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Biomedical subjects

G Deppe

Publications and source records attributed to G Deppe.

At least 37 records · Page 2Linked to original sources

[Emergency postpartum hysterectomy. A study over 5 years].

A retrospective review was conducted of 34 women who underwent emergency peripartum hysterectomy at Hutzel Hospital--Wayne State University, Detroit from January 1986 to December 1991. Indications for hysterectomy were placenta accreta, uterine rupture, uterine atony and unspecified uterine bleeding. The median age of the patients was 33 years (20-40 years). The median hospital stay was 6 days (4-26 days) and median blood loss was 2000 ml (1000-6000 ml), with a median blood replacement of 4 units of packed cells (0-16 RPC). Postoperative complications included urinary tract infection (2), vaginal cuff cellulitis (3), wound infections (2), septic thrombophlebitis (2), acute tubular necrosis (1) and wound hematoma (1). No patient died.

Adult↗

New understanding from Cf brachytherapy trials and considerations for neutron therapy of bulky gyn carcinoma for future.

PURPOSE: This study reviews the radiobiology of neutrons and the results and methods that have evolved in the Cf-252 neutron brachytherapy trials to postulate methods to explore for their potential applicability to fast neutron beam therapy. METHODS AND MATERIALS: The results of radiobiological experimental studies are reviewed for RBE for different fraction number and dose per fraction. RBE was always higher for fractionated neutrons based on comparison with isoeffective doses of photons. This is inherent in the basic radiobiological properties of photons. RBE was highest for low dose rate (LDR) Cf brachytherapy. RESULTS: Brachytherapy methods deliver radiation dose which is localized and conformal to the tumor. These methods have been used for Cf therapy and led to good tissue tolerance and local tumor control. The use of large dose/session (or fraction), small fraction number, short treatment times, followed by photon beam therapy has been the practice in Cf brachytherapy. It has been found that bulky or localized advanced tumors responded better if neutron treatment preceded the photon beam therapy. Therapeutic efficacy is dependent on the fraction size of neutrons and not the time duration of application. CONCLUSIONS: Available radiobiological data on neutron RBE with fraction number and size of dose and the favorable experience from Cf brachytherapy with up-front neutron applications suggest new avenues to explore for the neutron beam trials. The high efficacy noted for small volume dose, 10 to 20 Gy-eqs of dose per session, localized dose, conformal methods, small number of sessions, short treatment times and an up-front or early schedule in combining neutron and photon therapy suggests that similar schedules and methodology may also be effective for neutron beam therapy. Further clinical trials are indicated and bulky GYN tumors represents suitable tumors for study.

Animals↗

Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3.

Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have been partial and of short duration, results which indicate a need for new agents and therapeutic strategies. This study was undertaken to determine the effects of carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic agent that has activity against multiple solid tumors, including ovarian carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration-dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol also inhibited RL95-2 growth in a concentration-dependent manner. Maximal inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth inhibition. The degree of interaction between carboplatin and calcitriol was assessed using isobolographic analysis and was found to be additive at all drug concentrations and ratios examined. These results suggest that carboplatin and calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that the combination of these two agents acts additively to inhibit the growth of RL95-2 cells. These agents merit further investigation for their utility against endometrial carcinomas.

Adenocarcinoma↗

Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25-dihydroxyvitamin D3, retinoic acid and dexamethasone.

The role and regulation of the c-myc protooncogene in breast and ovarian neoplasms is receiving increased attention. The downregulation of the c-myc protooncogene by 1,25-dihydroxyvitamin D3 (calcitriol), retinoic acid (RA) and dexamethasone (Dex) is closely associated with growth inhibition in leukemic cells. Calcitriol, RA and Dex have anti-proliferative activity in breast and gynecologic carcinoma cells; however, the regulation of c-myc by these agents in breast and ovarian cancers is mostly unknown. We have addressed the regulation of c-myc in these cancers using an adaptation of a novel method which employs an immunohistochemical procedure to detect c-myc protein followed by quantification of c-myc staining with computerized image analysis. This system represents an alternative to protein product assay by Western blotting and is straightforward, rapid (1 day), can be carried out on a small scale and provides a sample size that readily facilitates statistical analysis of assay data. In MCF-7 human breast cancer cells, c-myc was suppressed 29% by 0.5 nM Dex, 45% by 0.01 nM RA and 54% by 100 nM calcitriol after 24 h of drug treatment. At the same hormone concentrations, growth was inhibited 18% by Dex, 18% by RA and 39% by calcitriol after 3 days of treatment (p < 0.05 for all hormones). Similar patterns of growth and c-myc inhibition were seen in T47D human breast cancer cells and NIH:OVCAR3 human ovarian cancer cells, with the exception of Dex in T47D cells, which caused no inhibition of c-myc or growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗

[Electrosurgical loop excision as diagnostic and simultaneously therapeutic intervention in cervical intraepithelial neoplasia].

109 women referred to our center for colposcopy because of suspicious cervical cytology and in whom an abnormal epithelial pattern was diagnosed on colposcopy, or in whom a discrepancy between cytology and colposcopy was encountered, concomitantly underwent loop electrosurgical excision procedure as an outpatient procedure. All removed specimens were examined and no invasive cancer was found in any of them. No serious complications occurred. Ambulatory loop electrosurgical excision procedure appears to be a cost-effective and well tolerated treatment modality for the management of women with cervical intraepithelial neoplasia, with the advantage that this conservative procedure allows histologic examination of the removed tissue.

Adolescent↗

Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

Calcitriol↗

Vaginal probe ultrasound guidance for internal jugular catheterization.

The use of ultrasound to assist needle cannulation of the internal jugular vein is well described. However, most ultrasound probes are too bulky to use easily on the neck. We describe a technique using a vaginal ultrasound probe to guide needle cannulation of the internal jugular vein. The small size of the vaginal probe permits visualization on the video screen of both the vein and the needle throughout the entire insertion of the needle, minimizing insertion attempts and preventing complications.

Catheterization, Central Venous↗

Combination chemotherapy for advanced adenocarcinoma of the cervix.

A patient with advanced adenocarcinoma of the cervix was treated only with cisplatin and mitomycin C (MMC). The regimen achieved a complete response, confirmed by chest radiograph and computed axial tomography scan, lasting 50 months. The patient is alive with recurrent disease 59 months after diagnosis. No severe drug-related toxicity occurred.

Adenocarcinoma, Mucinous↗

Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Ascites↗

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗

High-dose-rate afterloading brachytherapy, external radiation therapy, and combination chemotherapy in poor-prognosis cancer of the cervix.

Fourteen patients with poor-prognosis cervical cancer were treated with concurrent chemotherapy (cisplatin and mitomycin-C), external radiation therapy (RT), and high-dose-rate (HDR) brachytherapy. Pelvic RT was delivered as (a) external-beam radiation (four-field box technique, 40.0 Gy), (b) brachytherapy using HDR 60Co or 192Ir (3.80 Gy/fraction, thrice weekly; total dose, 46.83 Gy) with intrauterine stent, and (c) parametrial boost using an AP field with custom-fabricated step wedges. Post-radical-hysterectomy patients received 50.40 Gy external RT and 3.23 Gy/day vaginal cylinder HDR at 1/2-cm depth (total dose, 16.15 Gy). Complete clinical and radiographic response was noted in all evaluable patients who are alive with no evidence of disease, 3 to 27 months after completion of therapy (median, 9 months). Toxicity consisted of grade 2 to 3 hematologic toxicity (4 patients) and nausea and vomiting in all, but grade 3 in only 2 patients. One patient had grade 2 diarrhea. The only major complication (small bowel obstruction) occurred in a patient with lupus vasculitis. This pilot study demonstrates the feasibility of this regimen in an outpatient setting with acceptable toxicity. More prolonged follow-up of our patients is required to determine its impact on long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗

Ovarian cancer. Advances in management.

Substantial progress has been made in understanding the biologic behavior of ovarian cancer and in assessing disease states and response to therapy with transvaginal sonography, CT scan, and tumor markers such as CA-125. There is no longer controversy regarding the importance and feasibility of adequate surgical staging, the need for cytoreduction, and the utility of cisplatin- or carboplatin-based combination chemotherapy in the management of patients with ovarian cancer. Increasing chemotherapy dose through escalated systemic doses or intraperitoneal administration, revising multidrug resistance, the use of biologic response modifiers, and the development of new methods of chemosensitivity testing may help improve the current 5-year survival rate of less than 30% for patients with stage III ovarian cancer. Significant improvement in screening tests and diagnostic capabilities will be necessary for a dramatic increase in survival.

Adult↗

Intraperitoneal doxorubicin in combination with systemic cisplatinum and cyclophosphamide in the treatment of stage III ovarian cancer.

Recent concepts and technical development have led to the successful application of the principles of intraperitoneal chemotherapy in the management of advanced epithelial ovarian cancer. In a pilot study we treated five patients with Stage III ovarian cancer after maximal cytoreductive effort (residual tumor less than or equal to 2 cm) with combination chemotherapy consisting of intraperitoneal doxorubicin and intravenous cisplatinum and cyclophosphamide. Although intraperitoneal doxorubicin demonstrates a pharmacologic advantage over the intravenous administration of this drug, its use is limited by severe abdominal pain requiring narcotic analgesics. Chemical peritonitis and extensive peritoneal adhesions are frequent complications. The role of combination intraperitoneal and systemic chemotherapy in ovarian cancer warrants further study.

Aged↗

Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.

Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.

Adult↗

Pharmacokinetics of intraperitoneal doxorubicin in combination with systemic cyclophosphamide and cis-platinum in the treatment of stage III ovarian cancer.

The pharmacokinetics of intraperitoneal doxorubicin in three previously untreated patients with ovarian cancer are described. All patients were maximally cytoreduced (largest residual tumor less than or equal to 2 cm). The average total body clearance (TBC) was 16.3 ml/kg/min (range 10.6-20.4 ml/kg/min) and the mean volume of distribution (VD) was 42.4 liter/kg (range 27.6-46.9 liter/kg). Half-life of elimination (t 1/2 beta) was 2.6 hr. In spite of a therapeutic advantage of 60 when administered intraperitoneally, prohibitive local toxicity limited the use of doxorubicin via the intraperitoneal route in patients with ovarian cancer.

Aged↗

Benign teratoma of the omentum and ovary coexistent with an ovarian neoplasm.

Benign cystic teratoma of the omentum is a rare abdominal tumor. Review of the literature describes seven reported cases of omental teratomas in association with ovarian teratomas. Our patient is a 68-year-old woman who presented with an asymptomatic abdominal mass and uterine prolapse. Ultrasound revealed a right-sided, cystic and solid pelvic mass. CT scan revealed a second mass with calcifications situated along the right iliac crest. This is the first description of an omental teratoma in association with a benign ovarian cystic teratoma coexistent with a malignant neoplasm. Possible etiologies of the present case are discussed and additional literature investigated.

Aged↗

Results of treatment in locally advanced carcinoma of the endometrium.

The impact of treatment on survival was analyzed in 106 patients with carcinoma of the endometrium stage II (n = 61) and stage III (n = 45). There was no significant difference in survival in patients with stage II who were treated with radiation therapy alone or with combination of surgery and radiation therapy. Their five-year actuarial survival was 74.5% and 71.3% respectively (p = greater than 0.05). However, combined treatment was associated with significantly superior survival in patients with stage III disease where the survival was 57.3% versus 17.5% in patients who received irradiation alone (p = 0.01). Diagnosis of stage III disease based upon clinical (CS III) or pathological (PS III) findings was responsible for this difference in survival. Patients with CS III whose tumor could not be resected because of its extent carried poorer prognosis. Patients with stage II had excellent tumor control in pelvis as compared to patients with stage III. Treatment-related complications were minimal. Overall survival of patients with stage III was poor (33.8%) due to a high rate of pelvic and/or extrapelvic recurrences.

Adenocarcinoma↗

Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator.

Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.

Adult↗