Physicians' Hierarchy of Tumor Biomarkers for Optimizing Chemotherapy in Breast Cancer Care.

BACKGROUND: Tumor biomarkers are regularly used to guide breast cancer treatment and clinical trial enrollment. However, there remains a lack of knowledge regarding physicians' perspectives towards biomarkers and their role in treatment optimization, where treatment intensity is reduced to minimize toxicity. METHODS: Thirty-nine academic and community oncologists participated in semi-structured qualitative interviews, providing perspectives on optimization approaches to chemotherapy treatment. Interviews were audio-recorded, transcribed, and analyzed by 2 independent coders utilizing a constant comparative method in NVivo. Major themes and exemplary quotes were extracted. A framework outlining physicians' conception of biomarkers, and their comfortability with their use in treatment optimization, was developed. RESULTS: In the hierarchal model of biomarkers, level 1 is comprised of standard-of-care (SoC) biomarkers, defined by a strong level of evidence, alignment with national guidelines, and widespread utilization. Level 2 includes SoC biomarkers used in alternative contexts, in which physicians expressed confidence, yet less certainty, due to a lack of data in certain subgroups. Level 3, or experimental, biomarkers created the most diverse concerns related to quality and quantity of evidence, with several additional modulators. CONCLUSION: This study demonstrates that physicians conceptualize the use of biomarkers for treatment optimization in successive levels. This hierarchy can be used to guide trialists in the development of novel biomarkers and design of future trials.

Investigating whole-brain metabolite abnormalities in the chronic stages of moderate or severe traumatic brain injury.

BACKGROUND: Evidence suggests that neurometabolic abnormalities can persist after traumatic brain injury (TBI) and drive clinical symptoms such as fatigue and cognitive disruption. Magnetic resonance spectroscopy has been used to investigate metabolite abnormalities following TBI, but few studies have obtained data beyond the subacute stage or over large brain regions. OBJECTIVE: To measure whole-brain metabolites in chronic stages of TBI. DESIGN: Observational study. SETTING: University. PARTICIPANTS: Eleven men with a moderate or severe TBI more than 12 months prior and 10 age-matched healthy controls completed whole-brain spectroscopic imaging. MAIN MEASURES: Ratios of N-acetylaspartate (NAA), choline (CHO), and myo-inositol (MI) to creatine (CR) were measured in whole-brain gray and white matter as well as 64 brain regions of interest. Arterial spin labeling (ASL) data were also collected to investigate whether metabolite abnormalities were accompanied by differences in cerebral perfusion. RESULTS: There were no differences in metabolite ratios within whole-brain gray and white matter regions of interest (ROIs). Linear regression showed lower NAA/CR in the white matter of the left occipital lobe but higher NAA/CR in the gray matter of the left parietal lobe. Metabolite abnormalities were observed in several brain regions in the TBI group including the corpus callosum, putamen, and posterior cingulate. However, none of the findings survived correction for multiple comparison. There were no differences in cerebral blood flow between patients and controls. CONCLUSION: Higher MI/CR may indicate ongoing gliosis, and it has been suggested that low CHO/CR at chronic time points may indicate cell death or lack of healthy turnover and repair. However, with the small sample size of this study, we caution against the over interpretation of our results. None of the findings within ROIs survived correction for multiple comparison. Thus, they may be considered possible avenues for future research in this area.

No evidence of abnormal metabolic or inflammatory activity in the brains of patients with rheumatoid arthritis: results from a preliminary study using whole-brain magnetic resonance spectroscopic imaging (MRSI).

INTRODUCTION/OBJECTIVES: Many individuals with rheumatoid arthritis (RA) report persistent fatigue even after management of peripheral disease activity. This study used whole-brain magnetic resonance spectroscopic imaging (MRSI) to investigate whether abnormal inflammatory activity in the central nervous system may be associated with such symptoms. We hypothesized that RA patients would show higher brain choline (CHO), myo-inositol (MI), and lactate (LAC), and higher brain temperature than healthy controls. We further hypothesized that the metabolite levels would be positively correlated with self-reported fatigue. METHOD: Thirteen women with RA provided fatigue severity ratings and underwent whole-brain MRSI and a joint examination. Thirteen healthy controls (HC) provided comparison imaging and fatigue data. CHO, MI, LAC, and brain temperature in 47 brain regions were contrasted between groups using independent-samples t tests. Significant differences were determined using a false discovery rate (FDR)-adjusted p value threshold of ≤ 0.0023. Secondary analyses obtained correlations between imaging and clinical outcomes in the RA group. RESULTS: No brain metabolic differences were identified between the groups. In the RA group, fatigue severity was positively correlated with CHO in several brain regions-most strongly the right frontal lobe (rs = 0.823, p < 0.001). MI was similarly correlated with fatigue, particularly in the right calcarine fissure (rs = 0.829, p < 0.001). CHO in several regions was positively correlated with joint swelling and tenderness. CONCLUSIONS: We conclude that abnormal brain metabolites are not a common feature of RA, but may been seen in patients with persistent fatigue or disease activity after conventional treatment.Key Points• Whole-brain magnetic resonance spectroscopy revealed no metabolic abnormalities in the brain in patients with rheumatoid arthritis.• Brain choline levels were correlated with fatigue severity reported by RA patients and with peripheral joint swelling and tenderness.• Brain myo-inositol levels were similarly correlated with fatigue severity in RA patients.

[(124)I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection.

INTRODUCTION: Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [(124)I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [(124)I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [(124)I]FIAU, and investigated whether [(124)I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. METHODS: To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [(124)I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [(124)I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30h post IV injection of 185MBq (5mCi) [(124)I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [(124)I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). RESULTS: The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [(124)I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. CONCLUSIONS: [(124)I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [(124)I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity.

Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.

Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.

Impact of maternal body mass index on neonatal outcome.

INTRODUCTION: Maternal body mass index has an impact on maternal and fetal pregnancy outcome. An increased maternal BMI is known to be associated with admission of the newborn to a neonatal care unit. The reasons and impact of this admission on fetal outcome, however, are unknown so far. OBJECTIVE: The aim of our study was to investigate the impact of maternal BMI on maternal and fetal pregnancy outcome with special focus on the children admitted to a neonatal care unit. METHODS: A cohort of 2049 non-diabetic mothers giving birth in the Charite university hospital was prospectively studied. The impact of maternal BMI on maternal and fetal outcome parameters was tested using multivariate regression analysis. Outcome of children admitted to a neonatal ward (n = 505) was analysed. RESULTS: Increased maternal BMI was associated with an increased risk for hypertensive complications, peripheral edema, caesarean section, fetal macrosomia and admission of the newborn to a neonatal care unit, whereas decreased BMI was associated with preterm birth and lower birthweight. In the neonatal ward children from obese mothers are characterized by hypoglycaemia. They need less oxygen, and exhibit a shorter stay on the neonatal ward compared to children from normal weight mothers, whereas children from underweight mothers are characterized by lower umbilical blood pH and increased incidence of death corresponding to increased prevalence of preterm birth. CONCLUSION: Pregnancy outcome is worst in babies from mothers with low body mass index as compared to healthy weight mothers with respect to increased incidence of preterm birth, lower birth weight and increased neonate mortality on the neonatal ward. We demonstrate that the increased risk for neonatal admission in children from obese mothers does not necessarily indicate severe fetal impairment.

Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy.

A genetic association study was conducted to assess whether genetically determined alterations of the nitric oxide system are associated with clinical markers of pre-eclampsia. A large number of Caucasian women were consecutively included after delivery and genotyped for the endothelial nitric oxide synthase gene (NOS3) polymorphisms G894T, T789C (n=1502) and intron 4a/b (n=2186). There are no significant differences in mean blood pressure (BP), protein excretion or new-onset peripheral oedema between any of the genotypes over the course of pregnancy. Neither particular haplotypes nor the combined presence of any two alleles is associated with those markers of pre-eclampsia. The maternal polymorphisms do not seem to influence fetal growth, birth weight or the incidence of congenital malformations. We demonstrate in a large Caucasian population that maternal polymorphisms of the NOS3 gene are not related to clinical markers of pre-eclampsia. The functional relevance of the NOS3 variants alone does not seem to be strong enough to affect BP regulation during pregnancy.

[Peripartum changes of the pelvic ring: usefulness of magnetic resonance imaging]. / Peripartale Veränderungen des Beckenringes: Wie sinnvoll ist die Magnetresonanztomografie?

PURPOSE: Postpartum pelvic pain beyond the normal level poses a problem to obstetricians. Beyond normal physiologic loosening of the pubic symphysis and sacroiliac joints (SIJs) during pregnancy, symphyseal separation and rupture must be excluded. The aim of this prospective study was to determine whether magnetic resonance imaging (MRI) allows for reliable differentiation of normal postpartum findings and pathologic lesions. MATERIAL AND METHODS: The study included a total of 77 women (mean age 30), among them 21 healthy subjects (group A), 21 asymptomatic postpartum women (group B), and 35 patients with postpartum pelvic pain (group C). The analyzed parameters comprised symphyseal and iliosacral tenderness, subjective pain assessed on a visual analog scale, and data pertaining to obstetric history. All 77 women underwent 1.5T MRI of the pelvic ring using oblique angulated coronal T 1-weighted and STIR sequences for imaging of the symphysis and SIJs in one slice package. Analysis of the MR images comprised signal intensities of pelvic bone marrow, width of the symphyseal cleft, and the symphyseal capsule. RESULTS: Subjects in group A in general had a normal bone marrow signal. The STIR sequence showed increased signal intensity of the pubic bone near the symphysis in 16 women (76 %) of group B and 31 patients of group C (86 %) (not significant). An increased periarticular bone marrow signal of the SIJs on the STIR images was seen in 13 women (62 %) of group B and 23 patients (63 %) of group C. The mean width of the symphyseal cleft differed significantly among the three groups (3.4 mm vs. 5.4 mm vs. 6.7 mm). A width >10 mm was observed in only 4 cases (11 %). Moreover, associated findings such as interpubic hematoma (n=23) or tears of the symphyseal capsule (n=7) were detected in patients of group C. CONCLUSION: The wide overlap of findings between symptomatic and asymptomatic postpartum patients does not allow reliable differentiation by MRI of normal and abnormal findings. MRI contributes to the differentiation of symphyseal contusion and rupture and provides information on severe associated changes.

Reduction of surgical site infections after Caesarean delivery using surveillance.

Since 1997, the Krankenhaus Infektions Surveillance System (KISS) has collected data on surgical site infections (SSIs) following Caesarean delivery (CD). The aim of this study was to determine whether surveillance and feedback of healthcare-associated infections (HAIs) could reduce the infection rate after CD. Only departments that had participated in KISS for at least three years were included in the analysis. The CD infection rates of the first, second and third years of KISS participation were compared for significant differences. The relative risk was calculated for the first and the third year of KISS participation. Multi-variate logistic regression analysis was performed to detect significant risk factors for SSI after CD using the third year of participation as one parameter. Twenty-six of 52 obstetric and gynaecology departments met the study's inclusion criteria. In those 26 departments, 17,405 CD procedures were performed and 331 SSIs were recorded (1.9%). The SSI rate after CD procedures was significantly reduced in the third year of KISS participation (1.6%) compared with the first year of KISS participation (2.4%), with a relative risk of 0.63 [95% confidence interval (CI) 0.48-0.82]. Logistic regression analysis confirmed that KISS participation over three years was an independent factor for the reduction of SSI rate (odds ratio 0.64; 95% CI 0.49-0.83). As shown previously for other types of HAI, this study demonstrated that continuous surveillance and comparison with stratified reference data could reduce SSI infection rates after CD.

Association of maternal G protein beta3 subunit 825T allele with low birthweight.

Weight at birth has been associated with an increased risk for cardiovascular disease and type 2 diabetes in adult life. We found an association between the maternal G protein beta3 subunit 825T allele and low birthweight in babies born to women without other risks for reduced fetal growth.

[Nitroglycerin for intraoperative uterus relaxation in cesarean section. Results of a randomized clinical study]. / Nitroglyzerin zur intraoperativen Uterusrelaxation bei der Sectio caesarea. Ergebnisse einer randomisierten klinischen Studie.

Between June 1994 and July 1996, a prospective, randomized, double-blind clinical study was carried out on 97 patients scheduled for elective cesarean section under general anesthesia at the gynecology departments of the Virchow and Charité Hospitals (both university hospitals of the Humboldt University, Berlin) in order to test the efficacy of glycerol nitrate (GTN: syn.: nitroglycerin) as an intraoperative short-acting tocolytic agent to ease fetal extraction in cesarean section in comparison to a placebo. At the time of the uterine puncture incision, either 0.25 mg (n = 32 patients) or 0.5 mg (n = 34) of GTN or physiological saline (n = 31) was administered as an intravenous bolus. Maternal and fetal pulse rates and blood pressures were closely monitored. The authors developed a scale to evaluate the degree of decrease in uterine tone and the ease of fetal extraction. The statistical evaluation of these estimations revealed no significant easing of fetal extraction and no significant increase in the reduction of uterine tone after administration of both GTN dosages in comparison to the administration of placebo (p > 0.01). Easing of fetal extraction cannot be achieved with the administration of 0.25 or 0.5 mg GTN, at least not in elective cesarean sections of greater than 34 weeks of gestation.

Nitroglycerin to facilitate fetal extraction during cesarean delivery.

OBJECTIVE: To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin. METHODS: This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood. RESULTS: Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch. CONCLUSION: Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group.

[Immunologic parameters in women with normal pregnancy and pre-eclampsia]. / Immunologische Parameter bei Frauen mit normal verlaufender Schwangerschaft und Präeklampsie.

Immunological investigations were carried in women with normal pregnancy and patients with preeclampsia. Regarding the lymphocyte subpopulation distribution an elevated number of T lymphocytes, especially of CD-4 carrying helper-inducer T cells, was registered resulting in an altered CD4/CD8 ratio. The T lymphocytes in patients with pre-eclampsia seem to be activated in vivo, shown by an elevated expression of the CD25 (IL-2 receptor) marker. Their responsibility to phytohemagglutinin (PHA) in vitro was found to be depressed. Furthermore, a pre-stimulation of macrophages in vivo was registered (expression of the transferrin receptor). In comparison to the control group the serum levels of IgG and IgA were seen to be low in patients with pre-eclampsia.

[Vaginal ultrasound cervix imaging in pregnancy--predictive value of suspicious findings on the subsequent course of pregnancy]. / Vaginosonographische Zervixbeurteilung in der Schwangerschaft--Prädiktive Wertigkeit suspkter Befunde für den weiteren Schwangerschaftsverlauf.

To evaluate the use of serial measurement of cervical length and width of internal os by means of vaginal ultrasound 144 pregnant women were examined prospectively. We hypothesized, that cervical length and width of the internal os would be significantly different in normal patients and those with preterm labor or cervical incompetence. Predictive validity of suspicious findings indicating the occurrence of preterm labour and cervical incompetence in further course of pregnancy should be assessed. Anamnestic, sonographic and outcome data were analysed. To assess sensitivity, specifity, positive and negative predictive values, different values of cervical length and width of internal os between 20 and 27 weeks were analysed. Significant differences of cervical length and width of internal os in normal and pathologic pregnancies could be documented early in pregnancy course. By further investigation early suspicious findings indicating the developing pathology were found only for the subgroup with cervical incompetence. Sensitivity of vaginal ultrasound examination between 20 and 27 weeks indicating the whole pathologic collective was only 30%, whereas up to 55.5% of pregnancies complicated by cervical incompetence were detected. Specifity (up to 95%) and negative predictive value (90%) were high. The results show that cervical examination by vaginal ultrasound allows early detection of developing cervical incompetence. The high specifity and the high negative predictive value may be useful to exclude cervical incompetence in clinically unclear cases thus helping to avoid unnecessary therapeutical interventions.

[Clinical significance and fetal outcome in end-diastolic decreased flow in the umbilical artery and/or fetal aorta: analysis of 51 cases]. / Klinische Bedeutung und fetal outcome beim enddiastolischen Flowverlust in der A. umbilicalis und/oder fetalen Aorta: Analyse von 51 Fällen.

The AEDV in the umbilical artery or the foetal aorta is considered to be the most severe waveform abnormality. Using pulsed Doppler, we found such a waveform in 51 foetuses out of 954 high-risk pregnancies (33/51 in both vessels, 17/51 aorta only and 1/51 umbilical artery only). A reverse flow was registered in 24 foetuses. The outcome was compared with that of a control group (n = 72) showing normal Doppler findings. The following parameters were highly significant (p less than 0.001): Rate of Caesarean section owing to foetal distress (85.3% to 4.8%), of growth retardation (IUGR) (66.7% to 6.0%), of premature delivery (73.5% to 7.5%), of low postnatal pH- and Apgar score (73.5 to 12.1%), of admission to the neonatal intensive care unit (94.1% to 8.6%), of morbidity (35.3% to 2.3%) and of mortality (41.1% to 0%). We observed 17/51 intrauterine and 4/51 postnatal deaths. The rate of malformations was 35.3% with 4 cases of aneuploidy. Considering the malformations, the rate of corrected mortality was 23%. We found, that the association of an AEDV and the absence of severe IUGR is highly suspicious of malformation. We also observed, that congenital heart diseases (CHD) could lead to an AEDV too. An AEDV precedes a pathological cardiotocogram (CTG) with a latency of 0 to 35 days (mean 9.5 days). This latency is not predictable, but we think, that a reliable assessment of jeopardy is possible by analysing further vessels (Aa. arcuatae, A. renalis, A. carotis interna): 72.5% of the foetuses with AEDV had high indices in the carotid artery and 93.1% among these showed a pathological CTG pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prenatal use of pulsed Doppler ultrasound within the scope of the differential diagnosis of bilateral kidney abnormalities]. / Der pränatale Einsatz des gepulsten Doppler-Ultraschalls im Rahmen der Differentialdiagnostik bilateraler Nierenfehlbildungen.

Pulsed Doppler ultrasound was used in the differential diagnosis of 22 cases suspected of bilateral malformations of the foetal kidneys. In cases of kidney malformations, the pulsatility indices (PI) of the umbilical artery and the foetal aorta were in the normal range. In cases showing pathological PI values of both vessels, we found a severe intrauterine growth (IUGR) retardation with oligohydramnion. These results underline the importance of pulsed Doppler as a non invasive means in the management of oligohydramnions to differentiate among bilateral kidney malformations and IUGR.

[Qualitative analysis with Doppler spectra of the umbilical artery and fetal aorta in normal pregnancies]. / Qualitative Analyse von Doppler-Spektren der A. umbilicalis und der fetalen Aorta bei ungestörten Schwangerschaften.

Blood flow velocity waveforms were recorded between the 20th and 40th week of gestation from the umbilical and fetal aorta (n = 230 each) in 130 uncomplicated pregnancies. The S/D ratio, the Resistance Index (RI) and the Pulsatility Index (PI) were calculated. In the umbilical artery the indices showed a significant decrease in the observation interval. In the fetal aorta we could not register any significant change of these indices. All values are presented as reference curves. The importance of the Doppler assessment of the circulation in these vessels for the management of high-risk pregnancy is emphasized.

[Type and frequency of gynecological tumors in the Gondar region of Ethiopia]. / Art und Häufigkeit gynäkologischer Tumoren in der Region Gondar/Athiopien.

The present work was done to examine the type and frequency of benign and malignant gynecological tumors in patients treated during the 5 years period from 1982 to 1986 in the Gondar College of Medical Sciences. The different pathohistological findings were compared with the history and chief complaints of the patients. A total number of 208 patients with benign and of 93 patients with malignant tumors could be analyzed. In the group of benign tumors we observed most frequently breast tumors (25.5%), endometrial and cervical polyps (24.5%), and myoma uteri (23.1%). Patients with benign ovarian tumors were treated in 40 (19.2%) cases. In the group of malignant tumors we have seen breast carcinomas (31.2%) and cervical carcinomas (34.4%) most frequently followed by the endometrial (13.0%) and ovarian (11.8%) neoplasms. Comparison with the data of the literature has shown that the mean age of our patients is lower and the number of women with advanced carcinomas is higher than in other reports.

Development of enolase isoenzymes in various regions of the human brain.

Various brain regions from 4 fetuses (21st to 28th gestational week) and from a 3-month-old infant were investigated for the total enolase activity and their isoenzyme distribution. In the brain tissue from a 3-month-old infant, the activity of the so-called neuron-specific enolase amounted to about 50% of the total enolase activity. In various brain regions different developmental patterns emerged for nonneuronal (NNE) and neuron-specific enolase (NSE). By the 21st gestational week the medulla, pons and thalamus had already reached a relatively high NSE activity (about 60-90% of that of the 3-month values), whereas the cortex regions had 10-30% only. It is concluded that in phylogenetically old regions, the switch from NNE to NSE-subunits appears before the 21st gestational week, in the phylogenetically young regions between the 21st and 28th gestational week.