Adverse childhood experiences and the development of Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43–1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5–10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08–2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: −3.64–−1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.     

Multiple sclerosis presenting as catatonia

OBJECTIVE: Catatonic disorder due to general medical condition must be excluded in psychiatric patients presenting with this movement disorder. This report emphasizes the association of catatonia with multiple sclerosis. METHOD: A patient with catatonia, psychotic depression, and the subsequent diagnosis of multiple sclerosis is described and the literature reviewed. RESULTS: Mutism, immobility, cataplexy, waxy flexibility, and other aspects of catatonia occur in multiple sclerosis, usually as a consequence of a severe mood disorder and extensive cerebral demyelination. These symptoms may be the presenting manifestations of multiple sclerosis. CONCLUSIONS: A high index of suspicion for neurological disease is indicated in patients with new-onset catatonia. Neuroimaging and other studies may reveal underlying demyelination requiring specific therapy.     

Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome

BACKGROUND: Select pancreatic enzymes, primarily elastase, precipitate pulmonary injury similar to pancreatitis-associated adult respiratory distress syndrome and stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF-kappaB) activation. This study explores the effect of systemic pancreatic enzymes on pulmonary NF-kappaB and inhibitory kappa B (IkappaB) proteins and their role in enzyme-induced pulmonary injury. METHODS: Mice received pancreatic elastase, amylase, lipase, or trypsin intraperitoneally. Bronchoalveolar lavage IkappaBalpha/IkappaBbeta proteins were measured by immunoblot. Pulmonary NF-kappaB activation, tumor necrosis factor (TNF) gene expression, and neutrophil infiltration (myeloperoxidase) were determined and myeloperoxidase experiments repeated in p55 TNF receptor-deficient (TNF KO) animals. Additional animals received pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB activation, and TNF protein and pulmonary microvascular permeability were measured after elastase administration. RESULTS: Pancreatic elastase induced pulmonary IkappaBalpha/IkappaBbeta degradation (30 minutes), NF-kappaB activation (60 minutes), and TNF gene expression (60 minutes) with subsequent neutrophilic inflammation (4 hours) and microvascular leakage (24 hours), whereas amylase, lipase, and trypsin did not. Furthermore, lung injury was markedly reduced in TNF KO animals and PDTC significantly attenuated TNF production and pulmonary microvascular leakage. CONCLUSIONS: Pancreatic elastase induces cytokine-mediated lung injury and this pathway involves the NF-kappaB second messenger system, further supporting elastase as a factor linking pancreatic inflammation to systemic illness during severe acute pancreatitis.     

Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: role of the intranigral graft

The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216-7227; Mendez and Hong [1997] Brain Res 778:194-205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double-grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double-grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6-OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double-grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD.     

Optimal reproductive competence of oocytes retrieved through follicular flushing in minimal stimulation IVF

The objective of this study was to assess the reproductive competence of oocytes obtained by follicular flushing in poor responder patients. This prospective comparative study, at the University of Paris XI, Assistance Publique des Hopitaux de Paris, INSERM Unit 782, was performed on 165 infertile IVF embryo transfer candidates. A total of 271 consecutive minimal stimulation IVF cycles were studied. Oocyte retrieval was performed 34 h after human chorionic gonadotrophin administration and oocytes were allocated into two groups according to their retrieval method: oocytes obtained in the first follicular aspiration (FA, n = 127); and oocytes retrieved in the subsequent follicular flushing (FF, n = 102). The principal outcome was to evaluate clinical pregnancy and embryo implantation rates. Thus, patient characteristics, fertilization rate and clinical pregnancy rate per oocyte were comparable in both of groups. In contrast, embryo morphology (41 versus 59%, P < 0.01) and implantation rates (20.4 versus 34.8%, P < 0.04) were better in the FF group. In conclusion, an optimal reproductive competence was observed in oocytes retrieved by follicular flushing in minimal stimulation IVF in poor responder patients.     

液基细胞学结合阴道镜检查在北京市社区妇女宫颈病变筛查中的意义

目的探讨宫颈液基细胞学及阴道镜检查在北京市社区妇女宫颈病变筛查中的临床意义。方法2006年6月至2007年6月对北京市展览路社区的795位20～54岁有性生活的妇女进行筛查。筛查对象接受妇科检查时,留取宫颈超柏氏薄层液基细胞学检测标本,并对宫颈细胞学异常者行阴道镜检查及活组织检查。结果宫颈细胞学阳性[≥ASC-US（不能明确意义的不典型鳞状细胞）]45例,占5．7％（45／795）。其中ASC-US33例,占73．3％（33／45）;低度鳞状上皮内病变8例;高度鳞状上皮内病变3例;不典型腺细胞1例。细胞学阴性750例,占94．3％（750／795）。宫颈细胞学阳性的45例中,5例拒绝行阴道镜检查,占11．1％（5／45）。在行阴道镜活组织病理检查的40例中,慢性宫颈炎11例（27．5％）;宫颈湿疣14例（35．0％）;宫颈上皮内瘤样病变（CIN）1为7例（17．5％）;CIN2为3例（7．5％）;CIN3为4例（10．0％）;早期浸润癌1例（2．5％）。细胞学阴性的750例中,宫颈湿疣2例（0．3％）;CIN1为5例（0．7％）;宫颈低级别腺上皮内病变1例（0．1％）。宫颈液基细胞学筛查CIN1及以上宫颈病变和宫颈癌的敏感度71．4％,特异度94．2％,阳性预测值37．5％,阴性预测值99．2％;筛查CIN2及以上宫颈病变和宫颈癌的敏感度100．0％,特异度96．0％,阳性预测值20．5％,阴性预测值100．0％。结论应重视并及时进行北京市社区人群宫颈病变的早期筛查,薄层液基细胞学结合阴道镜活组织检查及病理学检查,对提高早期宫颈癌筛查的准确性效果明显。