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1.
Neurology ; 63(7): 1320-2, 2004 Oct 12.
Article in English | MEDLINE | ID: mdl-15477565

ABSTRACT

Reported is the change in cognitive function after neuronal cell transplantation as a treatment for basal ganglia stroke. Nine subjects (two controls, seven transplants), all over 2 years post stroke, completed a comprehensive neuropsychological test battery prior to and 6 months after treatment. Four transplanted subjects who had strokes in the nondominant hemisphere showed marked improvement on the Rey Complex Figure, a test of visuospatial/constructional ability and nonverbal memory.


Subject(s)
Basal Ganglia Cerebrovascular Disease/surgery , Brain Infarction/surgery , Cognition , Neurons/transplantation , Aged , Basal Ganglia Cerebrovascular Disease/physiopathology , Basal Ganglia Cerebrovascular Disease/psychology , Brain Infarction/physiopathology , Brain Infarction/psychology , Dominance, Cerebral , Humans , Mental Recall , Middle Aged , Neuropsychological Tests , Single-Blind Method , Stereotaxic Techniques , Task Performance and Analysis
2.
Gynecol Oncol ; 85(1): 89-94, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11925125

ABSTRACT

OBJECTIVE: Cisplatin is a standard treatment in advanced, recurrent cervical cancer. Because topotecan is an established treatment in gynecologic malignancies such as ovarian cancer and exhibits nonoverlapping toxicity with cisplatin, a phase II trial was conducted to evaluate the tolerability and antitumor activity of a cisplatin/topotecan doublet in persistent or recurrent cervical cancer patients. METHODS: Patients with bidimensionally measurable persistent or recurrent squamous cell and non squamous cell cervical cancer and adequate bone marrow were enrolled. Patients received 50 mg/m(2) of cisplatin intravenously over 1 h on Day 1 and 0.75 mg/m(2) of topotecan intravenously over 30 min on Days 1, 2, and 3 of 21-day cycles for six cycles or until disease progression. Tumor response and regimen toxicity were assessed using established Gynecologic Oncology Group criteria. RESULTS: Thirty-two of 35 enrolled patients were evaluable for toxicity and tumor response. All but 2 evaluable patients had received previous radiotherapy. No patient received prior chemotherapy. The cisplatin/topotecan doublet was well tolerated, with 77 and 78% of courses given without interruption or delay and at full doses, respectively. As anticipated, the most common toxicity was hematologic, with grade 3/4 neutropenia and thrombocytopenia reported in 30 and 10% of cycles, respectively. The overall response rate was 28% (9/32), with 3 complete and 6 partial responses. The antitumor response in nonirradiated fields (30%) was similar to the response observed in previously irradiated fields (33%), suggesting good drug penetration. Median duration of response was 5 months (range, 2 to 15+ months). An additional 9 (28%) patients achieved stable disease. Median survival was 10 months, with 3 patients in lasting remission. CONCLUSIONS: These results demonstrate that the cisplatin/topotecan combination is safe, well tolerated, and active in persistent or recurrent cervical cancer patients. A phase III, multicenter trial is under way (cisplatin/topotecan versus cisplatin) based on these favorable results to confirm the safety and efficacy profile in this patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Administration Schedule , Female , Hematologic Diseases/chemically induced , Humans , Middle Aged , Topotecan/administration & dosage , Topotecan/adverse effects
3.
Neurosurgery ; 49(3): 586-91; discussion 591-2, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11523668

ABSTRACT

OBJECTIVE: There is no known effective treatment for chronic stroke. In this report, we used positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) to map the metabolic brain response to neuronal cell implantation in the first human neuroimplantation trial for stroke. METHODS: Twelve patients (nine men, three women; mean age +/- standard deviation, 60.8+/-8.3 yr) with chronic basal ganglia infarction and persistent motor deficit underwent FDG PET within 1 week before and 6 and 12 months after stereotactic implantation of human neuronal cells. Serial neurological evaluations during a 52-week postoperative period included the National Institutes of Health stroke scale and the European stroke scale. RESULTS: Alterations in glucose metabolic activity in the stroke and surrounding tissue at 6 and 12 months after implantation correlated positively with motor performance measures. CONCLUSION: FDG PET performed as part of an initial open-label human trial of implanted LBS-Neurons (Layton BioScience, Sunnyvale, CA) for chronic stroke demonstrates a relationship between relative regional metabolic changes and clinical performance measures. These preliminary findings suggest improved local cellular function or engraftment of implanted cells in some patients.


Subject(s)
Basal Ganglia/metabolism , Fluorodeoxyglucose F18/pharmacokinetics , Neurons/transplantation , Radiopharmaceuticals/pharmacokinetics , Stroke/metabolism , Stroke/surgery , Tomography, Emission-Computed , Aged , Basal Ganglia/pathology , Cells, Cultured , Female , Glucose/metabolism , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Movement Disorders/diagnosis , Movement Disorders/epidemiology , Neurologic Examination , Severity of Illness Index , Stereotaxic Techniques , Stroke/pathology , Temporal Lobe/metabolism , Temporal Lobe/pathology , Temporal Lobe/surgery , Time Factors
4.
Gynecol Oncol ; 82(1): 7-10, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11426954

ABSTRACT

Objective. The goal of this study was to estimate the antitumor activity and toxicity of recombinant human interleukin-12 (rhIL-12) in patients with recurrent or refractory epithelial ovarian cancer. Methods. From December 1997 to March 1999, patients with recurrent or refractory epithelial ovarian cancer were entered on a Gynecologic Oncology Group phase II study of intravenous rhIL-12. All patients had measurable disease, had a performance status of 0-2, and had failed first-line platinum-based chemotherapy regimen. Eligible patients received rhIL-12, 250 ng/kg IV bolus, as a single dose on Day 1 followed by a 2-week rest period, with subsequent cycles administered daily for 5 days followed by a 16-day rest period per cycle, until disease progression or adverse effects prohibited further therapy. Results. Twenty-eight patients were entered and evaluable for toxicity, while 26 were evaluable for response. The median age was 59.5 years (range: 45-77). The median number of cycles was 2 (range: 1-9). There were no complete responders; however, one patient (3.8%) was a partial responder and 13 patients (50%) had stable disease. Grade 4 myelotoxicity occurred in 21% of patients. Two patients experienced capillary leak syndrome: one grade 2 and one grade 4. Conclusion. As a single agent, rhIL-12 is tolerable and shows a low response rate in recurrent epithelial cancer with measurable disease.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Interleukin-12/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Aged , Angiogenesis Inhibitors/adverse effects , Drug Evaluation , Female , Humans , Infusions, Intravenous , Interleukin-12/adverse effects , Middle Aged , Recombinant Proteins , Treatment Outcome
5.
Neurology ; 55(4): 565-9, 2000 Aug 22.
Article in English | MEDLINE | ID: mdl-10953194

ABSTRACT

Transplantation of cultured neuronal cells is safe in animal models and improves motor and cognitive deficits in rats with stroke. The authors studied the safety and feasibility of human neuronal cellular transplantation in patients with basal ganglia stroke and fixed motor deficits, including 12 patients (aged 44 to 75 years) with an infarct 6 months to 6 years previously (stable for at least 2 months). Serial evaluations (12 to 18 months) showed no adverse cell-related serologic or imaging-defined effects. The total European Stroke Scale score improved in six patients (3 to 10 points), with a mean improvement 2.9 points in all patients (p = 0. 046). Six of 11 PET scans at 6 months showed improved fluorodeoxyglucose uptake at the implant site. Neuronal transplantation is feasible in patients with motor infarction.


Subject(s)
Movement Disorders/therapy , Neurons/transplantation , Stem Cell Transplantation , Stroke/surgery , Adult , Aged , Basal Ganglia/blood supply , Basal Ganglia/metabolism , Cells, Cultured , Feasibility Studies , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Movement Disorders/etiology , Movement Disorders/physiopathology , Neurons/cytology , Neurons/metabolism , Severity of Illness Index , Single-Blind Method , Stem Cells/cytology , Stem Cells/metabolism , Stroke/complications , Stroke/physiopathology , Tomography, Emission-Computed , Treatment Outcome
6.
Obstet Gynecol ; 95(4): 553-6, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10725488

ABSTRACT

OBJECTIVE: To assess the accuracy of intraoperative lymph node palpation for identifying lymph node metastasis in gynecologic malignancies. METHODS: We prospectively evaluated 126 women who had lymphadenectomies for staging of various gynecologic malignancies from August 1995 to June 1997. Surgeries were done by obstetrician-gynecologists with subspecialty certification in gynecologic oncology from the American Board of Obstetrics and Gynecology, who had practiced gynecologic oncology for at least 5 years. Data were collected on gynecologic oncologists' opinions of lymph node status by palpation. Nodes believed to be positive were sent separately. We recorded operating time for lymphadenectomies, and intraoperative and postoperative complications. RESULTS: Mean (range) patient age was 55 (18-83) years. Mean (range) operating time was 188 (85-435) minutes. The mean (range) lymphadenectomy time was 46 (5-150) minutes. The total number of lymph nodes dissected was 2138. One hundred seven of 2138 (5%) nodes were positive for malignancy. Thirty-eight of 107 (36%) positive lymph nodes were missed by palpation. Fifty-six of 2031 (3%) negative lymph nodes were selected as positive. Sixty-nine of 107 (64%) positive lymph nodes were identified correctly. Sensitivity and specificity of palpation were 72% and 81%, respectively. The positive and negative predictive values of lymph node palpation were 56% and 89%, respectively. CONCLUSION: Intraoperative lymph node palpation has low sensitivity and positive predictive value even when done by experienced board-certified gynecologic oncologists.


Subject(s)
Genital Neoplasms, Female/pathology , Genital Neoplasms, Female/surgery , Lymph Node Excision , Palpation , Adolescent , Adult , Aged , Aged, 80 and over , Clinical Competence , Female , Humans , Intraoperative Period , Lymphatic Metastasis , Middle Aged , Prospective Studies , Reproducibility of Results
7.
Xenotransplantation ; 6(1): 6-16, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10355728

ABSTRACT

Hyperacute rejection (HAR) remains a critical immunologic hurdle in the development of xenogeneic organs for human transplantation. Strategies that simultaneously eliminate both natural antibody reactivity and complement activation on the xenogeneic cell surface may be the best approach to achieve clinical application of xenogeneic vascularized organ transplantation. We have developed multiple lines of genetically manipulated mice to evaluate the combination of different genetic approaches aimed at inhibiting antibody and complement-mediated cell lysis. We utilized transgenic mice expressing the human complement inhibitor, CD59, the human 1,2-fucosyltransferase (H-transferase, HT) and the alpha1,3-galactosyltransferase (alpha1,3-GT) knock-out mouse line (Gal KO). Our data show that expression of hCD59 in combination with HT expression or the null phenotype of alpha1,3-GT are equally effective at preventing human serum-mediated cytolysis. Interestingly, the triple combination affords no additional protective effect. Therefore, coexpression of HT and a complement inhibitor is the most immediate strategy to genetically engineer transgenic pigs to be used as xenogeneic donors.


Subject(s)
Cytotoxicity, Immunologic/genetics , Graft Rejection/genetics , Animals , Antibodies, Heterophile/biosynthesis , Base Sequence , CD59 Antigens/genetics , Complement System Proteins/metabolism , DNA Primers/genetics , Fucosyltransferases/genetics , Galactosyltransferases/genetics , Humans , Immunity, Innate , Mice , Mice, Knockout , Mice, Transgenic , Transplantation, Heterologous , Galactoside 2-alpha-L-fucosyltransferase
8.
Gynecol Oncol ; 73(1): 72-5, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10094883

ABSTRACT

PURPOSE: The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva. MATERIALS AND METHODS: In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor. RESULTS: From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3. 2 cm (0.5-7.0) and the mean depth of invasion was 9.1 mm (1.1-28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa. CONCLUSION: The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies.


Subject(s)
Carcinoma, Squamous Cell/pathology , Vulvar Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Neoplasm Invasiveness
9.
Int J Gynecol Cancer ; 9(2): 137-140, 1999 Mar.
Article in English | MEDLINE | ID: mdl-11240755

ABSTRACT

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t-test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.

10.
Cancer ; 83(1): 98-102, 1998 Jul 01.
Article in English | MEDLINE | ID: mdl-9655298

ABSTRACT

BACKGROUND: The authors evaluated the impact of body mass on survival and morbidity of patients with new International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2 cervical carcinoma treated with radical hysterectomy were studied in a multivariate logistic regression analysis. The body mass index (BMI) and the ponderal index (PI) were used as measures of body mass and were analyzed as predictors of recurrence, survival, and complications in light of the new staging system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low BMI or a high PI were predictive of poor survival. Tumor greatest dimension, lymph node involvement, BMI, and PI were all independent predictors of survival (P=0.0006). The only independent predictor of complications was para-aortic lymph node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low body mass, as indicated by a low BMI or a high PI, were found to have poor survival after undergoing radical hysterectomy. Additional predictors of poor survival included lymph node metastases and increased tumor size. BMI and PI are more important predictors of survival than the new FIGO Stages IB1 and IB2. Body mass is not predictive of complications.


Subject(s)
Body Mass Index , Hysterectomy , Uterine Cervical Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Survival Rate , Uterine Cervical Neoplasms/mortality
11.
Gynecol Oncol ; 66(3): 425-8, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9299256

ABSTRACT

OBJECTIVE: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy. METHODS: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes. RESULTS: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive. CONCLUSION: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique.


Subject(s)
Vulvar Neoplasms/diagnostic imaging , Vulvar Neoplasms/surgery , Female , Humans , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Monitoring, Intraoperative , Pilot Projects , Radionuclide Imaging , Radiopharmaceuticals , Technetium Tc 99m Sulfur Colloid
12.
Gynecol Oncol ; 64(1): 76-9, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8995551

ABSTRACT

Our experience with gynecologic oncology patients presenting preoperatively with a deep vein femoral thrombosis is reported. Over a 3-year period data were collected on all patients at the University of South Florida (USF) requiring surgery for a known or suspected gynecologic cancer and having a concomitant active femoral venous thrombosis. Twelve such patients were managed. Management was divided among three options: heparinization, preoperative inferior vena cava (IVC) filter, and intraoperative IVC ligation. For two patients a filter could not be placed preoperatively due to tumor compression of the IVC. Both underwent IVC ligation intraoperatively. One of the two died intraoperatively, possibly related to pulmonary embolism. One of eight with a preoperative IVC filter had obvious clot propagation postoperatively, managed with heparin. One of two managed with heparin only had severe bleeding and heparin-associated thrombocytopenia (HAT) preoperatively. Based on our experience and a review of the literature, we recommend therapeutic heparinization and a preoperatively placed IVC filter for most preoperative gynecologic oncology patients with femoral deep venous thrombosis.


Subject(s)
Femoral Vein , Genital Neoplasms, Female/surgery , Thrombosis/complications , Adult , Aged , Female , Follow-Up Studies , Genital Neoplasms, Female/complications , Humans , Middle Aged
13.
Gynecol Oncol ; 62(2): 139-47, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8751541

ABSTRACT

Two hundred twenty-nine patients with Stage IB cervical cancer treated with radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the impact of the new staging system for IB1 and IB2 cervical cancer on nodal status and survival. Additionally, we analyzed the morbidity of radical hysterectomy in light of the new staging system. The complications were similar between the two groups. Para-aortic lymphadenectomy was the only independent predictor of complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5-year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate stepwise logistical regression analysis indicated that the new staging system did not have an independent impact on survival. Stage acts through nodal status in its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index are all independent predictors of survival (P = 0.0001). Patients with Stage IB2 carcinoma of the cervix undergoing radical hysterectomy showed no significant increase in morbidity when compared with patients with Stage IB1 disease treated with the same procedure.


Subject(s)
Hysterectomy/adverse effects , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology , Analysis of Variance , Carcinoma/mortality , Carcinoma/pathology , Female , Humans , Logistic Models , Lymph Node Excision/adverse effects , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Uterine Cervical Neoplasms/surgery
14.
J Soc Gynecol Investig ; 2(6): 762-71, 1995.
Article in English | MEDLINE | ID: mdl-9420887

ABSTRACT

OBJECTIVES: The ascites-associated lymphocytes in ovarian cancer have altered immunologic function, and cell-free ascitic fluid has immunomodulating properties. We determined (1) whether interleukin (IL)-2 could induce lymphokine-activated killer (LAK) activity in normal peripheral blood mononuclear cells (PBMC) cultured in ovarian cancer ascitic fluid, and (2) whether IL-12 could synergize with IL-2 to generate LAK activity in normal PBMC cultured in ascitic fluid. METHODS: Normal PBMC were cultured in control medium and in media consisting of 50% ascitic fluid (ascitic medium), with and without IL-2 and IL-12. Cell activation to assess LAK activity (cell lysis) was determined in a 51Cr-release assay with the tumor cell lines FMEX and SKOV3 as target cells. To determine a possible mechanism for any synergistic effect, the expression of perforin, a pore-forming protein, was determined by Northern blot analysis. RESULTS: Interleukin-2 alone could not induce LAK activity in normal PBMC cultured in 50% ascitic fluid for up to 3 days. Interleukin-12 did mediate some or minimal LAK activity after 1, 2, or 3 days of incubation in control medium or in 50% ascitic fluid. When IL-2 and IL-12 were used in combination, PBMC cultured for 3 days in 50% ascitic fluid had remarkably high lytic activity against FMEX and SKOV3 tumor cells. In some experiments, this cytotoxicity was greater than that in PBMC cultured in control medium with IL-2 and IL-12. Lower concentrations of IL-12 (1 U/mL) with IL-2 (100 U/mL) were as effective as, and often more effective than, higher doses of IL-12 with IL-2. Very low-dose IL-12 (0.01-0.03 U/mL) in combination with IL-2 also induced a range of cytotoxicities. Only the combination of IL-2 and IL-12 up-regulated expression of perforin mRNA in ascitic medium. CONCLUSIONS: The cytotoxicity responses of PBMC cultured in ascitic fluid in the presence of IL-2 and IL-12 are complex. Low-dose IL-2 and IL-12 can overcome the inhibitory property of ascitic fluid on LAK generation and can restore and enhance cytotoxic activity, possibly by reconstituting the expression of perforin. These findings may have therapeutic potential.


Subject(s)
Ascites/immunology , Cytotoxicity, Immunologic , Interleukin-12/pharmacology , Interleukin-2/pharmacology , Killer Cells, Lymphokine-Activated/immunology , Ovarian Neoplasms/immunology , Transcription, Genetic/drug effects , Ascites/pathology , Cells, Cultured , Drug Synergism , Female , Humans , Killer Cells, Lymphokine-Activated/drug effects , Melanoma , Membrane Glycoproteins/biosynthesis , Ovarian Neoplasms/pathology , Perforin , Pore Forming Cytotoxic Proteins , RNA, Messenger/biosynthesis , T-Lymphocytes, Cytotoxic/drug effects , T-Lymphocytes, Cytotoxic/immunology , Tumor Cells, Cultured
15.
Gynecol Oncol ; 57(1): 86-95, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7705706

ABSTRACT

This study was designed to examine if interleukin-12 (IL-12) can induce cytolytic function of lymphocytes from ovarian cancer patients against either an ovarian cancer cell line or their own autologous tumor cells. Lymphocytes were obtained from the peripheral blood or ascites of ovarian cancer patients and activated with IL-12 alone or concomitantly with interleukin 2 (IL-2) for 2 to 3 days. Activation of lymphocytes and assessment of tumoricidal function by a chromium release assay were performed directly in a standard control medium (RPMI 1640 containing 2 mM glutamine, 100 micrograms/ml streptomycin, 100 units penicillin, 5% heat-inactivated human AB serum, and 5 mM 4-(2-hydroxyethyl)-1-piperazinesulfonic acid) and in 50% ascitic fluid (50% by volume filter-sterilized ascites with 50% of the above-mentioned control medium). Target cells were added directly into the medium in which the lymphocytes were activated in order to more closely mimic in vivo conditions. Lymphocytes, activated by IL-12 in 50% ascitic fluid, were able to lyse autologous tumor cells in 3 of 6 assays and were able to lyse SKOV3 cells (an ovarian cancer cell line) in 5 of 7 assays. The results were not significantly different in the control medium. When both IL-2 and IL-12 were used to activate lymphocytes in 50% ascitic fluid, significant cytotoxicity was generated in 6 of 6 autologous assays and in all 7 patient assays using SKOV3 as a target (P < 0.05). Synergy between the two cytokines was seen in all 13 patient assays in ascitic medium compared to only 5 of 13 assays in control medium. Additionally, when lymphocytes were stimulated with both IL-2 and IL-12, significantly greater cytotoxicity was seen in the ascitic fluid medium compared to the control medium in 13 of 14 assays (P < 0.05). No significant tumoricidal activity was seen by lymphocytes maintained in either medium without the addition of IL-2 or IL-12. Ascitic fluid consistently potentiates the synergy between IL-2 and IL-12 in generating cytotoxicity against ovarian cancer cells but does not increase cytotoxicity induced by IL-12 alone. IL-12 by itself activates tumoricidal activity of lymphocytes in ascitic fluid; however, the addition of IL-2 increases the degree and consistency of this effect. These data support the possibility that IL-12 may warrant further investigation as a potential therapeutic agent in the treatment of advanced ovarian cancer.


Subject(s)
Interleukin-12/pharmacology , Lymphocytes/pathology , Ovarian Neoplasms/pathology , Ascitic Fluid/pathology , Cells, Cultured , Culture Media, Conditioned/pharmacology , Drug Synergism , Female , Humans , Interleukin-12/therapeutic use , Interleukin-2/pharmacology , Killer Cells, Natural/drug effects , Killer Cells, Natural/pathology , Lymphocyte Activation , Lymphocytes/drug effects , Neoplasm Staging , Ovarian Neoplasms/drug therapy , Tumor Cells, Cultured
16.
J Reprod Med ; 40(3): 226-8, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7776310

ABSTRACT

Sciatic nerve endometriosis was previously treated primarily with surgery. Most commonly hysterectomy and bilateral salpingo-oophorectomy have been used; however, two reports also describe successful conservative surgery with resection of the endometriosis from the sciatic nerve. Only one case of sciatic nerve endometriosis has been reported to have responded to medical management. This report details the rapid and complete resolution of sciatica secondary to endometriosis after medical treatment with the gonadotropin releasing hormone analog leuprolide acetate for depot suspension.


Subject(s)
Endometriosis/drug therapy , Leuprolide/therapeutic use , Sciatic Nerve , Adult , Endometriosis/diagnosis , Female , Humans , Peripheral Nervous System Diseases/drug therapy
17.
Obstet Gynecol ; 84(4 Pt 2): 665-8, 1994 Oct.
Article in English | MEDLINE | ID: mdl-9205441

ABSTRACT

BACKGROUND: The English literature contains infrequent reports of neuroendocrine carcinoma during pregnancy. The chemotherapy for this type of malignancy can cause severe nausea and neutropenia. We used recently developed modalities to ameliorate these side effects. CASE: A 22-year-old woman, gravida 4, para 2-0-1-2, presented at 24 weeks' gestation with a complaint of massive lower-extremity edema. Computed tomography scan delineated a large retroperitoneal mass. Biopsy of a small neck mass revealed a poorly differentiated neuroblastoma. A multidisciplinary approach to therapy was undertaken. The patient received cisplatin and etoposide chemotherapy. Complications of the first course included severe neutropenia and nausea with vomiting. Filgrastim and ondansetron were used to treat these complications. She delivered an 1825-g healthy male by cesarean for fetal distress at 35 weeks. No anomalies were noted at birth. Neonatal hematologic indices were normal CONCLUSION: A multidisciplinary approach to rare malignancies is warranted in pregnancy. Filgrastim and ondansetron are effective agents in the treatment of chemotherapy-associated complications. Their use in pregnancy warrants further investigations.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neuroblastoma/drug therapy , Pregnancy Complications, Neoplastic/drug therapy , Retroperitoneal Neoplasms/drug therapy , Adult , Cisplatin/adverse effects , Etoposide/adverse effects , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Nausea/chemically induced , Nausea/prevention & control , Neutropenia/chemically induced , Neutropenia/prevention & control , Ondansetron/therapeutic use , Pregnancy , Recombinant Proteins , Vomiting/chemically induced , Vomiting/prevention & control
18.
Am J Obstet Gynecol ; 171(2): 309-13; discussion 313-5, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8059807

ABSTRACT

OBJECTIVE: The purpose of this study was to compare the intraoperative and postoperative complications of transvaginal morcellation and abdominal hysterectomy for the removal of moderately enlarged uteri. STUDY DESIGN: An observational study was performed on all uteri weighing > 200 gm removed transvaginally from July 1, 1987, to June 30, 1993. An abdominal hysterectomy control group was selected. RESULTS: There were 50 patients in the vaginal group and 112 in the abdominal group. At a p value < 0.05 there was no statistically significant difference between the two groups for age, parity, obesity, hypertension, insulin-dependent diabetes mellitus, or prior genitourinary surgery. The mean operative time in the vaginal hysterectomy group was 122 minutes and in the abdominal hysterectomy group 148 minutes (p < 0.05). The mean estimated blood loss was 527 and 586 ml, respectively (not significant). Twenty-two percent of the vaginal group and 70% of the abdominal group underwent bilateral oophorectomy (p < 0.05). The mean uterine weights were 335 and 336 gm, respectively (not significant). The mean day of starting a regular diet was 2.1 and 3.6, respectively (p < 0.05). The mean day of discharge was 3.6 and 5.1, respectively (p < 0.05). Complications were similar for the two groups. CONCLUSIONS: In selected patients transvaginal morcellation is a safe and effective alternative to abdominal hysterectomy for the removal of moderately enlarged uteri. The two procedures are comparable in operative time, blood loss, and complications. Both ovaries are more likely to be removed with abdominal hysterectomy. Cosmesis and recuperation may be advantages of the vaginal approach.


PIP: Obstetrician-gynecologists compared data on 50 women who underwent vaginal hysterectomy with piecemeal removal of uterine segments (transvaginal morcellation) between July, 1987, and June, 1993, with data on 112 age-, uterine weight-, and concomitant medical problem-matched women who underwent abdominal surgery for uterine leiomyomas between 1986 and 1992. The 2 groups were similar for parity, obesity, hypertension, insulin-dependent diabetes mellitus, and prior genitourinary surgery. The mean time needed to perform the vaginal approach was significantly shorter than the abdominal approach (122 vs. 148 minutes; p .05). Bilateral ovariectomy was concurrently performed about 4 times more often in abdominal hysterectomy controls than in vaginal hysterectomy cases (70% vs. 18%; p .05). Even though controls had more blood loss than cases (586 vs. 527 ml) and were more likely to need a blood transfusion (19% vs. 6%), the difference was not significant. As uterine weight increased, so did the operative time and estimated blood loss (p .05). Vaginal hysterectomy cases returned to a regular diet earlier than did abdominal hysterectomy controls (2.1 vs. 3.6 days; p .001). They also were discharged earlier than controls (3.6 vs. 5.1 days; p .001). Complications were similar for both groups (e.g., soft tissue infection, 10% for vaginal and 12% for abdominal). Transvaginal morcellation may be the best hysterectomy approach for the obese, women who are severely medically compromised, or women with concurrent pelvic relaxation defects. These findings show that transvaginal morcellation is a safe and effective alternative to abdominal hysterectomy.


Subject(s)
Hysterectomy, Vaginal/methods , Hysterectomy , Adult , Blood Loss, Surgical , Blood Volume , Female , Humans , Postoperative Complications , Treatment Outcome
19.
Am J Obstet Gynecol ; 166(1 Pt 1): 30-3, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1733213

ABSTRACT

Between Aug. 1, 1985, and July 31, 1990, 32 patients underwent upper vaginectomy for grade 3 vaginal intraepithelial neoplasia. Thirty-one of these patients had undergone hysterectomy, 25 because of cervical neoplasia. Fourteen patients had undergone treatment for vaginal intraepithelial neoplasia. Nine (28%) had invasive cancer on final pathologic examination. Among the remaining 23 patients, recurrence of vaginal neoplasia developed in four (17%), with a mean time to recurrence of 78 weeks, and one was found to have superficial invasion at the time of recurrence. The remaining 19 patients remain alive with no evidence of recurrent disease at a mean follow-up interval of 152 weeks. In our patients upper vaginectomy was efficacious for the diagnosis of occult invasive carcinoma of the vagina and for the treatment of in situ and superficially invasive carcinoma of the vagina.


Subject(s)
Carcinoma in Situ/surgery , Vagina/surgery , Vaginal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma in Situ/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Recurrence, Local , Uterine Cervical Neoplasms/complications , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery , Vaginal Neoplasms/complications , Vaginal Neoplasms/radiotherapy
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