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Biomedical subjects

G P Sutton

Publications and source records attributed to G P Sutton.

90 records · Page 5Linked to original sources
PubMed1986

Adenocarcinoma corpus et colli: analysis of diagnostic variables.

Between January 1973 and December 1983, 469 patients with carcinoma of the endometrium were seen at this institution. Eighty-one patients were identified with adenocarcinoma involving both the uterine body and the cervix. Patients were divided into three groups for evaluation. Group A (n = 58) had a positive cervical biopsy or endocervical curettage, but a normal-appearing cervix at clinical examination. Group B (n = 18) had gross tumor involving the cervix which was confirmed by biopsy. Group C (n = 5) had unsuspected cervical involvement revealed at hysterectomy. Fourteen Group A patients received preoperative radiation therapy. Thirty of the 44 Group A patients (68.2%) who did not receive preoperative radiation, had no involvement of the cervix by tumor in the hysterectomy specimen. Seventy-six patients were eligible for follow-up of at least 18 months. There were 24 recurrences among these 76 patients. Recurrence was more common with advancing grade and with increasing myometrial invasion. Pelvic failures occurred with comparable frequency in both Groups A and B. Only 4 of 11 patients who were found to have extrauterine disease at surgery are still alive. In this study, we found that endocervical curettage has a significant false-positive rate, both histologic grade and volume of cervical involvement should be considered in treatment planning, primary operation should be considered in the management of selected patients with Stage II endometrial carcinoma, and extrauterine disease is a grave prognostic factor.

Adenocarcinoma↗
PubMed1986

Estrogen and progesterone receptors in uterine sarcomas.

Estrogen and progesterone receptors were measured in tissues from 43 patients with various uterine sarcomas using the dextran-coated charcoal assay. Estrogen receptor was present in 55.5% and progesterone receptor in 55.8% of samples, at median estrogen and progesterone receptor concentrations of 10.7 and 15.8 fmol/mg cytosol protein, respectively. These median values are much lower than those in 30 consecutive endometrial adenocarcinomas and 50 breast carcinomas assayed in our laboratory. Progesterone receptor status correlated strongly with estrogen receptor status in uterine sarcomas (P = .001). Estrogen and progesterone receptor levels were not influenced by stage, grade, or mitotic count. Patients 50 years of age or less had significantly higher progesterone receptor than those over 50. No such age effect was seen for estrogen receptor. Endometrial stromal sarcoma had higher estrogen and progesterone receptor levels than other histologic types. Low-grade endometrial stromal sarcomas had higher median estrogen receptors (238.9 fmol/mg) and better survival (all patients alive at 6-12 months) than did high grade (N = 7) endometrial stromal sarcomas (median ER = 6.6 fmol/mg, all dead of disease at 8-27 months). For all histologic types, evaluable patients with stage I or II disease (N = 16) were more likely to survive longer than one year than those with stage III or IV disease (N = 13, P = .003). Evaluable patients with estrogen receptor-positive sarcomas were more likely to survive longer than one year than those with estrogen receptor-negative tumors (P = .006). With one exception, an endometrial stromal sarcoma, hormonal therapy exerted no beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Abdominal sacral colpopexy with Mersilene mesh in the retroperitoneal position in the management of posthysterectomy vaginal vault prolapse and enterocele.

During a 12-year study period from 1972 to 1984, 56 patients underwent abdominal sacral colpopexy with retroperitoneal interposition of a suspensory hammock between a prolapsed vaginal vault and the anterior surface of the sacrum. They were followed from 6 months to 12 1/2 years, and constitute the basis of this report. In most patients, a synthetic mesh was the material interposed. Hysterectomy had previously been performed on 53 patients, and in two patients there was congenital absence of the uterus. Indications for abdominal sacral colpopexy, surgical technique, complications, and results of operation are discussed. Seven additional patients underwent this operation after termination of the defined study period.

Abdominal Muscles↗
PubMed1985

Second-look laparotomy after chemotherapy in the management of ovarian malignancy.

Eighty-eight patients with ovarian malignancy underwent second-look laparotomy as part of their plan of management at Indiana University Hospital. Thirty-five patients (39.8%) were found to have no gross or microscopic evidence of persistent neoplasm, and an additional 16 (18.2%) had only microscopic tumor. Patients with initial Stage III or IV disease were less likely to have negative findings at laparotomy than were patients with Stage I or II disease. A complete initial cytoreductive operation (residual disease = 0 cm) correlated positively with negative findings at laparotomy. Endometrioid histologic findings were associated with a favorable condition at the second look, but tumor grade was associated with superior survival only for patients with grade 0 disease. Eight of 30 patients (26.7%) with invasive carcinoma and negative findings at second-look laparotomy have had tumor recurrence (2 to 63 months), and five of eight have died. Intraperitoneal chromic phosphorus salvage therapy for patients with microscopic disease was promising, with eight of 15 treated patients (53.3%) alive after therapy, with no evidence of disease from 16 to 56 months after the second look. Second-look laparotomy has been the major determinant of continued or alternative therapy for patients with ovarian malignancy. Second-look laparotomy has been incorporated into the standard management plan without a formal clinical trial. The need for a second look may be reduced by identifying patients who do not benefit from the procedure. Patients with persistent disease confirmed by noninvasive means can continue therapy without laparotomy. There is also a subgroup of patients with a favorable prognosis whose therapy could be safely discontinued without laparotomy.

Adenocarcinoma↗
PubMed1985

Mitoxantrone (NSC 301739) in patients with advanced cervical carcinoma. A phase II study of the Gynecologic Oncology Group.

Twenty-six evaluable patients with advanced or recurrent squamous cell carcinoma of the uterine cervix were treated with mitoxantrone at a dosage of 12 mg/m2 every 3 weeks. Twenty-five of 26 patients had had prior irradiation and 24 prior chemotherapy. There were two partial responses, one in a patient with pelvic recurrence and another in a patient with a right upper quadrant mass. Progression-free intervals for these two patients were 5.1 and 4.6 months, respectively. Toxicity was moderate and consisted mainly of leukopenia. No septic or bleeding complications were observed. Mitoxantrone is minimally active in patients with advanced cervical cancer who have been previously treated.

Adult↗
PubMed1985

Group B streptococcal necrotizing fasciitis arising from an episiotomy.

A case of extensive necrotizing fasciitis arising from an episiotomy is presented. Group B beta-hemolytic streptococcus and Staphylococcus aureus were isolated. Prompt recognition and aggressive therapy resulted in a favorable outcome despite significant morbidity. Salient clinical features of this rare postpartum complication are discussed and previous cases are reviewed. In addition to wide surgical resection, therapy included aggressive volume resuscitation with Swan-Ganz catheter monitoring, the use of military antishock trousers (MAST suit) to control diffuse hemorrhage, and temporary application of porcine xenografts.

Abdominal Muscles↗
PubMed1984

Assessment of primary gynecologic malignancies: comparison of 0.15-T resistive MRI with CT.

Thirty-eight patients with gynecologic malignancies (ovarian, cervical, and endometrial carcinoma) underwent computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and pelvis. Results of these studies were compared with each other as well as with clinical staging and surgical findings when possible. CT and MRI correctly staged 64% (nine of 14) of patients with cervical carcinoma. In patients suspected of residual or recurrent disease, CT and MRI were each correct in 75% (15 of 20), four of the errors being due to inability to distinguish inflammation or radiation changes from recurrent tumor. CT and 0.15-T resistive MRI are of equal value in screening for residual or recurrent disease and as an adjunct to clinical staging; further advances in MRI technology may alter this impression.

Adult↗
PubMed1984

Necrotizing fasciitis of vulvar origin in diabetic patients.

Necrotizing fasciitis is a rare, rapidly progressive, and often fatal infection of the superficial fascia and subcutaneous tissues. The integrity of the deep muscle fascia is usually not breeched, thus limiting the depth of involvement. Centrifugal spread within the planes of the superficial fascia and subcutaneous tissues is characteristic. Patients with diabetes mellitus constitute the group most vulnerable to necrotizing fasciitis, and a vulvar or perineal origin is associated with particularly high mortality. The authors report four such patients. Other apparent predisposing factors are advancing age, peripheral vascular disease, chronic debilitating illness, malnutrition, and possibly other states predisposing patients to immunodeficiency. None of these factors is an absolute prerequisite to the development of necrotizing fasciitis.

Adult↗
PubMed1980

Endocrine changes at operation under general anesthesia: reproductive hormone fluctuations in young women.

This study investigated changes in peripheral serum estrogen (E), Progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone, and prolactin (PRL) in 11 women of reproductive age undergoing a variety of operations under general anesthesia without compromise of ovarian vasculature. All hormone determinations were plotted in relation to the midcycle LH peak; eight women with cyclic ovulatory menses served as controls. The absolute value of E declined after surgery but did not reach statistical significance. P levels postoperatively were significantly lower following ovulation (P less than 0.01) on cycle days +1 through +5. Intraoperative and postoperative PRL values were significantly greater than those of control subjects (P less than 0.05). Aside from a transient intraoperative decline in LH, the pattern of gonadotropin secretion was similar to that of control subjects. The decline in peripheral ovarian steroid levels appeared to be independent of abdominal entry or pelvic manipulation. The evidence favors direct inhibition of ovarian steroidogenesis by (1) toxic effects of anesthetic agents or (2) stress-induced changes in other hormone levels, e.g., hyperprolactinemia.

Adult↗
PubMed1976

An intra-ovarian site for the luteolytic action of estrogen in the rhesus monkey.

To investigate whether estradiol can act within the ovary to induce luteolysis in the rhesus monkey, 100 mug estradiol-17beta were injected on one of days 2, 3, or 4 after the preovulatory LH peak into one of the following sites: the stroma of the ovary containing the developing corpus luteum, the stroma of the contralateral ovary, or sc. When estradiol was injected into the ovary containing the corpus luteum, the functional life span of the corpus luteum was shortened, reflected by a premature decline in circulating progesterone to levels characteristic of the follicular phase of the cycle and an early onset of menstruation. When estradiol was injected either sc or into the ovary contralateral to that containing the corpus luteum, the life span of the corpus luteum was not shortened. The differing responses could not be attributed to differing rates of efflux of estradiol from the various injection sites; patterns and levels of estradiol in peripheral serum were essentially the same regardless of injection site. Furthermore, the premature regression of the corpus luteum was not a consequence of surgical trauma associated with the intra-ovarian injection procedure, nor could it be mimicked by another ovarian hormone, progesterone. These findings lead to the conclusion that estrogens can induce functional luteolysis in the rhesus monkey by acting directly within the ovary containing the corpus luteum.

Animals↗
PubMedDate not supplied

Discovery and development of a novel class of nonsteroidal aromatase inhibitors.

Efforts to develop a novel class of nonsteroidal aromatase inhibitors began with the discovery that the infertility in male rats exposed to high levels of the agricultural fungicide, fenarimol (alpha-(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidine-methanol), was attributable to the inhibition of aromatase activity within the central nervous system during the critical neonatal period. Although fenarimol was not particularly potent in inhibiting rat ovarian microsome aromatase activity in vitro (50% inhibition (IC50) = 4.1 microM). Subsequent testing of a number of analogues led to the identification of LY56110 (alpha,alpha-bis(4-chlorophenyl)-5-methylpyrimidine) which exhibited an IC50 of 29 nM. LY56110 was orally active, blocking the testosterone-induced increase of uterine weight and ovarian estrogen biosynthesis in immature female rats. In rats with established DMBA-induced mammary carcinoma, complete tumor regression was observed in 80% of the animals. Development of LY56110 was, however, stopped because of its effects on hepatic microsomal enzymes and an unacceptably long half-life. Structural modifications resulted in the development of the indenopyrimidines. LY113174 (8-chloro-5-(4-chlorophenyl)-5H-indeno less than 1, 2D greater than pyrimidine) was highly effective in vitro (IC50 = 24 nM) and in vivo but was far less potent than LY56110 with respect to induction of hepatic microsomal enzymes. LY113174 exhibited an acceptable biological half-life and had no effect on cholesterol side-chain cleavage. The indenopyrimidines appear to be a novel class of nonsteroidal aromatase inhibitors which may prove useful in the treatment of estrogen-dependent diseases.

Animals↗
PubMedDate not supplied

Magnetic resonance imaging in the preoperative assessment of clinical stage I endometrial carcinoma.

Magnetic resonance (MR) imaging may aid in preoperative treatment planning of endometrial carcinoma by accurately estimating tumor volume, depth of myometrial invasion, and extrauterine extension. Preoperative MR scans were obtained on 24 women with clinical stage I endometrial cancer. MR scans were evaluated for uterine size, as an indirect measure of tumor volume, and depth of myometrial invasion. MR detected deep invasion (greater than or equal to 50% of myometrial thickness) with a sensitivity of 71% and specificity of 83% (accuracy 79%) when compared with the pathologic findings. MR staging may assist in deciding which patients should have lymph node dissection at surgery and may aid in decisions regarding adjunctive radiation therapy.

Adult↗
PubMedDate not supplied

The risk of nodal metastasis in early adenocarcinoma of the uterine cervix.

A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1-IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20-65). The median time of follow-up was 30 months (4-124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI </= 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI > 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI </= 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI > 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI </= 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.

Adenocarcinoma↗
PubMedDate not supplied

Synergistic cytotoxic and antitumor effects of irradiation and taxol on human HeLa cervix carcinoma and mouse B16 melanoma cells.

Several articles have appeared in the scientific literature which report that taxol has the ability to block and/or prolong cells in the G2/Mp phase of the cell cycle by inducing extremely stable microtubules. The G2/M phase is known to be the most radiosensitive phase of the cell cycle. It is the purpose of this study to evaluate the effect of combination taxol and ionizing radiation on tumor cell lines which have not been previously reported in the literature. Decrease in viability and inhibition of proliferation of HeLa and B16 cells induced by irradiation were dose-dependent and significantly enhanced by pretreatment the cells with taxol. Similar antitumor effects of irradiation and taxol were demonstrated by flow cytometric analysis of chromatic fragment formation induced in these cells. The exact mechanism by which taxol enhanced the tumoricidal effect of irradiation is not known. Cell cycle analysis showed that taxol was effective in blocking HeLa and B16 cells at the G2/M stage, at which the tumor cells are believed to be most sensitive to irradiation. This study is in agreement with others who have found that taxol is a powerful radiation sensitizer. Clinical research protocols have been developed and are under way to determine if taxol produces similar synergistic effects in patients undergoing radiation therapy.

Animals↗
PubMedDate not supplied

Increased thymidine kinase and thymidylate synthase activities in human epithelial ovarian carcinoma.

BACKGROUND: Thymidylate synthase (dTMP synthase, EC 2.1.1.45) is responsible for the de novo biosynthesis of thymidylate (dTMP) whereas thymidine kinase (TdR kinase, EC 2.7.1.21) is the salvage enzyme which leads to the production of dTMP even in presence of d TMP synthase inhibition. The current study was undertaken to compare the steady-state activities of d TMP synthase and TdR kinase in extracts of human epithelial ovarian carcinoma and normal ovaries. MATERIAL AND METHODS: Tissue extracts of epithelial ovarian carcinomas and normal ovaries were analyzed for activities of d TMP synthase (by a method that measures released 3H2O) and TdR kinase (by polyethyleneimine impregnated (PEI) cellulose plate radioassay), methods established in this laboratory. RESULTS: The dTMP synthase activity (mean +/- S.E.) in extracts of ovarian carcinomas (N = 11) was 0.198 +/- 0.069 and in extracts of normal ovaries (N = 12) it was 0.025 +/- 0.0004 nmol/hr/mg protein. By contrast, TdR kinase activity in extracts of ovarian carcinoma (N = 13) was 27.7 +/- 8.5 compared to 1.0 +/- 0.3 nmol/hr/mg protein in extracts of normal ovaries (N = 15). CONCLUSION: The observed 140-fold higher TdR kinase activity suggests that DNA synthesis may continue despite inhibition of dTMP synthase with current schedules of 5-fluorouracil (5-FU) and leucovorin. The addition of azidothymidine, a competitive inhibitor of TdR kinase, to 5-FU and leucovorin might be a rational biochemical strategy to employ in patients with refractory ovarian carcinoma.

Adult↗