Des-gamma-carboxyprothrombin (PIVKA II) and plasma vitamin K1 in newborns and their mothers.

Assessments of the vitamin K status in newborns and their mothers by means of des-gamma-carboxy-prothrombin (PIVKA II) measurement have given equivocal results. Part of the variability could be attributed to differences in sensitivity (i.e. the ability to detect small concentrations) and validity (i.e. ability to detect vitamin K deficiency) of the methods applied. None of these methods have yet been validated with respect to plasma vitamin K1. In 22 healthy mother/infant pairs PIVKA II was determined using three different assays including ratio Xa/ecarin (Xa/ec), crossed immunoelectrophoresis (CIE), and an ELISA with a monoclonal antibody (MAB). The results were compared with conventional clotting tests and plasma vitamin K1. The following results were obtained: Cord blood: Clotting tests within age-related normal ranges; PIVKA II detection rates: 0/22 (Xa/ec), 1/22 (CIE), 4/22 (MAB); plasma vitamin K1: undetectable in 20/22. Mothers: Clotting tests all within normal range; PIVKA II detection rates: 1/22 (Xa/ec), 0/22 (CIE), 5/22 (MAB); plasma vitamin K1 (pg/ml) for all mothers (median; range): 186; 55-833; for PIVKA II positive mothers: 213; 59-699. PIVKA II detectability in newborns and mothers was not correlated. The results show an increase in sensitivity for PIVKA II detection in the order of MAB >> CIE > Xa/ec. Due to the very low plasma vitamin K1 at birth, no correlation was possible between cord PIVKA II detectability and plasma vitamin K1. However, in mothers at term PIVKA II MAB appears to be unrelated to the vitamin K status.

[Intravaginal brachytherapy in surgically treated uterine cancer]. / Intravaginale Brachytherapie beim operierten Korpuskarzinom.

We analyzed retrospectively the clinical outcome of 108 patients with endometrial carcinoma operated at the Department of Obstetrics and Gynecology of Düsseldorf University regarding the effect of additional intravaginal brachytherapy. In 67 patients, we only performed an intraoperative rinsing of the vagina with alcohol and sutured the cervical canal to prevent vaginal recurrences. 41 patients received additional intravaginal brachytherapy. We observed only two vaginal recurrences in the 108 patients. There was no major difference in survival for patients with versus without additional intravaginal brachytherapy. We reviewed published studies critically regarding the efficacy and complications of intravaginal brachytherapy in operated endometrial cancer. These studies indicate that additional intravaginal brachytherapy can lower the rate of vaginal recurrences and that patients with dedifferentiated tumors, deep myometrial invasion and higher FIGO-stages might benefit most of this treatment modality.

[Autologous and heterologous blood transfusion in obstetrics]. / Eigen- und Fremdbluttransfusionen in der Geburtshilfe.

We retrospectively analyzed the frequency and details of blood transfusions in a group of 12,578 obstetrical patients. We found 250 patients who received red blood cell transfusions resulting in a transfusion rate of 2 in 100. In most of these cases, there were no risk factors placing patients at high risk for blood transfusions. The administration of one or two units of blood was adequate in 76% and of up to three units adequate in 87% of cases. Our results do not support a commercial blood bank's recent claim of frequent transfusions in obstetrical patients. We feel that the routine storage of blood for autologous transfusions is not warranted in obstetrical patients.

[Severe aplastic anemia and pregnancy]. / Schwere aplastische Anämie und Schwangerschaft.

Severe aplastic anaemia was diagnosed in a 24-year-old woman in the 16th week of her pregnancy. She was delivered by cesarean section in the 35th week of a healthy boy, treatment in the intervening period having been exclusively by supportive measures. Allogenic bone marrow transplantation, planned after delivery, had to be cancelled owing to the sudden death of the female donor. Immunosuppressive treatment with antithymocyte globulin, corticosteroids and cyclosporin A failed to improve the haematological picture and the patient died one year after the delivery of intracerebral haemorrhage.

[Nonpuerperal mastitis. 3 possible causes including mammography correlates]. / Nonpuerperale Mastitis. Drei mögliche Ursachen einschliesslich mammographischer Korrelate.

We present three cases of non-puerperal mastitis including the corresponding mammographies to illustrate three possible causes: mastitis with abscess, artificial mastitis and breast carcinoma. The clinic picture did not reveal the cause of mastitis. Ultrasonography and mammography should be performed early in the evaluation of non-puerperal mastitis.

[Experiences with after care of patients with breast cancer]. / Erfahrungen in der Nach-sorge von Patientinnen mit Mammakarzinom.

We retrospectively analyzed methods of follow-up and subsequent clinical outcome in 399 breast cancer patients treated with curative intent. Radioisotope liver scans, liver sonograms and laboratory investigations were of little value in detecting metastases. Mammography detected 2 of 6 contralateral breast cancers in an asymptomatic stage. Of 92 metastatic diseases, 24 were disclosed by a total of 871 radioisotope bone scans, and 17 were disclosed by a total of 2409 chest x-rays. The detection of distant metastases in an asymptomatic stage by diagnostic procedures vs detection by symptoms was not correlated with a survival benefit. The survival times for the two groups were 6.4 years vs 6.7 years (p = 0.7) after initiation of primary therapy, and 20.8 vs 20.4 months (p = 0.9) after the diagnosis of metastatic disease. Our study does not lend support to the hypothesis that the detection of metastatic disease in an asymptomatic stage or regular follow-up visits are associated with a survival benefit. We conclude that clinical history, physical examination, and mammography are the most important procedures in the follow-up of breast cancer patients.

[Beta-endorphin in premature labor and in mature newborn infants following vaginal and abdominal delivery]. / beta-Endorphin bei Frühgeburten und reifen Neugeborenen nach vaginaler und abdominaler Entbindung.

Umbilical venous plasma concentrations of beta-endorphin in 20 premature and 30 mature newborn infants after vaginal delivery or elective caesarean section were determined by specific RIA. In the premature infants the beta-endorphin levels after vaginal and abdominal delivery were significantly higher than in mature newborns. Our data indicate that for premature infants the delivery is more stressful and therefore most likely the release of beta-endorphin from the pituitary is more pronounced. Since high opioid levels can cause respiratory and circulatory difficulties, premature infants are exposed to risk of these problems.

Localization of 99mTc-diphosphonates in newly formed bone matrix as a measure of bone lesion detectability.

The lesion-to-normal-bone ratios of DBA-MDP (dibutylamino-methylene-diphosphonate), DPD (dicarboxypropane-diphosphonate) and MDP (methylene-diphosphonate) each labeled with 99mTc, were evaluated in experimental bone lesions. In 3-day old lesions this ratio was increased twofold for DBA-MDP in comparison with MDP and DPD which showed nearly equal ratios. Later on these differences became negligibly small. It is concluded that 99mTc-DBA-MDP is fixed more strongly in the immature bone matrix and that this will lead to an improvement in the detectability of lesions containing larger amounts of immature bone matrix.

The value of preoperative chest X-rays in gynecological patients.

We assessed the value of preoperative chest x-rays in gynecological patients. Abnormalities were noted in the chest x-rays of 10% of 1175 patients with genital or breast disorders. When the chest x-ray was abnormal, 48% of patients had no clinical features of intrathoracic disease. Abnormal chest x-ray results did not seem to have a major influence on the decision to operate or on the type of anesthesia used. In our series, probably only one patient would have received inappropriate treatment in the absence of a chest x-ray. We conclude that preoperative chest x-rays are of value in ruling out metastases in patients with a suspected neoplasm, but have little value in other circumstances.

Barium enema in the diagnostic work-up of gynecologic patients.

We evaluated the role of the barium enema in the diagnostic work-up of 120 gynecologic patients. Major abnormalities were detected in 10% of patients. We conclude that patients presenting with pelvic tumors or suspected gynecologic malignancies should have a pre-therapeutic barium enema in order to define the extent of the disease and to rule out colon cancer.

[Recurrent mastitis with an unusual etiology]. / Rezidivierende Mastitis mit ungewöhnlicher Atiologie.

We present the diagnostic and therapeutic problems in a patient presenting with recurrent, refractory necrotising mastitis that was caused by artifacts.

Role of culture conditions and exposure duration in determining sensitivity of human bone marrow progenitor cells to methotrexate.

The effect of drug concentration, exposure duration, and culture conditions on the cytotoxic activity of methotrexate (MTX) on normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) was studied using a bilayer soft agar system with nucleoside-free medium. The degree of inhibition of colony formation depended on the type of serum supplementation. A 1 h or 2 h pulse treatment with 2 X 10(-4) M (100 micrograms/ml) MTX failed to kill GM-CFUC, when the cells were subsequently plated in a system containing 15% undialyzed fetal bovine serum (FBS). For continuous exposure the observed LD50 of MTX in the agar system was higher than 10(-4) M for 15% undialyzed FBS, 10(-5) M for 15% dialyzed FBS plus 0.25% undialyzed FBS, 10(-6) M for 15% dialyzed FBS, and 10(-8) M for 15% undialyzed horse serum. The difference for dialyzed FBS versus horse serum can be explained by differences in nucleoside concentrations. The difference for dialyzed FBS versus horse serum may be secondary to an enhancer of MTX in horse serum. For studying MTX sensitivity of human tumor cells in vitro, we suggest testing conditions that lie within the dose survival curve of GM-CFUC.

The human tumor stem cell assay revisited.

The human tumor stem cell assay (HTSCA) is a bilayer soft agar system for growing fresh human tumor specimens in vitro to determine drug sensitivity and improve our understanding of tumor biology. Recent clinical correlations of 60% accuracy for predicting a positive clinical response and a 90% accuracy for predicting a lack of response to therapeutic agents suggest promising clinical usefulness. However, the clinician should be aware of the assay's inherent pitfalls, such as heterogeneity of the tumor specimen, inability to obtain pure single-cell suspensions, low cloning efficiency, unusual drug dose-dependent survival curves, uncertain validity of in vitro pharmacology, non-standardized criteria for in vitro sensitivity, and the variability of in vitro results. A brief summary of the concepts, potential, and limitations of this assay are discussed.

Differential cytotoxic activity of chemotherapy agents on colony-forming cells from human tumors and normal bone marrow in vitro.

We have compared the in vitro differential killing efficacy of doxorubicin, 5-fluorouracil, cis-platinum, etoposide, and bleomycin on human tumor cells in a new adhesive tumor cell culture system (ATCCS), and on normal bone marrow granulocyte-macrophage colony-forming units (GM-CFUC) in culture. All of the above chemotherapy agents were tested with continuous exposure against tumor cells and GM-CFUC. In addition, bleomycin was also tested with a short (60 min) exposure against GM-CFUC. In order to determine chemosensitivity against all five drugs, 48 tumor specimens from patients with heterogeneous tumor types were tested in the ATCCS. Each drug was tested at three different concentrations corresponding to their lethal doses against GM-CFUC. Our results show that all five drugs exhibited a dose-response relationship against tumor cells and GM-CFUC. Bleomycin also showed a pronounced GM-CFUC-sparing quality with 60-min exposure even at very high concentrations (86% survival of GM-CFUC at 10 micrograms/ml and 48% at 50 micrograms/ml). In addition, it has a high tumor response rate with continuous exposure at low concentrations (67% at GM-CFUC LD5 and 91% at LD40). These data suggest that the comparison of differential cytotoxicity of chemotherapy drugs between tumor cells and bone marrow cells may serve as a model to select agents suitable for in vitro chemotherapy of bone marrow for the purpose of autologous bone marrow transplantation. In particular, bleomycin appears very attractive and deserves further investigation.