Lithopaedion in a 92-year-old woman.
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Biomedical subjects
Publications and source records attributed to P Speiser.
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Lowering the total steroid dose in modern oral contraceptives (OCs) has been connected with a higher incidence of ovarian follicle and cyst formation. To investigate the presence of ovarian follicles and cysts by means of vaginal ultrasonography and serum hormone determinations during use of two low-dose OCs, 65 volunteers were randomized to receive either 20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel (group A) or 35 micrograms EE + 250 micrograms norgestimate (group B) for a 2-month study period. At baseline, 39% of women in group A and 31% in group B exhibited at least one follicle < 35 mm in diameter. By the end of the second treatment cycle, the frequency of these follicles had decreased to 14% in each group. Only one subject in the higher estrogen group developed an ovarian cyst > 35 mm. One subject in each group demonstrated hormone levels characteristic of ovulation; no pregnancy occurred in either group. The 20 micrograms EE preparation was not found to lead more often to ovarian follicles or cysts when compared with a 35 micrograms EE preparation, possibly because of the type and dose of the progestogen used.
Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.
PURPOSE: To facilitate the interpretation of the choroidal dye filling sequence, the use of simultaneous indocyanine green (ICG) and fluorescein angiography was evaluated. METHODS: A single-wavelength scanning laser ophthalmoscope (SLO) was modified to a two-wavelength system, permitting the simultaneous recording of ICG and fluorescein angiography. This method has been used in 340 cases. About two thirds of the patients had well-defined or occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD). RESULTS: Simultaneous ICG and fluorescein angiography is feasible with a two-wavelength SLO and provides images of good quality. Two corresponding ICG and fluorescein angiography pictures can be presented as one combined red-green picture. CONCLUSION: This method has three advantages: (1) it allows a precise comparison of the transit of both dyes through both circulations, and there are no differences in the injected bolus nor in the actual blood pressure; (2) the important features of the ICG angiograms are fully aligned with the critical retinal vascular landmarks provided by the fluorescein images; and (3) it is very time efficient--with a single injection and one photographic session, immediate results are obtained.
Chromosome 17 is a frequent target during breast-cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 151 pairs of tumor and cognate lymphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by PCR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thraI, gcsf and rara genes. Data presented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17:2 on 17p, 3 on 17q. Of the 2 regions on 17p, one involves tp53 while the second is located more distally toward the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long arm band q21, corresponding to the brcaI region; (ii) in a central region defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regions presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large portions of the chromosome, a high proportion of the analyzed tumors showed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor. The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer. METHOD: A Western blot analysis was used to investigate HER-2/neu expression, whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer (NK) cell activity. RESULTS: In patients with breast cancer, NK cell activity was significantly higher compared with patients with benign tumors (P = 0.006) or healthy control subjects (P = 0.002). Moreover, 23.3% of patients with breast cancer showed an overexpression of HER-2/neu protein. Within this group of patients, NK cell activity was significantly lower (45.6 +/- 16.1%) compared with the group with no HER-2/neu overexpression (57.3 +/- 11.0%). NK cell activity did not increase in patients with HER-2/neu overexpression. Thus, there was a statistically significant correlation of cytolytic effector cell function with HER-2/neu expression of the tumor (P = 0.003), and HER-2/neu overexpression correlated with a negative estrogen receptor status (P = 0.005). CONCLUSION: These data add further evidence to previous observations from the authors' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer.
In an attempt to verify the nature of amplification events at band q13 on chromosome 11 we surveyed the amplification status of ten molecular markers specific for this region (GSTP, SEA, D11S97, D11S146, BCLI, PRADI/CCNDI, HST/FGF4, INT2/FGF3, EMSI, and DIIS833E) in a panel of 389 primary breast carcinoma DNA samples. Eighty-eight tumors (23%) showed at least one of these markers amplified, but in a majority of the cases amplification encompassed more than one of the tested loci. Our data confirm that amplicons at 11q13 can cover large portions of DNA and are consistent with the existence of several cores of amplification. One important core seems to be, as previously described, centered around PRADI/CCNDI; 57 tumors (14.7%) showed amplification at PRADI/CCNDI either alone (one tumor) or along with amplification of BCLI or INT2/FGF3. The level of amplification of PRADI/CCNDI sometimes exceeded that of surrounding markers. Three additional amplification events occurring independently of amplification of PRADI/CCNDI were also detected. Centromeric to BCLI, probes to DIIS97, and DIIS146 detected amplification in 60 tumors (15.4%) and were often the only amplified markers. Telomeric to INT2/FGF3, DIIS833E was found amplified alone in ten tumors, and it was the most amplified marker in another six cases. At a shorter distance of INT2/FGF3, EMSI was the only amplified marker in two tumors, with a level of amplification that could exceed that of PRADI/CCNDI and DIIS833E. Our data thus suggest the existence of four independent amplified regions within band 11q13 in breast cancer.
BACKGROUND: Only a few patients with neovascularized age-related macular degeneration (AMD) have clinical and fluorescein angiographic manifestations that meet eligibility criteria for photocoagulation therapy. Angiography with indocyanine green (ICG) may expand those criteria. MATERIAL AND METHODS: Fifty-two patients with exudative AMD were studied by fluorescein and ICG angiography (using the Rodenstock scanning laser ophthalmoscope). The ICG-angiograms were studied in relation to the questions, how often subretinal neovascularizations (SNV) were visible and how often the results were helpful for laser treatment. RESULTS: In 18 cases (about one third) a SNV was detected by ICG-angiography and in 8 (15%) the result allowed a laser treatment. "Ideal" SNV presented as neovascular trees with a visible feeder-vessel. Other cases showed a circumscribed area of diffuse hyperfluorescence especially in the late phase. Macular edema often prevented the resolution of subretinal membranes. CONCLUSIONS: Only randomised studies will be able to show whether the combination of fluorescein and ICG angiography allows the possibility of treating more patients with SNV than fluorescein angiography alone. In the following circumstances this might be the case: 1. If in subfoveal SNV a feeder-vessel could be delineated with ICG-angiography that might be treated selectively. 2. If an occult SNV might be reclassified as manifest SNV due to findings provided by ICG-angiography. 3. Examination of patients with ICG-angiography immediately after laser photocoagulation might be a way of proving the completeness of the treatment.
In this study epidermal growth factor receptor (EGF-R), estrogen receptor (ER), and progesterone receptor (PR) status was evaluated in 326 primary breast carcinomas. Nineteen percent of samples were EGF-R positive, 63% were positive for ER, and 54% for PR. In 46% of the tumors both ER and PR were positive. These data are presented together, with grading, size of tumor, lymph node involvement, histological subtype, and age. Sixty-nine percent of EGF-R negative tumors were ER-positive and 51% were positive for ER as well as PR. In particular, negative correlation between EGF-R and steroid receptor status was found. A quantitative correlation was also shown. A combination of negative steroid receptor and positive EGF-R was found more often in the population of poorly differentiated tumors. Tumors bigger than 5 cm were related to a positive EGF-R status. No correlation between nodal status and any receptor status was found. Intraductal carcinomas were more often EGF-R positive than infiltrating ductal (NOS) or infiltrating lobular lesions. The age of patients correlated with the concentration of ER only. In our study we reaffirmed the negative correlation between steroid receptor status and the overexpression of EGF-R; furthermore the combination of EGF-R+ and ER- tumors was observed more often in histological high-risk tumors. Patient outcome did not show statistically significant differences concerning the EGF-R status, but was associated with the steroid receptor status.
In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.
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We describe the use of high-performance liquid chromatography (HPLC) for the rapid quantitative analysis of short DNA fragments generated in differential PCR, where a target gene and a control gene are in vitro coamplified in one single reaction. Using an anion-exchange nonporous column, both separation and quantitation of the differential PCR products are achieved in about 5 min per sample. The performance of this technique proved to be superior to that of conventional gel electrophoresis and subsequent analysis by a laser densitometer, a solid-state scanner and a charge coupled device video camera imaging system. The usefulness for clinical testing is described in the example of the quantitative analysis of the c-erbB-2 oncogene copy number of human breast carcinomas by differential PCR. The combined use of differential PCR and automated HPLC analysis of the PCR products may well substitute for classical Southern blot hybridization in routine clinical analysis of oncogene amplification.
Infections of the female genitals are among the most common conditions seen by primary care physicians. Approximately 75% of all women experience at least one episode of vaginitis during their reproductive life. Bacterial flora of the female genital tract is complex and dynamic. Those organisms which may cause gynecological infections in the appropriate setting are often present at a different stage in the woman's life as normal flora. The treatment of gynecological infections is dependent on the symptoms of the patient, the pathogen, and the medical history with regard to recurrences of the same disease. Since identification of the pathogen is often difficult, empirical therapy is administered frequently, which requires detailed knowledge of the most common bacterial pathogens and the resistance pattern of these organisms. An accurate initial diagnosis is the best basis for appropriate therapy, especially in view of the fact that once empirical antibiotic therapy has been administered, signs and symptoms are modified and the site of infection is rendered much more obscure.
Cell surface expression of leukosialin (sialophorin, CD43 antigen) on human neoplastic hematopoietic cell lines K-562, U-937, HL-60 and REH was determined with the aid of a new CD43 monoclonal antibody (Bra7G) by the immunochemical (radioimmunoprecipitation, immunoblotting) and immunocytofluorometric techniques. Interferon-gamma and TNF-alpha were utilized as the "physiological" inducers of differentiation-associated markers. The "non-physiological" inducer phorbol ester PMA induced down-regulation of leukosialin cell surface expression on immature erythroid-myeloid leukemia cell line K-562, but up-regulation of CD43 antigen on the promyelocyte leukemia cell line HL-60 and, to a lesser extent on the monocyte-like U-937 and CALLA+ ALL cell line REH. Retinoic acid down-regulated leukosialin on both U-937 monocyte-like cells and the CALLA+ ALL cell line REH. In contrast to these data, interferon-gamma, TNF-alpha, retinoic acid and 1,25(OH)2-vitamin D3 induced the up-regulation of leukosialin in a promyelocytic leukemia cell line HL-60.
The drug delivery systems which contain not only the active principle but also many auxiliary substances are often underestimated with respect to their desired and undesired effects. Due to their composition, their purity, their physical, chemical or biopharmaceutical properties, the pharmaceutical system may be taken into consideration at each pharmacodynamic and clinical evaluation. The importance of some pharmaceutical properties on nondesired effects are shown with the examples of insufficient degradation and drug release, too quick drug alteration, inhomogeneous distribution and the role of badly selected excipients as well as the negative influence of food on drug plasma levels.
The IL-1 alpha induced up-regulation of HLA class I and HLA class II (DR) antigen expression on the cell surface of the human breast cancer cell line ZR-75-1 was demonstrated. This was associated with a concomitant increase in TNF alpha production. Coincubation with an anti-TNF alpha neutralizing antibody partially inhibited the IL-1 alpha induced up-regulation of HLA DR antigen but had no effect on IL-1 alpha induced HLA class I up-regulation. These data indicate that IL-1 alpha induced HLA class II (DR) antigen up-regulation in ZR-75-1 cells is partially mediated by TNF alpha and that IL-1 alpha induced HLA class I and class II (DR) antigen up-regulation in ZR-75-1 human breast cancer cells in vitro are mediated by different mechanisms.
To determine overexpression of cathepsin D in head and neck tumours we examined cytosols from 53 primary tumours, nine cytosols of lymph node metastases and 12 cytosols from adjacent normal tissue. We found a significantly lower concentration in normal tissue compared with tumour cytosol as well as with metastases, even when we compared tumours and corresponding metastases pairwise. In addition, we found a significantly higher concentration of cathepsin D in five lymph node metastases than in the corresponding tumours. We conclude that the reported role of cathepsin D is not restricted to breast cancer but could also be important in head and neck cancer.