Potentiation of inhibition by general anaesthetics in neurones of the olfactory cortex in vitro

Pentobarbitone, phenobarbitone, methohexitone, chloralose and alphaxalone produced 10-fold increases in the duration of an inhibitory post-synaptic conductance (i.p.s.c.) as recorded intracellularly from neurones of the guinea-pig olfactory cortex in vitro. Higher concentrations slightly depolarised these neurones and reduced their input resistances (R_i), presumably a spontaneous activation of the inhibitory conductance. The excitatory potentials were also depressed. Ketamine, halothane and urethane doubled the i.p.s.c. duration. Higher concentrations depressed synaptic activity and the action potential, as did lignocaine. Ketamine also increased R_i. These results confirm the idea that these compounds produced anaesthesia by prolonging inhibition (accompanied by a depression of the e.p.s.p. with some anaesthetics).     

外源性糖皮质激素对大鼠下丘脑─垂体─肾上腺─胸腺轴的影响

本文观察大鼠每天皮下注射皮质酮（1~50mg/kg，连续14天）后下丘脑─垂体─肾上腺─胸腺（HPAT）轴的形态与机能改变。结果表明：实验大鼠垂体，肾上腺，胸腺重量减轻，下丘脑单胺类递质含量升高，下丘脑室旁核促肾上腺皮质素释放因子（CRF）分泌细胞及正中隆起CRY神经纤维和垂体前叶促肾上腺皮质激素（ACTH）分泌细胞等数量减少，染色变淡，血浆皮质酮（CORT）和ACTh浓度降低。淋巴细胞增殖反应及自然杀伤细胞活性减弱，T淋巴细胞产生IL-2、IFN－γ能力下降。提示：（1）外源性糖皮质激素剂量依赖性反馈抑制HPAT轴；（2）与此同时激活下丘脑单胺类递质，进一步支持糖皮质激素与儿茶酚胺共同构成HPAT重要调节因素的观点。     

Sources of common computer-cardiologist discord in e.c.g. interpretations in ambulatory population

Based on clinical experience in performing mass computerised interpretations of e.c.g.s, some common sources of computer-cardiologist disagreements are presented. Examples are given along with a discussion of the technological or logical bases for discord. It is concluded that computer interpretations are generally reliable and accurate; however, disagreements sometimes occur in borderline cases, in tracings with much electrical ‘noise’ or in those where the transitions between different segments of the QRS complex are not well demarcated. A computerised e.c.g. interpretation system can help the cardiologist by providing all required measurements and most of the diagnostic statements. Thus, only review and validation of the processed tracings are needed. By continuously refining the program criteria based on the accumulated experience of many cardiologists, the reliability and acceptability of computer e.c.g. interpretations could be enhanced and expanded to screen large populations.     

Early histogenesis in the mouse cerebral cortex: a Golgi study

The early histogenesis in the cerebral cortex of the mouse was studied with a modification of the rapid Golgi method. Three stages can be distinguished first, a period during which the telencephalon is exclusively populated with neuroepithelial cells (till E12); secondly the transient stage of the primordial cortical organization, characterized by the presence, in the outer part of the neural tube, of a loose network of primitive horizontal nerve cells and third, the appearance of the early cortical plate (E14) which contains closely packed, radial bipolar nerve cells. In addition to some salient morphological features of the various cell types, the technique also reveals the importance of efferent fibers from the cortex during the early cortical development.     

抗人肝癌导向药物的制备及其分析

本文报道了肝癌单克隆抗体Ａ２４－表阿霉素结合物的制备及其对肝癌细胞ＳＭＭＣ－７７２１的体外杀伤作用。先用高碘酸钠把葡聚糖氧化成多醛基葡聚糖，再以此为中介体连接单抗与表阿霉素。结合物中抗体与药物摩尔比为１：４０。单抗活性保存良好。该结合物对肝癌细胞的毒性显著高于游离药物及无关抗体结合物，而对非靶细胞的毒性则明显低于游离药物。说明结合物对肝癌细胞有较强的选择性杀伤作用，有可能用于肝癌导向治疗。     

Transtracheal aspiration studies in asthmatic patients in relapse with “infective” asthma and in subjects without respiratory disease

Exacerbations of bronchial asthma that cannot be accounted for by allergic reactions have sometimes been called “infective” asthma. The validity of this designation was tested by study of transtracheal aspirates (TTA) obtained from 27 asthmatic patients in relapse who had findings suggestive of respiratory infection and 12 subjects without respiratory disease. Aspirates were cultured for aerobic and anaerobic bacteria, Mycobacteria, fungi, Mycoplasma, and viruses. A comparable variety of bacterial and fungal growth in small numbers obtained from a majority of both groups. Microbial growth did not correlate with the presence of symptoms or signs compatible with infection. Aspirates from asthmatics with chronic bronchitis, immediate hypersensitivity to aeroallergens, or aspirin intolerance yielded no greater growth than did aspirates from asthmatics without these characteristics. In only one asthmatic was there suggestion that overt infection of the lower respiratory tract contributed to exacerbation of asthma. These results do not lend support to the empiric use of antibiotics in the management of unexplained asthmatic relapse.     

Mood disorder in women professionals

The lifetime prevalence of affective disorder in women with M.D.'s and Ph.D.'s was assessed by personal interview. The two groups were matched by age, race, and marital status. Thirty-nine percent of 111 white, women physicians and 30% of 103 white, women Ph.D.'s were found to have primary affective disorder. There was no excess of depression in women psychiatrists or psychologists. Eleven percent of the first degree relatives of the depressed M.D.'s and 7% of similar relatives of depressed Ph.D.'s had affective disorder by family history compared to only 2% of the well M.D.'s and 2% of the well Ph.D.'s relatives.The study confirms that depression is an extremely common problem for professional women. By emphasizing its heritability, it raises the question of the self-selection for professional careers of women with affective disorder.     

Sources of dependency in asthmatic children

The question of whether childhood asthma produces increased dependency is examined. Dependency scores of 60 asthmatic and non-asthmatic children with the same familial-constitutional allergic predisposition were divided into “low-dependent” and “high-dependent” groups. In each group, asthmatic and non-asthmatic children with the same familial-constitutional allergic predisposition were compared statistically for significant psychological differences. Dependency was not found to be associated with the severity of asthma, but was associated with family relationship patterns.     

Pharmacogenomics and Opioid Use Disorder: Clinical Decision Support in an African American Cohort

Opioid use disorder (OUD) constitutes a significant public health burden as opioid overdose deaths have continued to rise in the United States. Although treatment modalities are available to manage OUD, some patients experience challenges achieving their OUD management goals. Some of these challenges may be attributable to inherited genetic variations, or polymorphisms, on the genes that code for proteins impacting the pharmacokinetics or pharmacodynamics of medications used in OUD management. Clinical pharmacogenomics testing can elucidate these polymorphisms; however, a lack of real-world evidence for the use of pharmacogenomics in OUD management complicates the implementation process. We conducted a retrospective cohort study of 113 patients undergoing buprenorphine-based OUD management in Northeast Washington D.C. to determine if clinical pharmacogenomics testing for CYP3A4 and CYP3A5 would impact treatment outcomes. Data were collected from the electronic medical record (EMR) from December 30, 2015 to December 31, 2016. Study outcomes were based on presence of withdrawal symptoms, instances of unauthorized substances in urine drug tests (UDTs), and sublingual buprenorphine/naloxone (SBN) dose with standard-of-care (SOC) dosing versus pharmacogenomics (PGx)-based dosing. Pearson correlation tests, Wilcoxon signed rank tests, Wilcoxon rank sum tests, and one-way ANOVA tests were used. Linear and logistic regression analyses were used to assess predictors of withdrawal symptomatology. Kaplan-Meier survival analyses were used to assess time to first withdrawal. Our research suggests that patients with at least one copy of the CYP3A4*1B allele exhibit an accelerated rate of metabolism compared to the wild-type allele CYP3A4*1.     

Ultrastructural Morphologic Changes in Mycobacterial Biofilm in Different Extreme Condition

The aim of this study was to investigate the morphologic and ultrastructural features of biofilms of slow and fast-growing mycobacteria in different stress conditions, presence and absence of oleic acid albumin dextrose catalase (OADC) enrichment and at different temperatures: 30, 37 and 42?°C. Four hundred mycobacterial isolates were taken. The biomass of each biofilm was quantified using a modified microtiter plate assay method. Isolates were divided into those that formed fully established biofilms, moderately attached biofilms and weakly adherent biofilms by comparison with a known biofilm-forming strain. The large quantity of biofilm was produced by Mycobacterium smegmatis at temperature 37 and 42?°C as compared to 30?°C. Mycobacterium fortuitum and M. avium developed large amount of biofilm at 30?°C as compared to 37 and 42?°C. Mycobacterium tuberculosis developed strong biofilm at 37?°C and no biofilm at 30 and 42?°C in Sauton’s media. The selected non-tuberculous mycobacteria and H37Rv developed strong biofilm in the presence of OADC enrichment in Sauton’s medium. Microscopic examination of biofilms by scanning electron microscopy revealed that poorly adherent biofilm formers failed to colonize the entire surface of the microtiter well. While moderately adherent biofilm formers grew in uniform monolayers but failed to develop a mature three-dimensional structure. SEM analysis of an isolate representative of the group formed fully established biofilms with a textured, multi-layered, three-dimensional structure.     

A paper radioimmunosorbent test (PRIST) for the detection of larva-specific antibodies to toxocara canis in human sera

A paper radioimmunosorbent test (PRIST) was shown to be sensitive and reproducible when used with excretory/secretory antigen of Toxocara canis second stage larvae. Whatman No. 50 filter paper (5 mm discs) gave the most consistent and clear results with antigen at a concentration of 100 μg/ml, and could be stored for up to 3 weeks in vacuo at ?70°C. Antigen coated discs were incubated with test sera at 1 : 10 dilution for 3 h at room temperature (21°C), reacted with [¹²⁵I]anti-human IgG for 1 h and counts determined in a gamma counter. Sera from patients with fascioliasis, taeniasis, schistosomiasis, oxyuriasis, trichinellosis and ancyclostomiasis gave counts similar to cord serum controls. Sera from patients with ascariasis gave counts of up to twice as great as controls, but sera from patients with toxicariasis produced counts of 7,000–13,000, a 4–6-fold increase.     

Unique forms of fast-sedimenting BU lambda DNA in a superinfected E. coli lysogen

When a lysogenic (immune) culture of Escherichia coli C thy-321 is superinfected with lambda phage in which 5-bromouracil (BU) has been substituted for the normal DNA base thymine, a large percentage of the linear BU lambda DNA injected into the cells is converted into a covalently closed circular monomer while a smaller amount is converted into DNA forms which sediment faster than the covalently closed circular monomer in both neutral and alkaline sucrose gradients. These unique BU-DNA structures form independently of coinfecting thymine lambda DNA, which forms only the covalently closed circular monomer. It has been found that the formation of the unique forms of fast-sedimenting BU lambda DNA is dependent upon the multiplicity of infection, i.e., the percent of unique forms is greatly reduced in cells superinfected at a multiplicity of infection of less than 1.0. This suggests that there is some type of atypical, intracellular interaction between two or more BU λ DNA molecules. Other observations concerning certain physical characteristics of these unique forms, such as their sedimentation properties in alkaline and neutral sucrose gradients following exposure to ultraviolet (uv) light, indicate that they are structures which differ from each other in molecular weight rather than in superhelical density.     

急性缺氧大鼠血浆、呼出气NO含量的变化及吸入NO对缺氧性肺血管收缩的影响

观察了大鼠急性缺氧前后血浆和呼出气一氧化氮（ＮＯ）含量的变化，结果显示，动物吸人１０％，２０ｍｉｎ后，血浆ＮＯ＿２／ＮＯ＿３浓度从２３．５６±７．１３升至４１．６３±１０．１０μｍｏｌ／Ｌ（Ｐ＜０．０１）；呼出气ＮＯ浓度出０．０９９±０．０５５增至０．１６２±０．１０８ｐｐｍ（Ｐ＜０．０１）．提示急性缺氧时ＮＯ生成增多可能在缺氮性肺血管收缩（ＨＰＶ）中起调节作用。为探讨吸入ＮＯ对ＨＰＶ的影响，本文采用人工呼吸给缺氧大鼠吸入４０ｐｐｍＮＯ，发现动物缺氧（１０％Ｏ＿２）１０ｍｉｎ后，平均肺动脉压（ｍＰＡＰ）和肺血管阻力（ＰＶＲ）较基础值明显升高（Ｐ＜０．０１）：而缺氧同时吸入４０ｐｐｍＮＯ１０ｍｉｎ，ｍＰＡＰ和ＰＶＲ较缺氧时明显降低（Ｐ＜０．０１），与基础值无显著差别（Ｐ＞０．０５），且发现△ＰＶＲ％为２．９４±９．８５％，较缺氧时６６．１８±２３．３９％明显降低（Ｐ＜０．０１），但吸入ＮＯ对体动脉压、体血管阻力，心输出量、血气和高铁血红蛋白无明显影响。从而提示吸入ＮＯ选择性降低缺氧性肺动脉高压且完全逆转ＨＰＶ。