Cognitive visual dysfunctions in preterm children with periventricular leukomalacia

Aim  Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology.
Method  We studied 22 children born preterm (12 males, 10 females; mean age at examination 8y, range 6–15y; mean gestational age 30wks, range 28–36wks) with periventricular leukomalacia, spastic diplegia, normal intelligence (mean Full-scale IQ 84; mean Verbal IQ 97; mean Performance IQ 74), and normal visual acuity, focusing on higher visual functions. Brain magnetic resonance images (MRI) were analysed to establish the presence of lesions along the primary optic pathway, in the occipitoparietal and occipitotemporal regions.
Results  Most children displayed an uneven cognitive profile, with deficits in visual object recognition, visual imagery, visual–spatial skills, and visual memory, and sparing of visual associative abilities, non-verbal intelligence, and face and letter recognition. Conventional brain MRI did not document major alterations of parietal and temporal white matter, or cortical alteration of areas involved in visual associative functions.
Interpretation  We suggest a widespread involvement of higher visual processing systems, involving both the ventral and dorsal streams, in preterm children with periventricular leukomalacia. The lack of major alterations on conventional MRI does not exclude the possibility of malfunctioning of higher visual processing systems, expressing itself through discrete CVDs. Possible mechanisms underlying these neuropsychological deficits are discussed.     

Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in children

Aim Mortality from malignant middle cerebral artery infarction (MMCAI) approaches 80% in adult series. Although decompressive craniectomy decreases mortality and leads to an acceptable outcome in selected adult patients, there are few data on MMCAI in children with stroke. This study evaluated the frequency of MMCAI and the use of decompressive craniectomy in children. Method We retrospectively reviewed cases of MMCAI from five pediatric tertiary care centers. Results Ten children (two females, eight males; median age 9y 10mo, range 22mo–14y) had MMCAI, with a median Glasgow Coma Scale score of 6 (range 3–9). MMCAI represented fewer than 2% of cases of pediatric arterial ischemic stroke. Three patients who did not undergo decompression, all of whom had monitoring of intracranial pressure, developed intractable intracranial hypertension, and fulfilled criteria for brain death. In contrast, seven patients underwent decompressive craniectomy and survived, with rapid improvement in their level of consciousness postoperatively. All seven survivors now walk independently with mild to moderate residual hemiparesis and speak fluently, even though four had left‐sided infarcts. Interpretation Decompressive craniectomy can lead to a moderately good outcome for children with MMCAI and should be considered, even with symptomatic stroke and deep coma. Monitoring of intracranial pressure may delay life‐saving treatment.     

Sleep and sleepiness in children with attention deficit / hyperactivity disorder and controls

The present study assessed the association between habitual sleep patterns and one night of PSG measured sleep with daytime sleepiness in children with ADHD and typically developing children. Eighty‐two children (26 ADHD, 56 typically developing children), between 7 and 11 years, had nighttime sleep recorded using actigraphy over five nights (habitual sleep patterns) and polysomnography during one night (immediate sleep patterns), both within their home environments. Daytime sleepiness was examined using the multiple sleep latency test within a controlled laboratory setting the following day. Using Spearman correlations, the relationships between mean sleep latencies on the multiple sleep latency test and scores on a modified Epworth Sleepiness Scale with polysomnographic measures of sleep quality and architecture and with actigraphic sleep quality measures were examined. Longer sleep latency, measured using polysomnography and actigraphy, was related to longer mean sleep latencies on the multiple sleep latency test in typically developing participants, whereas actigraphic measures of sleep restlessness (time awake and activity during the night), as well as time in slow‐wave sleep, were positively related to mean sleep latency on the multiple sleep latency test in children with ADHD. These results show a differential relationship for children with ADHD and typically developing children between habitual and immediate sleep patterns with daytime sleepiness and suggest that problems initiating and maintaining sleep may be present both in nighttime and daytime sleep.     

A Sensitive Assay for Studying Dopaminergic Activity in Cultures of Rat Pituitary Cells

The dopaminergic and antidopaminergic activity of drags is frequently assayed in pituitary cell cultures. Here we describe a modified version of the assay based on the use of pituitary cells from prepubertal female rats. Under our experimental conditions (50000 cells well^?1, 2-day culture and 2-h drug-exposure) the assay yielded high selectivity and sensitivity for drug dopaminergic activity. D₂ agonistic activity of bromocriptine could be observed at a concentration as low as 10^?15 m, the antagonistic activity of haloperidol at 10^?16 m. The assay also proved reproducible and simple enough for routine screening of dopaminergic activity. The assay enabled dopaminergic agonist and antagonist activity to be revealed at very low drug concentrations. The high sensitivity of the assay could be of advantage in studying dopaminergic activity in samples containing active substances present at low concentrations or for disclosing the activity of substances with low dopaminergic potency.     

Culprit-Only or Multivessel Percutaneous Coronary Stenting in Patients with Non-ST-Segment Elevation Acute Coronary Syndromes: One-Year Follow-Up

Objective: To investigate the major cardiac events at 1-year follow-up of multivessel versus culprit-vessel stenting in patients presenting with non-ST elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD).
Introduction: Percutaneous coronary intervention is a standard revascularization strategy for patients with NSTE-ACS. However, when these patients have MVD it is not clear whether multivessel (MVR) is superior to culprit-vessel revascularization (CVR).
Methods: We screened 1,100 consecutive patients with NSTE-ACS from an institutional database. Comparisons of 1-year outcomes between multivessel and culprit-vessel revascularized patients were made. The primary outcome was the composite (MACE) of death, myocardial infarction (MI), or any revascularization. Secondary end-points were the components of the composite end-point. Regression analysis was performed to detect predictors of MACE.
Results: A total of 609 patients were considered for this analysis: 204 (33.5%) and 405 (66.5%) had MVR and CVR treatment, respectively. The strategy adopted was based on a clinical decision. The incidence of MACE was lower in MVR (9.45% vs. 16.34%, P = 0.02) with lower revascularization rate (7.46% vs. 13.86%, P = 0.04) than in CVR. There was no difference in death (1.99% vs. 1.98%, P = 0.8) nor death/MI (2.49% vs. 3.22%, P = 0.8) between MVR and CVR, respectively. Multivariate analysis showed CVR as the only independent predictor of improved MACE (OR 0.66, CI95% 1.12–3.47, P = 0.01).
Conclusion: Multivessel stenting in patients with NSTE-ACS and multivessel disease using a clinical decision of treatment is associated with lower rate of MACE driven by lower repeat revascularization, compared with culprit-vessel stenting, without difference in rates of death or MI.     

c-Src PROTEIN EXPRESSION IS INCREASED IN HUMAN BREAST CANCER. AN IMMUNOHISTOCHEMICAL AND BIOCHEMICAL ANALYSIS

In human breast cancer, c-Src activity is elevated compared to normal breast tissue. It is not yet known whether this increase in c-Src activity is accompanied by an increase in c-Src protein expression. In this study, c-Src activity and protein expression were determined in a series of human breast cancers and in normal breast tissue, using immune complex kinase assays and immunoblotting. As the heterogeneity of breast cancer is not taken into account in these biochemical experiments, immunohistochemistry was also used to distinguish between normal and malignant cells. In human breast cancers, the c-Src activity is increased 4- to 30-fold, compared with normal breast tissue. This enhanced activity is accompanied by an increase in c-Src protein expression, as shown by both immunoblotting and immunohistochemistry. Immunohistochemistry indicates that the majority of c-Src appears to be concentrated around the nucleus in malignant cells, whereas in normal cells, it is distributed more evenly in the cytoplasm. These data confirm that c-Src activity is increased in human breast cancer. In addition, this study provides strong immunohistochemical evidence that the c-Src protein is also overexpressed, enabling a distinction to be made between normal and malignant cells.     

Differential sensitivity of CD30+ neoplastic cells to gelonin delivered by anti-CD30/anti-gelonin bispecific antibodies

Summary. Lymphocyte activation antigens, such as CD30, represent suitable target molecules for antibody-driven drug delivery in haemopoietic malignancies. A ribosome-inactivating protein (RIP) type 1 of potential interest for mAb targeting is gelonin, which displays a lower toxicity, as compared to other RIPs. In this study, two anti-CD 3 0/anti-gelonin bispecific monoclonal antibodies (bimAbs), secreted by hybrid hybridomas, were used to deliver this RIP to CD30⁺ tumour cells. The two bimAbs, termed D4 and A18, were produced using the same anti-CD30 mAb and two anti-gelonin mAbs, directed to unrelated epitopes of the gelonin molecule. These bimAbs enhanced gelonin toxicity (IC₅₀ 5 × 10^?8 M, in the absence of mAbs) against the CD30⁺ L540 Hodgkin's lymphoma cell line in a protein synthesis inhibition assay. Thus, in the presence of 10^?9 M D4 bimAb, protein synthesis was inhibited with an ICs₀ of 5 × 1CT¹⁰M as gelonin, whereas with A18 bimAb the IC_S0 was 8 × 1CT¹¹ M. More interestingly, the combined use of the two bimAbs had a synergistic effect, since the IC₅₀ of gelonin reached 6 × 10^_12M. Among CD30 tumour cell lines, the Hodgkin's lymphoma L428 was also sensitive to gelonin delivered by bimAbs (IC₅₀ 6 × 1CT^U M), whereas the COLE Hodgkin's cell line and the T-ALL Jurkat were completely resistant to the toxic effect of gelonin and bimAbs. COLE and Jurkat cells were also resistant to a gelonin/anti-CD30 conventional immunotoxin, whereas they were sensitive to a saporin/anti-CD30 immunotoxin. This suggests that the resistance to gelonin is not related to a lack of internalization through the CD30 molecule but is associated with some property of the RIP.     

Atypical chronic lymphocytic leukaemia witht(ll;14)(ql3;q32): karyotype evolution and prolymphocytic transformation

Summary. In order to define better the cytological and clinical features of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with t(ll;14)(ql3;q32), sequential morphologic immunological and cytogenetic studies were performed in seven patients belonging to a series of 72 consecutive cases presenting with a diagnosis of CLL or atypical CLL according to the FAB criteria. Cytologic diagnosis in these seven patients with t(ll;14) was typical CLL in two cases presenting with < 10% large lymphocytes (LL) and prolymphocytes (PL) and atypical CLL in five cases in which LL and PL comprised between 10% and 55%. The diagnosis was supported by histologic findings on bone marrow biopsy (five cases) or splenectomy specimens (two cases). A progressive increase of peripheral LL and PL was observed, resulting in a switch of FAB diagnosis over a 6-60-month period from typical CLL into atypical CLL in two cases and from atypical CLL into prolymphocytic leukaemia in five cases. Immunophenotyping showed a mature B-cell phenotype with CD19, CD22, CD24 positivity and CD10 negativity in all patients. A bright-staining pattern for surface immunoglobulins (SIg) was detected in 6/7 cases, CD5 positivity in 6/7 cases, and CD23 positivity in 1/7 cases. The FMC-7 monoclonal antibody was positive in >40% cells in 5/6 cases. Chromosome changes in addition to t(11; 14) were seen in five cases; in two cases unbalanced translocations involving the 3q21 chromosome region, resulting in partial trisomy for the long arm of chromosome 3, were detected early in the course of the disease. Karyotype evolution that was associated with disease progression occurred in 3/6 assessable patients. Comparison of these findings with similar data from 65 B-CLL patients without t(ll;14) showed that atypical morphology, switch of FAB diagnosis during the course of the disease, and karyotype evolution were more frequently seen in cases with t(ll;14) (5/7 v 15/65 cases, P = (V015, 7/7 v 7/65 cases, P < 0-0001, and 3/6 v 5/45 assessable cases, P= 0-04, respectively). The frequency of positivity for CD2 3 and bright SIg staining differed significantly in the two groups. It is concluded that t(ll;14) identifies a cytologically atypical subset of B-CLL, characterized by frequent cytologic and cytogenetic evolution and by a distinct immunological profile, sharing some biological features with mantle cell lymphoma.