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Biomedical subjects

C E Iselin

Publications and source records attributed to C E Iselin.

At least 19 recordsLinked to original sources

Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation.

We have examined the role of mechanical tension in myofibroblast differentiation using two in vivo rat models. In the first model, granulation tissue was subjected to an increase in mechanical tension by splinting a full-thickness wound with a plastic frame. Myofibroblast features, such as stress fiber formation, expression of ED-A fibronectin and alpha-smooth muscle actin (alpha-SMA) appeared earlier in splinted than in unsplinted wounds. Myofibroblast marker expression decreased in control wounds starting at 10 days after wounding as expected, but persisted in splinted wounds. In the second model, granuloma pouches were induced by subcutaneous croton oil injection; pouches were either left intact or released from tension by evacuation of the exudate at 14 days. The expression of myofibroblast markers was reduced after tension release in the following sequence: F-actin (2 days), alpha-SMA (3 days), and ED-A fibronectin (5 days); cell density was not affected. In both models, isometric contraction of tissue strips was measured after stimulation with smooth muscle agonists. Contractility correlated always with the level of alpha-SMA expression, being high when granulation tissue had been subjected to tension and low when it had been relaxed. Our results support the assumption that mechanical tension is crucial for myofibroblast modulation and for the maintenance of their contractile activity.

Actins↗

Hand-assisted laparoscopic bilateral nephrectomy.

Open bilateral nephrectomy in renal transplant patients may be indicated for various reasons and is associated with a significant rate of morbidity and mortality. Laparoscopic bilateral nephrectomy may favorably influence postoperative recovery but is technically difficult. This case report is the first description of hand-assisted laparoscopic bilateral nephrectomy. We believe this technique significantly shortens the operative time, increases the safety of the procedure, and assures the patient the benefits of minimal invasive surgery in terms of postoperative pain and recovery.

Female↗

Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter.

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects.

Animals↗

Combined antegrade and retrograde endoscopic approach for the management of urinary diversion-associated pathology.

BACKGROUND: Endourologic management of stones and strictures in patients with a urinary diversion is often cumbersome because of the absence of standard anatomic landmarks. We report on our technique of minimally invasive management of urinary diversion-associated pathology by means of a combined antegrade and retrograde approach. PATIENTS AND METHODS: Five patients with urinary diversion-associated pathology were treated at our institution between May 1997 and October 1998. Their problems were: an obstructing ureteral stone in a man with ureterosigmoidostomy performed for bladder extrophy; two men with a valve stricture in their hemiKock urinary diversions; an anastomotic stricture in a man with an ileal loop diversion; and a long left ureteroenteric stricture in a man with a right colon pouch diversion. After percutaneous placement of an guidewire across the area of interest, the targeted pathology was accessed via a retrograde approach using standard semirigid or flexible fiberoptic endoscopes. Postoperative follow-up with intravenous urography, differential renal scan, or both was performed at 3 to 24 months (mean 12 months). RESULTS: The combined antegrade and retrograde approach allowed successful access to pathologic areas in all patients. Holmium laser/Acucise incision of stenotic segments or ballistic fragmentation of stones was achieved in all cases without perioperative complications. None of the strictures with an initially successful outcome has recurred; however, in one patient, the procedure failed as soon as the internal stent was removed. The patient with the ureteral calculus remains stone free, and his ureterosigmoidostomy is patent without evidence of obstruction on his last imaging study, 24 months postoperatively. CONCLUSIONS: Combined antegrade and retrograde endoscopic access to the area of interest is our preferred method of approaching pathologic problems in patients with a urinary diversion. An antegrade nephrostogram provides better delineation of anatomy, while through-and-through access enables rapid and easier identification of stenotic segments that may be hidden by mucosal folds. Furthermore, this approach allows the use of larger semirigid or flexible endoscopes in conjunction with more efficient fragmentation devices, resulting in enhanced vision from better irrigation. Finally, an initial endoscopic approach may be preferred because its failure does not compromise the success of future open surgery.

Aged↗

The nitric oxide pathway in pig isolated calyceal smooth muscle.

In pig and humans, whose kidneys have a multi-calyceal collecting system, the initiation of ureteral peristalsis takes place in the renal calyces. In the pig and human ureter, recent evidence suggests that nitric oxide (NO) is an inhibitory mediator that may be involved in the regulation of peristalsis. This study was designed to assess whether the NO synthase/NO/cyclic GMP pathway modulates the motility of pig isolated calyceal smooth muscle. Immunohistochemistry revealed a moderate overall innervation of the smooth muscle layer, and no neuronal or inducible NO synthase (NOS) immunoreactivities. Endothelial NOS immunoreactivities were observed in the urothelium and vascular endothelium, and numerous cyclic GMP-immunoreactive (-IR) calyceal smooth muscle cells were found. As measured by monitoring the conversion of L-arginine to L-citrulline, Ca(2+)-dependent NOS activity was moderate. Assessment of functional effects was performed in tissue baths and showed that NO and SIN-1 decreased spontaneous and induced contractions of isolated preparations in a concentration-dependent manner. In strips exposed to NO, there was a 10-fold increase of the cyclic GMP levels compared with control preparations (P < 0.01). It is concluded that a non-neuronal NOS/NO/cyclic GMP pathway is present in pig calyces, where it may influence motility. The demonstration of cyclic GMP-IR smooth muscle cells suggests that NO acts directly on these cells. This NOS/NO/cyclic GMP pathway may be a target for drugs inhibiting peristalsis of mammalian upper urinary tract. Neurourol. Urodynam. 18:673-685, 1999.

Animals↗

Radical perineal prostatectomy: oncological outcome during a 20-year period.

PURPOSE: We examined 4 postulates: 1) radical perineal prostatectomy provides a substantial disease control benefit in men with clinically confined prostate cancer, 2) postoperative prostate specific antigen (PSA) levels are an excellent surrogate end point for defining disease control, 3) the biology of primary malignancy defines the interval to death after recurrence and 4) the interval from intervention to death from recurrence is so long that current series of alternative curative therapies have insufficient duration of observation to permit a comparison with the results of surgery. MATERIALS AND METHODS: A total of 1,242 men with a median age of 65.2 years who had stage cT1 to 2 N0M0 disease underwent radical perineal prostatectomy. The final pathology specimen was characterized in regard to disease extent, and Gleason grade and score. Patients were followed at 2 weeks, at 2 months and then at 6-month intervals for biochemical, physical and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng./ml. or greater) and cancer associated death. RESULTS: Median time to noncancer death was 19.3 years. Median cancer associated death end point was not reached by patients with organ and specimen confined disease, while it was 12.7 years for margin positive disease. At 5 years 8, 35 and 65% of the patients with organ confined, specimen confined and margin positive disease, respectively, had PSA failure. This served as an excellent surrogate end point, preceding cancer associated death by 5 to 12 years depending on the biological aggressiveness predicted by Gleason grade or score. Biologically aggressive organ confined disease that had been surgically removed was associated with a high percentage of disease-free survival. CONCLUSIONS: Our study confirms our postulates. It also provides guidelines for comparing therapies among institutions and emphasizes that enthusiasm for new treatments may be based on insufficient followup. Patient selection may severely bias outcome independent of treatment when death is used as the end point. Our study establishes the value of PSA as a surrogate end point.

Aged↗

Renal lymphoma in an azotemic patient--usefulness of magnetic resonance imaging.

An azotemic patient benefited from diagnostic magnetic resonance imaging (MRI) in the evaluation of his renal mass. This led to suspicion of lymphoma, and provided guidance for percutaneous biopsy. Chemotherapy was then initiated, and an unnecessary nephrectomy was avoided. After a year of follow-up, evolution was stable and renal function significantly improved.

Humans↗

Periurethral collagen injections for incontinence following radical prostatectomy: does the patient benefit?

Promising early results have been reported with periurethral collagen injections in the treatment of incontinence after radical prostatectomy. However, a significant proportion of patients does not benefit from this minimally invasive option. Recently, the results of longer follow-up studies have become available in some series. Investigators have also attempted to identify the prognostic factors of success. This review reports the latest advances on periurethral collagen injections in the treatment of incontinence after radical prostatectomy.

Biocompatible Materials↗

Dorsal onlay graft urethroplasty for repair of bulbar urethral stricture.

PURPOSE: We report the early outcome of dorsal full-thickness penile skin grafts in the repair of bulbar urethral stricture. MATERIALS AND METHODS: During 27 months 29 men with a mean age of 43 years (range 10 to 81) underwent dorsal onlay graft urethroplasty. Followup included retrograde urethrogram at 3 weeks, 3 months and 12 to 18 months, and thereafter when needed. Urinary flow was recorded as subjectively reported by the patients. RESULTS: The technique was used only for bulbar urethral strictures. A total of 23 patients (79%) had undergone previous direct vision urethrotomy and/or open surgery. Dorsal onlay graft urethroplasty was used alone in 12 patients (41%), and was performed with partial stricture excision and ventral strip anastomosis in 13 (45%). In another 4 patients (14%) the procedure was combined with an Orandi flap because the stricture extended significantly into the penile urethra. Penile skin grafts were used in 27 patients (93%), whereas buccal mucosa was harvested in 2. Mean graft length was 6 cm. (range 3 to 9), and width ranged between 1.5 and 3 cm. Outcome was favorable in 28 patients (97%) for a median followup of 19 months (range 10 to 37). One patient had symptomatic proximal stricture recurrence and 3 had radiographic evidence of caliber decrease of the repair but with no impact on urinary flow. CONCLUSIONS: Dorsal onlay graft urethroplasty is a versatile procedure which may be combined with stricture excision and ventral strip anastomosis or an Orandi flap. Conceptually the technique offers the advantages of spread fixation of the graft on a fixed well vascularized surface, which may improve graft neovascularization, reduce graft shrinkage and avoid sacculation. Although the early outcome is promising, dorsal onlay graft urethroplasty has yet to stand the test of time.

Adolescent↗

The significance of the open bladder neck associated with pelvic fracture urethral distraction defects.

PURPOSE: As a result of pelvic fracture urethral distraction defects, urinary continence relies predominantly on intact bladder neck function. Hence, when cystoscopy and/or cystography reveals an open bladder neck before urethroplasty, the probability of postoperative urinary incontinence may be significant. Unresolved issues are the necessity, the timing and the type of bladder neck repair. We report the outcome of various therapeutic options in patients with pelvic fracture urethral distraction defects and open bladder neck. We also attempt to identify prognostic factors of incontinence before urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed the records of 15 patients with a mean age of 30 years in whom an open bladder neck was identified before posterior urethroplasty between January 1981 and October 1997. RESULTS: Of the 15 patients 6 were continent and 8 were incontinent postoperatively. One patient underwent artificial urethral sphincter implantation simultaneously with pelvic fracture urethral distraction defect repair and was dry postoperatively without sphincter activation. Average bladder neck and prostatic urethral opening on the cystourethrogram before urethroplasty was significantly longer in incontinent (1.68 cm.) than in continent (0.9 cm.) patients. Of the 8 patients who were incontinent 6 underwent bladder neck reconstruction, 1 artificial urinary sphincter and 1 periurethral collagen implant. Five patients with bladder neck reconstruction are totally continent and 1 requires 1 pad daily. The patient who underwent collagen implant requires 2 pads daily and the patient who received an artificial urethral sphincter has minor urge leakage. CONCLUSIONS: Open bladder neck before urethroplasty may herald postoperative incontinence which may be predicted by radiographic and cystoscopic features. Evaluation of the risk of postoperative incontinence may be valuable, and eventually guide the necessity and timing of anti-incontinence surgery, although our preference remains to manage the pelvic fracture urethral distraction defects and bladder neck problem sequentially. Bladder neck reconstruction provides good postoperative continence rates and is our technique of choice.

Adolescent↗

Surgical control of clinically localized prostate carcinoma is equivalent in African-American and white males.

BACKGROUND: Few studies have compared the outcome of radical prostatectomy between African-American males (AAM) and white males, and the results of the few studies that have are conflicting. Therefore, the authors examined the impact of radical surgery on localized prostate carcinoma in both patient populations, and assessed whether stratification by pathologic extent of local disease would yield an equivalent outcome. METHODS: Prostate specific antigen (PSA) failure and carcinoma-associated death rates were assessed in 1319 patients (115 AAM and 1204 white males), 872 of whom had a pretreatment serum PSA level taken. The percent of prostate involved by tumor, tumor wet weight, and DNA ploidy status were available in 755, 522, and 638 patients, respectively. RESULTS: AAM were diagnosed at an earlier age than white males (62.8 years vs. 65.4 years; P = 0.0001). The distribution of pathologic extent of local disease was similar in both races, and AAM had a statistically higher rate of tumors with a Gleason sum of 7-10 at surgery than white males (64% vs. 46%). Race did not play a role in the outcome of patients with organ-confined or specimen-confined tumors. However, in patients with positive surgical margins, the median time to PSA failure and the median carcinoma-associated survival were less in AAM compared with white males. Tumor volume was significantly larger in AAM compared with white males. After multivariate adjustment for the pathologic extent of local disease, tumor grade at surgery, preoperative PSA, tumor volume, and age, African-American race was not a significant prognostic indicator for carcinoma-associated death and PSA failure (P = 0.17 and 0.14, respectively). CONCLUSIONS: The outcome of radical prostatectomy was similar in both racial groups, although AAM with positive surgical margins tended to fail earlier than white males, suggesting greater biologic aggressiveness of residual disease. Because local extent of disease impacts on PSA failure and survival, and because the disease appears to present earlier in AAM, the AAM population may benefit from early detection programs.

Adult↗

Treatment options, selection, and satisfaction among African American and white men with prostate carcinoma in North Carolina.

BACKGROUND: In the U.S., prostate carcinoma mortality is greatest among African Americans. In North Carolina, the state with the fourth largest population of African Americans, the prostate carcinoma mortality rate is 2.5 times greater among African Americans than among whites and is the highest reported rate for any state in the nation. To explore potential reasons for the racial differential in mortality, a study was undertaken to determine whether differences related to treatment existed between African American and white men who were diagnosed with prostate carcinoma during the period 1994-1995. METHODS: Cases were selected from 16 institutions within a region comprising 63 contiguous counties where the overall population was >20% African American. A stratified design was employed to accrue subjects into groups of even size according to race and disease stage (n = 231). A telephone survey was conducted, which assessed treatment options discussed by patients with their physicians, treatment(s) received, factors influencing treatment, satisfaction with treatments discussed and options given, and sociodemographic information. RESULTS: All measures related to treatment were consistently associated with stage at diagnosis (P < 0.001) rather than other variables measured (i.e., race, age, income, comorbidity, education, and residential status). Furthermore, most subjects reported that their physicians presented several treatment options (65%), that they were satisfied with the options presented (90%), and that the physician was the most important factor influencing their treatment decision (57%). CONCLUSIONS: These data suggest that African American and white men in North Carolina receive comparable treatment for prostate carcinoma. Therefore, efforts to reduce the racial disparity in mortality should be directed toward lessening the high incidence of later stage disease at diagnosis and exploring potential biologic differences that may increase the risk of more aggressive disease among African Americans.

Aged↗

Dorsal onlay urethroplasty for urethral stricture repair.

Full-thickness penile skin grafts have long proved to be valuable in substitution urethroplasty. However, occasional cases of poor graft take, sacculation, or shrinkage of the repairs have mitigated their success. A determining factor in the outcome of grafts is their mechanical support. Historically, ventral placement of the graft has been used, primarily because of the simplicity of access and the excellent graft bed offered by the spongy tissue. However, mechanical support in this location is suboptimal in comparison with that offered by the corpora cavernosa. Recently, dorsal placement of the graft has been proposed, allowing the skin patch to be spread fixed on the tunica albuginea of the corporal bodies overlying the stricture. Fixation of the graft may minimize its retraction and increase its neovascularization. To date, this innovation has proved to be very promising.

Graft Survival↗

Transvaginal repair of vesicovaginal fistulas after hysterectomy by vaginal cuff excision.

PURPOSE: When repairing vesicovaginal fistulas after hysterectomy there is often reluctance to excise totally the fistula tract for fear of enlarging the tissue defect. It has been suggested that consequent tension on suture lines may cause recurrence of an even larger fistula. On the other hand, a basic surgical principle is that scar tissue margins will not heal as quickly or at all compared to fresh viable margins. We reviewed whether our technique of total excision of the fistula tract and vaginal cuff scar provides an efficient cure rate. MATERIALS AND METHODS: We retrospectively analyzed the outcomes of 20 women who underwent vaginal cuff excision repairs of a vesicovaginal fistula after total hysterectomy. Women who had complex fistulas and/or prior radiation therapy were excluded from study. RESULTS: Of the 20 patients 3 (15%) sustained a bladder lesion that was repaired intraoperatively and 7 (35%) underwent 1 or more attempts at secondary repair. All fistulas were at the vaginal cuff. Mean fistula size was 0.7 cm. (11 women). All repairs were performed as soon as possible after presentation except 2 (10%) that were delayed because of the fistula appearance. The fistula tract was excised totally in all patients. All patients were cured. There were no postoperative complications and no significant or symptomatic vaginal shortening. CONCLUSIONS: Transvaginal vaginal cuff excision repair is an effective first attempt cure of vesicovaginal fistulas after hysterectomy. Excision of the fistula tract and vaginal cuff scar enables the surgeon to suture viable tissues in every layer, thereby providing conditions optimal for wound healing. This procedure obviates the need to wait for tissue readiness and to interpose a flap in the majority of patients.

Adult↗

Pubovaginal sling using cadaveric allograft fascia for the treatment of intrinsic sphincter deficiency.

PURPOSE: Pubovaginal sling is the definitive management of female stress urinary incontinence due to intrinsic sphincter deficiency. Customarily, autologous fascia has been used, although synthetic material has its proponents. Harvesting autologous fascia at surgery is associated with postoperative discomfort, and synthetic material has a history of infection and erosion. To assess whether allograft fascia is free from these drawbacks, we retrospectively compared the outcome of women undergoing pubovaginal sling using either autologous or cadaveric allograft fascia. MATERIALS AND METHODS: We reviewed our experience during the last 28 months with patients treated with the pubovaginal sling for intrinsic sphincter deficiency. All patients underwent preoperative video urodynamics. The outcome was assessed using the SEAPI scoring system. Special attention was devoted to local sling tolerance. Operative time and length of hospital stay were compared between patients with allograft and autograft pubovaginal sling. RESULTS: A total of 92 women (mean age 60 years) underwent allograft (59) or autograft (33) pubovaginal sling. Preoperative parameters, such as percent of patients who had had previous incontinence surgery, mean leak point pressure and SEAPI incontinence score, were similar in both populations. Mean followup was 11.5 months (range 1 to 28) for the overall population. The SEAPI scoring system showed that patients were markedly improved, with no significant difference between the allograft and autograft groups. Allograft and autograft pubovaginal slings were equally well tolerated, and no infection or erosion was encountered. Mean operative time and hospital stay were significantly shorter when using allograft compared to autograft fascia. CONCLUSIONS: The success rates of allograft and autograft pubovaginal sling were equally high, and no complications related to the cadaveric origin of the allograft fascia were observed. Allograft pubovaginal sling was well tolerated, and its use significantly shortened operative time and hospital stay.

Adolescent↗

Office management of female urinary incontinence.

The majority of incontinent women are manageable using office-based techniques. This article reviews the basic causes of per urethram urinary incontinence, and summarizes how to optimally evaluate them from a clinical and urodynamic standpoint in the office setting. Emphasis is made on the progress and efficiency of the wide range of ambulatory treatment options, which include behavioral treatments, pharmacotherapy, periurethral injection of bulking agents, anti-incontinence devises, and the use of absorbent products. The economy-driven trend to decrease hospital management of disease and patient interest in noninvasive techniques will continue to increase the importance of the key role played by the office urologist in the management of female urinary incontinence.

Behavior Therapy↗

The higher injury risk of abnormal kidneys in blunt renal trauma.

OBJECTIVE: To investigate the vulnerability of abnormal kidneys in blunt trauma, and to determine clinical features which enable identification of patients at risk of renal abnormality, hence modifying their management. MATERIAL AND METHODS: The medical records of 120 patients with blunt renal trauma were reviewed. Presence of pre-existing renal abnormalities, clinical symptoms, contrast study findings, associated injuries and the estimated impact velocity were recorded. RESULTS: Pre-existing renal abnormalities were found in 23 patients (19%). Patients with renal abnormalities had a lower rate of associated trauma to other abdominal organs, a lower Injury Severity Score (ISS) and their kidneys were more frequently injured by low velocity impacts. Of the patients with normal kidneys requiring surgery, hemodynamics and/or severity of the renal lesions triggered the operative indications in all cases, whereas most (57%) of the abnormal kidneys were operated because of their underlying renal pathology. CONCLUSION: Patients at risk for harbouring renal pathology are characterized by the association of monotrauma, macroscopic hematuria and low impact velocity. In this clinical setting, contrast studies should be generously indicated, since the management of abnormal kidneys unmasked by trauma is, to a large extent, dependent on the type of pathology.

Abdominal Injuries↗