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Biomedical subjects

A Scharl

Publications and source records attributed to A Scharl.

At least 19 recordsLinked to original sources
PubMed2006

[Management of abnormal uterine bleeding].

Bleeding disorders are one of the most frequent gynecological problems. The causes of bleeding disorders, and their frequency in particular, vary depending on the age of the woman affected. In premenopause and perimenopause, the most frequent causes are hormonal, in up to 90 % of cases, as well as organic changes in the uterus such as myomas, adenomyosis uteri, or endometrial polyps, in up to 70 % of cases. Coagulation defects cause increased bleeding, particularly in girls and young women, with no other recognizable cause. The treatment of bleeding disorders is causally based, although if the woman does not wish to have children, the therapeutic algorithm in many cases leads to similar symptomatic measures. The following therapeutic approaches, listed in order of increasing efficacy, are mainly used in the treatment of increased bleeding: gestagen, estrogen-gestagen combination, levonorgestrel (Mirena) and endometrial ablation or myoma enucleation, with comparable success rates, and finally hysterectomy. Embolization of the uterine artery in myomas or adenomyosis uteri, nonsteroidal anti-inflammatory drugs, and antifibrinolytic agents represent alternatives that may be useful in individual cases. The paper provides an overview of the various causes, useful diagnostic measures, and treatment options in uterine bleeding disorders.

Algorithms↗
PubMed2005

[Vaginal foreign body -- cause for a rectovaginal fistula].

A case of 56-year-old patient is presented with the diagnosis "carcinoma of the cervix". She suffered from brown, bad smelling vaginal discharge since half a year without any pain. Three weeks before she had noticed a postmenopausal bleeding. At the examination under anaesthesia with cysto- and rectoscopy we saw a rectovaginal fistula. In the vagina a white plastic object was found which could not be removed. Some days later a hysterectomy with extraction of the foreign body (aerosol cap) was done and the fistula was treated together with the surgeons. There was no evidence of a carcinoma. The patient suffers from multiple sclerosis since 20 years. On asking she told us that the foreign body was in place since about two years. She was not willing to relate any other information.

Female↗
PubMed2005

[Suspicion for intraabdominal adhesions -- is open laparoscopy the gold standard?].

Laparoscopy is used for most surgical procedures in gynaecology. In general complications are rare. However, one of the most critical steps is the initial laparoscopic entry into the peritoneal cavity. According to the literature serious complications occur in approximately 1-2/1 000 cases. Whereas major vascular injuries are mainly recognised immediately, delayed recognition of bowel injuries is frequent. Complication rates of different entry procedures used in gynaecological laparoscopy are similar even in high risk patients (intraperitoneal adhesions, obesity). Utilising an open - instead a closed - entry (either by Veress needle or first trocar) technique or alternativ entry positions are suggested by some authors. This review presents data available in the literature and highlights that open laparoscopy is no gold standard.

Abdomen↗
PubMed2004

[Ipsilateral breast tumor recurrence after conservative breast cancer surgery -- diagnosis and therapy].

In spite of the fact that breast cancer is a systemic disease, local control plays an important role in its management. While surgical, radiotherapeutic and systemic therapy of primary breast cancer are performed according to widely accepted guidelines, the management of ipsilateral breast tumor relapse (IBTR) is still a matter of individualised concepts because of the lack of randomised studies. IBTR represents a significant medical problem, since the recurrence rate is 5-15 % after 5 years and 20-25 % after 10 years. Incidence is higher in younger patients, in tumors with an extensive intraductal component, positive tumor margins, axillary lymph node metastases, negative steroid hormone receptors and high proliferative activity. Distant metastases after IBTR occur more often if the interval between primary diagnosis and IBTR is short (e. g. less than 4 years). Diagnosis of IBTR include breast palpation, mammography and breast ultrasound. In addition breast MRI can be used to further differentiate between benign and malignant lesions after breast conservation. Standard therapy in this setting remains mastectomy. Breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Breast irradiation after secondary breast-conservation can be carried out in some cases. Some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. The heterogeneous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients.

Breast Neoplasms↗
PubMed2003

Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions.

Dynamic enhanced magnetic resonance (MR) mammography and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) of the breast were directly compared preoperatively in suspicious breast lesions. Forty-two breast lesions in 40 patients were examined with a three-dimensional dynamic MR imaging series and FDG-PET. The MR and PET examinations were evaluated separately and the results were compared with the histological findings. The sensitivity and specificity of each method were calculated. The diagnostic value of both modalities as single diagnostic tool and in combination was investigated. Nineteen malignant and 23 benign breast lesions were proven histologically. Magnetic resonance mammography and FDG-PET showed a sensitivity of 89 and 63%, respectively. The specificity was 74 and 91%, respectively. The combination of both imaging methods decreased the not-required biopsies from 55 to 17%. Only one false-negative finding-a patient pre-treated with chemotherapy-was observed in both methods. The combination of MR mammography and FDG-PET can help to decrease biopsies of benign breast lesions. Because of their high cost, these modalities should only be used in problematic cases to either rule out or to demonstrate malignancy. The best diagnostic strategy is achieved using MR mammography first. If the diagnosis is still questionable, FDG-PET can be performed.

Breast↗
PubMed2002

[Feather--data acquisition in gynaecology and obstetrics].

Nowadays many types of medical documentation are based on computer facilities. Unfortunately, this involves the considerable disadvantage that almost every single department and specialty has its own software programs, with the physician having to learn a whole range of different programs. In addition, data sometimes have to be entered twice - since although open interfaces are often available, the elaborate programming required to transfer data from outside programs makes the financial costs too high. Since 1995 the University's of Frankfurt am Main Department of Gynecology and Obstetrics has therefore developed a consistent program of its own under Windows NT for in-patient facilities, as well as for some outpatient services. The program does not aim to achieve everything that is technically possible, but focuses primarily on user requirements. In addition to the general requirements for medical documentation in gynecology and obstetrics, the program can also handle perinatal inquiries and gynecological quality control (QSmed [Qualitätssicherung in der Medizin] of the BQS [Bundesgeschäftsstelle Qualitätssicherung]).

Computers↗
PubMed2002

Is first-line single-agent mitoxantrone in the treatment of high-risk metastatic breast cancer patients as effective as combination chemotherapy? No difference in survival but higher quality of life were found in a multicenter randomized trial.

BACKGROUND: To determine whether patients with high-risk metastatic breast cancer draw benefit from combination chemotherapy as first-line treatment. PATIENTS AND METHODS: A total of 260 women with measurable metastatic breast cancer fulfilling high-risk criteria, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either mitoxantrone 12 mg/m(2) or the combination of fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) every 3 weeks. Treatment was continued until complete remission plus two cycles, or until disease progression. In the case of partial remission or stable disease, treatment was stopped after 12 cycles. Second-line treatment was vindesine, mitomycin and prednisolone. Gain from treatment was estimated using a modified Brunner's score composed of time to progression, patients' rating of the treatment benefit, alopecia, vomiting and performance status. RESULTS: After recruitment from 1992 to 1997 and observation from 1997 to 1999, the final evaluation showed that single-agent treatment with mitoxantrone does not differ significantly from combination treatment with FEC in terms of response, objective remission rate, remission duration, time to response, time to best response, time to progression or overall survival. There was, however, a significant difference in gain from treatment using a modified Brunner's score favoring the single-agent treatment arm. There was no evidence that any subgroup would fare better with combination treatment. CONCLUSIONS: No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.

Adult↗
PubMed2001

Molecular classification of breast cancer patients by gene expression profiling.

For many tumors, pathological subclasses exist which have to be further defined by genetic markers to improve therapy and follow-up strategies. In this study, cDNA array analyses of breast cancers have been performed to classify tumors into categories based on expression patterns. Comparing purified normal ductal epithelial cells and corresponding tumour tissues, the expression of only a small fraction of genes was found to be significantly changed. A subset of genes repeatedly found to be differentially expressed in breast cancers was subsequently employed to perform a classification of 82 normal and malignant breast specimens by cluster analysis. This analysis identifies a subgroup of transcriptionally related tumours, designated class A, which can be further subdivided into A1 and A2. Correlation with classical clinicopathological parameters revealed that subgroup A1 was characterized by a high number of node-positive tumours (14 of 16). In this subgroup there was a disproportionate number of patients who had already developed distant metastases at the time of diagnosis (25% in this subgroup, compared with 5% among the rest of the samples). Taken together, the use of these differentially expressed marker genes in conjunction with sample clustering algorithms provides a novel molecular classification of breast cancer specimens, which facilitates the identification of patients with a higher risk of recurrence.

Breast Neoplasms↗
PubMed2000

Cervical intraepithelial neoplasia in human immunodeficiency virus-positive patients.

Cervical intraepithelial neoplasia (CIN) is common in patients positive for human immunodeficiency virus (HIV). The questions are whether the management of CIN in these patients should be different from that of HIV-negative women, whether there are any prognostic factors to indicate the course of CIN, and whether the latter is influenced by antiretroviral therapy. A total of 267 HIV-seropositive women were counseled and examined in our colposcopic clinic. Of that number, 53 patients died during the observation period; 74% of these patients were immunosuppressed (CD4 count < 200 cells/mm3), and 45% were given diagnoses of CIN. The incidence of CIN was significantly higher in patients with CD4 less than 200 cells/mm3. Neither the route of HIV infection nor the HPV status nor smoking habits correlated with CIN. CIN relapse was histologically confirmed in 28% of patients who underwent complete surgical removal. Immune status plays an important role in HIV-positive women not only with respect to survival but with respect to CIN.

Adult↗
PubMed1999

Amplification of the mdr1-gene is uncommon in recurrent ovarian carcinomas.

Ovarian carcinomas are known to rapidly develop drug resistance against chemotherapeutic agents. This phenomenon is often associated with the expression of pl70-glycoprotein. A high rate of transcription of the corresponding mdr1-gene in resistant tumors is reported. Amplification of the mdr1-gene has been observed in tumor cell lines exposed to cytotoxic drugs; however, significant information is lacking as to whether this holds true in clinical carcinomas. To fill this gap, we investigated the rate of gene amplification of the mdr1-gene in 63 recurrent ovarian carcinomas and we determined the resistance pattern of these cells using an ex vivo assay. The tumors showed varying ex vivo resistance patterns which did not correlate to clinical parameters. Amplification of the mdr1-gene was not observed in any of the cancer specimens. Therefore, we conclude that mdr1-gene amplification is not a common pathway for the development of chemoresistance in clinical ovarian carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Cross-reactive staining of normal bone-marrow cells by monoclonal antibody 2E11.

The monoclonal antibody (MAb) 2E11 is commonly used for detection of microdisseminated epithelial cells in bone marrow of cancer patients. Surprisingly, in an earlier report 2E11 was shown to bind to mononuclear cells in bone marrow in 61% of healthy donors. In the present study we tested whether this cross-reaction with non-epithelial bone-marrow cells can be characterized further. In addition, we analyzed the influence of 2E11 concentration on the staining of mononuclear cells. We performed immunocytochemical double stainings of bone-marrow aspirations from breast-cancer patients using 2E11/A45-B/B3 (MAb against cytokeratin 8, 18, 19) and 2E11/CD45 (MAb against CD45-leukocyte common antigen), while tumor cell lines MCF-7 and K526 as well as bone marrow from breast-cancer patients were treated with different concentrations of 2E11. A portion of 2E11-positive cells was characterized as hematopoietic cells by CD-45-binding, while others were identified as epithelial cells by A45-B/B3-binding. We defined a concentration of 2E11 to immunolabel epithelial cells and distinguish hematopoietic cells. Higher concentrations of 2E11 enhance staining of hematopoietic cells, to match that of epithelial cells. We conclude that 2E11 shows cross-reactivity to epitopes displayed by hematopoietic cells. However, specific staining of epithelial cells can be achieved. As long as there is no antibody available which is highly specific for epithelial cells, detection of microdisseminated tumor cells in bone marrow by antigen-antibody reaction should be verified morphological criteria.

Antibodies, Monoclonal↗
PubMed1999

Expression of p16 and lack of pRB in primary small cell lung cancer.

The retinoblastoma protein (pRB), p16, and cyclin D1 are major components of the RB pathway, which controls the G1 checkpoint of the cell cycle. Proper regulation of this pathway is crucial for normal cell proliferation. Abnormal forms of these proteins have been found in various types of malignant tumours. In the present report, immunohistochemical techniques were applied to study the expression of pRB, p16, and cyclin D1 in 161 samples of primary small cell lung cancer (SCLC) and 20 samples of non-small cell lung cancer (NSCLC). While pRB and cyclin D1 staining was negative in 161 specimens of SCLC, expression of p16 was observed in 153 samples. In contrast to SCLC, 16 out of 20 NSCLC cases exhibited pRB expression and 15 showed cyclin D1 expression, but only very weak p16 staining was found in five samples. These observations could provide additional criteria for the distinction between SCLC and NSCLC. Furthermore, these findings, based on primary tissues, implicate different mechanisms in the tumourigenesis of SCLC and NSCLC.

Adenocarcinoma↗
PubMed1998

Immunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS.

Disseminated epithelial tumor cells have been detected in the bone marrow and blood of cancer patients by means of immunocytochemical or immunofluorescent staining of cytocentrifuge slides, multiparameter flow cytometry, and reverse transcriptase-polymerase chain reaction. However, it is hardly possible using such methods to detect tumor cells at a frequency below 10(-6). To increase the sensitivity of these detection techniques we have developed a new technology for the enrichment of disseminated epithelial tumor cells from hematopoietic cell samples by high-gradient magnetic cell sorting (MACS). Cells are permeabilized and fixed and carcinoma cells are magnetically labeled specifically with an anti-cytokeratin 8 monoclonal antibody (mAb) directly conjugated to superparamagnetic microbeads. Magnetically labeled cells are enriched on high-gradient magnetic columns. Tumor cells are detected in the enriched cell fraction by flow cytometry, fluorescence microscopy, or immunocytochemisty. In this study we demonstrated the method using a model system in which five to 5,000 cells from a breast cancer cell line were seeded into blood cell samples from a healthy donor containing 1.2 x 10(8) leukocytes. Tumor cells were 10,477+/-4242 (n=25)-fold magnetically enriched, and 57.7%+/-16.9% (n=33) of the initially seeded tumor cells were recovered. Applying the method to 20-40 mL blood samples from patients with advanced carcinomas of the breast, prostate, colon, rectum, or lung, we were able to detect between one and 6.8 x 10(4) cytokeratin-expressing tumor cells in 21 of 34 patients. This corresponds to frequencies of tumor cells between 6.8 x 10(-9) and 1.1 x 10(-3) among nucleated cells in the original sample. Enriched tumor cells were further analyzed for expression of tissue-specific and prognostic markers such as breast mucin glycoproteins, erbB2, and CD44v6 for additional characterization and to confirm their tumor origin. The technique described could become a valuable tool for the quantification and molecular characterization of metastatic carcinoma cells in hematopoietic tissue, and may ultimately prove useful in the diagnosis, prognosis, and monitoring of patients with carcinoma.

Adult↗
PubMed1998

Estrogen receptor scintigraphy.

Radio-labeled estrogen receptor ligands are tracers that can be used for functional receptor diagnosis. Their specificity towards receptors, together with the fact that only 50-70% of mammary carcinomas are receptor positive, renders them unsuitable for detection of primary tumors or metastases, and this means that estrogen receptor scintigraphy can be used neither for tumor screening nor for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are suitable for in vivo imaging of estrogen receptors. Their high specificity, established in animal experiments and in vitro studies has been reproduced in in vivo applications in humans. Tracers with positron radiation emitters are, however, hardly suitable for broad application owing to the short half-life of 18F, which would mean that users would need to be situated close to a cyclotron and a correspondingly equipped radiochemical laboratory. The number of available PET scanners, on the other hand, has increased over the last few years, especially in Germany, so that this, at least, does not present a limiting factor. All the same, 123I-labeled estradiol derivatives will find more widespread application, since the number of gamma-cameras incorporating modern multi-head systems is several times greater. The results of studies with 123I-E2-scintigraphy published to date are very promising, even given the initial technical problems mentioned above. As a method of examination, it could be optimised by using improved tracers with a higher tumor contrast and less disturbance from overlapping in diagnostically relevant locations, for instance, by selecting tracers with higher activities whose excretion is more renal than hepatobiliary. The use of modern multi-head camera systems can also be expected to improve the photon yield.

Animals↗
PubMed1998

[Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol-3,17beta].

AIM: The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells of a mamma carcinoma were investigated following incubation with [125I]E ranging from 1 h to 24 h. METHODS: The receptor status of the cells was confirmed by immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was tested in the presence and absence of radioinert E and [127I]E and in ER-negative cells in comparison to ER-positive cells. The subcellular distribution was investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity was assessed in ER-positive and negative cells by a standard colony forming assay after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and 24 h. RESULTS: A significant cytotoxicity was observed only when ER-rich MCF-7-cells were incubated with [125I]E alone. The maximal cytotoxic effect was a reduction of survival fraction to 20-25%. This was achieved at radioactivity concentrations > 37 kBq/ml. Maximal effect was seen after 8 h incubation, extension of incubation time did not further increase toxicity. CONCLUSION: The results suggest that the radioactivity was bound to ER. Through their nuclear localization radioestrogens tagged with radionuclides emitting very low energy electrons (Auger electrons) bear potential for therapy by ER-mediated deposition of lethal doses of ionizing radiation to single cells without affecting neighbouring cells. But, instead of 125I the shorter-living 123I shall be used for labelling because the deciding radiation effectes occur within the first 8 h.

Biological Transport↗