Search PubMed⌕ Search

Biomedical subjects

D H Moore

Publications and source records attributed to D H Moore.

At least 73 records · Page 4Linked to original sources

A prospective controlled trial of early postoperative oral intake following major abdominal gynecologic surgery.

OBJECTIVE: The objective was to determine whether, when compared with traditional dietary advancement, early oral intake following major gynecologic surgery leads to a reduction in the length of hospitalization. METHODS: Patients undergoing major abdominal gynecologic surgery were invited to participate in this study. After informed consent was obtained, they were randomized to one of two groups. The control group (group 1) was treated traditionally. Oral intake was initiated only after documentation of bowel function, which was defined by two of the following three criteria: (1) bowel sounds; (2) flatus or bowel movement; and (3) subjective hunger. Those assigned to the study group (group 2) were given a clear liquid diet on postoperative day 1. Once 500 cc was tolerated, a regular diet was given. Patients were evaluated on a daily basis for bowel sounds, flatus, bowel movement, hunger, nausea, vomiting, and need for nasogastric tube decompression. The groups were compared with regard to length of hospital stay, length of postoperative ileus, and incidence of adverse effects including nausea, vomiting, and postoperative complications. Statistical analyses were performed with the Student t and chi 2 tests. RESULTS: The demographic characteristics of the control (N = 47) and study groups (N = 49) were similar, with no significant differences in underlying medical conditions, prior abdominal surgery, or diagnosis of a malignancy. The groups did not vary statistically in the number of subjects who required postoperative antiemetics or postoperative biscodyl suppository. There was a statistically significant reduction in the length of hospitalization for those patients on the early feeding regimen. The average length of stay for group 1 was 4.02 days +/- 0.30 (SEM), while that for group 2 was 3.12 days +/- 0.16 (P = 0.008). While there was a significantly higher incidence of emesis in the study population, this was not associated with any untoward outcome, and this group actually tolerated a solid diet nearly one full day earlier (2.72 days +/- 0.14 vs 1.88 days +/- 0.14, P < 0.0001). CONCLUSIONS: Early postoperative oral intake results in a decreased length of hospitalization and is well tolerated when compared with traditional dietary management in patients undergoing abdominal surgery on a university gynecologic oncology service.

Enteral Nutrition↗

Chromosomal alterations in ulcerative colitis-related neoplastic progression.

BACKGROUND & AIMS: It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. METHODS: Fluorescence in situ hybridization (FISH) was performed on nuclei dissociated from sites of cancer, dysplasia, and UC-involved nondysplastic epithelium in five UC-related cancer colectomy specimens using a panel of pericentromeric probes. Comparative genomic hybridization (CGH) was used to detect clonal chromosomal losses and gains in DNA extracted from these sites. RESULTS: FISH analysis revealed significant and often dramatic alterations in chromosome copy number compared with controls in all biopsy specimens of cancer, dysplasia, and nondysplastic UC-involved epithelium. Clonal chromosomal losses and gains were detected by CGH in all but one analyzed site of dysplasia and cancer and in two of the five nondysplastic sites. FISH and CGH frequently detected the relative loss of chromosome 18. CONCLUSIONS: Chromosomal alterations may occur early in UC-related neoplastic progression and seem to precede the histological development of dysplasia. Relative loss of 18q may be important in the progression of UC-related neoplasia. The detection of chromosomal alterations as an intermediate end point may prove useful in identifying patients at high risk for the development of colorectal cancer.

Adult↗

Vulvar keratoacanthoma.

BACKGROUND: Keratoacanthomas are neoplastic proliferations of keratinocytes thought to originate from follicular epithelium. There is only one previously reported case in which keratoacanthoma involved the vulva. CASE: A 54-year-old woman presented with a nonulcerated vulvar lesion of approximately 1 month's duration. The lesion was 1 cm in diameter, located on the mid-right labium majus, with no surrounding induration or hyperkeratosis. The patient underwent wide local excision and the clinical-pathologic diagnosis was keratoacanthoma. After 2 years, she remains free of vulvar recurrence. CONCLUSION: Because of similarities in clinical presentation and histology to squamous cell carcinoma, the diagnosis of keratoacanthoma can be challenging. History and physical examination findings should be correlated with the histologic diagnosis, with consideration for dermatopathology consultation.

Diagnosis, Differential↗

A study of the effects of exposure on cleanup workers at the Chernobyl nuclear reactor accident using multiple end points.

Blood samples were collected from 192 exposed workers who participated in the cleanup after the April 26, 1986, nuclear reactor accident at Chernobyl, Ukraine. These samples, together with samples from 73 individuals living in Russia but not involved in Chernobyl cleanup activities, were collected during September 1991 to May 1996 and shipped to the U.S. for evaluation by three bioassays: cytogenetic analysis based on chromosome painting, HPRT mutation analysis and glycophorin A (GPA) variant analysis. Univariate statistical analyses of the results of each bioassay (including adjustments for age, smoking status and estimated precision of the bioassay) found greater frequencies of chromosome translocations and HPRT mutant T lymphocytes among the exposed individuals compared to the controls (P < or = 0.01). GPA analyses showed no significant difference for exposed compared to controls for either hemizygous, N/O, or homozygous, N/N, variant cell frequency. Multivariate analysis of variance of the subset of 44 exposed and 14 unexposed individuals with measurements from all three bioassays found elevated frequencies of chromosomal translocations and HPRT mutants, and reduced frequencies for both GPA end points among the exposed persons compared to the controls. However, none of these differences, considered singly or in combination, was statistically significant (although statistical power is low due to small sample sizes). Mean estimated dose, based on cytogenetic response, for those exposed was 9 cGy (range 0 to 51 cGy) and was less than that estimated by physical dosimetry (25 cGy). Correlation between the end points of the bioassays and estimated physical dosimetry was low (r < 0.2); the only significant correlation found was for physical dose estimate and dates worked at Chernobyl (r = 0.4, P < 0.01), with those working soon after the accident receiving greater estimated doses.

Adolescent↗

Analysis of Bax and Bcl-2 expression in p53-immunopositive breast cancers.

Bax and Bcl-2 are proteins that regulate programmed cell death and apoptosis. The expression of these proteins can be regulated, at least in part, by the tumor suppressor p53, but the effects of p53 are highly tissue specific. In an effort to better understand the relation between p53 and the in vivo control of the expression of Bax and Bcl-2 in adenocarcinomas of the breast, we evaluated by immunohistochemistry the expression of Bcl-2 and Bax in 149 invasive ductal carcinomas, 135 of which were chosen because of their p53 immunopositivity. The percentages of Bcl-2-immunopositive tumor cells were significantly lower in the p53-positive (median 20%) subsets as compared to the p53-negative (median 85%) subsets (P = 0. 004). Comparisons of the percentages of p53-immunopositive tumor cells with the percentages of Bcl-2- and Bax-positive cells (as continuous variables) revealed a significant inverse correlation between Bcl-2 and p53 (r = -0.41, P < 0.001) but not between Bax and p53. In the p53-positive subset, the percentages of Bax- and Bcl-2-immunopositive tumor cells were correlated positively (r = 0. 27, P = 0.002), suggesting that the expression of these genes may be co-regulated to some extent in these breast cancers. Higher percentages of Bcl-2-positive tumor cells were also associated with estrogen receptor positivity (P = 0.03), low histological tumor grade (P = 0.03), and low T stage (P = 0.02), whereas Bax immunostaining was associated only with c-erbB-2 immunopositivity (P = 0.02). Although the number of cases was small and treatment was non-uniform, preliminary correlations with clinical outcome data suggest that the prognostic significance of Bcl-2 may be enhanced by inclusion of Bax data in patients with p53-immunopositive adenocarcinoma of the breast, at least for patients with node-negative disease. Taken together, these data suggest that, despite the ability of p53 to bind directly to the Bax gene promoter, the regulation of Bax in human breast cancers does not necessarily correlate with p53 status, implying that regulation of this pro-apoptotic gene in these tumors is complex and probably influenced by several factors.

Breast Neoplasms↗

Interlaboratory variability in fluorescence in situ hybridization analysis. The NCI Bladder Tumor Marker Network.

Reliable interpretation of fluorescence in situ hybridization (FISH) data, especially data that have been generated in more than one laboratory, requires knowledge of the sources of variability inherent in FISH analysis. Possible sources of variation may derive from differences in sample preparation, probes used, intrasample heterogeneity, hybridization protocols, counting criteria within and between scorers, fluorescence microscopes, and filters. This study characterized the relative weight of some of these factors in order to determine the degree to which FISH results are comparable between laboratories. We used a hierarchical partitioned chi 2 analysis to measure sources of variation. We found that replicate counts varied no more than expected based on counting statistics (i.e., multinomial variation). However, with replicate hybridizations done in two separate laboratories, the variability increased significantly. Thus, care must be taken when interpreting FISH data that are derived from more than one institution. Previously agreed upon counting criteria as well as standardized FISH hybridization protocols may decrease this variability.

Chi-Square Distribution↗

Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping.

A newly developed method of comparative genomic hybridization (CGH) employing quantitative statistical comparisons was applied to DNA from two different types of advanced prostate cancer tissue. Multiple CGH analyses were obtained for each chromosome in each tumor, and the results of point-by-point comparison of the mean tumor:normal color ratio to a control normal:normal color ratio in each of 1247 evenly distributed data channels constituting the entire human genome were interpreted as loss, gain, or no change in copy number in the tumor genome. Group I tissue was obtained from prostate cancer metastases from 20 patients, 19 of whom had received no prior prostate cancer treatment. This DNA also was analyzed by Southern and microsatellite allelotyping at 53 different loci on 20 different chromosome arms. CGH results agreed with allelotyping results at 92% of the informative loci studied. These samples, which contained highly enriched tumor DNA, showed the highest rates of alteration yet reported in several chromosomal regions known to be altered frequently in prostate cancer: 8q gain (85%), 8p loss (80%), 13q loss (75%), 16q loss (55%), 17p loss (50%), and 10q loss (50%). Group II tissue was obtained predominately from primary or recurrent tumor from 11 patients who had been treated with long-term androgen-deprivation therapy and developed androgen-independent metastatic disease. Quantitative CGH analysis on DNA from these tissues showed chromosomal alterations that were very similar to those found in group I, suggesting that untreated metastatic tumors contain the bulk of chromosomal alterations necessary for recurrence to occur during androgen deprivation. In the entire data set, a number of previously undetected regions of frequent loss or gain were identified, including losses of chromosomes 2q (42%), 5q (39%), 6q (39%), and 15q (39%) and gains of chromosomes 11p (52%), 1q (52%), 3q (52%), and 2p (45%). Chi-squared analysis showed a significantly higher frequency of gain of the 4q25-q28 region in tumors from African-American patients, indicating a possible oncogene whose activation may play a role in the higher rate of progression seen in this ethnic group. Additional study of these frequently altered regions may provide insight into the mechanism of prostate cancer progression and lead to important tools for tumor-specific prognosis and therapy.

Adult↗

Micronuclei induced in round spermatids of mice after stem-cell treatment with chloral hydrate: evaluations with centromeric DNA probes and kinetochore antibodies.

The chromosomal effects of chloral hydrate (CH) on germ cells of male mice were investigated using two methods to detect and characterize spermatid micronuclei (SMN); (a) anti-kinetochore immunofluorescence (SMN-CREST) and (b) multicolor fluorescence in situ hybridization with DNA probes for centromeric DNA and repetitive sequences on chromosome X (SMN-FISH). B6C3F1 mice received single intraperitoneal (i.p.) injections of 82.7, 165.4, or 413.5 mg/kg and round spermatids were sampled at three time intervals representing cells treated in late meiosis, early meiosis, or as spermatogonial stem cells. No increases in the frequencies of SMN were detected for cells treated during meiosis using either SMN-CREST or SMN-FISH methods. After spermatogonial stem-cell treatment, however, elevated frequencies of SMN were detected by both methods. With SMN-FISH, dose trends were observed both in the frequencies of spermatids containing micronuclei and in the frequency of spermatids carrying centromeric label. These findings corroborate the recent report by Allen and colleagues [Allen JW et al.(1994): Mutat. Res. 323:81-88] that CH treatment of spermatogenic stem cells induced SMN. Furthermore, our findings suggest that chromosomal malsegregation or loss may occur in spermatids long after CH treatment of stem cells. Further studies are needed to understand the mechanism of action of the CH effect on stem cells and to determine whether similar effects are induced in human males treated with CH.

Anesthetics, Intravenous↗

Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolour fluorescence in situ hybridization painting.

We describe a fluorescence in situ hybridization (FISH) procedure for assessing zygotic risk of paternal exposure to endogenous or exogenous agents. The procedure employs multicolour FISH with chromosome-specific DNA painting probes plus DAPI staining for detecting both balanced and unbalanced chromosomal aberrations in mouse first-cleavage (1-Cl) zygote metaphases. Four composite probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a composite probe specific for chromosome Y labelled with digoxigenin, were used. We applied this method to evaluate the effects of paternal exposure to acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases, collected from untreated females mated to males whose sperm or late spermatids were treated with acrylamide, were scored for the induction of structural aberrations using both chromosome painting (PAINT analysis) and DAPI analysis. Structural chromosomal aberrations were observed in the sperm-derived, but not in the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT analysis (P < 0.001), illustrating the increased sensitivity for detecting translocations and insertions obtained by adding chromosome painting. These findings show that FISH painting of mouse 1-Cl zygotes when used in conjunction with DAPI analysis is a powerful model for investigating the cytogenetic defects transmitted from father to offspring.

Animals↗

Primary liver transplantation without transfusion of red blood cells.

BACKGROUND: This study examines factors associated with the performance of orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion. METHODS: Between January 1992 and December 1994, 306 primary OLTs were performed with recipients divided into two groups: group 1 patients (61 recipients, 20% of total) underwent transplantation without packed RBCs, and group 2 patients (245 recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs during operation. RESULTS: Recipients in group 1 compared with group 2 had less advanced liver disease (20% hospitalized and 48% Child's class C versus 58% hospitalized and 73% Child's class C, p < 0.01) and lower frequency of right upper quadrant surgery (13% versus 25%, p < 0.05). Group 1 recipients also had significantly higher preoperative hematocrits (38% versus 33%, p < 0.01), lower prothrombin times (15.4 versus 16.7 seconds, p < 0.001) and partial thromboplastin times (36.9 versus 42.2 seconds, p < 0.01), a greater proportion of patients transplanted by piggyback technique (87% versus 59%, p < 0.001), and shorter operative times (7.9 hours versus 9.2 hours, p < 0.001). Moreover, a greater percentage of patients underwent OLT without RBC transfusion in each successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p < 0.001). Logistic regression analysis showed the following factors to be independent predictors of OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing status, piggyback technique, operative time, and year of transplantation. CONCLUSIONS: OLT can be performed without transfusion of RBCs in recipients with less advanced liver disease, and surgical technique, along with increased experience by the transplant team, are important factors.

Adolescent↗

The importance of age and smoking in evaluating adverse cytogenetic effects of exposure to environmental agents.

Fluorescence in situ hybridization with chromosome-specific composite DNA probes (chromosome painting) is a reliable and efficient method for detecting structural chromosome aberrations. Painting is now being used to quantify chromosome damage in many human populations. In one such study we evaluated 91 unexposed people ranging in age from birth (cord bloods) to 79. We established a baseline frequency of stable aberrations that showed a highly significant curvilinear increase with age (p < 0.00001) that accounted for 70% of the variance among donors. The magnitude of this effect illustrates the importance of understanding the cytogenetic changes that occur with age, which is particularly important for quantifying the effects of prior adverse environmental, occupational, or accidental exposure. In this paper we use the data obtained in our previous study to characterize the distribution of stable aberrations by age and pack-years of cigarette smoking. We also provide estimates of the number of cell equivalents that need to be scored to detect a given increase in aberrations above the background level surveyed in this population.

Adolescent↗

What is the appropriate management of early stage cervical cancer (International Federation of Gynecology and Obstetrics stages I and IIA), surgical assessment of lymph nodes, and role of therapeutic resection of lymph nodes involved with cancer?

It is well recognized that lesion size, tumor volume, depth of stromal invasion, and lymphatic space permeation are all important predictors of lymph node involvement in early stage cervical cancer. Pelvic lymph node involvement is the most important (negative) predictor of survival for these patients with early stage cervical cancer. The number of involved nodes and the size of involved and unresected nodes may also be prognostically significant. It is uncertain whether lesion size, tumor volume, depth of stromal invasion, or lymphatic space permeation are independent negative predictors of survival when correcting for lymph node positivity. Lymphadenectomy has traditionally been considered a diagnostic procedure. There is accumulating evidence to suggest that lymphadenectomy may have therapeutic benefit for patients with cervical cancer metastatic to lymph nodes. This hypothesis awaits further evidence.

Female↗

Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma.

BACKGROUND: Tumor angiogenesis, as assayed by microvessel density, has been proposed as an independent prognostic marker for clinical outcome in breast cancer patients. PURPOSE: The present study evaluated the microvessel density assay and assessed its utility, alone and together with the evaluation of other tumor characteristics, in predicting outcome in patients with invasive ductal carcinomas. METHODS: In a blinded design, cases of invasive ductal carcinoma were selected from a registry containing the records of and tumor specimens from 386 breast cancer patients treated at the Massachusetts General Hospital from 1977 through 1982. After the exclusion of ineligible patients and inadequate specimens, 220 patients were included in the study; their median time of follow-up was 11.5 years. Half of these patients (n = 110) were positive for axillary lymph node metastases. Histologic sections of the tumors were stained immunocytochemically for factor VIII, a coagulation protein expressed by blood vessel endothelium, and for p53 protein. Independently, two analysts counted microvessels in three microscope fields selected from separate vascular regions of the tumor. Variability in microvessel scores between analysts and among different fields of the same tumor was summarized by the coefficient of variation. The kappa statistic tested for agreement between the analysts while correcting for chance agreement. The effects of tumor characteristics on metastasis-free survival and overall survival were tested univariately by the Harrington-Fleming rank test procedure. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. RESULTS: Microvessel count showed considerable variability between the two analysts and among regions within each tumor, with an overall concordance for tumor classification of 73%. Univariate analysis revealed no association between microvessel count and any other tumor or patient characteristic. Multivariate analysis indicated, for these patients, that nodal status and p53 staining predicted metastasis-free survival and that nodal status, estrogen receptor (ER) status and tumor grade predicted overall survival. CONCLUSIONS: Microvessel count showed much variation among different regions of each tumor. It did not predict metastasis-free survival or overall survival. Nodal status was the most powerful criterion to stratify these patients with invasive ductal carcinoma of the breast into different survival groups. Only ER status, tumor grade, and p53 staining had additional prognostic utility for these patients after they had been stratified by nodal status.

Analysis of Variance↗

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments.

To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (Mf), and glycophorin A (GPA) variant erythrocytes (Vf) of both allele-loss (phi/N) and allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean hprt Mf (1.40 +/- 1.11 x 10(-6), N = 66) and GPA Vf (phi/N 4.0 +/- 2.2 x 10(-6), N = 114; N/N 2.7 +/- 2.0 x 10(-6), N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt Mf was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 +/- 0.41 x 10(-6), N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt Mf (0.70 +/- 0.49 x 10(-6)) of this selected population was consistent with the published report and significantly lower than that of our initial population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated Mf revealed a significant decrease in the relative contribution of gross structural mutations to the overall Mf (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, chi 2 test), suggesting that the higher Mf resulted from an elevated level of "point" mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt Mf or GPA Vf.

Adult↗

A phase I study of intraperitoneal interferon-alpha 2b and intravenous cis-platinum plus cyclophosphamide chemotherapy in patients with untreated stage III epithelial ovarian cancer: a Gynecologic Oncology Group pilot study.

Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively. No patient completed planned treatment without interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.

Adenocarcinoma↗

The fate of the ovaries after radical hysterectomy and ovarian transposition.

To assess the effectiveness of lateral ovarian transposition in preserving normal ovarian function, the medical records of 200 consecutive women with stage I-IIA cervical cancer treated primarily with radical hysterectomy and pelvic lymphadenectomy were reviewed. Lateral ovarian transposition was performed at the time of radical hysterectomy in 132 (66%) patients and 28 (21%) received postoperative pelvic radiation therapy. Menopausal symptoms (vaginal dryness, hot flushes) and follicle-stimulating hormone (FSH) levels were used to define ovarian function. Only 3/104 (2.9%) patients who underwent lateral ovarian transposition without postoperative pelvic radiotherapy experienced menopausal symptoms; however, FSH levels in all three cases suggested continued ovarian function. In 14/28 (50%) patients who received postoperative pelvic radiation therapy ovarian failure occurred. The risk of ovarian failure with pelvic radiation therapy after lateral ovarian transposition was significant (RR = 17.3; 95% CI = 5.35-56.13). The incidence of adnexal disease in transposed ovaries requiring analgesics or further surgery was 3%. These data suggest minimal risk to the patient when the ovaries are conserved. Unfortunately, lateral ovarian transposition preserves ovarian function in only 50% of patients undergoing pelvic radiotherapy following radical hysterectomy.

Adult↗

Immunohistochemical analysis of alpha 1-integrins in cervical cancer.

OBJECTIVE: The purpose of this study was to determine and compare the expression of the alpha 2-, alpha 3-, alpha 4- and alpha 5-subunits of the beta 1-family of integrins in both the normal and the carcinomatous cervix. STUDY DESIGN: A total of 22 solid tissue specimens (18 cancer and 4 normal) were analyzed immunohistochemically. The double-stain technique used an avidin-biotin complex kit to identify the various integrins and alkaline phosphatase-anti-alkaline phosphatase kit to identify the epithelial cells. Staining intensity, the main outcome measured, was graded as absent, weak, moderate, or strong. Statistical analysis was performed with the Wilcoxon rank sum test for nonparametric data. RESULTS: The alpha 2- and alpha 3-integrins stained the normal cervix epithelium more intensely than the stroma (p = 0.03). The alpha 4- and alpha 5-integrins stained both the stroma and the normal epithelium similarly. The alpha 2-integrin was absent in the stroma of all 18 cancer specimens despite being present in the epithelial regions of 14 to 18 cancers. The alpha 3-integrin had a greater staining intensity in the stroma of the cancers than in the epithelial regions (p = 0.002). Both alpha 4- and alpha 5-integrins were absent in the epithelial regions of the cancers but present in the stroma. CONCLUSIONS: The distribution and intensity of integrin expression in cervical cancer differ from their expression in the normal cervix. In particular, the fibronectin receptors, alpha 4 and alpha 5, were absent in the epithelial regions of the cervical cancers, and alpha 3 also had diminished expression in the malignant epithelium. These changes correlate well with the changes expected in malignant transformation.

Antigens, CD↗

Use of the APACHE II scoring system to determine mortality of gynecologic oncology patients in the intensive care unit.

OBJECTIVE: To determine if an elevated score on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is associated with mortality of acutely ill gynecologic oncology patients. METHODS: Gynecologic oncology patients admitted to the surgical intensive care unit (ICU) were identified from the ICU data base. Their admission APACHE II score and type of gynecologic cancer were also extracted from the data base. Charts were reviewed to determine the disease status and reason for admission to the surgical ICU. Patient mortality was correlated with APACHE II scores. RESULTS: Forty-five gynecologic oncology patients were admitted to the surgical ICU from June 1988 to January 1992. They had a mean age of 62 years and various cancers: ovarian (24), cervical (16), and endometrial (five). The mean APACHE II score was 12 (range 2-26). Eight of 45 (18%) patients died. There was a significant correlation between APACHE II scores and mortality; patients with an APACHE II score of 20 or greater had a 78% risk of death compared to a 3% risk if the score was less than 20 (P < .001, chi 2 test). CONCLUSION: Elevated APACHE II scores are associated with mortality in acutely ill gynecologic oncology patients.

APACHE↗