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Biomedical subjects

B E Miller

Publications and source records attributed to B E Miller.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prognostic factors in adult granulosa cell tumor of the ovary.

BACKGROUND: The clinical course of adult granulosa cell tumor of the ovary is characterized by indolent growth tending toward late recurrence. A variety of clinical and pathologic parameters have previously been evaluated for prognostication with inconclusive results. METHODS: The clinical records and tumor sections of 70 patients with adult granulosa cell tumors of the ovary were reviewed. Patients with recurrent tumors (REC) (n = 19) were compared with patients who remained without disease (NED) (n = 51). RESULTS: Significant differences in stage and tumor size were noted between the two groups; however, after logistic regression analysis, only stage remained statistically significant. Pathologic evaluation revealed that Call-Exner bodies occurred more frequently in tumors of the NED patients. Cellular atypia and high mitotic rates were more frequent in the REC group; however, after logistic regression analysis, only atypia remained statistically significant. When early (< 10 years) and late recurring tumors (> 10 years) were compared, statistically significant differences were again noted: early recurring tumors had fewer Call-Exner bodies, higher mitotic rates, and higher degrees of atypia; late recurring tumors were similar to tumors in the NED patients. CONCLUSIONS: Tumor stage and, to a lesser extent, tumor size are the only clinical parameters of prognostic importance in adult granulosa cell tumors. Cellular atypia and, to lesser extents, mitotic rate and the absence of Call-Exner bodies are the only significant pathologic prognosticators. It is difficult to predict early recurrences and impossible to predict late recurrences using these clinical and pathologic parameters.

Adult↗
PubMed1997

Colon cancer with metastasis to the ovary at time of initial diagnosis.

Colon cancer with a synchronous ovarian metastasis is occasionally diagnosed at the time of laparotomy for a pelvic mass. The purpose of this retrospective study is to evaluate the clinical presentation as well as the impact of the type of metastatic spread and surgical intervention on overall survival. We reviewed charts of 23 patients treated between 1980 and 1995. Pain was the initial symptom in 14 patients (61%), with only four patients (17%) complaining of rectal bleeding, but with five patients (22%) complaining of uterine bleeding. At the time of laparotomy, the ovarian capsule was intact in 12 patients. Metastatic disease to the peritoneum was seen in seven patients and to the liver in six patients. On pathological evaluation, the median ovarian tumor size was 10 cm, significantly larger than the median colon tumor size of 4.5 cm. Surgical treatment consisted of colon resection in all but one patient, bilateral or unilateral salpingo-oophorectomy in 22 patients, and hysterectomy in nine patients. Only one patient survived 5 years. Sixteen patients died of colon cancer. The median survival time was 17.8 months, ranging from 1 to 86 months. Tumor size was of no prognostic importance. Median survival time of patients with peritoneal disease (10.8 months) was significantly shorter compared to patients without peritoneal disease (25.2 months). In the presence of liver metastasis, the median survival time was, likewise, significantly reduced from 20.1 months to 8.1 months. In conclusion, macroscopic metastatic disease to the ovary is a poor prognostic factor in colon cancer. In selected patients who can be rendered disease-free by surgery, prolonged survival is possible and an aggressive approach is recommended. Survival of patients with peritoneal disease or liver metastasis is short and a mainly palliative approach is recommended.

Adult↗
PubMed1997

An approach to teaching ethical, legal, and psychosocial aspects of gynecologic oncology in a residency program.

An approach to teaching ethical, legal, and psychosocial issues in gynecologic oncology has been integrated into an obstetrics and gynecology residency program. Team-teaching is used, involving gynecologic oncology faculty members and a medical ethicist with experience teaching in the clinical setting of obstetrics and gynecology. The teaching takes place as part of ongoing teaching rounds in the division of gynecologic oncology. Articles from clinical journals are used to inform and stimulate discussion of clinical ethical, legal, and psychosocial issues. Integrating the teaching of ethical and legal aspects of gynecologic oncology into residency education is challenging, given the competing demands on the residents' time and the need for teaching to be clinically relevant. The program described in this article illustrates that such teaching can be carried out in a manner that covers main issues and has practical value for residents.

Curriculum↗
PubMed1997

The inflammatory response to cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass is the product of a complex interplay of humoral and cellular components. Contact activation cascades, the complement system, and cytokines comprise the humoral elements and interact in such a way as to propagate their own cascades and to activate the cellular elements. Neutrophils and endothelial cells are the cellular components and become involved after their "activation" by the humoral mediators. Neutrophil-endothelial cell adherence is the initial step of the cellular inflammatory response and is promoted by the expression of specific adhesion molecules on the surfaces of both of these cells leading to the emigration of neutrophils into the extravascular space where they release toxins that damage surrounding tissues. The resulting organ dysfunction produces the clinical picture referred to as the "postperfusion syndrome." Strategies to attenuate this response include the administration of corticosteroids, aprotinin, and anticytokine monoclonal antibodies, as well as various modifications of the bypass circuit. The existence of multiple pathways to trigger this inflammatory response hampers efforts at its attenuation and leaves much investigation to be done as the quest to understand the body's inflammatory response to cardiopulmonary bypass continues.

Adrenal Cortex Hormones↗
PubMed1997

Association of positive Chlamydia trachomatis and Chlamydia pneumoniae immunoglobulin-gamma titers with increasing age.

STUDY OBJECTIVES: To use Chlamydia trachomatis immunoglobulin-gamma (IgG) titers to investigate the possibility of their association with ovarian cancer, and to evaluate the effectiveness of this titer in algorithmic protocols in infertility. DESIGN: Prospective, age-matched, pilot study (Canadian Task Force classification II-2). SETTING: University and university-affiliated office practice. PATIENTS: The original 30 patients were seen for follow-up of ovarian cancer (19) and at yearly examination for nonmalignant disease (10). An additional group of 21 women seen for pelvic pain and infertility was added to clarify questions that arose during the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Chlamydia trachomatis IgG titers were positive in 15 (79%) of 19 of women with ovarian cancer, 9 (90%) of 10 age-matched controls, and 14 (67%) of 21 patients with infertility and pain. When analyzed by age, 4 (40%) of 10 patients under 30 years and 34 (85%) of 40 patients 30 years of age or older had positive titers (p = 0.007). Of 21 women with positive Chlamydia pneumoniae titers, 17 (81 %) had positive C. trachomatis titers, and 17 (85%) of 20 with positive C. trachomatis titers had positive C. pneumoniae titers. CONCLUSION: The test kit used in this study may not be adequate in older patients due to cross-reaction with C. pneumoniae titers. Further evaluation of C. trachomatis IgG titers as a marker in the study of ovarian cancer will require titers that are more specific than those we used. Although these titers may be useful as an immunologic screening marker in infertile patients, results should be interpreted with caution. A positive test may not be evidence of C. trachomatis infection and is not an indication for specific therapy. Successful use of some currently available C. trachomatis IgG titers in algorithms for infertility may be related to a patient's age.

Adolescent↗
PubMed1997

The African-American Health Project (AAHP): study overview and select findings on high risk behaviors and psychiatric disorders in African American men.

The AAHP investigated the neurobehavioral and psychosocial sequelae of HIV-1 and substance use in urban African American men. A community resident sample of 502 African American men stratified by HIV-1 serostatus, drug use and sexual orientation were recruited. A comprehensive battery of measures of neurobehavioral and health status, lifestyle and psychosocial characteristics were administered to all participants, and a stratified sub-sample of 120 participants were tested using state of the art brain imaging techniques to investigate differences in the functional and neurophysiologic effects of HIV-1 and substance use. An overview of the methodology of the AAHP and results on high risk sexual and substance use behaviors, and psychiatric disorders are presented and discussed. The sample was primarily HIV-negative (63%), heterosexual (49% gay or bisexual) and a high percentage used substances during the past year (56% used drugs and 30% moderate/heavy drinkers). High-risk sexual practices were relatively prevalent, and a high percentage reported a history of STDs and other infections. Finally, 25% had a current psychiatric disorder, with gays/bisexuals and HIV-seropositives evidencing greater psychiatric vulnerability. More research is needed to further explore the apparent greater risk for psychiatric disorders among gay and bisexual men, and to determine whether being African American and lower social class exacerbate this risk.

Adult↗
PubMed1997

A comparison of the hemodynamic effects of amrinone and sodium nitroprusside in infants after cardiac surgery.

The phosphodiesterase inhibitor amrinone (AMR) increases cardiac output in children after cardiac surgery. In vitro, amrinone has both positive inotropic and vasodilatory effects. However the relative contribution of these effects to the increases in cardiac output observed clinically is unclear, and it has not been demonstrated that amrinone offers a hemodynamic advantage above that of pure vasodilators in infants. We compared the hemodynamic effects of AMR and sodium nitroprusside (SNP) in 10 infants after cardiac surgery. Cardiac index (CI) was measured by thermodilution after SNP administration, titrated to decrease mean blood pressure (MBP) by 20%, and then after a 1.5-mg/kg bolus dose of AMR. Each patient served as his or her own control. Preload, as measured by left atrial pressure and transesophageal echocardiography (in eight patients), was kept constant throughout the protocol. Both SNP and AMR caused significant decreases in MBP and systemic vascular resistance index (SVRI). However, only AMR resulted in a significant increase in CI. The ratio of fractional increase in CI to fractional absolute decrease in MBP was significantly greater for AMR than SNP, indicating greater efficacy for AMR in the treatment of low cardiac output syndrome and suggesting that, in infants after cardiac surgery, AMR has clinically relevant positive inotropic effects.

Amrinone↗
PubMed1997

Functional maturity of the coagulation system in children: an evaluation using thrombelastography.

There are quantitative deficiencies in the coagulation system for at least the first 6 mo of life. Clinical experience, however, does not indicate an increased risk of excessive bleeding during surgical procedures. Thrombelastography, a test providing a functional evaluation of coagulation, was used to assess the hemostatic system of pediatric patients under 2 yr of age. Thrombelastographic data were obtained from 237 healthy pediatric patients less than 2 yr of age undergoing elective noncardiac surgery. Five groups were distinguished: under 30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Thrombelastography revealed no defects in coagulation when these groups were compared to each other or to adults, indicating a functionally intact hemostatic process even in neonates. Indeed, children less than 12 mo of age were found to initiate and develop clot faster than adults, with the coagulation process slowing to adult rates after 1 yr of age. In addition to defining functional integrity, our data represents a set of pediatric control thrombelastographic values that have not been previously reported and that may become important in understanding coagulation changes that accompany disease states and surgery in pediatric patients.

Age Factors↗
PubMed1997

Predicting and treating coagulopathies after cardiopulmonary bypass in children.

UNLABELLED: Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children <8 kg had more bleeding and required more coagulation products than children >8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children <8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing >8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. IMPLICATIONS: Children <8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.

Anticoagulants↗
PubMed1997

Bone health is not affected by luteal phase abnormalities and decreased ovarian progesterone production in female runners.

The primary purpose of this study was to determine whether decreased ovarian progesterone production, associated with short and inadequate luteal phases in exercising women, was associated with decreased bone mineral density (BMD) and altered bone metabolism. Thirty-three eumenorrheic menstruating women participated in this study for 3 months. Subjects were required to collect daily urine samples for three consecutive menstrual cycles and have blood and urine collected weekly. Daily urine samples were analyzed for free LH, estrone conjugates (E1C), and pregnanediol 3-glucuronide (PdG), adjusted for creatinine, whereas weekly blood and urine samples were analyzed for bone markers, estradiol, progesterone, FSH, and LH. Based on the analyses of these samples, subjects were divided into three groups: sedentary ovulatory (SedOvul; n = 9), exercising ovulatory (ExOvul; n = 14), and exercising luteal phase defects (ExLPD; n = 10). The three groups were matched for age (27.6 +/- 1.0 yr), weight (60.6 +/- 1.9 cm), and reproductive maturity (14.5 +/- 1.0 yr), PdG production during the luteal phase was lower (P = 0.004) in the ExLPD women compared to that in the SedOvul group (2.4 +/- 0.4 vs. 5.1 +/- 0.6 ng/mL creatinine, respectively). The ExOvul group also had less (P < 0.01) PdG production during the luteal phase (3.5 +/- 0.3 ng/mL creatinine) compared to the SedOvul group. The total production of PdG, as assessed by area under the curve analysis, was also lower (P < 0.001) in the ExOvul and ExLPD groups compared to that in the SedOvul group. E1C production, however, was not different (P > 0.05) among the groups, except for E1C during the early follicular phase, which was lower (P = 0.043) in the ExLPD group than that in the SedOvul group. BMD and biochemical markers of bone metabolism were unaffected by and not associated with the compromised progesterone environment, but BMD values at the proximal femur (r = 0.354; P = 0.061) and total body (r = 0.359; P = 0.056) were associated with decreased early follicular E1C production. We conclude the following. 1) Luteal phase disturbances occur independent of training volume, and volume of training does not have to be severe to result in menstrual disturbances. 2) As a result of exercise, disturbance in progesterone production is not associated with decreased bone mass. 3) Long follicular phases are associated with reduced estrogen production during the early follicular phase, which are both associated with decreased bone mass. 4) Provided the estradiol status is adequately maintained, BMD is unaffected by decreased progesterone production associated with short and inadequte luteal phases in exercising women.

Adolescent↗
PubMed1997

The effect of endurance training on reproductive function in male runners. A 'volume threshold' hypothesis.

Investigations on reproductive function in male athletes are not as abundant in the literature as the research available on female athletes. The primary reason for this is the absence of an obvious clinical sign indicative of an alteration in reproductive function in male athletes. While alterations in the reproductive status of female athletes may be easily detected by the loss of menstrual regularity, a distinctive clinical sign reflective of reproductive dysfunction in the male is not apparent. In male runners, an effect of endurance training on reproductive function related to a specific 'volume threshold' of training is proposed. Data are supportive of this 'volume threshold' effect, provided careful and consistent definitions of volume of training are applied. In fact, if volume of training is carefully defined endurance-trained male runners exhibit a rather consistent range of subclinical modifications in the gonadal hormones and semen profile, and clinical (oligospermia) alterations in reproductive function. The precise mechanism responsible for these observed alterations remains unknown, although several peripheral and central mechanisms have been suggested. Clearly, more research is necessary to confirm, and to elucidate, the nature of the 'volume threshold' hypothesis in male runners.

Humans↗
PubMed1996

Clinical, hematologic, and biochemical features of a syndrome in Bernese mountain dogs characterized by hepatocerebellar degeneration.

Seven related Bernese Mountain Dogs developed a syndrome Characterized by progressive cerebellar and hepatic disease. Clinically, stiffness in the hind limbs, mild incoordination, and a slight head tremor were first noticeable when pups were 4 to 6 weeks old. The condition progressed, causing pups to assume a wide-based stance. Other signs included head bobbing, spontaneous nystagmus, and, finally, paresis. Hematologic findings included leukocytosis with a left shift; normocytic, normochromic anemia; hypoproteinemia, low serum creatinine, and urea nitrogen concentrations; excessive fasting plasma ammonia concentration; and an increase in concentration of serum bile acids. Portal venography performed on 1 dog revealed a small liver and extensive extrahepatic varicosities. Necropsy revealed cerebellar hypoplasia, nodular liver, extensive abdominal varicosities, and ascites. Histologically, degeneration and depletion of Purkinje's cells and vacuolation, degeneration, and nodular regeneration of hepatic tissues were evident. Preliminary analysis of the pedigree was suggestive of an autosomal recessive pattern of inheritance.

Animals↗
PubMed1996

Rates of development of methotrexate resistance in heterogeneous mouse mammary tumor cell cultures.

Our previous studies have indicated that the expression by tumor cells of sensitivity to chemotherapeutic drugs such as methotrexate can be affected by the presence of other tumor cells; thus, otherwise methotrexate-resistant cells may respond to that drug in the presence of methotrexate-sensitive cells. In order to determine whether tumor heterogeneity also affects the emergence of drug resistance, we measured the rate of development of methotrexate resistance in mixed monolayer cultures of three mammary tumor subpopulation lines (66, 168TFAR, 4T07) that differ in degree of sensitivity to methotrexate. Cultures were treated weekly with 80 nM or 200 nM methotrexate. Each individual cell line was re-isolated from the mixture by passage in selective medium and then assayed for methotrexate sensitivity. Cultures of each of the three lines were treated and assayed in parallel. Few differences in the rate of development of methotrexate resistance were seen among cells from mixtures and cells cultured alone; line 4T07 appeared to become resistant somewhat more rapidly in mixtures. In untreated mixed cultures, line 66, the line least sensitive to methotrexate, gradually became dominant; this process was accelerated in treated cultures. One methotrexate-resistant subline from each parent cell line was tested to determine the mechanisms by which methotrexate resistance was increased. Two lines appeared to have increased levels of dihydrofolate reductase, and one exhibited decreased methotrexate transport as well. The third cell line had neither mechanism. Others have shown that tumor heterogeneity can act as a brake on the rate of development of new metastatic or immunogenic variants. Our data indicate that, at least in the model system we have tested, the rate of development of extrinsic drug resistance is substantially independent of pre-existing clonal diversity.

Animals↗
PubMed1995

Inhibition of mature IL-1 beta production in murine macrophages and a murine model of inflammation by WIN 67694, an inhibitor of IL-1 beta converting enzyme.

The proinflammatory cytokine IL-1 beta is synthesized by activated monocytes and macrophages as a 31-kDa, biologically inactive precursor that is proteolytically processed to the biologically active 17-kDa mature molecule by the IL-1 beta converting enzyme (ICE). WIN 67694, Z-Val-Ala-Asp-CH2O(CO)[2,6-(CI2)]Ph, is a potent, selective inhibitor of human ICE. In activated murine peritoneal macrophages, WIN 67694 inhibited the release of mature IL-1 beta with an IC50 of 1.8 microM without any effect on the release of IL-1 alpha, IL-6, or TNF-alpha. The effect was specific to mature IL-1 beta release; the ICE inhibitor did not effect IL-1 beta RNA levels or precursor protein synthesis. In vivo, WIN 67694 was also able to inhibit selectively the release of IL-1 beta in a dose-dependent manner in a subcutaneous tissue chamber implant model of inflammation. IL-1 beta levels in tissue chamber fluid were inhibited 35 and 55% at 10 and 100 mg/kg, respectively. IL-1 alpha, IL-6, and TNF-alpha levels were not affected. The ability to selectively inhibit mature IL-1 beta release in vivo with ICE inhibitors will allow for detailed studies of the role of IL-1 beta and ICE in inflammatory diseases.

Amino Acid Sequence↗
PubMed1995

Cathepsin D from Alzheimer's-diseased and normal brains.

An acid protease activity from human brain was found to cleave a fluorogenic peptide substrate encompassing the amino terminus of Alzheimer's amyloid-beta peptide (A beta). The protease was isolated and determined to be cathepsin D based on chromatographic, immunological, and enzymatic data. Analysis of the cleavage sites indicated that cathepsin D hydrolyzed the methionine--aspartate bond generating the in vivo amino terminus of A beta. These data suggested that cathepsin D could be involved in amyloidogenic processing of the amyloid precursor protein. Consequently, cathepsin D from both Alzheimer's-diseased and control brains was compared to determine whether there were any differences which could account for an increase in A beta production in Alzheimer's disease. No differences were detected in isoform composition or tissue content of cathepsin D as measured by 2-D IEF-SDS-PAGE. Enzymological characterization of brain cathepsin D demonstrated that it could undergo a previously undescribed pH-dependent reversible activation. However, that activation appeared identical for both AD and normal brain enzymes. These data demonstrate that concentration, isoform distribution, and several enzymological characteristics of cathepsin D are not distinguishable between AD and normal brain. The pH dependence of cathepsin D activity suggests, however, that its intracellular localization may be important in considering the potential role of cathepsin D in Alzheimer's disease.

Aged↗