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Biomedical subjects

M A Keating

Publications and source records attributed to M A Keating.

At least 37 records · Page 2Linked to original sources

Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility.

PURPOSE: We characterized small intestinal submucosa regenerated canine bladder. MATERIALS AND METHODS: We subjected 15-month small intestinal submucosa regenerated canine bladder strips to in vitro muscle bath compliance, contractility testing and immunohistochemical staining. RESULTS: Compliance studies demonstrated no significant difference between small intestinal submucosa regenerated and control bladders, which were 30-fold more compliant than native small intestinal submucosal graft material. Contractility studies demonstrated contractile responses and innervation similar to those of normal canine bladder. Afferent nerves were demonstrated through immunohistochemical techniques. CONCLUSIONS: These characteristics further support the regenerative capacity of small intestinal submucosa and its potential use as a bladder augmentation material.

Animals↗

New chemotherapeutic agents in acute myeloid leukemia.

Only two classes of chemotherapeutic agents have shown activity in acute myeloid leukemia (AML): ara-C and topoisomerase II reactive agents. Frontline combinations of these agents produce complete response (CR) rates of 70% and long-term event free survival rates of 25%. New agents with different mechanisms of action are being explored. Nucleoside analogs such as chlorodeoxyadenosine (2-CdA) or fludarabine have shown single-agent efficacy and may be synergistic with ara-C. Combination therapy with ara-C and nucleoside analogs have shown promising results both as salvage therapy and in newly diagnosed patients. Combinations of topotecan with ara-C, VP16, and anthracyclines are being pursued, as is testing of other Topo-I inhibitors. Hypomethylating agents (5-azacytidine, decitabine) are showing activity in AML, producing CR rates of 5% to 30% as AML salvage therapy as a single agent, and 40%-60% in combinations. Decitabine may be synergistic with topo I inhibitors, biologic agents, and differentiating agents. Homoharringtonine has modest anti-AML activity, with CR rates of 10% to 30% as salvage therapy. Other classes of agents worthy of continuing investigation are platinum analogs and agents with novel mechanisms of action such as tallimustine.

Acute Disease↗

Ectopic ureters and ureteroceles in adults.

Ectopic ureters and ureteroceles are typically diagnosed in childhood and rarely present in adults. Nevertheless, ureteral ectopia should be included in the differential diagnosis of older patients who present with urinary tract infections or urinary incontinence. Detection is often delayed because of inadequate evaluation and heightened awareness is necessary on the part of treating physicians. Earlier detection and proper diagnosis serves to minimize morbidity and, in some cases, may maximize the possibility of renal preservation. Case reports serve to highlight the spectrum of these uncommon but clinically important anomalies.

Adolescent↗

Experimental assessment of small intestinal submucosa as a bladder wall substitute.

OBJECTIVES: This study determined the feasibility of promoting urinary bladder regeneration with porcine-derived small intestinal submucosa (SIS). METHODS: Twenty-two Sprague-Dawley rats underwent partial cystectomy with immediate bladder augmentation with SIS. Bladders were harvested for histologic evaluation at 2, 4, 8, 12, 24, and 48 weeks. RESULTS: Histologically at 2 weeks, there was infiltration of the graft material with viable host cells consisting of fibroblasts, macrophages, and blood vessels covered by complete mucosal urothelium comprised of transitional cells. During the next 10 weeks, collagen formation and maturation were noted, and by the end of 12 weeks, the SIS graft was comprised of a mature collagen matrix admixed with thinly scattered disorganized smooth muscle bundles and covered by normal urothelium. At 48 weeks, all three layers of the normal bladder (urothelium, smooth muscle, and serosa) were present and were grossly and microscopically indistinguishable from the normal rat urinary bladder. CONCLUSIONS: This study further supports the concept of bladder regeneration and suggests that SIS may be a viable material for bladder augmentations.

Animals↗

True hermaphroditism and normal male genitalia: an unusual presentation.

True hermaphroditism, the rarest form of intersex, is usually diagnosed during the newborn period in the course of evaluating ambiguous genitalia. As an exception, we present an unusual case of a 15-year-old boy with phenotypically normal male genitalia and bilaterally descended ovotestes, who was seen for evaluation of intermittent scrotal swelling and pain. Although rare, true hermaphroditism should be included in the differential diagnosis of apparently normal males presenting with similar complaints.

Adolescent↗

Posterior urethral valves, pressure pop-offs and bladder function.

The pop-off mechanisms that sometimes occur with posterior urethral valves have well recognized implications for renal function, such that 1 or both kidneys can be protected from the deleterious effects of elevated bladder pressures. What has not been defined is the significance, if any, of pressure pop-offs to the developing bladder and ultimate bladder function. To answer this question we reviewed the records of 63 boys with posterior urethral valves. Eight boys who were not yet toilet trained had unevaluable bladder outcomes. Of the 55 remaining boys there was 1 or more pressure pop-off in 39 (71%), including massive (grade 5) reflux, massive reflux associated with ipsilateral renal dysplasia, a patent urachus, large diverticula and urinomas. Bladder outcomes were judged as favorable or unfavorable on the basis of urodynamic parameters and/or patient clinical status. A statistically significant positive correlation was found between the presence of a pop-off and a favorable outcome. Favorable characteristics were found in 34 of 39 bladders (87%) with pressure pop-offs. In contrast, only 9 of 16 bladders (55%) without pressure vents had favorable outcomes. In addition, 5 of the remaining 7 boys without pressure vents have required augmentation cystoplasty. A direct correlation between absolute number of pop-offs and favorable bladder outcome was also noted, further emphasizing this relationship. The presence of a pressure pop-off is a favorable prognostic sign for ultimate bladder function in boys with posterior urethral valves.

Adolescent↗

Cloacal exstrophy: the neurological implications.

Congenital anomalies commonly accompany the abdominal wall defects of cloacal exstrophy with an incidence as high as 100% in some series. The urological literature cites an incidence of vertebral and/or spinal cord anomalies in 75% of cases. We reviewed the records of the 17 patients with cloacal exstrophy treated at our institution since 1978. Abnormalities of the vertebral column or spinal cord were identified in 16 patients, including 11 of 12 (92%) fully evaluated by myelography, computerized tomography or magnetic resonance imaging of the lumbosacral spinal cord. Nine patients had a lipomeningocele and 4 had a lipomyelocystocele. Spinal exploration, repair and cord untethering were done in 11 patients of whom 2 subsequently underwent reoperation for re-tethering the cord. A total of 15 patients is ambulatory although 5 require lower extremity braces. The incidence of spinal cord or vertebral anomalies in our patients with cloacal exstrophy approaches 100%, which is higher than commonly cited in the urological literature. We recommend magnetic resonance imaging of the spinal cord as part of the initial evaluation of newborns with cloacal exstrophy. Lifelong attention to the risk of spinal cord tethering can optimize neurological outcome in affected individuals.

Abnormalities, Multiple↗

Stomach in combination with other intestinal segments in pediatric lower urinary tract reconstruction.

PURPOSE: We report the results of combining gastric and ileal segments in a small group of predominantly pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed the records of 6 children and 1 adult who underwent lower urinary tract reconstruction using stomach and ileum, including 3 simultaneous and 4 staged procedures. Followup was 13 to 59 months. RESULTS: No patient had deterioration of renal function due to impaired upper tract drainage. One patient had an episode of hyponatremia during a gastrointestinal illness. The adult has the hematuria-dysuria syndrome and receives omeprazole. No ulceration developed in the 6 evaluable patients. CONCLUSIONS: The combined use of stomach and ileum has been effective in this small group of challenging patients. Long-term followup is mandatory.

Adolescent↗

The flip-flap technique to lengthen the urethra (Salle procedure) for treatment of neurogenic urinary incontinence.

We report the clinical results of a urethral lengthening procedure for neurogenic urinary incontinence. The urethra is lengthened by using a full thickness anterior bladder wall flap that is based at the urethra. This flap is approximated to a longitudinal strip of the trigonal mucosa and musculature. This neourethra is covered by urothelium creating a tunneled urethra, which creates a compressible flap valve mechanism that occludes with bladder filling. The ureters are reimplanted superior to the repair. Technical feasibility was first documented in the dog. Four myelomeningocele children with low urethral resistance and urinary incontinence refractory to medical management have undergone this procedure since July 1992. The 3 patients who have been followed for longer than 1 year are described. Two patients require concomitant bladder augmentation. Comparison of preoperative and postoperative urodynamics revealed increased urethral resistance. All 3 patients are clinically improved and dry on intermittent catheterization during the day. The patient without bladder augmentation has occasional nocturnal wetting. Since the posterior urethra and bladder wall remain intact without suture lines there have been no problems with catheterization. The upper tracts remain normal. We believe that this procedure is a helpful addition to the care of children with neuropathic incontinence. The technical aspects and results of this procedure are discussed in detail.

Child↗

Urologic manifestations of Goldenhar syndrome.

OBJECTIVE: Goldenhar syndrome (oculoauriculovertebral dysplasia) is associated with anomalies in multiple organ systems. Renal abnormalities have also been reported with the complex, but the incidence of associated genitourinary malformations has not been defined. METHOD: We have reviewed our experience with 28 children with Goldenhar syndrome evaluated during the past twelve years. Twenty children underwent imaging evaluation of the urinary tract and 14 (70% of those imaged) children had urinary tract anomalies. RESULTS: The majority of anomalies presented as an incidental finding on a screening ultrasound (8 patients) or during cardiac catheterization (2 patients). Two children presented with urinary tract infection, 1 child presented with renal failure, and another was diagnosed antenatally. The genitourinary anomalies included the following: ectopic and/or fused kidneys (8 patients), renal agenesis (7), vesicoureteral reflux (5), ureteropelvic junction obstruction (2), ureteral duplication (2), and multicystic kidney (1 patient). Four children have undergone surgical intervention. CONCLUSION: Our experience in children with Goldenhar syndrome suggests that the incidence of genitourinary anomalies is higher than previously reported. A screening ultrasound in the neonatal period allows for early intervention in those children with significant urologic abnormalities.

Abnormalities, Multiple↗

Bladder outlet reconstruction: fate of the silicone sheath.

The placement of a 1.5 cm. wide silicone sheath around a newly constructed urethra/bladder neck to ensure maintenance of repair length and to facilitate future placement of a sphincter cuff was reported by our institution in 1985. We present our long-term followup and new recommendations for use of the silicone sheath. A total of 15 silicone sheaths was placed between March 1981 and July 1984. Of the sheaths 14 were placed at the time of urinary reconstruction around the Young-Dees-Leadbetter bladder neck repair and 1 was placed after erosion of an artificial urinary sphincter cuff. Of the 15 sheaths 10 have eroded into the urethra and 4 sheaths remain in situ. Another sheath was replaced 2 years after its original insertion with an artificial urinary sphincter cuff. Mean time to erosion was 48.2 months, with a range of 2 to 108 months. Long-term followup of 10 patients revealed that 4 ultimately required ligation of the bladder neck and construction of continent stoma after erosion, 1 is dry after placement of a bulbar artificial urinary sphincter, 2 remain dry after removal of the eroded sheath alone, 2 required bladder neck revision to achieve continence after erosion and the most recent patient remains diverted with a suprapubic tube. All 4 patients with sheaths still remaining are dry without evidence of erosion (mean duration 116 months). These long-term results using a silicone wrap around a newly constructed bladder neck reveal an unacceptably high rate of erosion. Therefore, we no longer recommend or support the use of the silicone sheath in the manner we have described for bladder neck reconstruction.

Adolescent↗

Seromuscular trough modification in construction of continent urinary stomas.

The creation of an effective flap-valve continent stoma requires use of supple, catheterizable conduit that is implanted in a submucosal bed having adequate backing. In some patients the backing that has been routinely used, colonic teniae or bladder detrusor for instance, is deficient or unavailable. As an alternative, the seromuscular layers of the recipient urinary reservoir can be simply reconfigured to provide the support required of a continent stoma. The technique has been effective in 4 patients and offers additional flexibility with challenging cases of continent urinary reconstruction.

Adolescent↗

Anatomical, morphological and volumetric analysis: a review of 759 cases of testicular maldescent.

Undescended testis is the most frequent disorder of male sexual differentiation affecting 0.8% of all boys by age 1 year. Anatomical and descriptive features of undescended testis lack standardization, and often do not reflect intraoperative findings. We review a large cohort of patients treated for undescended testis and analyze anatomical, morphological and volumetric findings at orchiopexy. Of 759 patients 1 month to 9 years old entered into the study between 1985 and 1990 at our hospital 55% underwent surgery between ages 8 months and 4 years, 15.5% had bilateral undescended testis and 27.6% had a nonpalpable gonad. Preoperative physical findings correlated poorly with intraoperative observation with respect to testicular position. An ectopic gonad was diagnosed in 15% of the patients, most of whom had a patent processus vaginalis. Gubernacular attachment was in the scrotum in only a third of all cases studied. Undescended testes were softer and smaller than the contralateral gonad in the majority of cases. To our knowledge ours is the first study to correlate preoperative and intraoperative findings in cases of undescended testis. New anatomical as well as morphological and volumetric data are provided.

Age Factors↗

A surgical approach to reoperative orchiopexy.

While techniques for initial orchiopexy are well known, descriptions of a surgical approach to the more difficult reoperative case are scarce. We describe 25 patients undergoing reoperative orchiopexy following prior herniorrhaphy, hydrocelectomy or attempted orchiopexy. A technique of en bloc spermatic cord mobilization from an inferior approach is detailed. This approach is designed to minimize the potential for spermatic cord injury during reoperation, and has proved to be safe and reliable.

Child↗

Appendicovesicostomy: a useful adjunct to continent reconstruction of the bladder.

Appendicovesicostomy is a useful adjunct to continent reconstruction of the bladder. During the last 3 years we have used this procedure in 14 children with difficult incontinence due to spina bifida (7), exstrophy/epispadias (5), imperforate anus (1) and urethral agenesis (1). In 4 patients in whom previous operations had failed to achieve continence the bladder neck was closed. In the remaining 10 children, all of whom had difficulty or discomfort catheterizing the native urethra, the bladder neck/urethra was preserved or reconstructed to serve as a vent for elevated bladder pressures. Continence was achieved in all 14 children with no complications related to the appendix. All children in whom the bladder neck/urethra was salvaged preferentially empty via the appendix and remain dry, except when the bladder is overly full.

Adolescent↗

Managing apparent ureteropelvic junction obstruction in the newborn.

A total of 97 newborns with apparent ureteropelvic junction obstruction was evaluated from mid 1984 to 1989. Evaluation and management are described. Of these patients 39 with an affected kidney showing good initial differential function (greater than 35%) by diethylenetriaminepentaacetic acid scan and 2 showing diminished function (less than 35%) were followed nonoperatively. Six patients (15%) eventually required pyeloplasty for diminishing function (4), urinary tract infections (1) or symptoms of colic (1). The 4 patients with diminishing function improved after pyeloplasty to at least the initial level. A total of 12 patients with good initial function (greater than 35%) of the affected kidney underwent early pyeloplasty (within 6 weeks of diagnosis). They were compared to the similar group of patients managed nonoperatively and followed by sequential renal scans. Eventual changes in percentage differential function in the nonoperative and early surgery groups were +2.8% and +4.1%, respectively. Changes in extraction factor were +0.8% (nonoperative group) and +0.9% (surgery group). No statistically significant difference was found. In the kidney with apparent ureteropelvic junction obstruction and good function, an initial nonoperative approach with sequential renal scan followup and pyeloplasty as needed appears to be reasonable and has resulted in no permanent loss of function.

Follow-Up Studies↗