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K J Manahan

Publications and source records attributed to K J Manahan.

11 recordsLinked to original sources
PubMed2004

Heat shock protein 27 in the placentas of women with and without severe preeclampsia.

BACKGROUND: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls. METHODS: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27. RESULTS: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046). CONCLUSION: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Adolescent↗
PubMed2004

HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up.

OBJECTIVE: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up. METHODS: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients. CONCLUSION: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Adenocarcinoma, Clear Cell↗
PubMed2004

Evaluation of DNA methylation in the human genome: why examine it and what method to use.

PURPOSE: Since its discovery 50 years ago, DNA methylation has been found to be an important part of gene regulation. Newer methods of analysis over the last decade have helped further the understanding of this epigenetic phenomenon. The purpose of this article is to describe current methods of analysis and discuss advantages and disadvantages of each and their possible roles in gynecologic malignancies. RESULTS: The methods for analysis of DNA methylation are divided into two major categories: 1) methods which utilize chemical methods or restriction enzymes to differentially cleave at cytosine versus 5-methylcytosine sites, 2) methods which utilize sodium bisulfite (NaHSO3) to specifically convert unmethylated cytosines to uracil (thymine after PCR). This recently developed method appears to be more sensitive and allows the investigator to specifically delineate the study site(s). CONCLUSION: DNA methylation is important in the human genome. Its role in tumorigenesis is just beginning to be understood. While relying upon newly designed methods of analysis, further understanding of this epigenetic phenomenon and its role in gene expression and tumorigenesis will be forthcoming.

DNA Methylation↗
PubMed2004

Chemotherapy for ovarian cancer: an evidence-based approach.

Although cytoreductive surgery is the most influential factor in treatment for ovarian cancer, chemotherapy is needed for almost all patients diagnosed with this disease. The mainstay of chemotherapy is platinum. Different platinum compounds are used for different histologies, and different combinations are used for different histologies also. We will present the data so that each reader can understand the knowledge behind chemotherapy decisions.

Antineoplastic Agents↗
PubMed2001

Clonal heterogeneity of p53 mutations in ovarian cancer.

We analyzed clonal populations of ovarian cancer cells for heterogeneity in p53 mutations (exons 4-9) and chemosensitivity. UL-3A cells were developed from a patient with stage IIIC ovarian adenocarcinoma. Heterogeneity in p53 mutations was demonstrated, ranging from point mutations to deletions in exons 4, 6 and 7. UL-3A cells contained two point mutations, in codon 248 of exon 7 and in codon 76 of exon 4. Five groups of clones were identified according to the p53 mutations. UL-3A clones with low p53 levels were more sensitive to CDDP (LD50 <8.0 microg/ml). Heterogeneity of p53 mutations may provide growth advantage during disease progression or chemotherapy.

Antineoplastic Agents↗
PubMed1999

Loop electrosurgical excision procedure for partial upper vaginectomy.

OBJECTIVES: Partial upper vaginectomy consists of removal of the vaginal apex and is indicated for the diagnosis and treatment of vaginal intraepithelial neoplasia and recurrent cancer. We present a novel surgical approach to partial upper vaginectomy by use of the loop electrosurgical excision procedure. STUDY DESIGN: A total of 15 consecutive patients with abnormal vaginal cytologic results were treated by the loop electrosurgical excision procedure for partial upper vaginectomy. After submucosal injection of local anesthetic, the loop electrode was used to resect the upper third of the vagina. An iodoform vaginal pack was placed for 24 hours. All patients with high-grade vaginal intraepithelial neoplasia received intravaginal 5-fluorouracil cream postoperatively. RESULTS: The mean blood loss was 0 mL, and the mean surgical time was 30 minutes. A complication developed in 1 patient (7%). One case of invasive carcinoma was diagnosed. No recurrences have developed in any patients with vaginal intraepithelial neoplasia after hysterectomy. CONCLUSIONS: The loop electrosurgical excision procedure for partial upper vaginectomy can be performed quickly, with minimal blood loss, minimal complications, and minimal recurrence of neoplasia, and it provides a histologic specimen for evaluation.

Adult↗
PubMed1999

Peritoneal fluid urea nitrogen and creatinine reference values.

OBJECTIVE: To evaluate urea nitrogen and creatinine levels in peritoneal fluid. METHODS: We prospectively evaluated 20 consecutive women having radical hysterectomy with lymphadenectomy. On postoperative days 2 and 3, serum, urine, and peritoneal fluid samples were tested for urea nitrogen and creatinine. Using power analysis we calculated an adequate sample size to be 16 patients. RESULTS: The mean urea nitrogen was 11 mg/dL in serum, 11 mg/dL in peritoneal fluid, and 469 mg/dL in urine. The mean creatinine was .9 mg/dL in serum, 1.0 mg/dL in peritoneal fluid, and 141 mg/dL in urine. Urea nitrogen and creatinine values in peritoneal fluid and serum were essentially identical. Urine urea nitrogen and creatinine values were significantly greater than serum and peritoneal values (47 to 157 times greater) (P < .011). On postoperative days 2 and 3, serial levels of serum, peritoneal fluid, and urine urea nitrogen and creatinine in the same subject showed no significant variation (P ranging from .19 to .31). CONCLUSION: Normal reference values of urea nitrogen and creatinine in peritoneal fluid are equivalent to serum values and significantly less than urine levels.

Adult↗
PubMed1997

Modified radical vulvectomy without lymphadenectomy under local anesthesia in medically compromised patients.

INTRODUCTION: Our objective was to review our experience with vulvar cancer treated with modified radical vulvectomy without lymphadenectomy under local anesthesia and sedation. METHODS: A retrospective review of surgical case lists revealed five patients who underwent modified radical vulvectomy without lymphadenectomy under local anesthesia with sedation. All patients had significant medical diseases which precluded regional or general anesthesia. Modified radical vulvectomy was performed in standard fashion under sedation and local anesthesia. Inguinal lymphadenectomy was not performed. RESULTS: Median operative time was 1.5 h and median blood loss was 100 cc. Median diameter of tissue resected was 5 cm and median depth was 5 cm. Median length of hospital stay was 4 days. No patient complained of pain during the operative procedure. At a median follow-up of 2.5 years, there has been one local recurrence. CONCLUSION: Five patients with symptomatic vulvar cancer who were not candidates for regional or general anesthesia underwent modified radical vulvectomy without lymphadenectomy under local anesthesia with sedation. The procedure was well-tolerated and produced minimal morbidity and adequate short-term local control.

Aged↗
PubMedDate not supplied

Nuclear and cytoplasmic c-myc staining in endometrial carcinoma and their relationship to survival.

OBJECTIVE: The role of the c-myc proto-oncogene in genomic instability is just becoming more fully understood. However, its role in endometrial cancer is essentially unknown. The objective of this study was to determine the relationship between cytoplasmic and nuclear c-myc staining, DNA index, and survival in patients with endometrial carcinoma. METHODS: One hundred and twenty-one patients with endometrial carcinoma were studied. Image analysis was used to determine DNA index. In addition to cytoplasmic and nuclear c-myc staining and DNA index, histologic type, stage, grade, depth of invasion, lymphvascular space invasion, and peritoneal cytology were evaluated as prognostic indicators. Univariate and multivariate analyses were performed. RESULTS: One hundred and twenty-one patients were followed for over 5 years. c-myc cytoplasmic staining was present in 75.2% of the patients' tumors, and nuclear staining was present in 66.9% (P = 0.99). DNA index was significantly higher in patients with nuclear c-myc staining and no cytoplasmic staining (DNA index 1.38) as compared to those patients whose tumors displayed cytoplasmic c-myc staining but no nuclear c-myc staining (1.18) (P = 0.016). Patients whose tumors stained positively for nuclear c-myc and negatively for cytoplasmic c-myc had significantly worse survival by Kaplan-Meier analysis (P < 0.0001). Seventeen patients died during the follow-up period of this study. By multivariate analysis, positive cytoplasmic c-myc staining with negative nuclear staining (P = 0.0076), negative cytoplasmic c-myc staining with positive nuclear staining (P = 0.011) and FIGO stage (P < 0.0001) were shown to be independent prognostic indicators predictive of survival. CONCLUSION: Nuclear and cytoplasmic c-myc staining, as well as FIGO stage, when assessed by multivariate analysis, were demonstrated to be important factors in predicting survival in the 121 patients in this study. While increasing FIGO stage was prognostic of decreased survival, the specific location of c-myc staining was also associated with prognosis. The expression of the c-myc protein is related to survival in patients with adenocarcinoma of the endometrium.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Nuclear size, shape, and density in endometrial carcinoma: relationship to survival at over 5 years of follow-up. Does analyzing only cells occupying the G0-G1 peak add useful information?

OBJECTIVE: The authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0-G1 peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up. METHODS: Tumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis. RESULTS: Fifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1 only) values (both P < 0.001). Multivariate analysis showed both the original (P = 0.0001) and G0G1-only (P = 0.046) NUSZ and the original (P = 0.0002) and G0G1-only (P = 0.018) NUSD to be independent prognosticators of survival. CONCLUSION: Image analysis is able to quantify cellular and nuclear parameters not otherwise quantifiable. NUSD and NUSZ correlated with traditional prognostic indicators, were demonstrated independent predictors of survival at over 5 years of follow-up. Although the re-measured NUSZ and NUSD from only the G0-G1 peak were significantly different from the original NUSZ and NUSD, they were not as valuable as prognostic factors. Nuclear size and summed optical density measured from the entire cell cycle are independent prognostic indicators of survival at greater than 5 years of follow-up. Measuring nuclear morphometric features in the G0-G1 peak only does not add any new prognostic information.

Adenocarcinoma, Clear Cell↗