Oestrogen receptor content and cancer cell/stroma ratio in mammary carcinoma

In a study of 86 human breast cancers the volume fraction of the neoplastic epithelium was estimated semiquantitatively and a significant association was found between the oestrogen receptor (ER) content and volume fraction of cancer cells of tumours (p less than 0.00001). Tumours with very low cellularity could thus be falsely ER negative. When quantitative ER concentration is used to predict the response of tumours to hormonal therapy the cellularity of tumours should be taken in consideration. The cellularity was not related to ER positivity. Although a correlation was seen between the contents of oestrogen and progesterone (PR) receptors, no correlation between PR content and volume fraction of the neoplastic epithelium was observed.     

Prognostic and predictive value of changes in tumour cell proliferation in locally advanced breast cancer primarily treated with doxorubicin

We previously reported that high tumour cell proliferation evaluated by Ki-67 expression, high mitotic frequency and high histological grade were associated with resistance to primary doxorubicin monotherapy in locally advanced breast cancer harbouring wild-type (wt) TP53. The aim of our present study was to evaluate the predictive and prognostic impact of proliferation parameters assessed in tumour tissue obtained after chemotherapy, and alterations induced in tumour cell proliferation. While we found a significant reduction in Ki-67 expression and mitotic frequency in tumours with wtTP53 (p=0.001 and p=0.008, respectively), no significant change was recorded in tumours expressing mutant TP53. For histological grade there was no significant change in either group. There was a direct correlation between pre- and post-treatment values for Ki-67 and mitotic frequency in tumours harbouring wtTP53 (p=0.0001 for both), but no correlation in tumours harbouring mutated TP53. High post-treatment Ki-67 expression and mitotic frequency were found to predict doxorubicin resistance only in patients with wtTP53 (p=0.04 and p=0.03, respectively). The prognostic importance of proliferation markers and histological grade was found to be similar whether they were determined in the pre- or post-treatment samples (Ki-67; pre: p=0.02; post: p=0.03; mitotic frequency; p=0.002 and p=0.01, respectively; histological grade; p=0.0001 and p=0.002, respectively). While the reduction in mitotic frequency was associated with improved survival (p=0.03), no significant associations between changes in other parameters and outcome were recorded.     

Impact of rapid socio-economic changes on teenage pregnancies in Estonia during 1992-2001

BACKGROUND: Major socio-economic changes, including health care reforms and changes in the school curriculum, took place in Estonia after the country regained its independence in 1991. These changes affected people's reproductive behavior in many ways. In this article, the impact of the changes on the reproductive behavior of teenage girls, measured by adolescent fertility and abortion rates between 1992 and 2001, is analyzed. METHODS: National data on abortions and births were obtained from official medical statistics, particularly from the Estonian Abortion Registry and the Estonian Medical Birth Registry. Female population denominators for the age group 15-19 were obtained from the Statistical Office of Estonia. RESULTS: In teenagers, the birth rate decreased more than two times, from 49.7 per 1000 in 1992 to 23.8 per 1000 in 2001. The abortion rate per 1000 decreased from 55.5 in 1992 to 30.4 in 2001. Compared with all women of fertile age (15-49 years), at the beginning of the decade, teenagers decided more often to have a baby, and, at the end of the decade, they decided more often to terminate the pregnancy. Two-thirds of all pregnancies in teenagers end in abortion--either legally induced abortion (legal abortion and therapeutic abortion) or spontaneous abortion. In 2001, the abortion ratio was 116.4 among ethnic Estonians and 147.9 among non-Estonians. CONCLUSIONS: The case in Estonia again proves that the availability of information, contraceptives, services and education, and the existence of other goals in life besides childbearing, have an impact on teenage birth and abortion rates. Successful health promotion activities should take into consideration the differences in the reproductive behavior of different ethnic groups.     

Emergency cesarean delivery in induction of labor: an evaluation of risk factors

BACKGROUND: Induction of labor has been associated with an increased risk of emergency cesarean delivery. Knowledge of factors that influence the risk of cesarean delivery in women with induced labor is limited. METHODS: We performed a case-control study, nested within a population-based cohort of women with induced labor at term during 1991-1996 in Uppsala County, Sweden. Cases were women delivered with emergency cesarean delivery, and controls were women vaginally delivered (n = 193, respectively). Using logistic regression, analyses were performed. Odds ratio (OR) with 95% confidence intervals (CI) was used as a measure of relative risk. RESULTS: Women with a previous cesarean delivery had high risks of cesarean delivery (adjusted OR = 10.10, 95% CI = 3.30-30.92). The risk of cesarean delivery was also increased among nulliparous (adjusted OR = 4.92, 95% CI = 2.81-8.61), short (adjusted OR = 2.20, 95% CI = 1.06-4.59), and obese women (adjusted OR = 2.03, 95% CI = 1.07-3.84). A cervix dilatation less than 1.5 cm doubled the risk of cesarean delivery (adjusted OR = 2.26, 95% CI = 1.09-4.66). Mother's age, epidural analgesia, oxytocin augmentation, gestational age, and birthweight were not significantly associated with risks of cesarean delivery. CONCLUSIONS: Women with a previous cesarean delivery, nulliparous, short, and obese women with induced labor are at high risk of a cesarean delivery. When there is a need to deliver a woman with a previous cesarean section or a nulliparous woman with other risk factors for cesarean delivery, it may be prudent to consider an elective cesarean section.     

Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter

We tested the hypothesis that inhibiting glycogen degradation accelerates compound action potential (CAP) failure in mouse optic nerve (MON) during aglycemia or high-intensity stimulation. Axon function was assessed as the evoked CAP, and glycogen content was measured biochemically. Isofagomine, a novel inhibitor of central nervous system (CNS) glycogen phosphorylase, significantly increased glycogen content under normoglycemic conditions. When MONs were bathed in artificial cerebrospinal fluid (aCSF) containing 10 mM glucose, the CAP failed 16 min after exposure to glucose-free aCSF. MONs bathed in aCSF plus isofagomine displayed accelerated CAP failure on glucose removal. Similar results were obtained in MONs bathed in 30 mM glucose, which increased baseline glycogen concentration. The ability of isofagomine to increase glycogen content thus was not translated into delayed CAP failure. This is likely due to the inability of the tissue to metabolize glycogen in the presence of isofagomine, highlighting the importance of glycogen in sustaining neural function during aglycemia. The hypothesis that glycogen breakdown supports intense neural activity was tested by blocking glycogen breakdown during periods of high-frequency stimulation. The CAP area declined more rapidly when glycogen metabolism was inhibited by isofagomine, explicitly showing an important physiological role for glycogen metabolism during neural activity.     

Factor solution of the BPRS-expanded version in schizophrenic outpatients living in five European countries

RATIONALE: The expanded version of the Brief Psychiatric Rating Scale (BPRS-E) has improved the instrument's coverage and interrater reliability, but there is little knowledge on its subsyndromes. OBJECTIVES: To assess: (1) whether there are common underlying BPRS-E subscales in patients living in different countries and (2) if this is the case, whether these subscales behave the same in all populations and, if not, what are the differences over these populations. METHODS: Data are part of the EPSILON study, a collaborative project carried out in Denmark, England, Holland, Italy and Spain. A random representative sample of 404 adult patients with a ICD-10 diagnosis of schizophrenia who have been in contact with mental health services of a defined catchment area in each site were assessed. Simultaneous component analysis (SCA) was used to find component weights that optimally explain the variance of the variables in different populations simultaneously. RESULTS: Symptom severity differed significantly among the five EPSILON sites in 12 out of 24 BPRS-E items, but a common component solution could be found. It explained 48.8% of the variance and gave four well-interpretable components: manic excitement/disorganization, depression/anxiety, negative and positive symptoms. Each component's internal consistency and intercomponent correlation matrix differed significantly among sites. The four components mean score differed significantly among sites for negative symptoms and depression/anxiety. CONCLUSIONS: In spite of the heterogeneity of symptom's severity in the various countries, the way symptoms cluster in schizophrenia is rather stable cross-culturally. Data demonstrate that to explore schizophrenia a third component, including mania/disorganization items, is necessary beside the positive-negative symptom dimensions. The subscales derived from these analyses can be readily used in clinical trials and epidemiological studies.     

Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects

BACKGROUND: In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well-established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day. METHODS: This was a double-blind, single dose, randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg, ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to severe pain 1 day after orthopaedic surgery. Outcome variables were pain intensity (0-100 VAS), pain relief (0-4 PAR) and rescue opioid consumption. RESULTS: Methylprednisolone was not significantly different from ketorolac and gave significantly lower pain intensity from 1 h (0-6 h, P < 0.02), and more pain relief 2-6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain intensity was lower in both active drug groups compared with placebo (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat (NNT) calculated from patients having more than at least 50% of maximum obtainable total pain relief during the first 6 h (>50%maxTOTPAR(6 h)) was 3.6 for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated from the percentage reporting at least 50% pain relief for at least 4 h (>50%PAR(4 h)) was 2.8 for both groups. Opioid consumption was significantly reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and placebo (P < 0.003). CONCLUSION: Methylprednisolone 125 mg i.v. 1 day after surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h compared with ketorolac and placebo indicate sustained analgesic effects of methylprednisolone.     

Local activation of dendritic cells leads to insulitis and development of insulin-dependent diabetes in transgenic mice expressing CD154 on the pancreatic beta-cells

The initial events leading to activation of the immune system in type 1 diabetes are still largely unknown. In vivo, dendritic cells (DCs) are thought to be the only antigen-presenting cells (APCs) capable of activating na?ve T-cells and are therefore important for the initiation of the autoimmune response. To test the effect of activating islet-associated APCs in situ, we generated transgenic mice expressing CD154 (CD40 ligand) under control of the rat insulin promoter (RIP). RIP-CD154 mice developed both insulitis and diabetes, although with different incidence in independent lines. We show that activated DCs could be detected both in the pancreas and in the draining pancreatic lymph nodes. Furthermore, diabetes development was dependent on the presence of T- and B-cells since recombination-activating gene (RAG)-deficient RIP-CD154 mice did not develop diabetes. Finally, we show that the activation of immune cells was confined to the pancreas because transplantation of nontransgenic islets to diabetic recipients restored normoglycemia. Together, these data suggest that expression of CD154 on the beta-cells can lead to activation of islet-associated APCs that will travel to the lymph nodes and activate the immune system, leading to insulitis and diabetes.     

Craniotomy for supratentorial brain tumors: risk factors for brain swelling after opening the dura mater

OBJECT: Cerebral swelling often occurs during craniotomy for cerebral tumors. The primary aim in this study was to determine risk factors (intracranial pressure [ICP], patient characteristics, histopathological features, neuroimaging characteristics, anesthetic regimen, and perioperative physiological data) predictive of brain swelling through the dural opening. As a secondary aim the authors attempted to define subdural ICP thresholds associated with brain swelling. METHODS: The study population consisted of 692 patients (mean age 50+/-15 years) scheduled for elective craniotomy for supratentorial brain tumors. Brain swelling through the dural opening was estimated according to a four-point scale. The patients were dichotomized as those without cerebral swelling (that is, brain below the dura mater [59 patients] or brain at the level of the dura mater [386 patients]) and those with cerebral swelling (that is, moderate brain swelling [205 patients] or pronounced brain swelling [42 patients]). Logistic regression analysis was used to identify subdural ICP (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.72-2.1, p < 0.0001), midline shift (OR 1.06, 95% CI 1.02-1.11, p = 0.008), a diagnosis of glioblastoma multiforme (OR 2.1, 95% CI 1.01-4.3, p = 0.047), and metastasis (OR 2.9, 95% CI 1.3-6.9, p = 0.01) as independent risk factors of intraoperative brain swelling. Thresholds for ICP associated with brain swelling were defined as follows: at an ICP less than 5 mm Hg, brain swelling rarely occurred (5% probability); at an ICP greater than 13 mm Hg, brain swelling occurred with 95% probability; and at an ICP greater than 26 mm Hg, severe brain swelling occurred with 95% probability. CONCLUSIONS: Subdural ICP is the strongest predictor of intraoperative brain swelling. It is possible to define thresholds of cerebral swelling and the authors recommend subdural ICP measurement as a tool to initiate preventive measures to reduce ICP before opening the dura mater.