such an association exists and, if so, with any particular anatomical subgroup. MATERIALS AND METHODS: Isolated deoxyribonucleic acid from the penile tissue of 40 patients undergoing reconstructive surgery was screened for mutations of the coding regions of the androgen receptor gene using single strand conformational polymorphism analysis. In cases with abnormal single strand conformational polymorphism findings sequence analysis of the deoxyribonucleic acid was performed to define the mutation. RESULTS: A missense mutation of exon 2 of the androgen receptor gene was noted in 1 patient with isolated distal penile shaft hypospadias. Sequence analysis revealed that the mutation changed amino acid residue 546 from proline to serine. No abnormalities were detected in the other 39 patients. CONCLUSIONS: Isolated distal shaft hypospadias is associated with mutations of the androgen receptor gene but these mutations appear to be a rare cause of hypospadias.

Child↗
PubMed1995

The role of surgery in the management of pediatric pelvic rhabdomyosarcoma.

PURPOSE: We assessed the role of surgery, particularly exenteration, in the treatment of children with lower urinary tract and pelvic rhabdomyosarcoma. MATERIALS AND METHODS: We treated 23 children with bladder and/or prostate (11), or pelvic retroperitoneal tumors (12). Initial management was tumor resection in 6 cases, anterior pelvic exenteration in 5 and biopsy only in 12, combined with chemotherapy in 23 and radiotherapy in 20. RESULTS: The bladder salvage rate for surviving patients with pelvic tumors was 92% versus 27% for those with prostate/bladder tumors. Estimated 5 and 10-year survival probability for patients with pelvic retroperitoneal tumors was 49 +/- 50% compared to 81 +/- 24% for those with bladder and/or prostate tumors (log rank test, p = 0.11). CONCLUSIONS: Exenterative surgery is frequently required to achieve a durable complete response.

Actuarial Analysis↗
PubMed1994

Repair of hypospadias complications using the meatal based flap urethroplasty.

While long used for primary hypospadias repair, meatal based flap urethroplasty has not been widely considered a viable alternative for a secondary procedure. We reviewed 200 patients who underwent meatal based flap urethroplasty and identified 9 (4.5%) who underwent the procedure for correction of complications of previous hypospadias repair, including urethrocutaneous fistula, severe meatal retraction, persistent chordee and hair in the urethra. The complication was corrected with a single operation in 8 of the 9 patients (89%). A single small fistula developed in 3 patients, which closed spontaneously in 2 and required another procedure in 1. Meatal based flap urethroplasty should be considered for correction of distal complications of hypospadias repair.

Child↗
PubMed1994

Current indications for cutaneous ureterostomy.

OBJECTIVE: To assess the current indications for cutaneous ureterostomy in children. METHOD: A total of 32 children underwent cutaneous ureterostomy at Texas Children's Hospital from 1975 to 1990. Medical records were reviewed to determine the urologic diagnosis, the indication for urinary diversion, the type of ureterostomy performed, and the outcome for each patient. RESULTS: Twenty patients underwent loop cutaneous ureterostomy (LCU) or pyelostomy and 12 patients underwent end cutaneous ureterostomy (ECU). The main indication for LCU was obstructive uropathy unresponsive to lower urinary tract drainage, and the most common cause was posterior urethral valves. Other indications for LCU included obstruction requiring delayed surgical correction, high-grade reflux into a solitary kidney, and obstruction with infection. The children who required ECU were an older, more diverse group than those who underwent LCU. The main indication for ECU was poor bladder function secondary to a variety of congenital anomalies, including prune-belly syndrome, posterior urethral valves, bladder exstrophy, and urogenital sinus defect. CONCLUSION: LCU is easy to perform and is an excellent method for achieving temporary upper urinary tract drainage. ECU is suited for long-term or permanent urinary diversion in children with at least one dilated ureter, and can provide a socially acceptable stoma when delayed reconstruction is necessary. Many children who were "permanently" diverted by ECU may be undiverted using newer reconstructive techniques.

Child, Preschool↗