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Biomedical subjects

Michael E Mitchell

Publications and source records attributed to Michael E Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

A case of true hermaphroditism reveals an unusual mechanism of twinning.

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Molecular and cellular basis of congenital heart disease.

The cellular and molecular basis of congenital heart disease (CHD) is an evolving area of rapid discovery. This article introduced the basic mechanisms underlying cardiac development and CHD in order to permit a clear understanding of current diagnostics and therapeutics and their future development. It is clear that although significant advances have been made in understanding mechanisms controlling heart formation, the direct causes of CHD remain poorly defined. Future studies tha delineate the complexity of these mechanisms are required to provide a comprehensive understanding of the etiologies of CHD. Such understanding will lead to the development of novel approaches to prevention and therapy.

Animals↗
PubMed2005

Intermediate outcomes after the Fontan procedure in the current era.

OBJECTIVE: This study was undertaken to investigate the intermediate outcomes after the Fontan operation in the current era. METHODS: A cross-sectional analysis was performed by using data gathered between October 13, 2003, and February 22, 2005, on all 310 survivors of the Fontan procedure between January 1, 1992, and December 31, 1999. Medical records were reviewed, and a customized questionnaire was administered to caregivers. Outcome variables included failure of the Fontan operation (ie, death, takedown of Fontan, or transplantation), number of cardiac-related rehospitalizations, parental assessment of health, school performance, and cardiac functional status. RESULTS: A total of 332 patients underwent the Fontan procedure during the study period. A lateral tunnel was constructed in 281 (85%), and an extracardiac Fontan procedure was performed in 51 (15%). A total of 210 (63%) children had undergone previous stage I reconstruction, and 162 (49%) had received an initial diagnosis of hypoplastic left heart syndrome. There were 310 hospital survivors of the Fontan procedure (93.4%), with an additional 16 deaths (5.2%) during follow-up and 1 living heart transplant patient before the cross-sectional period. For initial hospital survivors, Kaplan-Meier estimates of freedom from death or transplantation were 98.0% (95% confidence interval, 95.6%-99.1%) at 1 year after the Fontan procedure, 94.9% (91.6%-97.0%) at 5 years, and 93.9% (90.1%-96.2%) at 8 years. Questionnaires were completed for 240 (81.9%) of the 293 available patients. By parental recollection, a total of 130 (54.2%) children required cardiac-related rehospitalization at some point during the follow-up period. At a median follow-up of 8.6 years (range, 4.1-12.8 years), 94.6% of guardians described their child's overall health as excellent or good, and 5.4%, as fair or poor. School performance was described as above average in 30.2%, average in 39.9%, and below average in 29.8%. With regard to cardiac functional status, 34.2% responded that their child had no limitations to physical activity, 52.5% reported a slight limitation, 12.1% reported a significant limitation, and 1.2% reported a severe limitation. CONCLUSIONS: Acceptable survival outcomes have been observed at intermediate follow-up of the Fontan operation in this cohort; a significant proportion of patients had hypoplastic left heart syndrome. Although cardiac-related rehospitalization is common, the parents and guardians believed that overall health, school performance, and cardiac functional status were good to excellent for most patients.

Child↗
PubMed2005

Symptomatic refluxing distal ureteral stumps after nephroureterectomy and heminephroureterectomy. What should we do?

PURPOSE: We hypothesize that residual ureteral stumps following nephroureterectomy (NU) or heminephroureterectomy (HNU) are associated with an increased risk of urinary tract infection (UTI) that is decreased by distal ureterectomy. MATERIALS AND METHODS: We performed a retrospective review of 71 patients who underwent NU or HNU for reflux into a nonfunctioning system between 1990 and 2003. The indications for all renal surgery included recurrent UTIs in 44 patients, hypertension in 8 and a combination of these conditions in 19. Voiding cystourethrogram and urine cultures were performed in all patients with recurrent symptomatic UTIs. RESULTS: Followup in all 71 patients averaged 52 months. A total of 11 patients who underwent laparoscopic NU or HNU to the hiatus of the bladder were excluded because they did not have a ureteral remnant. The remaining 60 patients all underwent an open procedure. Of these patients 32 (53%) had refluxing distal ureteral remnants. Six of these 32 patients with refluxing stumps (19%), all girls, became symptomatic during followup. Symptomatic UTIs recurred in these 6 patients an average of 12 times per year (range 8 to 21), which significantly decreased after distal ureterectomy. CONCLUSIONS: If surgery is indicated in patients with reflux into a poorly functioning system, we recommend NU or HNU to the level of the bladder hiatus. If a symptomatic ureteral remnant is present, then distal ureterectomy decreases the rate of symptomatic UTIs in these patients. Laparoscopic distal ureterectomy is a viable surgical technique for this patient population.

Adolescent↗
PubMed2005

Recurrent urinary tract infection in the post-transplant reflux nephropathy patient: is reflux in the native ureter the culprit?

We assessed the prevalence of symptomatic, refluxing systems as a cause of recurrent urinary tract infection (UTI) in patients who underwent renal transplantation as result of renal failure from reflux nephropathy. Eleven patients from the age of 8 to 19 yr underwent renal transplantation for renal failure because of reflux nephropathy, between 1992 and 2003. Culture documented UTI were investigated and correlated with pre- and postoperative infection rates, voiding dysfunction (VD), concomitant nephrectomy, or nephroureterectomy with refluxing native remnants, and pretransplant ureteral reimplantation. Four patients with nephroureterectomies and no VD were infection free post-transplant. Two of three patients reimplanted pretransplant with a history of VD had one or more UTI per month. Patients with nephrectomies without partial ureterectomies with or without VD also had one or more UTI per month. Refluxing systems in the immunosuppressed transplant patient may play a role in UTI especially when associated with VD. Surgical intervention of native refluxing systems may be warranted.

Adolescent↗
PubMed2004

The pediatric caliceal diverticulum: diagnosis and laparoscopic management.

PURPOSE: To describe the laparoscopic management of anterior caliceal diverticula in pediatric patients and to emphasize the importance of intraoperative retrograde pyelography for the diagnosis of symptomatic lesions when preoperative radiologic evaluation is inconclusive. PATIENTS AND METHODS: We performed laparoscopic transperitoneal excision of a large symptomatic caliceal diverticulum in three patients. Ultrasonography was consistent with a cyst, and a CT scan did not show layering on delayed images. Prior to surgical intervention, we localized the diverticulum by cystoscopy and fluoroscopic retrograde ureteropyelography. RESULTS: Complete ablation of the caliceal diverticulum cavity was achieved in all cases without open conversion. The mean operative time was 134 minutes. Blood loss was minimal in all cases. The mean hospital stay was 37 hours. There were no intraoperative or postoperative complications. Because the preoperative studies were consistent with large anterior cysts, we found retrograde ureteropyelography as an adjunct to laparoscopic surgery invaluable to identify the patent diverticular neck. CONCLUSION: Patients with a large, symptomatic Type 2 caliceal diverticulum with thin overlying parenchyma are ideal candidates for laparoscopic intervention. The laparoscopic technique of caliceal diverticulum ablation in the pediatric population is feasible in appropriate patients.

Adolescent↗
PubMed2004

Comparison of dismembered and nondismembered laparoscopic pyeloplasty in the pediatric patient.

BACKGROUND AND PURPOSE: Laparoscopic dismembered pyeloplasty is an acceptable option for ureteropelvic junction (UPS) obstruction in the pediatric population. We compared our results with dismembered and nondismembered laparoscopic pyeloplasty. PATIENTS AND METHODS: A series of 26 children between the ages of 8 months and 15 years (mean age 5 years) underwent transperitoneal laparoscopic pyeloplasty for an obstruction not caused by a crossing vessel. Nineteen had an Anderson-Hynes dismembered pyeloplasty (AH), while the remaining seven had a nondismembered pyeloplasty in a Heineke-Mikulicz fashion (HM). The outcome measures were operative time, length of hospital stay, and resolution of obstruction by ultrasonography and diuretic radionuclide imaging. RESULTS: The mean operative time was 3.1 hours and 2.5 hours for AH and HM, respectively. No difference in hospital stay was noted, with a mean of 3 days. The stent was removed 6 weeks later. Four of the seven patients having nondismembered procedures presented with acute flank pain within 3 days of stent removal. The AH pyeloplasty produced a 94% rate of resolution of UPJ obstruction, while the HM patients did poorly, with a success rate of only 43% (P = 0.002; Fisher's exact test). CONCLUSIONS: We believe that for UPJ obstructions in children not involving a crossing vessel, laparoscopic dismembered (AH) pyeloplasty may be considered a safe alternative.

Adolescent↗
PubMed2004

A novel approach to the laparoscopic antegrade continence enema procedure: intracorporeal and extracorporeal techniques.

PURPOSE: The use of laparoscopic techniques in the construction of an antegrade continence enema (ACE) channel is evolving as a minimally invasive procedure that attempts to address issues of morbidity commonly associated with the technique as originally described. Because of our experience with "open" ACE construction, we maintain that true fecal continence of the ACE channel requires more than dependence on the appendicocecal sphincteric mechanism. Therefore, we have implemented intracorporeal or extracorporeal suturing to create a reliable continence mechanism. MATERIALS AND METHODS: We retrospectively reviewed 6 patients who underwent laparoscopic ACE and compared the outcome to 20 consecutive conventional open ACE procedures. Outcome measures included operative time, perioperative pain control, length of hospital stay, channel leakage, stenosis and herniation. RESULTS: There was no significant difference in operative time between the laparoscopic and conventional groups. The laparoscopic approach was associated with decreased postoperative pain and hospital stay. Difference in complication rates for leakage, stenosis and herniation was insignificant. CONCLUSIONS: Laparoscopic ACE, performed either completely intracorporeally or with laparoscopic assistance as described, provides another option in the surgical armamentarium to create an antegrade continence enema with decreased postoperative morbidity.

Adolescent↗
PubMed2004

Transperitoneal laparoscopic pyelolithotomy after failed percutaneous access in the pediatric patient.

PURPOSE: We present our experience with transperitoneal laparoscopic pyelolithotomy in pediatric patients in whom percutaneous renal access failed and the stone burden warranted open intervention. MATERIAL AND METHODS: A transperitoneal laparoscopic approach was used for pyelolithotomy in 8 patients 3 months to 10 years old (mean age 4 years). Percutaneous access failed secondary to a nondilated system and/or an occluding lower pole calculus. Inclusion criteria were failed percutaneous access secondary to a nondilated system and/or stone occlusion of the lower pole system and failed shock wave lithotripsy or a stone burden of greater than 2.5 cm2. A posterior pelviotomy was made. Stones in the renal pelvis were removed with rigid graspers under direct laparoscopic vision. A flexible cystoscope was introduced through a port if caliceal stones were present. The renal pelvis was reconstructed. A watertight anastomosis was verified. RESULTS: Average operative time was 1.6 hours (range 0.8 to 2.3). Mean hospital stay was 2.15 days (range 2 to 3). A range of 1 to 3 stones (median of 1) were removed and the mean stone burden was 2.9 cm2. No intraoperative complications were noted. Stone analysis revealed 3 patients with calcium oxalate stones, 1 with a calcium phosphate stone and 4 with cysteine stones. There was 1 patient with stone recurrence at a mean followup of 12 months (range 3 to 20). Thus, the overall long-term stone-free rate was 87.5%. CONCLUSIONS: Transperitoneal laparoscopic pyelolithotomy is feasible when percutaneous access fails and open pyelolithotomy is considered due to a large stone burden.

Child↗
PubMed2004

The ureter as a pedicle for construction of a ureteral urethra: the double tunnel.

PURPOSE: Clean intermittent self-catheterization has been shown to be an effective method for the prevention of upper tract urinary disease in patients who are unable to void efficiently. When the urethra is not available for catheterization surgeons can construct a catheterizable channel from the appendix or retubularized bowel. However, for patients without an appendix and limited bowel segments we have reimplanted the ureter to prevent reflux and tunneled the distal portion of the same ureter to construct a catheterizable stoma, the "double tunnel." MATERIALS AND METHODS: We retrospectively reviewed our 10-year experience with the double tunnel ureteral pedicle. A total of 10 patients (8 girls and 2 boys) were included in this study. The left ureter was used in 7 cases and the right ureter was used in 3. Mean followup for these patients was 4.1 years, with a range of 0.5 to 8.5 years. Outcome measures included intraoperative complications, reoperation rates, postoperative complications and upper urinary tract deterioration. RESULTS: There were no intraoperative complications. Furthermore, there were no cases of stomal stenosis or strictures that required reoperation or excision of the ureteral pedicle in the followup period. In our cohort the renal function associated with the ipsilateral double tunnel ureteral pedicle remained stable or improved. All patients reported that their catheterizable stoma is still functional. CONCLUSIONS: The double tunnel ureteral pedicle provides another option in the urological armamentarium when there are minimal resources with which to construct a catheterizable stoma.

Bladder Exstrophy↗
PubMed2004

Cloacal exstrophy variants. Can blighted conjoined twinning play a role?

PURPOSE: For normal single births with evidence of first trimester twinning, vanishing twin rates of 13% to 78% have been reported. We propose that blighting of a conjoined twin can result in an infant with a variation of cloacal exstrophy. MATERIALS AND METHODS: We retrospectively reviewed the records of 26 patients with cloacal exstrophy treated from January 1989 to November 2003, all of whom had prenatal evaluations readily available to determine the presence of twinning. The criterion for establishing the prenatal diagnosis of twins was the documentation of 2 fetal heart tones on Doppler and/or 2 fetal poles on ultrasound. RESULTS: All 26 patients had prenatal care including prenatal fetal Doppler studies and followup ultrasound. Of the patients 15 had classic cloacal exstrophy (58%) with no evidence of twin gestations documented. Of the 26 cloacal exstrophy cases 11 (42%) were cloacal exstrophy variants, including 8 of the 11 (73%) with consistent findings of twin gestation on prenatal studies. All 8 patients had documented 2 fetal heart tones in the first trimester, and 4 had 2 fetal poles in 1 amniotic sac on prenatal ultrasound. Five patients had subsequent ultrasound studies showing a single fetus by the second trimester. Two patients were born conjoined with 1 of the twins lifeless at birth in both cases. CONCLUSIONS: We propose that blighted conjoined twinning may be a cause of cloacal exstrophy variant cases.

Bladder Exstrophy↗
PubMed2004

Autoaugmentation gastrocystoplasty: further studies of the sheep model.

OBJECTIVE: To report our experience with autoaugmentation gastrocystoplasty (AAGC, reported to result in an inconsistent augmentation effect in children) in a sheep model, specifically addressing issues of surgical techniques and postoperative bladder drainage that may affect the augmentation result, as many factors have been implicated in the poor outcome. MATERIALS AND METHODS: Ten 6-month-old male lambs had a suprapubic catheter placed by an open laparotomy. Intraoperative urodynamics were evaluated before and after detrusorotomy for autoaugmentation and after completing AAGC. The bladder was drained with no distension for 1 week after surgery and the urodynamic evaluation repeated on control and experimental animals 6 months after surgery. The animals were then killed and the bladders evaluated for gastric flap survival and histological changes in the native bladder and augmentation segments. The results were analysed using a one-sided Student's t-test. RESULTS: The median (range) native bladder volume at leak-point pressure was 110 (40-490) mL. Intraoperative bladder volumes after completing AAGC confirmed adequate augmentation segments in all animals. The urodynamic evaluation at 6 months after AAGC showed increases in bladder volumes in nine of 10 animals (0-1336 mL), significantly greater than the increase in volume in the control sheep (median 337.5 vs 115.3 mL; P < 0.05). The bladder compliance (volume/pressure at leak capacity) 6 months after AAGC was slightly better but not significantly higher than in controls (median 17.3 vs 10.8 mL/cmH(2)O; P > 0.05). The median (range) ratio of surviving gastric flap to native bladder circumferences was 34.5 (31-53)%. Histology showed scarring of the submucosal layer in one of 10 augmentation segments and normal urothelium in all bladders. CONCLUSION: AAGC produces reliable bladder augmentation and excellent bladder compliance in a sheep model of a non-neurogenic bladder. The gastric flap survived well and there was no bladder wall separation with simple postoperative catheter drainage.

Animals↗
PubMed2003

Induction of urothelial cell proliferation by fibroblast growth factor-7 in RAG1-deficient mice.

Fibroblast growth factor-7 (FGF-7, keratinocyte growth factor, KGF) is a 163 amino acid glycoprotein synthesized and secreted by mesenchymal cells (e.g. fibroblasts/fibrocytes) in epithelial organs, thereby functioning as a paracrine mediator of epithelial cell proliferation. In the urinary bladder, FGF-7 is transported from the lamina propria across the urothelial basement membrane to where it ultimately binds to splice variants of the FGFR2 receptor present on the basolateral surface of transitional epithelial cells. We administered 100 micrograms/ml (i.p.) recombinant FGF-7 (rFGF-7) to RAG1-deficient mice (n = 3) for 7 days and observed a striking expansion of the urinary bladder urothelium. This expansion was characterized by a layer of stratified urothelium > 20 cells thick and by positive immunostaining for the proliferation marker Ki-67. In contrast, RAG1-deficient mice (n = 3) that received only buffer injection did not exhibit detectable urothelial expansion. rFGF-7 was detected by immunoblot analyses in the serum, but not in the urine, from RAG1-deficient mice that received the recombinant protein. Mice that have a targeted disruption in the gene encoding the V(D)J recombination activation gene RAG1 have small lymphoid organs with no mature B and T lymphocytes, due to the inability of cell progenitors to perform V(D)J recombination. The biological activity of FGF-7 in RAG-1 mice indicates that immuno-dependent mechanisms are not required for the induction of urothelial cell proliferation by this epithelial cell-specific growth factor.

Animals↗
PubMed2003

Flow cytometry analysis of proliferative lesions at the gastrocystoplasty anastomosis.

PURPOSE: Proliferative epithelial metaplasia that develops in the anastomotic line after gastrocystoplasty has unknown malignant potential. Flow cytometry analysis of cell cycle profiles is used to predict the neoplastic progression of metaplastic lesions in other proliferative epithelium. We used this technique to evaluate transitional cell metaplasia in rat gastrocystoplasty specimens. MATERIALS AND METHODS: A total of 50 prepubescent female Long-Evans rats were randomly assigned to an experimental group (gastrocystoplasty) or a control group (sham operation). At 21 to 27 months (mean 24.9) after operation 12 rats per group survived to sacrifice. Metaplastic lesions were microdissected to yield a minimum of 10(4) cells for DNA flow cytometry and cell cycle analysis. Transitional cell epithelium from sham specimens and gastric epithelium from experimental animals served as controls. RESULTS: Transitional cell hyperplasia and metaplasia with cyst formation were found in the anastomotic line in all 12 augmented bladders (100%). No proliferative lesions developed in control animals. No nuclear pleomorphism or mitotic changes were identified on routine histological examination. The epithelial cell turnover rate was 10 times higher in the gastrocystoplasty junctional zone than in control bladders (mean 2.2% versus 0.1% S phase) but lower than in native stomach epithelium (mean 3.3% S phase). Of 12 experimental specimens 1 showed near diploid DNA aneuploidy. No DNA abnormalities were detected in control bladder or stomach specimens. CONCLUSIONS: In this animal model histologically benign appearing proliferative lesions that develop in the anastomotic zone after long-term gastrocystoplasty harbor cell cycle and DNA ploidy abnormalities.

Anastomosis, Surgical↗