Biomedical subjects

R D Jeffs

Publications and source records attributed to R D Jeffs.

At least 19 recordsLinked to original sources

PubMed1992

Recombinant human tumor necrosis factor enhances radiosensitivity and improves animal survival in murine neuroblastoma.

An analysis of the potential of recombinant human tumor necrosis factor to enhance the radiosensitivity of C1300 murine neuroblastoma was undertaken. Female A/J mice bearing C1300 murine neuroblastoma (right hindlimb) underwent the following treatments: group 1-0.25 cc normal saline intraperitoneally times 2, group 2-0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2, group 3-400 cGy. right hindlimb, group 4-800 cGy. right hindlimb, group 5-400 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2 and group 6-800 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2. All animals were followed for 21 days after treatment initiation with interval measurements of tumor volume. All single modality treatments were more effective than normal saline in reducing average tumor volumes during the study period (800 cGy. equals recombinant human tumor necrosis factor greater than 400 cGy. greater than normal saline). The addition of recombinant human tumor necrosis factor to radiotherapy moderately augmented antitumor response at radiation doses of 400 cGy. but marked enhancement was attained at radiation doses of 800 cGy. (p less than 0.02). This enhancement was achieved without increased animal morbidity or mortality. Animals receiving recombinant human tumor necrosis factor in addition to 800 cGy. demonstrated increased survival when compared with animals receiving 800 cGy. alone (p less than 0.02). Although statistical synergy was not proved, recombinant human tumor necrosis factor appears to augment significantly radiation-induced tumor regression at no toxic cost to the animal.

Animals↗

PubMed1992

The Cantwell-Ransley technique for repair of epispadias.

A total of 26 boys with bladder exstrophy (20) and epispadias (6) underwent initial urethral reconstruction between 1988 and 1991 using the Cantwell-Ransley technique. Penile reconstruction included wide mobilization of the urethral plate from the underlying corpora based on a mesentery from the ventral penoscrotal skin, corporeal lengthening by dividing the suspensory ligaments and attachments to the undersurface of the pubis, urethral and glandular tubularization, chordee correction by medial incision of the corpora with anastomosis dorsal to the urethra and penile skin coverage. All exstrophy patients had adequate phallic length, with 13 having an intact urethral plate and 13 having had prior paraexstrophy skin flap interposition. Postoperatively, repairs were intubated with silicone stents for 10 days. Two urethrocutaneous fistulas developed, 1 of which closed spontaneously. One patient had a small degree of penile skin loss that did not affect the neourethra. All patients currently have a cosmetically acceptable penis and all but 1 (previously diverted) are voiding per urethram. The neourethra in such patients allows for easier access for endoscopy and the ventral position aids in maintaining correction of the dorsal chordee. The low complication rate of this procedure coupled with the better anatomical configuration of the neourethra makes it useful for urethral and penile reconstruction in the exstrophy and epispadias patient.

Adolescent↗

PubMed1992

Late massive hematuria as a complication of conservative management of blunt renal trauma in children.

The conservative management of blunt renal trauma in children is well accepted and well documented in the medical literature. The majority of children who sustain blunt renal trauma do well with such an approach. However, the complications of conservative management are also well documented. We present 2 patients with blunt renal trauma who were treated conservatively and suffered massive life threatening hemorrhage several weeks after the initial injury. Angiography was not performed until late and in both cases it identified the cause of bleeding. Percutaneous transcatheter embolization provided immediate definitive treatment in both patients.

Adolescent↗

PubMed1991

Bladder exstrophy-epispadias complex: prostatic evaluation by transrectal ultrasonography.

Seven patients with bladder-exstrophy-epispadias complex underwent high resolution prostatic ultrasonography in order to establish the presence and appearance of their prostate gland and seminal vesicles. Six patients had been born with classic bladder exstrophy, and one patient with complete epispadias. The size of the prostate gland was in the normal range in three patients. Three patients had small glands, and in one patient no prostatic tissue could be identified. Two patients showed an unusual position or echoappearance of their glands. The seminal vesicles in five patients were relatively large, contained multiple cystic spaces, and/or extended posteriorly and inferiorly to the prostate gland proper. Our study demonstrates that the prostate gland and seminal vesicles are present in patients with bladder exstrophy. The unusual appearance, position, and size in most patients, however, suggests faulty embryologic development or changes secondary to surgery reflecting the complex nature of the condition. Likewise, the enlarged seminal vesicles may indicate impaired drainage of these structures secondary to the initial bladder closure or subsequent bladder neck reconstruction.

Adolescent↗

PubMed1991

Chemoimmunotherapy in conjunction with surgery: strategies for management of murine neuroblastoma.

The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A/J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P less than .05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P less than .02) compared with surgical controls. In addition, 30% of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14% had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.

Animals↗

PubMed1991

Pediatric testicular tumors: the Johns Hopkins experience.

Testicular neoplasms constitute 1 percent of all childhood malignancies and rank eighth in childhood cancer mortality. From 1970 to 1988, 25 testicular tumors in children eighteen years and under were seen. The majority of the patients were white (88%). Pathologic analysis of the tumors revealed that 68 percent were germinal and 32 percent were nongerminal. Staging was undertaken in all patients with serum markers, chest x-ray film, and computerized tomography scans or lymphangiography. All patients underwent radical orchiectomy, and further therapy was given dependent on tumor type and stage. The survival among this cohort was excellent, with only 3 patients succumbing to their disease. Detailed results of treatment, and approaches to avoid excess treatment morbidity are reviewed.

Adolescent↗

PubMed1991

Anterior innominate osteotomies for failure or late closure of bladder exstrophy.

The bony pelvis was analyzed in 12 patients undergoing a further operation after initial bladder closure. Of the patients 5 had undergone a prior posterior osteotomy. All patients had wide diastasis of the pubis (average 5.5 cm.). In 9 of these patients late closure or reclosure of a failed initial bladder repair was done and 3 underwent a repeat bladder neck reconstruction. In all patients a new procedure, anterior iliac osteotomy with internal or external fixation, was performed. This procedure provides increased mobility of the pubis and increased correction. It avoids turning of the patient while under anesthesia for repeat preparation and in most cases postoperative traction is not needed. There were no instances of dehiscence, nonunion or infection. Three cases of transient femoral palsy were noted. All patients had a normal gait 4 months postoperatively. The mobility obtained after anterior osteotomy allows for excellent approximation. In view of evidence that approximation of the pubis improves closure and eventual continence results, we believe that osteotomies, even when repeated, are useful in revision surgery if there is bony diastasis.

Bladder Exstrophy↗

PubMed1991

Management of the failed exstrophy closure.

In the last 5 years we have seen 15 boys and 9 girls with failure of exstrophy closure, including 20 who had classical bladder exstrophy and 4 who had cloacal exstrophy. At the time of presentation 18 patients had undergone 1 closure while 6 patients had undergone 2 prior exstrophy closures. Closure was performed for complete bladder dehiscence in 16 cases and for significant bladder prolapse in 8. None of the patients underwent any form of osteotomy at the time of initial closure and in 19 closure was done within 72 hours of birth. Two patients underwent posterior iliac osteotomy elsewhere at the time of secondary closure. All patients referred to our institution underwent either posterior iliac osteotomy (8 patients) or anterior innominate osteotomy (16 patients). Epispadias repair along with reclosure of bladder exstrophy was done in 13 boys. The upper tract remained normal in all patients. There were no instances of failure in this group of reclosures. Eight patients have undergone subsequent bladder neck reconstruction of whom 7 are dry for 4 hours and 1 remains totally incontinent. Two patients have undergone simultaneous bladder neck reconstruction and augmentation cystoplasty, and they are dry on intermittent self-catheterization. The failed exstrophy closure presents a formidable dilemma. However, a secure reclosure can be achieved with careful surgical technique, a well performed osteotomy (even if previously performed) and concomitant epispadias repair for male subjects.

Bladder Exstrophy↗

PubMed1991

Techniques to create urinary continence in the cloacal exstrophy patient.

Of 15 patients with cloacal exstrophy currently under management 11 have undergone procedures for the establishment of urinary continence. There were 8 genetic female subjects, 6 genetic male subjects raised as girls and 1 genetic male subject raised as a boy. The genetic female subjects had all undergone urethral reconstruction. In 4 patients urethral reconstruction was done with local tissues and they have subsequently undergone bladder neck reconstruction: 1 is continent and voids through the urethra, 2 are dry on intermittent catheterization and 1 is dry on intermittent catheterization after augmentation with a hindgut patch. One girl underwent a Kropp procedure along with bladder augmentation, and she is dry on intermittent catheterization, in 1 urethral reconstruction was done with an ileal nipple through which she performs intermittent catheterization and 2 await a continence procedure. The urethral reconstructions in the genetic male subjects were more difficult. Of the 6 genetic male subjects raised as girls 5 have undergone continence procedures and 1 awaits establishment of urinary continence. In only 1 patient was urethral reconstruction possible from local tissues to allow intermittent catheterization. In the other 4 the perineal urethra was closed in favor of an abdominal stoma for intermittent catheterization. Ileal plication with nipple formation of the stoma was done in 3 patients and a Benchekroun stoma was used in 1. The genetic male subject raised as a boy underwent exstrophy reclosure plus epispadias repair and subsequent bladder neck reconstruction and augmentation. Augmentation was performed in 5 patients with hindgut segments in 3 and ileum in 2. All 5 patients are currently dry on intermittent catheterization, although 1 required revision of the ileal nipple to a Benchekroun stoma. Staged reconstruction can produce acceptable urinary continence in this complex anomaly. An innovative approach is required to find the most suitable solution for each patient anatomy, bladder size and function, and mental, neurological and orthopedic status.

Bladder Exstrophy↗

PubMed1991

Failed bladder neck reconstruction: options for management.

During the last 10 years 17 patients have been seen at this institution for persistent urinary incontinence after Young-Dees-Leadbetter bladder neck reconstruction. Of these patients 16 were born with classical bladder exstrophy and 1 with complete epispadias. Six patients underwent 1, 10 underwent 2 and 1 underwent 3 prior bladder neck procedures. As salvage procedures 8 patients underwent another Young-Dees-Leadbetter procedure, 1 repeat bladder neck reconstruction and augmentation cystoplasty, 3 augmentation alone, 4 bladder augmentation with creation of a continent abdominal stoma and 1 augmentation with implantation of an artificial urinary sphincter. Of the 8 patients who underwent a repeat Young-Dees-Leadbetter procedure 7 are dry for 3 hours or more and 1 is dry for greater than 3 hours on intermittent self-catheterization. All of those who are dry for greater than 3 hours are dry at night and 1 wears pads when engaging in strenuous physical activity. Of the 9 patients who underwent augmentation cystoplasty along with other adjunctive procedures 8 are continent for greater than 3 hours on intermittent catheterization, 6 are dry at night if they perform catheterization at bedtime and 1 remains totally incontinent after removal of the artificial urinary sphincter. Thus, with persistence and creativity a child with a previously failed bladder neck reconstruction or even multiple failed repairs can be made socially continent, providing a satisfactory alternative without resorting to urinary diversion.

Adolescent↗

PubMed1991

Endoscopic injection of glutaraldehyde cross-linked bovine dermal collagen for correction of vesicoureteral reflux.

From November 1986 through May 1989, a Food and Drug Administration approved investigational study was done to assess the safety and efficacy of glutaraldehyde cross-linked bovine dermal collagen in the endoscopic treatment of vesicoureteral reflux. Over-all, 57 patients (92 ureters) were treated. The majority of ureters (68.5%) had grade II to III/V vesicoureteral reflux (international classification). One treatment was given in 61.4% of the patients, while 33.3% required 2 and 5.3% required 3 treatments. Nonduplicated/primarily refluxing ureters comprised 68.5% of the total, while 13% were duplex/primarily refluxing and 18.5% were surgical failures. The procedures were performed on an outpatient basis in all but 3 patients. Patients were evaluated by voiding cystourethrogram and renal/bladder sonography before and after treatment at 1 month and 1 year. Cure at 1 month after the last treatment was achieved in 75% of the ureters. Among the ureters cured at 1 month the cure persisted in 79% at 1 year after treatment. Cure at 1 year was achieved in 65% of all ureters evaluated, regardless of the status at 1 month. Procedure-related morbidity was minimal and there were no adverse reactions to the implant substance. Thus, glutaraldehyde cross-linked bovine dermal collagen appears to be safe and effective in the endoscopic treatment of vesicoureteral reflux.

Animals↗

PubMed1991

Use of the Benchekroun hydraulic valve as a catheterizable continence mechanism.

Problems with continence and access for catheterization with previous continent stoma techniques have led us to search for an alternate method. We report our initial experience with the Benchekroun hydraulic valve in 9 patients. Five patients underwent creation of an ileocolic bladder: for myelodysplasia in 1, after cystectomy for bladder cancer in 2 and for exstrophy in 2. Two patients underwent conversion from an uncatheterizable Indiana pouch because of exstrophy (1) and interstitial cystitis (1). Two patients underwent small bowel augmentation of a small, poorly compliant bladder with an abdominal Benchekroun stoma: 1 had exstrophy and 1 had myelodysplasia. Patient age ranged from 7 to 63 years. Two patients had de novo creation of an ileocolic bladder, whereas 7 had bladder or previous bowel conduits incorporated in the continent reservoirs. At up to 20 months of followup all patients had diurnal and nocturnal continence, and none had experienced serious long-term complications. Problems were encountered in 5 patients. One patient had a valve fistula that was surgically revised. One patient experienced transient difficulty with catheterization when the reservoir was overdistended and a false passage developed. Three patients had stomal stenosis and require periodic dilation. We believe the Benchekroun hydraulic valve to be a useful adjunct in the construction of a continent urinary reservoir. It is easy to construct, provides reliable continence and is easy to catheterize. Furthermore, it may be applied to standard ileocolic bladders either de novo or as a salvage procedure for failed efferent limbs.

Adolescent↗

PubMed1991

Childhood urolithiasis: experiences and advances.

Between June 1979 and June 1989, 54 children with urolithiasis were evaluated and treated at the Johns Hopkins Children's Center. The most common symptoms were flank or abdominal pain (58%) and gross hematuria (28%). In 46 children (86%), stones were secondary to a preexisting condition and in only 8 (14%) no apparent cause of stone formation could be found. Thirty-six patients (66%) had a solitary stone, most commonly found in the kidney. Urinary tract infections were present in 25 (47%) of the patients who had stones. Stones composed either of calcium oxalate or struvite were the most frequently recovered in these patients with infections. Twenty-one patients (39%) spontaneously passed their stones whereas 23 (43%) required either surgery or extracorporeal shock-wave lithotripsy to resolve stones. Ten (20%) showed recurrence of their urolithiasis, with follow-up examination periods ranging from 1 month to 10 years. Recent advances in the management of urolithiasis and their applicability to the pediatric population are discussed.

Adolescent↗

PubMed1990

Continent urinary reservoirs in pediatric urological practice.

During the last 3 years 20 patients (median age 8 years) have undergone construction of a continent urinary reservoir at our pediatric urology service. Of the patients 12 had failed exstrophy reconstruction, 7 had myelodysplasia with a neurogenic bladder and 1 had extensive bladder damage as a result of a previous operation. In 5 patients a continent reservoir was constructed after cystectomy performed in early childhood. Techniques of reconstruction included the Mitrofanoff procedure (4 patients), a modification of the Indiana pouch (12), a modification of the Benchekroun procedure (2), the use of the appendix in situ as a continence mechanism (2) and a modified Kropp procedure using a duplicate vagina for catheterization (1). The morbidity from these procedures was acceptable and consisted primarily of chronic diarrhea (4 patients), stone formation within the pouch (5) and the need to revise the continence mechanism (7). All but 1 patient maintained stable or improved upper tracts after diversion. Over-all, 85% of the patients experienced diurnal continence on an intermittent catheterization regimen, while 75% were dry at night. The plicated/intussuscepted ileal nipples required revision because of difficulty with catheterization (7 patients) and urinary leakage. We currently favor the use of the Benchekroun or Mitrofanoff techniques for the ease of construction and minimal requirements for revision.

Bladder Exstrophy↗

PubMed1990

Nuclear morphometry as a prognostic indicator for genitourinary rhabdomyosarcoma: a preliminary investigation.

Rhabdomyosarcoma of the urogenital tract is a malignant mesenchymal tumor seen primarily in childhood. Multimodal therapy, encompassing surgery, radiotherapy and chemotherapy, has dramatically improved the survival of patients with this disease. However, the quest for markers of tumor aggression is important to decrease the morbidity of treatment given to patients with good prognosis tumors, while at the same time intensifying treatment of tumors with poor prognosis. Using archival tumor specimens from 13 patients with genitourinary rhabdomyosarcoma, a multivariate analysis of multiple nuclear shape descriptors was done with the Hopkins Morphometry System. Three nuclear shape descriptors clearly separated patients with no evidence of disease recurrence or progression from those with recurrent disease, progressive disease or death of disease. These nuclear shape descriptors were standard error of the chain code standard deviation analysis (p = 0.010), range of the feret ellipticity distribution (p = 0.016) and standard error of the chain code range analysis (p = 0.037). With multivariate analysis these shape descriptors taken together separated patients with good and poor prognoses to a level of significance of p = 0.007. Thus, nuclear morphometric analysis may prove to be useful as an individual prognostic indicator in childhood genitourinary rhabdomyosarcoma and warrants further analysis in a much larger, blinded, controlled study.

Cell Nucleus↗

PubMed1990

Local tissue reaction to the subureteral injection of glutaraldehyde cross-linked bovine collagen in humans.

Although the technique of subureteral injection has been widely accepted as an alternative to reimplantation in the treatment of vesicoureteral reflux, the choice of the material to be used is controversial. We have used glutaraldehyde cross-linked bovine collagen to correct vesicoureteral reflux within the context of a Food and Drug Administration approved investigational study. We report the local tissue reaction to the implanted collagen in 7 patients who underwent reimplantation 3 to 19 months after failed endoscopic therapy. Glutaraldehyde cross-linked bovine collagen engendered a minimal localized inflammatory reaction without causing granuloma formation. Subsequent reimplantation was not hindered by the presence of the implant materials.

Child↗

PubMed1990

Cloacal exstrophy: radiologic findings in 13 patients.

Cloacal exstrophy is a complex, multisystem malformation that has not received much attention in the radiologic literature. The clinical histories and imaging studies of 13 cases of cloacal exstrophy proved surgically or at autopsy were reviewed. Radiologic observations were based on skeletal plain films (13), contrast-enhanced examinations of the genitourinary system (12), abdominopelvic sonograms (nine), gastrointestinal studies (seven), CT scans of the pelvis and CNS (seven), MR images of the pelvis and CNS (six), renal nuclear medicine scans (three), myelography (three), and three-dimensional scans of the pelvis (two). Genitourinary and gastrointestinal abnormalities identified in our 13 patients included bladder malformations (13), hindgut anomalies (13), undescended testes (five), malrotation (five), duplicated müllerian structures (four), and renal ectopia (four). Skeletal abnormalities included symphysis pubis diastasis (13), posterior element dysraphism (12), vertebral segmentation anomalies (12), clubfeet (six), and hip dislocations (five). CNS anomalies included meningocele (nine) and Chiari malformation (one). Immediate surgical closure of the defect with maximal bowel preservation and diverting colostomy offers optimal chances for survival. Appropriate preoperative gastrointestinal and genitourinary evaluation is essential.

Abnormalities, Multiple↗

PubMed1990

Fetal genitourinary tract anomalies: evaluation, operative correction, and follow-up.

The prenatal diagnosis of a genitourinary anomaly was made in 53 fetuses. Sonographic findings, antenatal course, and postnatal treatment and outcomes were examined. No interventional therapy was undertaken in utero, and the natural history could be examined in the 44 of 53 (83%) who did not electively terminate their pregnancies. Twenty-three of the total 53 (43%) had unilateral disease and 30 (57%) had bilateral involvement. Thirty-five of 53 (66%) survived, with 22 undergoing operative therapy postnatally. In all but one of the 35 survivors, the anomaly was isolated to the genitourinary tract, and the majority of surviving fetuses had unilateral disease. Oligohydramnios was present in only three of 35 survivors, and none had severe oligohydramnios. Nine of 53 women underwent termination of pregnancy and nine others experienced a neonatal death. All 18 of their fetuses had bilateral disease, with oligohydramnios present in 14 (78%). All five fetuses with chromosomal abnormalities were found in this group of 18. The majority of fetuses with a genitourinary anomaly will do well postnatally. Pulmonary hypoplasia, extrarenal anomalies, and chromosomal defects are frequent findings in the minority with poor outcomes. A multidisciplinary approach to management of the pregnancy with a fetal genitourinary tract anomaly is essential to optimize outcome.

Abortion, Eugenic↗