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Background and Objectives Serological evaluation of maternal sera for platelet antibodies in suspected fetal/neonatal alloimmune thrombocytopenia (FNAITP) discloses in only ≈ 30% of individuals a platelet-specific antibody. Transfusion-induced alloimmunization against human platelet antigen-15 (HPA-15) has been reported to be about as common as against HPA-5, the second most common platelet antibody. Thus, anti-HPA-15 may also contribute significantly to yet-unclear cases of FNAITP. Materials and Methods In this retrospective analysis, we provide data on maternal platelet antibodies from 309 mothers who delivered an offspring with suspected FNAITP. Results Genotyping maternal and paternal samples (together n = 573) revealed a gene frequency of 0·496 for HPA-15a and a gene frequency of 0·504 for HPA-15b. HPA-15 antibodies were detected in 2% of all samples. Anti-HPA-15a and -15b were detected in two and three samples, respectively. One serum reacted equally with HPA-15a and -15b platelets. The most frequent platelet-specific antibodies were anti-HPA-1a (22%), but anti-HPA-5b (8·4%) were more frequent than anti-HPA-15. In addition, panreactive (5·5%) or autoreactive (5·2%) anti-GPIIb/IIIa or anti-GPIb/IX were detectable in maternal samples. Conclusions These data indicate that HPA-15 alloimmunization needs only to be considered in subjects with suspected FNAITP if no other platelet-specific antibody is detectable. The presence of panreactive or autoreactive antibodies should also be considered in neonatal thrombocytopenia.

Objective: To investigate the effects of low-dose oral hormonal contraception on the immune system during certain phases of the hormonal cycle. Design: Prospective, nonrandomized, controlled study. Setting: Academic research setting. Patient(s): Women with regular menstrual cycle using hormonal oral contraception (OC; Cileste®, 250 μg of norgestimat and 35 μg of ethinylestradiol, or Marvelon®, 150 μg of desogestrel and 30 μg of ethinylestradiol) and women not using hormonal or other forms of contraception. Intervention(s): Peripheral blood lymphocyte subsets were determined by flow cytometry on the first day of menstruation (day 1), in the follicular phase (day 8), midcycle (day 15), and in the luteal phase (day 22). Main Outcome Measure(s): Levels of lymphocyte subpopulations. Result(s): Women using OC had significantly higher levels of CD3+ CD8+ cells throughout their pill cycle compared to controls. Furthermore, women taking Cileste® had lower levels of natural killer (NK) cells during their cycle and also women taking Marvelon® but only from days 8–15. Within the pill cycle of Cileste® we observed an increase in CD20+ and CD20+ CD5+ cells from days 1–8. Conclusion(s): Cytotoxic lymphocytes, which are responsible for first-line immune defense, and B cells, which are involved in autoimmune disorders, are affected by OC.

Fragestellung: Die Immunreaktion mütterlicher Lymphozyten gegen den Embryo wird für die fetale Wachstumsretardierung mitverantwortlich gemacht. Die Sekretion von plazentarem Isoferritin (PLF) während der Schwangerschaft kann diese Immunreaktion verringern. In dieser multizentrischen Studie soll die Bestimmung von PLF zur Früherkennung einer Wachstumsretardierung untersucht werden. Methodik: Die PLF-Konzentrationen im Serum wurden bei 402 schwangeren Frauen zwischen der 12. und der 16. Schwangerschaftswoche mit Enzym-Immunoassay bestimmt und mit dem Geburtsgewicht, der Perzentile des Geburtsgewichtes und mit dem Gestationsalter verglichen. Ergebnisse: Frauen mit gemäss dem Gestationsalter untergewichtigen Neugeborenen (d.h. auf oder unter der 10. Perzentile des Geburtsgewichtes) wiesen im Vergleich zu Frauen mit normalgewichtigen Kindern (19,9 E/ml, n = 295) signifikant niedrigere (11,4 E/ml, n = 107) Serum-PLF-Konzentrationen auf (p < 0,004). Schlussfolgerung: Die Bestimmung der PLF-Konzentration im Serum während der ersten Hälfte der Schwangerschaft kann ein wichtiger zusätzlicher Parameter sein, um fetale Wachstumsretardierungen frühzeitig zu erkennen.

Regular screening mammographies and increasing knowledge of high-risk groups have resulted in an improvement in the rate of detection of smaller malignant lesions. However, uncertain minimal mammographic features frequently require further costly and often uncomfortable investigation, including repeat radiological controls or surgical procedures, before cancerous lesions can be identified. Placental isoferritin (p43), a protein with immunosuppressive effects, has been detected on the surface of lymphocytes taken from peripheral blood in patients with breast cancer. In this study we evaluated the sensitivity and specificity of the expression of p43-positive lymphocytes as a marker in early stage breast cancer and also investigated its expression on T-cell subpopulations. The presence of p43-positive lymphocytes was investigated using the monoclonal antibody CM-H-9 and flow cytometry in 76 women with controversial, non-palpable mammographic findings who were undergoing surgical biopsy. Patients with early breast cancer (n = 48) had significantly higher p43-positive cell values (median 3.83%, range 0.98–19.4) than patients with benign lumps (n = 28, median 1.43%, range 0.17–3.7) or controls (n = 22, median 1.3%, range 0.4–1.87) (P < 0.0001). At a cut-off level of 2% p43-positive cells a sensitivity of 91.7% and a specificity of 89.3% for detection of breast cancer could be reached. While the median ratio of total CD4+/CD8+ cells was 2.6, a ratio of 1.3 was found for the p43-positive subpopulation (P < 0.001), thus indicating a significant link between p43 and CD8+ cells. The determination of p43-positive lymphocytes in peripheral blood could serve as an additional diagnostic tool in patients with controversial mammographic findings and could also reduce the need for cost-intensive and often uncomfortable management of these patients. © 1999 Cancer Research Campaign

Tumor samples of 240 patients with primary breast cancer were biochemically and immunohistochemically investigated for estrogen receptors (ER) and, in 130 of the samples, for progesterone-receptors (PgR) in order to examine reasons for discordant findings. The biochemical (DCCA) and immunohistochemical assays (ICA) yielded positivity in 71% for ER, and in 44% for PgR. Concordant ER-DCCA and ER-ICA results were obtained in 84%; two thirds of the discordant ER-findings manifested as DCCA-neg/ICA-pos. Concordance in the case of PgR amounted to 72%, and of the discordances 60% were DCCA-neg/ICA-pos. Significant association with postmenopausal status existed only for ER positivity in ICA (p = 0.01), whereas ER-DCCA, PgR-DCCA and PgR-ICA were all more or less independent of the menopausal status. The frequency of discordances was independent of menopausal status. Discordance for ER-assays increased significantly near the respective cut-off point; this was not unequivocally true for PgR-assays. The correlation of tumor types of sparse cellularity, as well as prominent stroma content ('scirrhous carcinoma') with increased frequency of the constellation DCCA-neg/ICA-pos was of borderline significance for PgR (p = 0.06), but not for ER. The percentage of discordant ER-findings, figuring as DCCA-neg/ICA-pos, was statistically significantly increased in locally advanced breast cancer (p = 0.03). Fibrocystic disease in peritumoral breast tissue had no impact on receptor-assay discordance. In any case, the models derived from theoretical thought, laboratory data and singular observations can only in part explain the discordance in steroid receptor values measured with different methods.

Ziel dieser prospektiven Diagnosestudie war es, die Effektivitat des Vaginalultraschalls in der Nachsorge von Brustkrebs-Patientinnen unter Tamoxifentherapie zu uberprufen. Zusatzlich sollten spezifische sonomorphologische Veranderungen des Endometriums unter Tamoxifentherapie aufgezeigt werden. 82 symptomlose, postmenopausale Patientinnen, welche zwischen 20 und 40 mg Tamoxifen durchschnittlich 25 ± 16 Monate genommen hatten, nahmen an einer vaginosonographischen Untersuchung teil. Beurteilt wurde das gesamte innere Genitale mit besonderer Berucksichtigung der Cavumbreite, Homogenitat und Abgrenzbarkeit des Endometriums. In 49 Fallen wurde ein homogenes, gut abgrenzbares Cavumecho 10 mm, or endometrium > 5 showing bizarre struetures not clearly separated from the myometrium was an indication for performing curettage. In 49 patients, ultrasound yielded a normal result. Twelve patients showed homogeneous, well-definable endometrial thickness between 6 and 10 mm. In 21 cases, the endometrium was thickened to more than 10 mm, losing homogeneity and sonographie separability from the underlying tissue. Thus, in 21 of the 82 patients, curettage had to be performed. In 8 cases only, an atrophic endometrium could be found. In a control after curettage, the sonographie appearance of endometrial hyperplasia was unchanged in these 8 patients. In the other 13 patients that showed an enlarged, atypical endometrium, we found 10 cases with endometrial polyps and 3 cases with hyperplasia, one of them atypical. We think that transvaginal ultrasound is a good means to detect and evaluate endometrial alterations induced by tamoxifen treatment of postmenopausal breast cancer patients. With tamoxifen we suggest the cut-off level for enlarged endometrium to be definitely higher than starting at 6 mm. Nevertheless, loss of homogeneity and loss of endometrial separability should immediately lead to further diagnostic procedures. Because of the tamoxifen-specific phenomenon of „pseudoendometrial hyperplasia“, it is very important not to overinterpret ultrasonographic findings in the further follow-up of tamoxifen-treated patients who have already undergone curettage.

The conversion of plasminogen to active plasmin is thought to be a crucial step in the process of extracellular matrix degradation associated with metastatic spread. Activation of plasminogen is initiated by urokinase plasminogen activator (uPA). The binding of uPA to the uPA cell surface receptor (uPA-R) accelerates plasmin generation from plasminogen and localizes uPA activity to the cell surface. We investigated the mRNA-expression of uPA-R in 19 different human breast cancer cell lines. In a competitive reverse transcription polymerase chain reaction (cRT-PCR) we simultaneously co-amplified two different RNA templates bearing the same primer recognition sequences, the cell line RNA and a known amount of an in vitro synthesized uPA-R-RNA internal standard. We analyzed the two PCR products differing 50 bp in size by agarose gel electrophoresis and calculated the initial uPA-R-RNA template concentration from the relative intensities of the bands quantified by video densitometry. We grouped the investigated cell lines according to their in vitro invasiveness according to literature. Cell lines with a high potential of invasiveness showed a higher expression of uPA-R compared to those with a low potential of invasiveness (Student's t-test, p 0.04). In addition to that we compared the uPA-R mRNA levels with uPA-R, uPA, and PAI-1 protein levels in culture supernatants and cell lysates. The obtained results in breast cancer cell lines with different invasiveness and in benign epithelial cell lines revealed the complex cooperation of the urokinase type proteolytic pathway. uPA, uPA-R, and PAI-1 are to be considered as a diagnostic tool rather than assaying a particular molecule alone. Our findings support the hypothesis that the urokinase proteolytic pathway plays a central role in the acquisition of an invasive phenotype and favors its potential use as a prognostic marker in patients with breast cancer.

The secretion of placental isoferritin (PLF) during pregnancy could be responsible for the diminished immunoreaction of maternal lymphocytes against the embryo. In this study, serum levels of PLF in 335 pregnant women were correlated with birth weight, percentile of birth weight, gestational age, and pulsatility index of the uterine artery, as well as with diastolic notching. Women with small-for-gestational age (SGA) infants (birth weight below or equal to the tenth percentile) showed significantly lower PLF levels (11.7 U/ml) compared with women whose newborns were of normal weight (19.4 U/ml) (P < 0.05). In line with this finding, a strong correlation was observed between PLF levels and the percentile of birth weight, pulsatility index of the uterine artery, and the presence of diastolic notching. The strong correlation of low PLF values and SGA newborns suggests that determination of PLF could serve as a marker to identify women at risk of having such babies.

S.R., a 66-year old woman, was referred to our department because of an axillary mass in the right side. The patient had observed an increasing, painless swelling in the right axilla for the last two months. In the region of the right axilla in the middle axillary line an ovoid and solid tumour of 3 cm in diameter, quite well distinguishable, moving against the skin and the surrounding tissue, could be palpated. A subsequent mammography yielded an unsuspicious visualisation of both breasts and the left axilla. In the right axilla a circular solidification was detected, which then turned out on ultrasound examination to be a 2.6-cm diameter axillary lymph node. In the course of the lymph node extirpation of the right axilla two lymph nodes were dissected with histological evidence of metastatic nodes of a solid tumour, most likely in accordance with a breast carcinoma. Several immunohistochemical methods had been applied to determine the origin of the tumour cells and were thus identified as breast cancer cells. To detect primary causative carcinoma, different examinations were performed postoperatively without identifying any cancerous lesions. At least accurate research concerning the history of the patient was required to reexamine the histologic material of an operation of the right breast in 1989. The histological diagnosis of the dissected node of that time had been defined as a benign intracanaliculary papilloma in the right side without evidence of malignancy. The reexamination of the paraffin-embedded material from the operation of the right breast in 1989 revealed a lobular carcinoma of the right breast. The "occult" (undetectable) carcinoma of the breast occurs in less than 1% of all breast carcinomas. Thus it represent a rare clinical event and hence no standardised therapy schemata exist. To confirm the diagnosis of an occult carcinoma of the breast efficient reexamination of histological material from earlier breast operations indicated.

A retrospective nationwide evaluation of primary fallopian tube carcinomas for a period of 10 years (1980-1990) was performed to evaluate the prognostic impact of various factors. Sixty-six cases were investigated for the prognostic influence of estrogen (ER) and progesterone (PgR) status, mitotic activity, degree of nuclear anaplasia, and inflammatory reaction. ER and PgR receptors were detected by immunohistochemistry from paraffin sections. Forty-two percent were PgR-positive and 26% were ER-positive. However, no correlation of steroid receptors with survival could be found. Ninety-two percent of all tumors showed a moderate and high degree of nuclear anaplasia and only 8% showed a low degree of nuclear anaplasia. Thirty-four (52%) samples from all patients revealed low mitotic activity compared to 32 (48%) with an intermediate and high mitotic rate. Twenty-four (37%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. This finding was also confirmed in multivariate analysis as an independent prognostic factor.

A retrospective evaluation of 68 Fallopian tube carcinomas (FTC) of a period of ten years (1980-1990) in stage I and II was performed. The aim of this study was to evaluate the prognostic impact of various factors. 68 cases were investigated for the prognostic influence of mitotic activity, degree of nuclear anaplasia and inflammatory reaction. Histological grading (p=0.08), and inflammatory reaction (p=0.003) showed to have a prognostic impact for survival in univariate analysis. Whereas, mitotic activity did not show any statistically significant influence. 47 (69%) tissue samples showed a positive inflammatory reaction which correlated with a significantly better outcome compared with tumors without this feature. However, this influence was proved in multivariate analysis for inflammatory reaction only (p=0.01). Although no data on the influence of the inflammatory reaction on prognosis in FTC has been published up to now, we can state that the determination of this factor can be useful for prognosis in this rare but highly aggressive tumor.

Staging and surgical as well as post-operative treatment of primary Fallopian tube carcinoma (FTC) followed the lines established for primary ovarian cancer (OC). In a nationwide retrospective analysis we were able to find a distinct difference between these two tumours. A total of 262 patients, 68 with FTC and 194 with OC, in stage I and II were included into this study. A univariate as well as a multivariate analysis for survival was performed, including factors such as age, histological type, grading and surgical and adjuvant treatment. A significantly poorer outcome (P = 0.0002) for FTC patients with a 5-year survival of 50.8% compared with 77.5% for OC patients was observed. This finding was persistent and independent of any investigated factor, in univariate as well as multivariate analyses. Therefore, we feel that a more aggressive therapeutic approach to the treatment of FTC even in early stages can be recommended. On the other hand, the retrospective character of our study has to be taken into account.

The Breast Center in Van Nuys, California was the first free-standing, truly multidisciplinary, breast treatment center in the United States (Silverstein et al. 1986a). Housed in a 14000 square foot area, it includes a home-like waiting room, an operating and recovery suite, diagnostic and education center, clinical center, physicians offices, and psychiatric center. Members of the diagnostic and therapeutic teams are always available. The diagnostic center contains four modern mammography machines, a digital stereotactic unit, and ultrasonography equipment. The staff includes surgical, medical and radiation oncologists, a diagnostic radiologist, two reconstructive surgeons, two pathologists and a psychologic team headed by a psychiatrist (psycho-oncologist).

Summary. Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies to fetal platelet antigens. This prospective study was carried out to evaluate the incidence of anti-platelet antibodies in 933 mother-child pairs where the mother and child were typed for the human platelet antigens (HPA)-l, -2,-3,-5. Sera from mismatched mother-child pairs were screened for anti-platelet antibodies, anti-HLA class I and blood group ABO IgG antibodies. Platelet-specific antibodies were anti-HPA-3a in one and anti-HP A-5b in 17 neonates, respectively. All these neonates had normal platelet counts. One woman had autoreactive antibodies. Anti-HLA class I and anti-blood group A IgG antibodies were detected in five and four neonates, respectively, born with a platelet count

The immunohistochemnichally determined receptor status, as well as first-generation risk factors (tumor size, lymph node status, histologic grading including subfactors, tumor histology, and biochemically determined receptor status) were prospectively analyzed in 288 cases of primary breast cancer for their impact on recurrence-free survival (RFS) and overall survival (OS) after a median observation period of 41 months. Immunohistochemically (ER-ICA) and biochemically determined estrogen receptors (ER-DCC), as well as tumor size, lymph node status, histologic grading, mitotic rate, and nuclear polymorphism, were of prognostic value for recurrence-free survival and/or overall survival. In multivariate analysis, lymph node status, tumor size, and mitotic rate proved to be independent prognosticators; ER-ICA showed significance in the univariate analysis which dropped, however, when multivariate analysis was applied. The prognostic power of histologic grading in our series seemed to depend mainly on the subfactors which relate to nuclear features.

Levels of CA-125 were determined pre- and postoperatively in 13 patients with fallopian tube cancer. Values before surgery were significantly higher (Median 1220 IU/ml, 90-5000 IU/ml) compared with postoperative levels (Median 194 IU/ml, 67-880 IU/ml) (P = 0.0052). Correlation analysis with FIGO stage and grading failed to show any statistical significance, but a trend for a positive correlation with FIGO stage and preoperative values could be observed. The CA-125 antigen is expressed by fallopian tube carcinoma and should therefore be used in diagnosis and follow-up.

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We report on the first observation of νμ‐induced nuclear transitions νν12C→μ−12N. From a sample of νμ interactions on carbon near the muon production threshold, events with a 12N nucleus in the final state were isolated by observing the subsequent beta decay of the 12N ground state. This exclusive process represents (31+12)% of the inclusive cross section for νμ12C→μ−X. (Theoretical estimates of this fraction suggest a maximum of only 3%.) The muon kinetic energy for both the inclusive and exclusive channels was also measured. Using the muon kinetic energy distribution we identify the contributions to the cross sections from the 12N* and compare our results to theory.

Air pollution control efforts by federal, State, regional, and municipal agencies and by industry have expanded tremendously within the past few years. That this increased effort is a reflection of...