Search PubMed⌕ Search

Biomedical subjects

J P Connor

Publications and source records attributed to J P Connor.

At least 37 records · Page 2Linked to original sources
PubMed1996

p53 gene mutation analysis and antisense-mediated growth inhibition of human ovarian carcinoma cell lines.

Targeting dysfunctional gene expression in the cancer cell with gene-specific therapeutics requires knowledge of the structure and expression of the designated gene. Because of the prevalence of p53 dysfunction in epithelial ovarian carcinoma, modulation of the expression of this tumor suppressor gene is an attractive target for gene therapy. We sequenced the p53 gene and analyzed its expression in 10 ovarian cancer cell lines. Only five cell line mutations were encountered, three associated with a loss of heterozygosity. Thus, neither p53 mutation nor allelic loss is required for ovarian carcinogenesis or propagation of ovarian cancer cell lines in vitro. SSCP screening, but not immunohistochemical staining, correlated with results of direct genomic sequencing. All p53 immunohistochemical-negative cell lines differed from that reported by another laboratory, underscoring the importance of the knowledge of target gene expression in a given cell line in a given laboratory. We designed pilot studies of antisense oligodeoxynucleotides directed against the p53 gene based on our sequence data. Differential growth inhibition of the A2780-CP-20 cell line (mutant p53 protein), but not of the OVCAR-3 cell line (wild-type p53 protein) confirmed the potential usefulness of this strategy.

Base Sequence↗
PubMed1996

Obesity and prognosis in endometrial cancer.

OBJECTIVE: We tested the null hypothesis that morbid obesity as measured by the Quetelet index has no influence on survival in endometrial cancer. STUDY DESIGN: A retrospective study of 492 women with endometrial carcinoma was performed. Age, height, weight, Quetelet index, stage, cell type, grade, node status, peritoneal cytologic findings, and depth of myometrial invasion were analyzed for influence on survival. RESULTS: Mean Quetelet index was 34 (range 16 to 89). Quetelet index was < 30 in 45% of patients, 30 to 40 in 33%, and > 40 in 22%. Five percent of those with a Quetelet index > 40 had positive nodes, but 64% of patients with a Quetelet index > 40 did not have lymph node sampling done. Lack of sampling of lymph nodes in the entire group had no adverse effect on survival. In a proportional hazards regression model for time from diagnosis to death from disease, grade, node status, myometrial invasion, and stage had highly significant effects. When Quetelet index was analyzed as a continuous variable, as Quetelet index increased, time to recurrence was significantly increased (p = 0.0136), and significance was approached for survival (p = 0.0645). Quetelet index was strongly related to grade (p = 0.013), depth of myometrial invasion (p = 0.031), negative cytologic findings (p = 0.004), and stage (p = 0.011) with obese patients having better differentiated, less invasive tumors of lower stage with negative washings. CONCLUSIONS: Morbid obesity positively affects survival in endometrial carcinoma. This effect is accounted for by the association of obesity with less aggressive disease. Morbid obesity is not associated with increased death from other causes. Lack of sampling of negative lymph nodes does not adversely affect survival.

Adult↗
PubMed1996

Extravesical ureteral reimplantation: results in 128 patients.

PURPOSE: We evaluated the results of extravesical ureteral reimplantation in children. MATERIALS AND METHODS: We reviewed the records of 128 children (174 ureters) who underwent ureteral reimplantation via extravesical techniques. Primary vesicoureteral reflux was the most common diagnosis (73 patients). RESULTS: The extravesical technique produced a successful result in all patients (no reflux or obstruction). The 2 complications included postoperative urosepsis and transient urinary retention. CONCLUSIONS: Extravesical ureteral reimplantation is a reliable procedure with predictable results comparable to those of more traditional intravesical techniques.

Adolescent↗
PubMed1996

Hypospadias repair by laser tissue soldering: intraoperative results and follow-up in 30 children.

OBJECTIVES: We examined the use of laser tissue soldering (LTS) as an adjunct to suturing of, as well as a primary means of, tissue closure in urethral reconstruction. METHODS: Since June 1994, 26 boys ranging in age from 3 months to 14 years (mean 3.0 years) underwent hypospadias repair using LTS techniques. The classification of hypospadias was subcoronal in 13, midpenile in 5, penoscrotal in 7, and scrotal in 1. Laser tissue soldering was used in an additional 4 patients: tunica vaginalis patch graft corporoplasty in 2 (scrotal hypospadias), epispadias fistulae in 1, and urethral diverticulum in 1. Of these cases, 3 hypospadias repairs were completely sutureless. An intraoperative comparision was made between suturing and LTS with respect to operative time and degree of difficulty in performing LTS. Postoperatively, patients were examined to determine complications, including stricture, fistula, or impaired wound healing. An unselected group of 25 consecutive boys undergoing hypospadias repair between 1991 and 1992 served as a historical control group. RESULTS: No intraoperative complications resulted from laser activation. In 5 of the 30 procedures (16.6%), suture disruption was noted to occur, with a higher incidence seen with finer, dyed suture material. For hypospadias repair, the average time to suture was 6.7 min/cm (n = 23), whereas it was 3.1 min/cm for adjunctive LTS (n = 23) and 1.4 min/cm for sutureless urethroplasty (n = 3). Follow-up ranged from 3 to 22 months (average 9.6). Four fistulae were noted (1 onlay, 2 skin tube grafts, 1 Thiersch tube) each following penoscrotal or scrotal hypospadias repair; a fifth fistula developed following a traumatic catheterization in a sutureless repair. The overall complication rate in the LTS group was 19% (5 of 26) versus 24% (6 of 25) for controls, whereas that for the distal forms of hypospadias was 11% (2 of 18) and 13.6% (3 of 22), respectively. CONCLUSIONS: Tissue soldering with laser and chromophore-doped solder is feasible, safe, and easy to perform. Laser tissue soldering may be an alternative to standard microsuture technique for hypospadias repair.

Adolescent↗
PubMed1996

Priapism associated with sickle cell hemoglobinopathy in children: long-term effects on potency.

PURPOSE: Children with sickle cell priapism have traditionally been treated conservatively with surgery done as a last resort. Only sparse subjective data are available on the long-term assessment of potency in these patients. MATERIALS AND METHODS: We retrospectively reviewed the charts of all pediatric patients with sickle cell priapism who presented to Children's Hospital of Michigan between 1972 and 1992, and subsequently assessed erectile capabilities subjectively by questionnaire and objectively by RigiScan. RESULTS: Of the 15 patients interviewed 5 had undergone shunt procedures. The return of potency tended to vary inversely with patient age at onset and duration of priapism. CONCLUSIONS: Shunts performed within 48 hours, especially in postpubertal children, seemed more likely to preserve potency.

Adolescent↗
PubMed1995

Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer.

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.

Antineoplastic Agents↗
PubMed1995

Comparison of a novel redox dye cell growth assay to the ATP bioluminescence assay.

Antisense oligodeoxynucleotides (ASOs) are being studied with increasing frequency to determine their potential role as anticancer drugs. The overwhelming majority of this research continues to be done in vitro. Reliable and accurate determination of cell proliferation and/or inhibition, therefore, is essential for the production of meaningful results. The Alamar Blue assay, a colorimetric/fluorometric redox dye assay, was recently marketed by Alamar Biosciences (Sacramento, CA). In order to determine a potential role for this assay in ASO research, it was extensively tested on ovarian cancer cells in culture under a variety of conditions including uninhibited cell growth, cell kill with cytotoxic chemotherapeutic agents, and growth inhibition with ASOs. Results were compared directly with the ATP bioluminescence assay. We conclude that the Alamar Blue assay correlates poorly with the ATP assay, and it should be used only as a rapid preliminary screening assay. The ATP bioluminescence assay should continue to be considered as the standard in this setting.

Adenosine Triphosphate↗
PubMed1995

Intraoperative autologous blood collection and autotransfusion in the surgical management of early cancers of the uterine cervix.

OBJECTIVES: To evaluate intraoperative autologous blood collection with autotransfusion (Cell Saver) with respect to patient acceptance, risk of tumor cell co-transfusion, and risk of recurrence in patients undergoing radical hysterectomy for cervical cancer. METHODS: All patients explored for radical hysterectomy between August 1991 and July 1994 were offered the use of intraoperative autotransfusion. Clinical-pathologic and transfusion-related characteristics were compared for a group of historic controls surgically treated for similar disease. The risk of tumor cell co-transfusion was assessed intraoperatively with peritoneal cytology before blood collection, and postoperatively with Cell Saver blood cytology. RESULTS: Ninety-eight patients were offered enrollment; four declined Cell Saver use, and 71 were acceptable for analysis. Thirty-one women (mean estimated blood loss 1338 mL) were reinfused with their own blood collected in the Cell Saver, whereas 40 patients (mean estimated blood loss 631 mL) were not autotransfused. There was no significant difference in preoperative hemoglobin concentration between groups. Cell Saver use significantly reduced the need for homologous transfusions, intraoperatively (P < .001) and postoperatively (P = .02). Historic controls (mean operative blood loss 1743 mL) were nearly four times more likely to have been transfused and three times more likely to have been transfused postoperatively than was the auto-transfused Cell Saver group. The mean hemoglobin concentration at discharge was lower in the autotransfused group, 9.3 g/dL, than in the historic controls, 10.8 g/dL. Nontransfused Cell Saver blood and all peritoneal cytologies were negative for tumor cells. Three pelvic recurrences, but no disseminated disease, have been noted over a mean follow-up of 24 months: one in the autotransfused group and two in the group in which the collected blood was discarded. CONCLUSION: Cell Saver use is well accepted by patients, decreases the need for homologous transfusions, and does not appear to co-transfuse tumor cells.

Adult↗
PubMed1995

Laser tissue soldering in urinary tract reconstruction: first human experience.

OBJECTIVES: Laser tissue soldering (LTS) in the urinary tract provides an immediate leak-free seal and may avoid complications seen with conventional repair (such as fistula and stricture). We have begun a Phase I clinical trial investigating the use of LTS in performing urologic reconstructive surgery. METHODS: Ten patients (aged 3 months to 38 years) underwent urologic reconstruction using LTS with a protein solder composed of human albumin (42%) and indocyanine green dye. In each case standard microsuture repair preceded laser-soldered suture line reinforcement. Anastomotic closure time and immediate leak pressure were measured. Postoperatively, all patients were evaluated for evidence of complications, including stricture, fistula formation, or impaired healing. RESULTS: Using LTS as an adjunct to suturing added an average of 7.9 +/- 3.0 minutes (28%) to the overall mean anastomotic time of 28.3 +/- 9.4 minutes. Intraoperative leak pressure measurements for laser-soldered anastomoses (> or = 94.2 +/- 24.2 mm Hg) were significantly higher (P < 0.001) than primarily sutured anastomoses (20 +/- 2.9 mm Hg). Two instances of suture disruption (20%) occurred during laser activation, neither of which were repaired with sutures. Average follow-up for all patients was 7.1 + - 2.2 months. There were no intraoperative or postoperative complications, including the 2 patients with suture disruption. CONCLUSIONS: These initial clinical results indicate that LTS is safe, easy to perform, and, contrary to conventional suturing, provides an immediate leak-free closure. Follow-up in these and other patients, as well as those undergoing sutureless and stent-free procedures, will determine whether our method of LTS benefits patients undergoing urologic reconstruction.

Anastomosis, Surgical↗
PubMed1995

Laser welding versus suturing in tunica vaginalis and venous patch graft corporoplasty.

Congenital penile curvature may result from corporeal disproportion in nearly 40% of cases, while in adults scarring of the corporeal bodies or periurethral fibrosis accounts for the majority of cases. Some surgeons advocate lengthening the fibrosed corporeal bodies by excising tunica albuginea and grafting such defects to straighten the penis. Tunica vaginalis, dermis, dorsal vein and lyophilized dura have been used for this purpose. Traditionally, these graft biomaterials have been sutured to the tunica albuginea. We assessed the feasibility, short-term safety and efficacy of diode laser tissue welding using albumin based solder and indocyanine green dye to perform patch graft corporoplasty in the dog. Ten animals were subjected to bilateral transverse excision of 1 x 2 cm. sections of tunica albuginea. Corporoplasty was performed using grafts composed of saphenous vein (5) or tunica vaginalis (5). Microsurgical repair with 7-zero polydioxanone suture (10) was compared to contralateral laser welded repair (10) by recording operative time, initial and short-term bursting pressures (mean plus or minus standard deviation) and histological analysis. Operative time on the laser side (9.8 +/- 2.3 minutes) was significantly shorter (p < 0.05) than on the suture side (17.1 +/- 5.1 minutes). Leak pressures, initially (laser 105.7 +/- 23.8 mm. Hg versus suture 35.3 +/- 8.0 mm. Hg), at 3 to 5 days (greater than 333.3 +/- 62.4 mm. Hg versus 136.6 +/- 39.4 mm. Hg) and at 7 to 10 days (greater than 397.8 +/- 39.8 mm. Hg versus 191.5 +/- 46.4 mm. Hg) were higher (p < 0.05) in the laser side compared to controls. Graft failure (necrosis) occurred in 3 repairs (2 laser on day 4 and 1 suture on day 10). Viable tissue with minimal differences in foreign body reaction between groups was observed in the remaining grafts. We conclude that laser welded patch graft corporoplasty using tunica vaginalis or vein is easy to perform, and provides excellent initial and short-term leak pressures. The use of laser welding in conjunction with suturing may be beneficial in corporoplasty for congenital or acquired penile curvature.

Animals↗
PubMed1995

Sutureless rabbit bladder mucosa patch graft urethroplasty using diode laser and solder.

Fistula and strictures at the site of sutured anastomoses are frequent complications of major urethroplasty. We harvested bladder mucosa in 26 rabbits to repair large defects in the proximal urethra using laser-activated solder in the hope that such a repair would be stronger, faster to create and avoid common complications seen with conventional repair. Large oval defects were created in the proximal urethra in all animals undergoing urethroplasty. Twelve animals underwent bladder mucosa graft closure via diode (808 nm.) laser activation of an albumin-based solder (50% were suture-free). Fourteen additional animals underwent closure with 7-zero polydiaxanone suture (controls). Leak pressure and time of repair were recorded for each graft. Additional sections of bladder mucosa were harvested, transected and repaired by laser welding to determine tensile strength. In both groups, radiography, urethroscopy and clinical course were evaluated for as much as 6 weeks postoperatively. Urethroplasty time was significantly (p < 0.01) shorter for the laser group (13.8 +/- 2.5 minutes) than for the sutured repair group (24.0 +/- 5.3 minutes). Initial leak pressures for the lasered grafts averaged at least 4 times those of sutured grafts (p < 0.01). The tensile strength for lasered bladder mucosa was 3.16 +/- 1.12 kg./cm.2 Early retrograde urethrograms (RUG) performed at 7 days (n = 5) revealed urinary extravasation and fistula formation in 2 control animals compared with a normal urethral appearance in 3 lasered repairs. Early retrograde urethrograms performed at 21 days (n = 21) demonstrated smooth-walled urethras with no evidence of fistula, stricture, or urinary extravasation in the lasered group; varying degrees of reactive mucosal proliferation were seen in the controls. Urethroscopy confirmed these observations. At 6 weeks, histologic examination confirmed the presence of viable graft in all animals. We conclude that bladder mucosa patch graft urethroplasty using diode laser welding and albumin-based solder is an attractive alternative to conventional methods.

Animals↗
PubMed1994

In vitro growth effects of colony-stimulating factors in ovarian cancer.

Human recombinant colony-stimulating factors may be used to treat or prevent neutropenia caused by marrow toxic chemotherapeutic agents administered to patients with cancer. Despite their common clinical use, little is known about the potential adverse effects that these cytokines may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that colony-stimulating factors may act as stimulating growth factors in some human malignancies. To evaluate these effects in ovarian cancer, we investigated the possible growth effects of granulocyte colony-stimulating factor (G-CSF/Filgrastim) and granulocyte-macrophage colony-stimulating factors (GM-CSF/Sargramostim) on four established ovarian cancer cell lines, as well as five primary ovarian cancer cultures over a wide range of pharmacologic doses. Cell viability was measured by an ATP bioluminescence assay and expressed as a percentage of untreated control cultures. G-CSF showed no growth-stimulating effects in any of the four established cell lines tested. In the OVCAR-3 cell line, a decrease in growth (> 10%) was seen at 10, 100, and 1000 ng/ml after 5 days of continuous treatment. In the same cell line, GM-CSF caused an increase (> 10%) in growth at the same doses. However, these changes did not demonstrate statistical significance in a dose-dependent fashion. In the five primary cultures treated with G-CSF, only one demonstrated statistically significant increases in growth in a dose-dependent manner. GM-CSF treatment had no significant growth alterations in these same five primary cultures. These results would suggest that colony-stimulating factors may act as growth factors in some but not all ovarian cancer cells. Further investigations into the receptor status of ovarian cancer cells for these cytokines are underway to clarify this issue.

Cell Division↗
PubMed1994

Effects of GnRH analogs on six ovarian cancer cell lines in culture.

The objective was to evaluate the possible direct anti-tumor effects of the GnRH agonists buserelin and leuprolide acetate and the GnRH antagonist antide on ovarian cancer cell lines in culture. Evidence from several hormone-responsive tumor systems suggests that GnRH analogs may have direct anti-tumor effects at the cellular level. In small clinical trials, the use of GnRH analogs in advanced refractory ovarian cancer has produced some dramatic responses. With this in mind, we evaluated the growth effects of the GnRH agonists buserelin and leuprolide and the GnRH antagonist antide over a range of concentrations on six established ovarian cancer cell lines over a period of 7 days. Cell viability was measured by an ATP-bioluminescence assay and expressed as a percentage of untreated control cultures. Analysis of variance was used to evaluate significant growth differences from control cultures. Although we were able to demonstrate statistically significant reduction in cell growth in two of six cell lines with buserelin, no dose-related response patterns were seen. While buserelin caused a maximum 16% inhibition of growth, antide had no effect on tumor growth at the same doses. Leuprolide acetate produced significant dose-dependent inhibition of growth in all six cell lines when doses were increased to supraphysiologic levels, but demonstrated no significant inhibition at doses that are clinically attainable. Furthermore, competitive binding assays showed no specific GnRH binding in any of the six ovarian cell lines tested. Although GnRH analogs have growth inhibitory effects on ovarian cancer cells in vitro, the magnitude of this effect at doses that are clinically achievable is insufficient to support direct tumor effects as the mechanism behind the clinical responses reported.

Analysis of Variance↗
PubMed1994

Lactobacillus sepsis with pelvic abscess.

Although lactobacillus species are among the most common commensal organisms of the mouth, digestive tract, and female genital tract, they rarely cause serious infection. A case of lactobacillus septicemia and pelvic abscess formation in a posthysterectomy patient with mixed Mullerian tumor of the uterus is presented.

Abscess↗
PubMed1994

Acute renal failure secondary to ciprofloxacin use.

We report on a 22-year-old woman with a continent urinary diversion in whom acute renal failure developed on ciprofloxacin therapy for pelvic osteomyelitis. Renal failure resolved rapidly once the drug was withheld. Because ciprofloxacin is used extensively by the urological community, we believe that it is important to be aware of this potential complication of therapy. We review the literature on the association of ciprofloxacin and renal failure.

Acute Kidney Injury↗
PubMed1994

Early cystometrograms can predict the response to intravesical instillation of oxybutynin chloride in myelomeningocele patients.

Recent reported experiences with intravesical medications in neurogenic bladder patients prompted us to evaluate this form of therapy in 28 myelomeningocele patients who could not tolerate oral anticholinergic agents or did not have adequate control on these agents. A pretreatment cystometrogram was performed followed by intravesical administration of oxybutynin chloride, with a repeat cystometrogram 3 hours later. Patients then began twice daily intravesical oxybutynin for a minimum of 4 months. The mean bladder capacity increased by 41%, the mean intravesical pressure decreased by 47% and compliance improved. Five patients achieved continence and 62% had less wetting while on intravesical therapy. The immediate posttreatment cystometrogram was predictive of the response to intravesical therapy on followup studies. Unfortunately, patient compliance was poor, with only 13 of the 28 patients remaining on therapy for the duration of the study.

Administration, Intravesical↗