Short-term outcomes of patients with neovascular exudative AMD: the effect of COVID-19 pandemic

Graefe's Archive for Clinical and Experimental Ophthalmology - To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with...     

对乙酰氨基酚引起的急性肝衰竭：一项美国多中心前瞻性研究结果

严重的对乙酰氨基酚肝毒性常常会引起急性肝衰竭（ALF），作者在美国的22所三级护理中心调查了由对乙酰氨基酚引起的肝衰竭的发生率、危险因素和预后，用超过6年的时间收集到662例完全符合ALF（包括肝源性凝血症和肝性脑病）标准的患者资料，详细分析后发现：其中有275例（45％）是由对乙酰氨基酚引起的。调查发现，对乙酰氨基酚相关性ALF的年度百分比由1998年的28％上升至2003年的51％。对乙酰氨基酚的中位摄入量为24g（相当于48个高含量的片剂）。在上述275例中，误服过量者有131例（48％），有意服用者（即有自杀倾向者）有122例（44％），还有22例（8％）为不明意图。在误服组中38％同时服用了两种或多种对乙酰氨基酚制剂，63％患者服用了含有镇静剂的复合制剂。据报道，81％患者因为急性或慢性疼痛误服了对乙酰氨基酚和（或）其他镇痛剂。总体上，有178例研究对象（65％）存活，74例（27％）未经肝移植而死亡，23例（8％）进行了肝移植，其中71％的患者仅存活了3周。未接受移植的存活率和肝移植存活率在误服组和有意服用组差别不明显。     

Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.
DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences.
Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.
The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Production of nitrite by primary rat astrocytes in response to pneumococci

Recent studies using a rat model of pneumococcal meningitis have shown that nitric oxide synthase (NOS) inhibitors greatly attenuated microvascular changes and brain edema formation. The site of NO production during bacterial meningitis is unknown. In this study we tested whether primary astrocyte cultures from neonatal rat cortex can be induced to release NO upon stimulation with pneumococci. NO production was assessed by measuring nitrite in the cell culture supernatant using the Griess reaction. Stimulation with heat-killed unencapsulated pneumococci (HKP) increased nitrite concentrations in astrocyte culture supernatants in a dose-dependent fashion. Administration of AT-nitro-L-arginine (L-NA), aminoguanidine, L-canavanine, cycloheximide, and dexamethasone prevented the increase in nitrite concentrations. Addition of L-arginine, but not of o-arginine, partially reversed the inhibitory effect of L-NA. Administration of SOD increased nitrite accumulation. Moreover, at 72 h after stimulation with heat-killed pneumococci (10⁷ cfu/ml) astrocytes showed an inducible NOS-like immunoreactivity. Accumulation of nitrite was also observed when rat cerebellar neurons and microglia were stimulated with HKP, whereas there was only a slight increase of nitrite in media of rat C6 glioma cells, but no increase of nitrite when the human glioblastoma cell line LN-229 was stimulated with HKP. There was a stronger increase in nitrite levels when astrocytes from Lewis rats were used compared to that from Wistar rats. In conclusion, our study indicates that astrocytes, neurons and microglia are inducible for NO production upon stimulation with pneumococci.     

Chronic anxiolytic treatment effects on conflict behavior in the rat

The present studies examined the effects of chronic posttest treatment with the antipanic agent alprazolam (ALP) or the traditional anxiolytic agents chlordiazepoxide (CDP) and phenobarbital (PhB) on conflict behavior. In daily ten-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.25 or 0.5 mA). Electrification was signalled by a tone. Chronic ALP (10 mg/kg/day), CDP (40 mg/kg/day), PhB (80 mg/kg/day) or vehicle were injected IP after conflict testing (in some experiments again 12-16 hours later) for a minimum of 6 weeks. Chronic ALP (but not CDP or PhB) resulted in a time-dependent increase in punished responding, with a latency to onset of 3-4 weeks; this effect was not antagonized by the benzodiazepine antagonist Ro15-1788. These data support the hypothesis that conflict paradigms may serve as animal models for the study of antipanic agents. Moreover, these data suggest that not all anxiolytics will exhibit antipanic efficacy.