Heterogeneity in induced heat resistance and its relation to synthesis of stress proteins in rat tumor cell clones.

Tumor cell clones isolated from a rat 13762NF mammary adenocarcinoma and its spontaneous metastases were heterogeneous in their survival responses to continuous 42 degrees heating. Clones MTLn3 and MTF7 had similar initial survival responses; they were significantly less sensitive than clone MTC. Following the first decrease in survival, different magnitudes of induced thermal resistance were observed. When ratios of the first and resistant slopes of survival curves were compared (the thermotolerance ratio), the order of induced thermal resistance was MTLn3 greater than MTF7 greater than MTC. These clones were compared for the rates of synthesis of heat stress proteins (HSP). The same four major HSP at Mr 112,000, 90,000, 70,000, and 22,000 were induced or enhanced in all 3 clones. The rates of synthesis of these HSP were analyzed through a unique system of computer-assisted video densitometry and digitization. When all 4 HSP were analyzed as a group, the rates were significantly different (p less than 0.017), and the rank order of rates of synthesis was significant with MTLn3 greater than MTF7 greater than MTC. Induction kinetics of the individual HSP were different. Individually, the HSP at Mr 112,000, 90,000, and 22,000 were synthesized at significantly different rates between clones (p less than 0.001) but the Mr 70,000 HSP was not. Absolute total protein synthesis was highest for clone MTLn3, and MTF7 was higher than MTC but only marginally. Although absolute accumulations of these HSP could not be directly compared between these clones, the higher rates of HSP synthesis in these tumor cell clones correlated with more thermal resistance. These data support the working hypothesis that one or more of these HSP have a direct role in the mechanism(s) for inducing thermal resistance in rat tumor cells, but other factors such as total protein synthesis could modify the complex bio-chemical and phenotypic pathways involved in induced HSP and thermal resistance.

Heterogeneity in induced thermal resistance of rat tumor cell clones.

Four 13762NF rat mammary adenocarcinoma clones were examined for their survival response to heating under conditions that induced transient thermal resistance (thermotolerance). Clones MTC and MTF7 were isolated from the subcutaneous locally growing tumor, whereas clones MTLn2 and MTLn3 were derived from spontaneous lung metastases. There was heterogeneity among these clones in thermotolerance induced by either fractionated 45 degrees C or continuous 42 degrees C heating, but the order of sensitivity was not necessarily the same. The clones developed thermal resistance at different rates and to different degrees within the same time intervals. There was heterogeneity between clones isolated from within either the primary site or metastatic lesions. However, clones derived from metastatic foci did not intrinsically acquire more or less thermotolerance to fractionated 45 degrees C or continuous 42 degrees C heating than did clones from the primary tumor. Further, there was no apparent relationship between any phenotypic properties that conferred more or less thermotolerance in vitro and any phenotypic properties that conferred enhanced metastatic success of these same clones by spontaneous (subcutaneous) or experimental (intravenous) routes in vivo. These tumor clones also differ in their karyotype, metastatic potential, cell surface features, sensitivity to x-irradiation and drugs, and ability to repair sublethal radiation damage. These results provide further credence to the concept that inherent heterogeneity within tumors may be as important in therapeutic success as other known modifiers of outcome such as site and treatment heterogeneity.

Use of Interceed Absorbable Adhesion Barrier for vaginoplasty.

Vaginal agenesis is a rare condition that can be treated successfully with a variety of nonoperative as well as surgical procedures. The difference between most of the surgical techniques lies in the material used to line the newly created canal. Skin grafts, peritoneum, and amnion have all been reported for this purpose. In the present study, four women with vaginal agenesis underwent surgical construction of an artificial vagina using Interceed Absorbable Adhesion Barrier to cover an inflatable stent placed within the neovagina. There were no intraoperative or postoperative complications, and epithelialization of the neovagina was complete by 3-6 months. All four subjects were satisfied with the results of the surgery and none of the women reported difficulty complying with postoperative care. This modification of the Abbe-McIndoe technique does not require a separate operative procedure to harvest a lining for the neovagina. The use of Interceed may reduce the cost, operative time, and morbidity associated with other vaginoplasty techniques.

Tension-free vaginal tape: outcomes among women with primary versus recurrent stress urinary incontinence.

OBJECTIVE: To evaluate the outcomes of tension-free vaginal tape in the treatment of primary versus recurrent genuine stress urinary incontinence. METHODS: A retrospective, multicenter study of 245 consecutive women who were treated with tension-free vaginal tape for genuine stress urinary incontinence (157 for primary and 88 for recurrent genuine stress urinary incontinence) over a 27-month period was performed. Concurrent surgical repairs were performed as required. Subjective and objective outcome data were assessed from routine postoperative visits. Office and hospital records were reviewed to determine patient characteristics, intraoperative findings, and surgical outcomes. RESULTS: Women with recurrent genuine stress urinary incontinence were older (mean age 64.6 versus 59.4 years, P =.004) than those with primary incontinence; they were less likely to have an intact uterus (22.7% versus 66.9%, P <.001), and were more likely to have intrinsic sphincter deficiency (70.5% versus 47.1%, P <.001). The mean duration of follow-up was 38 (+/-16) weeks. Cure rates among patients with recurrent versus primary genuine stress urinary incontinence were similar (85% and 87%, respectively, P =.23). Complication rates were similarly low in both groups (4.5% versus 7.6% for recurrent and primary genuine stress urinary incontinence, respectively, P =.35). Postoperative voiding dysfunction occurred at low rates in both groups. CONCLUSION: Tension-free vaginal tape is a highly effective treatment among patients with recurrent stress incontinence, with outcomes comparable with those among patients with primary incontinence.

Release of tension-free vaginal tape for the treatment of refractory postoperative voiding dysfunction.

OBJECTIVE: To report our experience with surgical release of tension-free vaginal tape (TVT) for the treatment of persistent post-TVT voiding dysfunction. METHODS: A total of 1175 women underwent TVT placement for treatment of genuine stress urinary incontinence and/or intrinsic sphincter deficiency over a 2-year period. Additional procedures and vaginal repairs were performed as indicated. Among these patients, 23 women (1.9%) had persistent voiding dysfunction (urinary retention, incomplete bladder emptying, or severe urgency or urge incontinence) refractory to conservative management. This cohort underwent a simple vaginal TVT release procedure, performed on an outpatient basis. Preoperative characteristics, intraoperative, and postoperative details were assessed by review of operative notes, medical records, and office notes. Continence status was assessed using subjective and objective information. RESULTS: Mean age was 67 years (range 46-86 years), and the mean interval between TVT placement and release was 17.3 weeks (range 2-69 weeks; median 8.6 weeks). For the release procedure, there were no intraoperative complications, and all patients were discharged on the day of surgery. All cases of impaired emptying were completely resolved, and all cases of irritative symptoms were resolved (30%) or improved (70%) by 6 weeks. Fourteen (61%) patients remained continent 6 weeks after the release procedure, six (26%) were improved over baseline, and three patients (13%) had recurrence of stress incontinence. CONCLUSION: Refractory voiding dysfunction after TVT is a relatively uncommon situation and can be successfully managed with a simple midline release procedure. In most cases, the release procedure does not compromise overall improvement in symptoms of stress incontinence.

The effect of posterior wall support defects on urodynamic indices in stress urinary incontinence.

OBJECTIVE: To determine if posterior vaginal wall defects affect urodynamic indices and mask stress urinary incontinence. METHODS: Ninety women with grade 0, 1, 2, or 3 posterior wall defects were evaluated prospectively by complete urodynamics to assess their urinary complaints. None had severe anterior or apical support defects. Urethral pressure profilometry and cough stress test were performed with the posterior wall in the unretracted position and then with the posterior wall retracted using a split speculum. Analysis of covariance was used to compare adjusted mean differences in maximum urethral closure pressure, functional urethral length, and units of leakage volume during the cough stress test in the unretracted and retracted positions among the posterior wall grade groups. RESULTS: In women with grade 3 posterior wall defects, there were significant changes from the unretracted to the retracted position in maximum urethral closure pressure of -7.0 cm H20, (99% confidence interval [CI] -12.4, -1.6), functional urethral length of -0.3 cm (99% CI -0.5, -0.1), and leak volume units of +0.7 (99% CI 0.4, 1.0) during the cough stress test. There were four women with grade 3 posterior wall defects who demonstrated potential stress incontinence when their posterior wall was retracted. CONCLUSION: A grade 3 posterior wall defect may artificially raise maximum urethral closure pressure, increase functional urethral length, and mask urinary stress incontinence during a cough stress test. Women with grade 3 posterior wall defects should be tested with the posterior wall retracted during urodynamic evaluation.

Patient satisfaction with laparoscopic Burch retropubic urethropexy.

OBJECTIVE: To assess six-month and three- to four-year patient-oriented outcomes after laparoscopic Burch retropubic urethropexy. STUDY DESIGN: Twenty-two women with urodynamically proven genuine stress incontinence with urethral hypermobility underwent laparoscopic Burch retropubic urethropexy. Preoperatively, all 22 women completed a questionnaire concerning their incontinence. Postoperative measures of symptoms of incontinence, impact of incontinence on daily activities and patient satisfaction were assessed at six months and three to four years postoperatively. In those women who were followed, the questionnaire data at the three-time points (preoperative, six months and three to four years) were compared. RESULTS: Thirteen women (59%) completed postoperative questionnaires at six months and three to four years. When compared to preoperative data, there was a significant improvement in symptoms of stress incontinence at six months (P = .0005) and at three to four years (P = .002). There was also a significant reduction in limitations on daily activities at six months (P = .0005) and at three to four years (P = .0005) as compared to preoperative data. Twelve of the 13 women considered their surgery successful at six months and at three to four years. CONCLUSION: After laparoscopic Burch retropubic urethropexy, there was a significant improvement in patient-oriented outcomes, including complaints of incontinence and functional status.

Some determinants of cellular adhesiveness in an embryonic cell line from Drosophila melanogaster.

We have examined, under a number of conditions, the aggregation behavior of Schneider Line 2 cells established originally from embryos of Drosophila melanogaster. The work presented in this paper further establishes appropriate conditions for the study of cellular adhesion in Drosophila cell lines; shows that the adhesive capacity of Drosophila cell line cells, under our experimental conditions, depends upon the presence of CA2+ but not Mg2+; shows that Drosophila cell line cells will not aggregate in the cold; and shows that trypsin treatment inhibits the aggregation of cell line cells, although high concentrations of calcium ions interfere with the action of trypsin.