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Biomedical subjects

E J Thomas

Publications and source records attributed to E J Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1998

Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage.

Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.

Adult↗
PubMed1998

Historical prospective cohort study of the recurrence of pain after discontinuation of treatment with danazol or a gonadotropin-releasing hormone agonist.

OBJECTIVE: To determine the duration of time to the recurrence of pain attributable to endometriosis after the discontinuation of treatment with danazol or a GnRH agonist (GnRH-a) in patients who have had a satisfactory response to the treatment. DESIGN: Retrospective study. SETTING: Nine academic medical centers in three countries. PATIENT(S): Three hundred twenty-seven women with diagnosed and staged endometriosis who were treated with at least 6 months of danazol or a GnRH-a and who experienced significant pain relief with therapy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Duration of pain relief after completion of treatment as determined by a patient-initiated report of pain recurrence or increase in pain severity requiring intervention. RESULT(S): The median time to the recurrence of pain was 6.1 months for patients treated with danazol and 5.2 months for patients treated with a GnRH-a. CONCLUSION(S): Although there was a lack of uniformity in treatment effects across sites, the analyses have taken into account major covariant effects. The time to the recurrence of endometriosis-associated pain after danazol treatment was slightly longer than that after GnRH-a treatment.

Adult↗
PubMed1998

Predictive value of creatine kinase (CK)-MB for diagnosis of acute myocardial infarction after major noncardiac surgery.

BACKGROUND: The aim of this study was to provide insight into the interpretation of CK-MB data after major noncardiac surgery. METHODS: Some 3,321 patients who underwent major non-emergent noncardiac procedures (orthopedic 31%, intrathoracic 12%, vascular 22%, other 35%) were studied. All patients had at least two CK samples measured postoperatively. RESULTS: Acute myocardial infarction was diagnosed in 43 (1.3%) patients using study criteria including CK-MB and electrocardiographic data. All of the various threshold values of peak CK-MB values and peak CK-MB as a percentage of total CK had poor positive predictive values because of high false positive rates and the low rate of acute myocardial infarction. CONCLUSION: These data demonstrate the need for markers of myocardial injury with greater cardiac specificity after noncardiac surgery.

Aged↗
PubMed1998

Endometriosis: a continuing enigma?

Endometriosis is a common gynaecological disease but remains a poorly understood condition. Fundamental questions about the aetiology, pathophysiology, diagnosis, natural history and treatment are still unanswered by the extensive research into endometriosis. This article will outline present understanding of endometriosis and the advances provided by recent research.

Endometriosis↗
PubMed1997

Body mass index as a correlate of postoperative complications and resource utilization.

PURPOSE: To describe the relationship of body mass index (BMI) with postoperative complications and resource utilization. PATIENTS AND METHODS: Two thousand nine hundred and sixty-four patients 50 years or older undergoing elective noncardiac surgery with an expected length of stay > or = 2 days were enrolled in a prospective cohort study to measure major cardiac complications, noncardiac complications, length of stay, and costs. The setting was an urban teaching hospital. A preoperative history, physical, electrocardiogram (ECG), and chart review were performed by study personnel. Postoperative complications were detected by ECGs, creatine kinase and creatine kinase MB levels, and daily chart review. Total costs were obtained from the hospital's computerized database. RESULTS: Complication rates were not different among BMI groups (underweight < 20, normal 20 to 29, overweight 30 to 34, most overweight > 34), but patients with BMI 30 to 34 and > 34 who underwent abdominal or gynecologic procedures had significantly higher wound infection rates (11% each) than normal weight patients (4.7%) or the underweight (0%). After adjusting for age, race, gender, smoking history, comorbid diseases, procedure type, and insurance status, there were nonsignificant trends toward increased resource utilization by the most overweight patients (BMI > 34). These patients stayed 0.8 days longer (P = 0.13) and had total costs that were $843 higher (P = 0.17) than patients of normal weight (BMI 20 to 29). The underweight patients stayed 0.9 days longer (P = 0.23) and had total costs that were $3,150 higher (P = 0.04) than patients of normal weight. Quadratic models to test for a U-shaped relationship found no correlation between BMI and length of stay, but did find that BMI was significantly correlated with total costs (P = 0.04). This relationship persisted when patients who had complications were excluded from the analysis. CONCLUSIONS: Overall, BMI was not significantly correlated with postoperative complications or length of stay. However, overweight patients who underwent abdominal or gynecologic procedures had higher wound infection rates, and patients with the highest and lowest BMIs had significantly higher adjusted total costs.

Age Distribution↗
PubMed1997

Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data.

OBJECTIVES: We sought to evaluate the prognostic significance of cardiac troponin T (TnT) serum levels after noncardiac surgery. BACKGROUND: Cardiac TnT has been found to be marker for myocardial injury, but elevations of TnT are common in patients undergoing noncardiac surgery without clinical evidence of severe ischemia. METHODS: We studied 772 patients who underwent major noncardiac procedures and did not have major cardiovascular complications during their inpatient course. Total serum creatine kinase (CK) and cardiac TnT were measured according to a protocol that included sampling in the recovery room and during the next 2 days. A 6-month follow-up interview was performed for 722 (94%) of the patients. RESULTS: Elevated cardiac TnT and CK-MB results were detected for 92 (12%) and 211 (27%) patients, respectively. During the follow-up period, there were 19 (2.5%) major cardiac complications, including 14 cardiac deaths, 3 nonfatal myocardial infarctions and 2 admissions for unstable angina. Compared with patients with cardiac TnT values < 0.1 ng/ml, patients with elevated TnT had a relative risk for cardiac events of 5.4 (95% confidence interval: 2.2 to 13, p = 0.001), whereas CK-MB was not correlated with postdischarge cardiac events. In multivariate logistic regression analysis adjusting for preoperative clinical and CK-MB data, a cardiac TnT value > 0.1 ng/ml was in independent correlate of cardiac events (adjusted odds ratio 4.6, p < 0.05). This correlation was a function of the relation of elevated TnT levels with postoperative in-hospital congestive heart failure and new sustained arrhythmias, suggesting that elevated postoperative TnT levels detected myocardial ischemia during these clinical events. CONCLUSIONS: We conclude that an abnormal TnT level in patients undergoing noncardiac surgery may be a useful marker of ischemic disease and a predictor of 6-month prognosis.

Arrhythmias, Cardiac↗
PubMed1997

Gonadotrophin regulation of production of tissue inhibitor of metalloproteinases-1 by luteinized human granulosa cells: a potential mechanism for luteal rescue.

Human granulosa cells were maintained in culture with extracellular matrix in the presence or absence of human chorionic gonadotrophin (HCG) using a defined culture medium. Such cultures are maintained by gonadotrophin in a manner suggesting that features of 'luteal rescue' may be occurring in vitro. Western analysis of culture medium demonstrated that the granulosa cells produced tissue inhibitor of metalloproteinases (TIMP)-1 but not TIMP-2. The presence of TIMP-1 in cultured cells was also detected immunocytochemically. Immunoassay of TIMP-1 output revealed that HCG exposure for 7 days caused a 2-fold increase in TIMP-1 production versus control reaching maximum at approximately 1 ng HCG/ml. The sensitivity of this response to HCG was similar to that observed for stimulation of progesterone production. Delayed addition of HCG, from day 4 of culture, elicited increases in TIMP-1 which were evident within 24 hours, and were not explained by changes in cell replication or survival. Removal of HCG from cultures previously luteinized with HCG for 6 days resulted in a fall in TIMP-1 production. Thus TIMP-1 production by luteinized granulosa cells in culture is gonadotrophin dependent. We speculate that prolonged cellular function associated with 'luteal rescue' may result from increased extracellular matrix stability mediated by up-regulation of TIMP-1 production.

Cells, Cultured↗
PubMed1996

Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci.

Endometriosis is a very common gynecological condition in which tissue similar to endometrium proliferates at sites outside the uterine cavity, most commonly the ovary. Although it generally remains a benign condition, malignant transformation has been documented. and it is commonly found in association with endometrioid subtype ovarian cancer. Tumor suppressor genes are commonly altered in ovarian cancers, and the development of endometriosis may involve mutations in the same class of genes. We have investigated this possibility by examining DNA from 40 cases of endometriosis for clonal status, alterations in TP53 and RASK, and allelic losses at candidate ovarian tumor suppressor loci on chromosome arms 6q, 9p, l1q, 17p, l7q, and 22q. The majority of endometriotic cysts were monoclonal, but interestingly, 8 of 10 normal endometrial glands were also monoclonal, demonstrating that both are able to develop from a single progenitor cell. No mutations were detected in TP53 or RASK. Loss of heterozygosity (LOH) was detected on chromosomes 9p (18%), 1lq (18%), and 22q (15%). In total, 11 of 40 (28%) cases demonstrated LOH at one or more of these loci. This study, which is the first to report LOH in endometriosis, supports the notion that tumor suppressor gene inactivation may play a role in the development of at least a subset of cases.

Base Sequence↗
PubMed1996

Troponin T as a marker for myocardial ischemia in patients undergoing major noncardiac surgery.

To assess the diagnostic performance of cardiac troponin T as a marker for myocardial injury in patients undergoing major noncardiac surgery, we prospectively collected preoperative and postoperative clinical data, including measurements for creatine kinase (CK), CK-MB, and troponin T for 1,175 patients undergoing major noncardiac surgery. Acute myocardial infarction was diagnosed in 17 patients (1.4%) by a reviewer who was blinded to troponin T data and who used CK-MB and electrocardiographic criteria to define acute myocardial infarction. Other predischarge major cardiac complications were detected for another 17 patients. Troponin T elevations (>0.1 ng/ml) occurred in 87% of patients with and in 16% of patients without myocardial infarction. Among patients without myocardial infarction, troponin T was elevated in 62% of patients with and in 15% of patients without major cardiac complications. Receiver-operating characteristic analysis indicated that troponin T had a performance for the diagnosis of acute myocardial infarction similar to CK-MB, and a significantly better correlation with other major cardiac complications in patients without definitive infarction. Future research should seek to determine the significance of troponin T elevations in patients without complications.

Aged↗
PubMed1996

Patient noncompliance with medical advice after the emergency department visit.

STUDY OBJECTIVE: To determine the correlates of compliance with follow-up appointments and prescription filling after an emergency department visit. METHODS: This prospective cohort study was undertaken as part of the Emergency Department Quality Study evaluation of five urban teaching hospital EDs in the northeastern United States. Of 2,757 eligible patients who presented with abdominal pain, asthma, chest pain, hand lacerations, head trauma, or first-trimester vaginal bleeding and were enrolled during 1-month period, 2,315 (84%) completed on-site baseline questionnaires. Information about diagnoses, socioeconomic status, discharge instructions, insurance status, and primary care was obtained from the on-site patient surveys and from reviews of medical records. A 76% random sample of patients who completed the questionnaire was generated, and 1,386 patients (79% of the sample) were interviewed by telephone approximately 10 days after their ED visit to determine compliance with follow-up appointments and prescription filling. RESULTS: Of the 1,386 patients interviewed at 10 days, 914 (66%) had been discharged from the ED, and 408 (45%) of those discharged recalled being advised to take a medication. Fifty of these patients (12%) reported that they did not obtain the medication. Significant independent correlates of not filling prescriptions were lack of insurance (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1 to 5.5) and dissatisfaction with discharge instructions (OR, 2.8; 95% CI, 1.2 to 6.4). Two hundred thirty-five (26%) of the discharged patients said they were given follow-up appointments and did not have an appointment pending at the time of the interview; 77 (33%) of these patients reported having missed their appointment. The only significant independent correlate of missing follow-up appointments was being given a telephone number to call instead of leaving the ED with an appointment scheduled (OR, 3.8; 95% CI, 1.7 to 8.8). CONCLUSION: Not having an appointment made before leaving the ED was an independent correlate of missing follow-up appointments. Lack of insurance and dissatisfaction with discharge instructions were independent correlates of not filling prescriptions.

Adult↗
PubMed1996

Spouse enabling of alcohol abuse: conception, assessment, and modification.

This article presents a conception of spouse enabling of partner alcohol abuse, a review of its dysfunctions, and an approach to assessment and modification to reduce spouse enabling behavior. Based on experience with its use in unilateral family therapy with many spouses of treatment-refusing alcohol abusers, procedural guidelines, treatment methods, two case examples from a crossover experimental dyad, and clinical results for the two cases in the dyad are described. Also presented are practice issues, characteristics of spouse enabling as they relate to disenabling intervention, and areas of possible application of the disenabling program.

Adult↗
PubMed1996

Effect of human chorionic gonadotrophin on the detachment of human granulosa cells from extracellular matrix layered onto glass or plastic.

We have previously shown that human granulosa cells cultured on a thin layer of extracellular matrix (ECM) are lost from culture in the absence of gonadotrophin. We now examine the effect of plating ECM onto glass or plastic. Such a comparison revealed that loss of cells from control cultures was more rapid when ECM was on glass, whereas cultures maintained with human chorionic gonadotrophin (HCG) showed greater stability when ECM was on plastic. The dose range of HCG required for the effect on cell retention was similar to that required for stimulation of progesterone production. Electron microscopy of cells freshly released as clusters revealed that many cells appeared undamaged, and confocal microscopy of cells stained with propidium iodide showed an absence of fragmented nuclei. Taken together, this evidence suggests that apoptosis is not the cause of cell release. We conclude that cells are released from culture, not as a result of cell death, but via an active process suppressed by HCG.

Cell Adhesion↗
PubMed1996

The relevance of asymptomatic endometriosis.

Asymptomatic endometriosis is likely to be a physiological phenomenon of very limited relevance to both the physician and the patient. The evolution of our understanding of this phenomenon is a parable for modern medicine. It is likely that access to a new diagnostic technique, a powerful armoury of medical and surgical treatments and the necessity for doctors to feel they are doing something positive for the patient, have created an incorrect disease model for asymptomatic endometriosis. As responsible clinicians and medical scientists it behoves us to honestly re-examine our approach to this phenomenon.

Endometriosis↗
PubMed1996

Effect of gonadotrophin on cell and matrix retention and expression of metalloproteinases and their inhibitor in cultured human granulosa cells modelling corpus luteum function.

Granulosa cells were prepared from follicular aspirates obtained at oocyte collection for in-vitro fertilization (IVF) and maintained in culture. Substantial loss of cells from the culture surface occurred in the absence of gonadotrophin when cells were maintained on a thin layer of extracellular matrix (ECM) using a defined, serum-free medium. This cell loss was clearly and significantly reduced in the presence of human chorionic gonadotrophin (HCG) by days 4-6 of culture, and occurred in conjunction with loss of ECM. Analysis of culture medium by zymography using gelatin as substrate demonstrated the presence of metalloproteinases (MMP), MMP-9 (gelatinase B) appearing as the predominant band. Measurement of overall gelatinase activity in culture media revealed a progressive fall in gelatinase expressed on a per cell basis in media from HCG-treated cultures and this was less marked in controls. This suppression of gelatinase activity was consistent with an observed increase in production of tissue inhibitor of metalloproteinase-1 (TIMP-1) by HCG-treated cells, which was significant by days 6-8 of culture. We speculate that stabilization of the ECM may be an important aspect of HCG action in the corpus luteum.

Cells, Cultured↗
PubMed1996

Nuclear retinoid receptor expression in normal human endometrium throughout the menstrual cycle.

Previous work has shown that retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are expressed in human endometrial epithelial and stromal cells. These nuclear receptors mediate the biological effects of retinoic acid, a vitamin A derivative which may have an important, though poorly characterized role in the functional differentiation of secretory epithelia. The aim of this study was to find out whether the expression of RAR and RXR mRNA in endometrial epithelial and stromal cells varies in relation to the menstrual cycle. The expression of RARs and RXRs was investigated by Northern blotting and, for stromal cells, there were no differences in expression of RAR-alpha, RAR-beta, RAR-gamma and RXR-alpha between the proliferative and secretory phases of the menstrual cycle. Similarly, for epithelial tissue, there were no significant differences between the proliferative and secretory phases with respect to the expression of RAR-alpha, RAR-gamma and RXR-alpha. However, RAR-beta was expressed at a 1.7-fold higher level in epithelial samples from the proliferative phase compared to the secretory phase. Overall, the levels of expression of RAR-alpha, RAR-beta and RAR-gamma were 1.7- to 4-fold higher in stromal cells compared to epithelial cells whereas RXR-alpha was expressed at a similar level in both cell types. We have previously suggested that retinoic acid has a role in endometrial differentiation or function which may be reflected by cyclical changes in intracellular retinoic acid levels. These data indicate that RARs and RXRs are expressed at a similar level throughout the menstrual cycle, with the possible exception of RAR-beta, implying that any menstrual cycle-related function of RARs in controlled by ligand availability rather than by changes in expression of the receptors.

Blotting, Northern↗
PubMed1996

Serum relaxin and the major endometrial secretory proteins in in-vitro fertilization and down-regulated hormone-supported and natural cycle frozen embryo transfer.

Relaxin has been postulated to be a modulator of the expression of the endometrial secretory proteins, insulin-like growth factor binding protein (IGFBP-1) and placental protein 14 (PP14). This study evaluated the expression of relaxin in relation to concentrations of these secretory proteins along with oestradiol, progesterone and human chorionic gonadotrophin in groups of pregnant and non-pregnant patients who underwent differing assisted conception treatments. Serum samples were taken from 88 patients at 8 and 12 days after embryo transfer. At 12 days after embryo transfer, relaxin concentrations in the pregnant patients who had undergone in-vitro fertilization (IVF) or natural cycle frozen embryo transfer were significantly higher than those who did not conceive in these groups (mean concentrations 8334 versus 28 and 2608 versus 62 pg/ml respectively, P<0.001). However concentrations in the pregnant patients who had hormone support and transfer of frozen embryos were not significantly different from the patients who did not conceive after the same treatment. Although relaxin expression was associated with corpus luteum activity, it was not related to the number of corpora lutea in IVF patients. A wide range of relaxin concentrations was seen to be compatible with a healthy pregnancy. These serum relaxin concentrations were not found to be directly related to the serum concentrations of IGFBP-1, PP14 or the other factors assessed in this study.

Chorionic Gonadotropin↗
PubMed1996

Endometrial progesterone receptor expression during the human menstrual cycle.

The human endometrium undergoes regular cyclical changes under the endocrine control of oestrogens and progesterone acting via specific nuclear receptors. The molecular and cellular events mediating these changes are not understood. The present study examined the changes in the endometrial progesterone receptor and its mRNA during the menstrual cycle. Forty-four endometrial samples obtained from women with normal menstrual cycles were divided into four categories: early proliferative (days 6-9), late proliferative (days 10-14), early secretory (days 15-21) and late secretory (days 22-28). The progesterone receptor protein was determined using a human progesterone receptor enzyme-linked immunoassay kit. Total RNA was extracted using RNAzol and the abundance of mRNA encoding the progesterone receptor was determined by reverse transcriptase-polymerase chain reaction and by northern blot analysis. The concentration of the progesterone receptor in the endometrium was highest during the late proliferative phase and was lowest in the late secretory phase. Significant differences were observed between the menstrual cycle phases (P < 0.003). No cyclical variation was observed in the concentration of mRNA encoding for the progesterone receptor in the endometrium when analysed by reverse transcriptase polymerase chain reaction or by northern analysis. There appears to be no association between the amounts of mRNA encoding the progesterone receptor and progesterone receptor protein during the menstrual cycle suggesting that the control of the expression of the progesterone receptor may not occur solely at the transcriptional level.

Adult↗