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Biomedical subjects

C Drescher

Publications and source records attributed to C Drescher.

13 recordsLinked to original sources
PubMed2004

Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma.

OBJECTIVES: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier. METHODS: We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program. RESULTS: CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125. CONCLUSION: The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.

CA-125 Antigen↗
PubMed2002

Worry about ovarian cancer risk and use of ovarian cancer screening by women at risk for ovarian cancer.

OBJECTIVE: This study examined reports of perceived risk of ovarian cancer, worry, and screening use in a large sample of women. While screening for asymptomatic women is not generally recommended, in 1994 a consensus conference concluded that women with multiple affected relatives are at high risk for ovarian cancer and should be encouraged to participate in screening. The consensus report also suggested that women with a single affected first-degree relative are at elevated risk and while these women were not encouraged to get screening it was suggested that they may choose to pursue screening outside of a randomized trial [NIH Consensus Conference. JAMA 1995;273(6) 491-7]. METHODS: A total of 3257 women participated in this research by completing a mailed survey on ovarian cancer risk, worry, and use of screening. One hundred forty-two of these women were at high risk for this disease due to a strong family history. An additional 144 women were at elevated risk due to a single first-degree affected relative with ovarian cancer. RESULTS: Family history did predict perceived risk, difficulties due to worry, and use of ovarian cancer screening. However, the group of women most likely to report high levels of perceived risk and to have received screening for ovarian cancer were women with a single affected relative rather than those at high risk, for whom screening is recommended. CONCLUSIONS: These results suggest that many women need additional education about ovarian cancer risk. Most women overestimated their risk for this disease. Some average-risk women get screening although it is not recommended outside of randomized trials, and a significant percentage of women at high risk fail to get recommended screening.

Adolescent↗
PubMed2001

Collagen-induced proMMP-2 activation by MT1-MMP in human dermal fibroblasts and the possible role of alpha2beta1 integrins.

Culture of human dermal fibroblasts within a three-dimensional matrix composed of native type I collagen fibrils is widely used to study the cellular responses to the extracellular matrix. Upon contact with native type I collagen fibrils human skin fibroblasts activate latent 72-kDa type IV collagenase/ gelatinase (MMP-2) to its active 59- and 62-kDa forms. This activation did not occur when cells were cultured on plastic dishes coated with monomeric type I collagen or its denatured form, gelatin. Activation could be inhibited by antibodies against MT1-MMP, by the addition of TIMP-2 and by prevention of MT1-MMP processing. MT1-MMP protein was detected at low levels as active protein in fibroblasts cultured as monolayers. In collagen gel cultures, an increase of the active, 60-kDa MT1-MMP and an additional 63-kDa protein corresponding to inactive MT1-MMP was detected. Incubation of medium containing latent MMP-2 with cell membranes isolated from fibroblasts grown in collagen gels caused activation of the enzyme. Furthermore, regulation of MT1-MMP expression in collagen cultures seems to be mediated by alpha2beta1 integrins. These studies suggest that activation of the proMMP-2 is regulated at the cell surface by a mechanism which is sensitive to cell culture in contact with physiologically relevant matrices and which depends on the ratio of proenzyme and the specific inhibitor TIMP-2.

Cell Culture Techniques↗
PubMed2000

Genetic system for reversible integration of DNA constructs and lacZ gene fusions into the Escherichia coli chromosome.

A plasmid system for site-specific integration into and excision and recovery of gene constructs and lacZ gene fusions from the Escherichia coli chromosome was developed. Plasmid suicide vectors utilizing the origin of replication of R6K plasmids and containing the attP sequence of bacteriophage lambda, multiple cloning site, and antibiotic resistance markers facilitate reversible integration into the E. coli chromosome by site-specific recombination. Additional vectors permit construction of lacZ gene fusions in three possible reading frames for recombination with the bacterial chromosome. These suicide vectors can be propagated in newly constructed E. coli strains that harbor different pir alleles. Two helper plasmids that encode the necessary gene products for integration (Int) and excision (Int and Xis) were also constructed. This plasmid system was shown to be a reliable and efficient means to integrate and subsequently recover plasmids from the E. coli attB site.

Artificial Gene Fusion↗
PubMed2000

Reported ovarian cancer screening among a population-based sample in Washington state.

OBJECTIVE: To assess the prevalence of reported ovarian cancer screening among a population-based sample of women from Washington state and identify factors that influence the decision to be screened. METHODS: A population-based sample of 6749 women aged 54-84 years, living in 40 predominately rural communities in Washington state, was surveyed about their utilization of ultrasonography and CA 125 for ovarian cancer screening. We also assessed relevant demographic, family history, psychosocial, and health behavior variables. RESULTS: After exclusions, data from 4938 respondents were available. Two percent (n = 96) reported having been screened. Multiple logistic regression identified ovarian cancer worry, contact with an obstetrician-gynecologist, and family history of ovarian cancer as independently associated with screening. Based on self-reported family histories, 27 women had pedigrees consistent with high risk of ovarian cancer, but none of those women reported having been screened. CONCLUSION: Ovarian cancer screening is rare. Women at high risk of it might not be getting recommended screening.

Aged↗
PubMed1997

Use of a stochastic simulation model to identify an efficient protocol for ovarian cancer screening.

The intervention protocol for an ovarian cancer screening trial should be efficient as well as effective, because it may become the standard of care if the trial demonstrates mortality reduction. To identify an efficient ovarian cancer screening protocol, the effectiveness and cost-effectiveness of selected single modality and multimodal screening strategies were estimated using a stochastic simulation model. Screening was simulated over a 30-year period in a hypothetical cohort of 1 million women aged 50 at the beginning of the period. The net present value of the cost per year of life saved was estimated for six protocols involving transvaginal sonography (TVS) and/or the tumor antigen CA 125. Internal and external validation was performed, and sensitivity analyses were conducted to assess the robustness of the ranking of the strategies. A multimodal strategy involving CA 125 with a threshold for positivity of either elevation above 35 U/ml or doubling since the previous screen, followed by TVS only if CA 125 is positive, was found to be efficient in the sense that no other strategies saved as many years of life at lower cost per year of life saved. Used annually, this strategy cost under $100,000 per year of life saved over a range of assumptions. The model's predictions are consistent with results reported in the literature regarding the performance of TVS and CA 125. The multimodal strategy used annually or every six months was efficient compared to either ultrasound or CA 125 used alone, over a range of assumptions. Simulation of screening may be useful in selecting a screening protocol to be tested in a randomized controlled trial.

Aged↗
PubMed1993

Primary treatment of stage III ovarian carcinoma with sequential chemotherapy and whole abdominal radiation therapy.

A prospective phase II clinical treatment trial of 13 patients with previously untreated optimal surgically resected (< or = 1 cm stage III ovarian carcinoma was conducted at the University of Michigan Hospitals. The treatment regimen after surgical resection consisted of chemotherapy followed by whole abdomen and pelvic radiation therapy. Chemotherapy consisted of four cycles of 50 mg/m2 cisplatin and 1000 mg/m2 cytoxan. This was followed by whole abdomen radiation therapy with a planned total dose of 30 Gy to the whole abdomen and then a 20-Gy boost to the pelvis. Six of 13 patients received a paraaortic radiation boost. There was minimal acute toxicity, but delayed toxicity was encountered with 38% of patients developing a bowel obstruction. Nine patients had reassessment laparotomy: 5 second-look laparotomies and 4 laparotomies for bowel obstruction. Two of these 9 patients died of septic complications after surgery. Nine patients died with disease, 1 patient is alive with advanced disease, and only 3 patients are alive with no evidence of disease. Actuarial 3-year survival and progression-free interval was 26 and 20%, respectively. Primary treatment consisting of sequential chemotherapy and whole abdomen radiation in the dose and scheme utilized did not improve the survival over what could be expected utilizing one of these treatments alone. It was associated with increased delayed toxicity.

Abdomen↗
PubMed1988

The incidence of urogenital Chlamydia trachomatis infections among patients in Kumasi, Ghana.

The incidence of urogenital chlamydia infections among selected patients in Kumasi, Ghana was evaluated using an immunofluorescent monoclonal antibody technique. Chlamydia trachomatis was identified in 4 of 110 patients presenting for prenatal care, 2 of 55 female patients with infertility and 6 of 15 males with acute urethritis. The findings demonstrate that C. trachomatis is a frequently identified pathogen among male patients presenting with symptoms of acute urethritis; however, the incidence of chlamydia infections among asymptomatic patients is relatively low.

Acute Disease↗
PubMed1988

Vesicovaginal fistula revisited.

Vesicovaginal fistulas remain common and serious problems for women in West Africa. Thirty-six surgical repairs done during visiting professorships by American gynecologists between the years 1978-1987 are documented. The overall success rate was 70%. The management of large (greater than 4 cm) obstetric fistulas was especially difficult until the Latzko technique was abandoned for the technique of wide mobilization of vaginal flaps over the fistula site. This technique reduced the failure rate from 75% through 1986 to approximately 25% in 1987. Ongoing controversies and basic principles of surgical techniques in fistula repair are reviewed.

Africa, Western↗