Nijmegen paediatric CDG rating scale: a novel tool to assess disease progression

Congenital disorders of glycosylation (CDG) are a group of clinically heterogeneous inborn errors of metabolism. At present, treatment is available for only one CDG, but potential treatments for the other CDG are on the horizon. It will be vitally important in clinical trials of such agents to have a clear understanding of both the natural history of CDG and the?corresponding burden of disability suffered by patients. To date, no multicentre studies have attempted to document the natural history of CDG. This is in part due to the lack of a reliable assessment tool to score CDG's diverse clinical spectrum. Based on our earlier experience evaluating disease progression in disorders of oxidative phosphorylation, we developed a practical and semi-quantitative rating scale for children with CDG. The Nijmegen Paediatric CDG Rating Scale (NPCRS) has been validated in 12 children, offering a tool to objectively monitor disease progression. We undertook a successful trial of the NPCRS with a collaboration of nine experienced physicians, using video records of physical and neurological examination of patients. The use of NPCRS can facilitate both longitudinal and natural history studies that will be essential for future interventions.     

Synthesis and Anticonvulsant Properties of New Mannich Bases Derived from 3,3-Disubstituted Pyrrolidine-2,5-diones. Part IV

A library of 21 new N-Mannich bases of 3,3-diphenyl- (5a-g), 3-methyl-3-phenyl- (6a-g), and 3-ethyl-3-methylpyrrolidine-2,5-diones (7a-g) were synthesized and evaluated for their anticonvulsant activity in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests after intraperitoneal injection into mice. The acute neurological toxicity was determined applying the rotarod screen. The results in mice showed that 13 compounds were effective in the MES or/and scPTZ screen. From these, seven molecules were tested in the MES seizures after oral administration in rats. The quantitative studies showed that N-[{4-(2-hydroxyethyl)-piperazin-1-yl}-methyl]-3-methyl-3-phenylpyrrolidine-2,5-dione (6c) and N-[(4-benzylpiperidin-1-yl)-methyl]-3-methyl-3-phenylpyrrolidine-2,5-dione (6f) revealed higher protection in the MES and scPTZ tests than valproic acid or ethosuximide which were used as reference antiepileptic drugs. Four compounds (5c, 6c, 6e, 6f) showed high effectiveness in the 6-Hz psychomotor seizure model of partial and therapy resistant epilepsy.     

Anthraquinone antitumour agents, doxorubicin, pirarubicin and benzoperimidine BP1, trigger caspase-3/caspase-8-dependent apoptosis of leukaemia sensitive HL60 and resistant HL60/VINC and HL60/DOX cells

We examined the effect of selected anthraquinone antitumour agents - doxorubicin (DOX), pirarubicin (PIRA) and benzoperimidine BP1 - on inducing apoptosis of the sensitive leukaemia HL60 cell line and its multidrug resistance sublines overexpressing P-glycoprotein (HL60/VINC) and multidrug resistance-associated protein 1 (HL60/DOX). All agents used at IC50 and IC90 were able to influence the cell cycle of sensitive HL60 and resistant cells and induce apoptosis. Interestingly, it was seen that HL60/VINC cells were more susceptible to undergo caspase-3/caspase-8-dependent apoptosis induced by the studied anthraquinone compounds compared with HL60 and HL60/DOX cells. However, the examined agents did not change the expression of Fas receptors on the surface of HL60-sensitive and-resistant cells.     

Prevalence of paraneoplastic rheumatic syndromes and their antibody profile among patients with solid tumours

The aims of this study were to assess the prevalence of paraneoplastic rheumatic syndromes in a cohort of patients with newly diagnosed solid tumours and to describe their autoimmune profile, comparing it to the controls. Screening questionnaires (3,770) were distributed, and during a three-step study, 94 patients were confirmed to have both paraneoplastic syndrome and oncology diagnoses. Three control groups–patients with undifferentiated arthritis, Raynaud's phenomenon for non-malignant causes and solid tumours only–were designed to compare with the paraneoplastic cases and their immunology profile. The prevalence of paraneoplastic rheumatic syndromes was 2.65% (95% CI 0.21–3.20). The group of patients with arthritis and the group of patients with Raynaud's syndrome were found to prevail among other clinical presentations of paraneoplastic rheumatic syndromes. Both paraneoplastic syndromes were linked to malignancies of the urogenital system. Antinuclear antibodies were found to be similarly frequent in the paraneoplastic arthritis, paraneoplastic Raynaud's phenomenon and the solid tumour groups. No differences were observed when comparing paraneoplastic arthritis and undifferentiated arthritis, except that the patients with paraneoplastic arthritis were older. Comparing paraneoplastic Raynaud's to Raynaud's phenomenon, male preponderance in the paraneoplastic Raynaud's phenomenon group was observed, and the patients were obviously older. Paraneoplastic rheumatic syndromes are rare and more often occur in older patients. Among them, paraneoplastic arthritis and Raynaud's syndrome were the most frequent. The immunology profile does not help in discriminating between arthritis and paraneoplastic arthritis patients and is of limited use in Raynaud's differential diagnosis.     

Does lack of ST-segment resolution still have prognostic value 6 years after an acute myocardial infarction treated with coronary intervention?

Background

Limited data exist in regard to the correlation between ST-segment resolution (STR) in patients treated with primary percutaneous coronary intervention (pPCI) and very late mortality. The aim of the study was to determine the correlation between STR and 6-year mortality in patients successfully treated with pPCI.

Methods

We prospectively studied a group of 303 patients who had sustained an acute myocardial infarction with ST-segment elevation and subsequently exhibited TIMI 3 flow after pPCI. The patients were analyzed in 2 groups according to STR.

Results

There were 222 patients (73.3%) with STR and 81 patients (26.7%) without it. The mean “pain-to-balloon” time was 4.3 ± 2.1 hours in the former group vs 4.9 ± 2.8 hours in the latter (P = 0.016). In total, 64 people (21%) died during the 6-year follow-up period: 37 (17%) showed STR and 28 (35%) did not (P < 0.001). In multivariate analysis, STR, ejection fraction, and maximum creatine kinase and creatine kinase-MB levels were all associated with death. Anterior myocardial infarction, “pain-to-balloon” time, and ejection fraction were all further associated with lack of STR.

Conclusions

Lack of early STR is associated with significantly higher mortality rates after successful pPCI during a 6-year follow-up period. Absence of an early STR appears to identify patients who are less likely to benefit from the early restoration of infarct-affected artery, possibly due to microvascular damage. STR therefore appears to be a powerful prognostic marker for the occurrence of an acute myocardial infarction 6 years later.