Children of mothers with mental ilness: attachment, emotional and behavioural problems

This study describes the pattern of emotional and behavioural difficulties of children whose mothers have mental illness, and explores the relationship between children's behavioural and emotional difficulties and maternal perceptions of attachment. Thirteen mothers previously admitted to psychiatric hospital for mental illness completed a measure of their own symptoms (Brief Symptom Inventory), their children's emotional and behavioural problems (Strengths and Difficulties Questionnaire (SDQ)), and attachment security (Parent/Child Reunion Inventory) (n = 21). Mean scores for child SDQ profiles were found to be within the 'normal' range, although (on some indices) mothers reported more 'case' scores for their children, than would be expected from standardized norms. It was found that there were significant positive correlations between 'insecurity' scores and all problem scales of the SDQ. Best predictors from the Parent/Child Reunion Inventory factors for each SDQ scale are reported and discussed.     

Distinctive gene expression profiles by cDNA microarrays in endometrioid and serous carcinomas of the endometrium.

Endometrial carcinomas are classified by their morphology into two major subtypes. Endometrioid carcinomas (type I) are generally estrogen dependent, well-differentiated, superficially invasive, and have a good outcome. Serous carcinomas (type II) are hormone independent, frequently deeply invasive and widely metastatic, and have a poor prognosis. Microarray technology and analysis allows us to determine if the global gene expression profiles of these two subtypes correlate with their morphologic phenotype. Fresh tissue from 18 endometrial carcinomas was studied: 7 well-, 2 moderately, and one poorly differentiated endometrioid, 4 serous carcinomas, and 4 high-grade mixed endometrioid-serous carcinomas. Labeled cDNA probes were synthesized (Cy5 for tumor, Cy3 for reference) and applied to microarrays containing 18,098 cDNA clones or ESTs. A pool of equal amounts of total RNA from each tumor served as the reference RNA. By unsupervised cluster analysis, the endometrioid carcinomas clustered together and were separate from the serous carcinomas. The high-grade mixed carcinomas clustered with the serous carcinomas. Using a statistical algorithm based on gene expression pattern and conducting a supervised analysis of the two defined groups, we have identified 315 genes that statistically differentiate type I from type II endometrial carcinomas. In addition to corroborating the predicted overexpression of known markers (e.g., ras and catenin in endometrioid carcinomas), the cDNA microarray technique has revealed novel alterations in gene expression relevant to cell cycle, cell adhesion, signal transduction, apoptosis, and tumor progression not previously implicated in endometrial carcinomas. For serous carcinomas, these include aldolase, desmoplakin, integrin-linked kinase, PKC, and metallopeptidase. In conclusion, the gene expression profiles of type I and type II endometrial carcinomas are different. Refinement of these profiles will permit more accurate diagnostic tumor classification and the development of prognosis assays.     

Partial left ventriculectomy: which patients can be expected to benefit?

Background. Although some patients with end-stage heart disease will benefit from a partial left ventriculectomy, no criteria have been found for identifying this group preoperatively. Our experience with partial left ventriculectomy at two institutions—the Texas Heart Institute in Houston, TX, USA, and Dedinje Cardiovascular Institute in Belgrade, Yugoslavia—showed a higher survival rate and better postoperative myocardial function in the Yugoslavian patients.

Methods. We reviewed data from 42 patients (21 at each center) who had idiopathic cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm, wall thickness of 1 cm or greater, and New York Heart Association class III or IV symptoms. The only significant difference in preoperative status between the two groups was duration of symptoms. Histologic specimens, blinded as to origin, were graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis. Computer-assisted myocyte and nuclear morphometry was also performed.

Results. Immediately postoperatively, there were no significant intergroup differences in the reduction in cardiac dimension or in corrections of mitral regurgitation. During 6-month follow-up, however, the Texas Heart Institute patients had a lower cardiac index (1.8 versus 3.0 L·min⁻¹·m⁻²; p = 0.001) and left ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje Cardiovascular Institute patients. The Texas Heart Institute patients differed from the Dedinje Cardiovascular Institute patients in the degree of severe or moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte diameter (35 ± 7 μm versus 27 ± 4 μm; p = 0.0002) and median nuclear size (15 ± 4 μm versus 12 ± 2 μm; p = 0.0029).

Conclusions. In the Texas Heart Institute patients, the significant intergroup difference in clinical outcome may have been related to increased myocyte hypertrophy and fibrosis. Further studies should be performed to determine the usefulness of these criteria in selecting patients for partial left ventriculectomy.     

B7-h4 is highly expressed in ductal and lobular breast cancer.

PURPOSE: This study was designed to investigate the expression of B7-H4 protein, a member of the B7 family that is involved in the regulation of antigen-specific immune responses, in normal breast and in primary and metastatic breast carcinomas. EXPERIMENTAL DESIGN: Archival formalin-fixed tissue blocks from breast cancers and normal somatic tissues were evaluated for B7-H4 expression by immunohistochemistry with manual and automated image analysis. The proportion of B7-H4-positive cells and the intensity of B7-H4 staining were compared with histologic type, grade, stage, hormone receptor status, and HER-2/neu status. RESULTS: B7-H4 was detected in 165 of 173 (95.4%) primary breast cancers and in 240 of 246 (97.6%) metastatic breast cancers. B7-H4 staining intensity was greater in invasive ductal carcinomas [24.61 relative units (RU)] and in invasive lobular carcinomas (15.23 RU) than in normal breast epithelium (4.30 RU, P = 0.0003). Increased staining intensity was associated with negative progesterone receptor status (P = 0.014) and history of neoadjuvant chemotherapy (P = 0.004), and the proportion of B7-H4-positive cells was associated with negative progesterone receptor (P = 0.001) and negative HER-2/neu (P = 0.024) status. However, there was no statistically significant relationship between the proportion of B7-H4-positive cells or staining intensity and grade, stage, or other clinicopathologic variables. Low levels of B7-H4 expression were also detected in epithelial cells of the female genital tract, lung, pancreas, and kidney, but B7-H4 was generally absent in most other normal somatic tissues. CONCLUSIONS: The nearly ubiquitous expression of B7-H4 in breast cancer, independent of tumor grade or stage, suggests a critical role for this protein in breast cancer biology.     

Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemia.

PURPOSE: To assess the maximum tolerated dose, toxicities, pharmacokinetics, and antileukemic activity of topotecan and carboplatin in adults with recurrent or refractory acute leukemias. EXPERIMENTAL DESIGN: Patients received topotecan and carboplatin by 5-day continuous infusion at nine dose levels. Patients achieving a complete remission received up to two additional courses for consolidation. Plasma topotecan and ultrafilterable platinum were assayed on days 1 to 5. In addition, pretreatment levels of various polypeptides in leukemic cells were examined by immunoblotting to assess possible correlations with response. RESULTS: Fifty-one patients received a total of 69 courses of therapy. Dose-limiting toxicity consisted of grade 4/5 typhlitis and grade 3/4 mucositis after one course of therapy or grade 4 neutropenia and thrombocytopenia lasting >50 days when a second course was administered on day 21. Among 45 evaluable patients, there were 7 complete remissions, 2 partial remissions, 1 incomplete complete remission, and 1 reversion to chronic-phase chronic myelogenous leukemia. Topotecan steady-state plasma concentrations increased with dose. No accumulation of topotecan or ultrafilterable platinum occurred between days 1 and 5 of therapy. Leukemic cell levels of topoisomerase I, checkpoint kinase 1, checkpoint kinase 2, and Mcl-1 correlated with proliferating cell nuclear antigen but not with response. In contrast, low Bcl-2 expression correlated with response (P = 0.014, Mann-Whitney U test). CONCLUSIONS: The maximum tolerated dose was 1.6 mg/m(2)/d topotecan plus 150 mg/m(2)/d carboplatin. The complete remission rate in a heavily pretreated population was 16% (33% at the highest three dose levels). Responses seem to correlate with low pretreatment blast cell Bcl-2 expression.     

Age-specific associations between underlying health conditions and hospitalisation,death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data,June to December 2020

BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition–age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5–5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.     

Croton oil pleurisy induces pulmonary hyperreactivity

Inflammatory process of the airways has been claimed to be relevant to the development of bronchial hyperreactivity in different experimental models. We investigated the consequences of pleural inflammation induced in the guinea-pigs by croton oil injection into the pleural space. Croton oil injection was followed by the development of an inflammatory reaction localized to the pleura as shown by recovery of inflammatory exudate from the pleural cavity of treated animals. An increased number of white cells was observed in the pleural fluid of treated animals as compared to control. Moreover, the croton oil induced inflammation was characterized by development of pulmonary hyperreactivity which involved both airway and vascular smooth muscles. We also studied this phenomenon in an animal model of asthma, such as the actively sensitized guinea-pigs. Polymorphonuclear leukocyte and particularly eosinophil recruitment was increased in this experimental condition and a different trend in the development of the hyperreactive phenomenon was observed. Our data support the relationship between inflammatory process within the pleural space and increased reactivity of pulmonary tissues. The possible involvement of different classes of white cells in this phenomenon has also been discussed.     

Effect of dopamine agonists and antagonists on neurotensin-induced antinociception

In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.