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Biomedical subjects

C Zielinski

Publications and source records attributed to C Zielinski.

At least 19 recordsLinked to original sources

Verapamil decreases accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in human breast cancer and soft tissue sarcoma cell lines.

99Tcm-methoxyisobutylisonitrile (99Tcm-MIBI) and 99Tcm-tetrofosmin are cationic tracers recognized by the efflux pump P-glycoprotein (Pgp). Verapamil has been shown to be a competitive inhibitor of Pgp, and was one of the first multidrug-resistant reversing agents identified. The aim of this preclinical in vitro study was to evaluate the effects of verapamil on the accumulation of 99Tcm-MIBI and 99Tcm-tetrofosmin in the human breast cancer cell lines MCF-7 and SK-BR-3 and in the human soft tissue sarcoma cell lines SW 982 and SW 1353, in comparison with respective control cells, i.e. without preincubation with verapamil. After preincubation with 10 or 100 microM of verapamil for 15 or 30 min, the 99Tcm-MIBI and 99Tcm-tetrofosmin accumulation in cells was assessed at 10, 30 and 60 min after incubation with these tracers. Addition of verapamil caused a decline in the accumulation of the two tracers at all incubation times, as compared with control cells. These effects of verapamil were neither dose- nor preincubation time-dependent in most cells. Our data indicate that verapamil is not a promising agent for increasing the sensitivity of scintigraphy with 99Tcm-MIBI or 99Tcm-tetrofosmin, or for evaluating Pgp tumour status in these types of tumours.

Adenocarcinoma↗

[Informed consent and responsibility for patient education in oncology. Review of Austrian and German jurisprudence].

Informed consent is currently an ethical, medical and legal requirement. Increasing public discussion concerning real or supposed malpractice has caused patients to adopt a critical attitude and has caused courts to increasingly demand informed consent for patients. Unfortunately, the legal requirements for informed consent have developed from atypical situations involving dissatisfied and injured patients rather than from the more common occurrence of physicians helping patients and having satisfied patients. In addition, the law has failed to establish explicit guidelines for physicians. We review the elements of informed consent based on current Austrian and German jurisdiction in the particular field of oncology and summarise the legal and medical realities with the aim of delineating specific criteria for decision making.

Austria↗

Attitude towards prophylactic surgery and effects of genetic counselling in families with BRCA mutations. Austrian Hereditary Breast and Ovarian Cancer Group.

The intent of this study was to evaluate the effect that an awareness of being a BRCA1 or BRCA2 mutation carrier has on the attitude towards prophylactic surgery and on developing depression symptoms. Thirty-five families were selected on the basis of previously detected BRCA1 or 2 mutations and 90 family members were given the appropriate questionnaires. Prophylactic mastectomy (PM) was considered by 21% of the Austrian mutation carriers (29% affected and 8% non-affected carriers). The majority of affected and non-affected carriers expected PM to impair the quality of their life. Fifty per cent would undergo prophylactic oophorectomy (53% affected and 46% non-affected carriers). The self-rating depression scale indicated that following mutation result disclosure the depression scores of carriers decreased (40 baseline vs 38 after result disclosure, P = 0.3), whereas, for non-carriers, scores increased (36 baseline vs 40 after result disclosure, P = 0.05). We conclude that information about carrier status is not associated with increased depression symptoms in mutation carriers. In non-carriers, depression scores increased slightly, probably reflecting survivor guilt. The option of having PM was associated with a negative impact on the quality of life and was declined by the majority of Austrian mutation carriers.

Adult↗

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients.

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.

Adult↗

Uptake of 99mTc-MIBI and 99mTc-tetrofosmin into malignant versus nonmalignant breast cell lines.

UNLABELLED: The kinetics and cellular uptake of 99mTc-2-hexakis 2-methoxyiso-butyl-isonitrile (MIBI) and 99mTc-1 ,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) into malignant versus nonmalignant human breast cell lines were investigated and compared. METHODS: At specific intervals after incubation at 37 degrees C and 22 degrees C with 99mTc-MIBI or 99mTc-tetrofosmin, the uptake characteristics of radiotracers into human adenocarcinoma breast cell lines MCF-7 and SK-BR-3 and human breast, nontumor cell line HBL-100 were assessed. RESULTS: The uptake of 99mTc-MIBI and 99mTc-tetrofosmin was lower at an incubation temperature of 22 degrees C than that at 37 degrees C in the 3 cell lines. In MCF-7 and in SK-BR-3 cells the uptake of 99mTc-MIBI was significantly higher than the uptake of 99mTc-tetrofosmin. The uptake of 99mTc-MIBI was significantly higher into MCF-7 and SK-BR-3 cells than that into HBL-100 cells. In comparison with HBL-100 cells, uptake of 99mTc-tetrofosmin into SK-BR-3 cells was significantly higher, whereas uptake into MCF-7 cells was similar. CONCLUSION: In vitro data suggest that 99mTc-MIBI may be a better tracer than 99mTc-tetrofosmin for discrimination between malignant and nonmalignant breast disease.

Adenocarcinoma↗

A windows based viewing application for image postprocessing in DICOM format.

OBJECTIVE: To design, implement and evaluate a PC-based medical viewing application including image postprocessing for DICOM images for use within an existing hospital infrastructure. MATERIAL AND METHODS: A user-friendly DICOM compliant viewing application including image postprocessing (spatial frequency and contrast enhancement) and HL7 communication ability was designed and implemented on PC basis to run under Windows OS. To assess its quality compared to high-end workstations, an ROC analysis was performed. RESULTS: The use of image postprocessing on a PC significantly improved the perception of low-contrast details in computed radiographs. Review at a radiological workstation was superior to review at a PC with image postprocessing.

Computer Communication Networks↗

Comparative 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin uptake in human soft tissue sarcoma cell lines.

The uptake characteristics of technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI), 99mTc-tetrofosmin and 99mTc-furifosmin in human soft tissue sarcoma cell lines were investigated and compared. After 10-120 min of incubation at 37 degrees C, 32 degrees C and 22 degrees C with 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin, the kinetics of cellular uptake of these tracers in human soft tissue sarcoma cells SW 684 (fibrosarcoma), SW 872 (liposarcoma), SW 982 (synovial sarcoma) and SW 1353 (chondrosarcoma) was assessed. The uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin was temperature dependent. The kinetics of uptake of 99mTc-MIBI and of 99mTc-tetrofosmin was similar between fibrosarcoma and liposarcoma cells, as well as between synovial sarcoma and chondrosarcoma cells. 99mTc-furifosmin showed similar uptake kinetics in all cell lines. The uptake of 99mTc-furifosmin was, however, significantly higher in liposarcoma than in the other cells. The data indicate that the cellular uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin is dependent on cellular metabolic activity.

Cell Survival↗

99m-Tc-tetrofosmin scintigraphy and breast cancer.

BACKGROUND: 99m-Tc-tetrofosmin holds significant interest among medical oncologists because of its high positive predictive value (>90%) in pilot trials, exceeding sensitivity and specificity rates of mammography. Objective. Our objective was to assess the diagnostic accuracy of 99m-Tc-tetrofosmin whole-body scintigraphy in outpatients. PATIENTS AND METHODS: Thirty-one patients with an abnormal mammograph (n = 22) or follow-up patients (n = 9), 7 of whom were known to have metastatic disease, were included. Tracer (550 MBq) was injected into the cubital vein. Whole-body planar and single photon emission computed tomography images of regions of interest were obtained. Histology, computed tomography (CT), or magnetic resonance imaging (MRI) were performed to confirm scintigraphic results. Correlation between scintigraphy and CT or MRI was assessed by two independent radiologists. Accuracy, sensitivity, and specificity rates for the diagnosis of local and distant breast cancer lesions were given. RESULTS: Of the 22 first-visit patients, 15 had breast cancer, and 7 had no evidence of any malignant disease. Of all patients examined (n = 31), 21 had distant metastases. Breast tumors were correctly diagnosed in 14/15 patients (93%), with only 1 false-negative result. Extrahepatic metastatic lesions (n = 16) were correctly diagnosed in 14 (88%) patients, whereas the method was not suitable for the diagnosis of liver metastases. CONCLUSION: Tetrofosmin scintigraphy has shown very high detection rates of breast tumors and of metastatic lesions and is therefore a valuable option in breast cancer diagnosis.

Adult↗

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations.

The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non-coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10(-4)), respectively].

Africa↗

BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics.

We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high-performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non-Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node-negative control group. The prevalence of grade III tumors was marginally significant. Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age-related, node-negative comparison group, showed no statistical difference.

Adult↗

[Comparative findings of digital thoracic images and digital images of statistical phantoms as film copy, a radiological work station and a PC].

INTRODUCTION: An ROC analysis was carried out in order to determine the reliability of digital luminescence radiography review at a PC and this was compared with a radiological work station and with X-ray film on a viewing box. MATERIAL AND METHOD: 54 chest images obtained by digital luminescence radiography were selected, 31 of these contained small pulmonary nodules. In order to evaluate critical detail, five images of a phantom showing round foci were used. Five radiologists examined these, using a Siemens Magic View work station, a PC with proprietary software (ViewMed) and X-ray films on a viewing box. Image processing of the work station used the standard clinical application. ViewMed performs linear scaling of grey levels to 8 Bit. The results were examined statistically by means of a t-test. RESULTS: As far as the chest images were concerned there was no significant difference in the diagnostic value of these methods. There was, however, a highly significant loss of diagnostic information with respect to the round focus phantom when using the PC compared with the other methods. CONCLUSION: In the configuration in which it was used, the PC should not be relied on as a primary means of examination since critical details cannot always be seen. In routine use these play a subordinate role and there was no significant diagnostic loss where the chest images were concerned. We expect that by improvements in the frequency and contrast processing the PC accuracy will be considerably increased.

Humans↗

Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. The Epirubicin High Dose (HEPI 010) Study Group.

PURPOSE: A phase III study was performed in patients with metastatic breast cancer (MBC) to evaluate the effect on response rate and survival of a doubling of the epirubicin dose intensity. PATIENTS AND METHODS: Four hundred fifty-six patients were randomised to receive either epirubicin 100 mg/m2 or 50 mg/m2 in combination with 5-FU (500 mg/m2) and cyclophosphamide (500 mg/m2) (FEC 100 vs. FEC 50) i.v., every 21 days for a maximum of six cycles (eight in case of CR). RESULTS: Of 456 patients, 390 were evaluable for efficacy. Objective response (CR + PR) was seen in 57% (FEC 100) vs. 41% (FEC 50) of the evaluable patients (P = 0.003). The CR rate was higher in the FEC 100 arm (12% vs. 7%, P = 0.07). FEC 100 produced significantly higher response rates in patients with visceral localisation (50% vs. 34%, P = 0.011) and in patients with more than two metastatic organ sites (64% vs. 37%, P = 0.001). Median time to progression (7.6 vs. 7 months) and overall survival (18 months vs. 17 months) were similar. Myelosuppression was the principal toxic effect, with grade IV neutropenia observed in 57% of the patients treated with FEC 100 vs. 9% of those on FEC 50. Grade IV infection or febrile neutropenia were observed in 8% (FEC 100) vs. 0.4% (FEC 50), but the incidence of septic death was the same in the two arms (two patients each). Cardiac toxicity was similar in the two treatment groups, with 5% vs. 3% of the patients taken off study due to cardiac events, primarily due to a decline in LVEF. Only three patients (two in FEC 100) experienced congestive heart failure. CONCLUSION: This trial shows that FEC with epirubicin at 100 mg/m2 can be administered for repeated cycles without bone marrow support with increased, though acceptable, toxicity and with a significant increase of antitumor effect (especially in visceral and/or high-burden disease), but no increased survival.

Adult↗

[How certain is teleradiological telediagnosis for the tomographic procedure?].

PURPOSE: To define the value of teleradiographic studies, a comparison was carried out between digitised copies of CT examinations of the skull with the original images. Differences in image quality obtained from a digital scanner and a camera were quantified. MATERIAL AND METHOD: 56 CT examinations of the skull, 28 of which had discrete abnormalities, were chosen for ROC analysis. The original films were digitised with a Vidar VXR-12 scanner and Panasonic WV-160 and WV-BP 500 cameras. The images were evaluated by five radiologists after image transfer with Video Conference software to a personal computer. RESULTS: For the analysis of the films the area under the ROC curve was 0.91 +/- 0.04, for the digital scanner it was 0.85 +/- 0.04, for camera WV-BP 500 0.89 +/- 0.06 and for camera WE-160 0.87 +/- 0.09. Comparison with the film findings showed. a minimal p-value of 0.17 which indicated that there was no significant reduction in diagnostic value following digitization. CONCLUSION: The probable reason for the slight deterioration using the digital scanner was the reduction to 75 dpi compared with 134 dpi on the CT films. The cameras produce image noise comparable to CT with low window settings and reduced local resolution. We expect similar results for CT with soft tissue windows or for MRT of the skull. Conventional radiographs containing high local resolution, wide grey scale and low image noise would presumably make higher demands on methods of digitization.

Computers↗

["Second opinion" in online radiology via Internet: report on implementation and analysis of reliability of findings in sectional images].

Numerous medical on-line services have already been established in the world-wide internet. In connection with the Information service TELESCAN, sponsored by the EU, a pilot project has been initiated which offers a radiological "second opinion" via the transmission of radiological findings and images that have been previously rendered anonymous. In addition to a description of the basic implementation, tests of the diagnostic certainty of the transmitted cranial computed tomographs have been performed. The CT images were digitized with a document camera, transmitted over the Internet, and then evaluated on the receiver's monitor. Both the transfer of originally generated digital image files (in ACR-NEMA or DICOM) as well as graphic files after digitization of X-ray films, for example by a document camera, is possible via electronic post (e-mail). Visualization by the receiver requires the use of current proprietary software for special medical image formats, while standard graphic formats such as GIFF or JPEG can be visualized with the usual Internet software. In an ROC analysis, 56 individual images of cranial computed tomographs, half with pathological findings such as space-occupying lesions, infarcts, or brain edema, were tested with regard to the diagnostic certainty after digitization and transmission. In comparison with the original film findings, there was a slight but statistically not significant reduction in diagnostic certainty of the images evaluated on screen after transfer via the Internet. We believe that this result is due to the low local resolution, low dynamic range, the high image noise and of CT arising from the window technique. The same parameters are probably valid for MRI. The result cannot be applied to conventional radiography including mammography because, in comparison to the mentioned image techniques, their local resolution is high and image noise is considerably lower.

Computer Communication Networks↗

Apolipoprotein A and biological half-life of prostaglandin I2 in HIV-1 infection.

Disturbances in lipid and lipoprotein metabolism being reported for HIV-1 infection are a common sign of severe infections. Apolipoprotein A being the main constituent protein of HDL has been described to function as the prostaglandinI2 (PGI2)-stabilising factor. PGI2 is not only one of the most potent biological antiaggregatory substances but seems to exert cell-protective properties in the central nervous system, too. PGI2 half-life as well as lipid [total-cholesterol (total-c), triglycerides] and (apo)lipoprotein [LDL-c, HDL-c and apolipoprotein (apo) AI] levels were investigated in 14 HIV-1 positive patients (13 males, 1 female, aged from 29 to 57 yrs). Patients exhibited decreased levels of total-c, LDL-c, HDL-c and apo AI, respectively, while elevated triglyceride levels were observed. PGI2 half-life was shortened (median 53, range: 15-161 seconds) in the patients' plasma as compared with normal controls ranging from 9-12 minutes. In patients with neurological manifestation (n = 8) the decrease of PGI2 half-life (median: 34 seconds, range: 15-67 seconds) was significantly more pronounced (p < 0.05) than in patients (n = 6) with the absence of any central nervous manifestation (median: 83.5, range: 29-161 seconds). The dramatic changes in both HDL-c and apolipoprotein AI as seen during HIV-1 infection are likely to impair PGI2-stabilisation thus being associated with the presence of peripheral neuropathy, dementia and haemostatic imbalance.

AIDS Dementia Complex↗