美心力与硝酸甘油联用治疗充血性心力衰竭的临床观察

目的 探讨美心力对充血性心力衰竭（ＣＨＦ）患者的治疗效果。方法 选择ＣＨＦ心功能Ⅲ～Ⅳ级住院患者６０例。随机分为治疗组３０例。采用美心力和硝酸甘油联用;对照组３０例,单用硝酸甘油。比较治疗前后两组的临床症状、体征和心功能分级、心功能指标。并观察疗效和记录有无副作用。结果 治疗组临床总有效率８３．３％。对照组总有效率７６．６％（Ｐ〈０．０５）。心功能测定,治疗组治疗前后比较各项指标改善均有显著性差异（Ｐ〈０．０１）,对照组收缩功能改善有显著性差异（Ｐ〈０．０１）。舒张功能无改善（Ｐ〉０．０５）。治疗组与对照组比较。收缩功能改善无差异（Ｐ〉０．０５）。而舒张改善有显著差异（Ｐ〈０．０１）。治疗组在用药过程中未见毒副作用。结论 美心力是治疗ＣＨＦ患者安全有效的药物,可作为ＣＨＦ综合治疗药物之一用于临床。     

Thiopentone inhibits beta-adrenergic responses in myocardial tissue

The purpose of this study was to determine the importance of inhibition of beta-adrenergic function in thiopentone-induced myocardial depression. Using an isolated, electrically stimulated rat left atria model, contractile dose-response curves to thiopentone (200 μM, 400 μM, 600 μM, 800 μM) were shifted to the right in preparations treated with 10^{− 3} M dibutyryl cyclic adenosine monophosphate (cAMP) compared with atria stimulated with 10^{− 6} M isoprenaline, demonstrating that inhibition of beta-adrenergic mechanisms by thiopentone is physiologically important. Depression by thiopentone was similar in atria treated with 10^{− 5} M forskolin compared with preparations stimulated with 10^{− 6} M isoprenaline, indicating that thiopentone does not block beta-adrenergic receptors. It is concluded that thiopentone depresses myocardial function by several mechanisms, one of which involves inhibition of the adenyl cyclase cascade. The adenyl cyclase enzyme is a likely site where thiopentone inhibits the system; however, other components of the cascade may also be involved. L’objectif de cette étude consiste à déterminer l’influence de l’inhibition de l’activité β-adrenergique sur la dépression myocardique induite par le thiopentone. A l’aide d’un modèle constitué d’une oreillette gauche de rat stimulée électriquement, la relation dose-effet du thiopentone sur la contractilité (200 μM, 400 μM, 600 μM, 800 μM) se déplace vers la droite dans des préparations traitées avec de l’adénosine monophosphorique cyclique (cAMP) 10^{− 3} M comparativement à des oreillettes stimulées avec de l’isoprénaline 10^{− 6} M, ce qui démontre que l’inhibition β-adrénergique provoquée par le thiopentone est physiologiquement importante. La dépression de l’oreillette provoquée par le thiopentone est identique à celle que produit la forskoline 10^{− 5} M comparativement à celle de l’isoprénaline 10^{− 6} M, ce qui indique que le thiopentone n’inhibe pas les récepteurs β-adrénergiques. Les auteurs concluent que le thiopentone déprime la fonction myocardique par plusieurs mécanismes qui impliquent l’inhibition de la cascade de l’adényl cyclase. L’inhibition du système se produit vraisemblablement au niveau de l’enzyme adényl cyclase; cependant, il est possible que d’autres éléments de la cascade de l’adényl cyclase soient impliqués.     

Decreased β2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: An additional cause of severe hypoglycaemia in childhood diabetes?

Little is known about the receptor and post receptor mechanisms of sympathoadrenal signal transmission in type I diabetes mellitus. Therefore, we examined the maximum binding of granulocyte ₂-adrenoceptors and the in vitro c-AMP accumulation in lymphocytes of 24 children and adolescents with diabetes mellitus and 14 similarly aged healthy subjects. The number of high affinity ₂-adrenoceptors on granulocytes correlated significantly with unstimulated (r=0.6,P<0.004) and with isoproterenol stimulated c-AMP values in lymphocytes (r=0.68,P<0.0007) showing the proportional changes of ₂-adrenoceptors and c-AMP in two different cells. The number of ₂-adrenoceptors on granulocytes was significantly reduced in diabetic as compared to healthy children (median 1397, range 599–3405 vs. 2205, 825–3200 ₂-adrenoceptors per granulocyte,P=0.014). Moreover, the percentage in vitro stimulation of c-AMP by isoproterenol in lymphocytes was significantly reduced in diabetic children as compared to healthy individuals (120%, 39%–278% vs. 225%, 66%–500%,P=0.012). These results indicate a decreased sympathoadrenergic signal transmission in peripheral blood cells as a model for the liver probably contributing to severe hypoglycaemia in diabetic children.     

Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosine

Summary Adenine nucleotides cause adenosine receptor-mediated increases in cyclic AMP in the VA13 human fibroblast line. Levels of adenosine accumulated in the medium are insufficient to account for the responses to adenine nucleotides. Since rapid conversion of the nucleotides to adenosine by 5-nucleotidase in the vicinity of the receptor might account for the responses, six experimental methods were developed to distinguish between local conversion and direct action of the nucleotides. Results of all six methods favored local conversion. (1) 5-Nucleotidase inhibitors blocked the accumulations of cyclic AMP elicited by AMP, ADP, and ATP, but did not affect the response to adenosine. The most potent inhibitor of both conversion of AMP and response to AMP was ,-methylene-ADP (APCP). (2) Adenosine deaminase blocked the responses to AMP, ADP, ATP, and adenosine-containing coenzymes. (3) Theophylline, a specific competitive adenosine antagonist, was an insurmountable inhibitor of the increases in cyclic AMP caused by AMP, ADP, and ATP. The insurmountability was presumably due to substrate sataration of the converting enzyme 5-nucleotidase. (4) Although ADP and ATP had partial agonist-like dose-response curves, they did not inhibit the response to adenosine. (5) Nine cell lines which responded to adenosine were tested for response to AMP. Cell lines with high levels of 5-nucleotidase had large responses to AMP, those with intermediate levels of 5-nucleotidase had large or intermediate responses to AMP, and those with low 5-nucleotidase levels did not respond to AMP. (6) Inhibition of the uptake of labelled adenosine was used as an indicator of unlabelled adenosine concentrations near the cell membrane. Unlabelled AMP inhibited uptake nearly as effectively as unlabelled adenosine. APCP reversed the inhibition by AMP but not the inhibition by adenosine.The adenosine receptor is concluded to be an enity distinct from adenine nucleotide receptors.Submitted in partial fulfillment of the requirements for the degree Doctor of Philosophy in Neurosciences, University of California, San Diego. Supported by NIMH DA-00265 and PHS RR 05665. The author has been a NSF Graduate Fellow. An abstract of this material has been published (Bruns 1977)     

Cyclic adenosine 3′,5′monophosphate in cerebrospinal fluid of multiple sclerosis patients

Summary Cyclic adenosine 3,5monophosphate (cAMP) was assayed in CSF and plasma obtained from patients with multiple sclerosis. Decreased CSF cAMP levels were found in more than half of the patients while plasma cAMP was normal. The decrease is correlated significantly with the disability of the patient and with the progression of the disease. A low CSF cAMP level can be considered as prognostically unfavorable, particularly in the early stage of the disease. There was no correlation between the cAMP levels and the duration of the disease or with bouts and remissions. ACTH therapy did not normalize the decreased values. Obviously the decrease of CSF cAMP is related to the demyelination and not to the intensity of the pathological immunoreactions.

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Zusammenfassung Es wurde das cyclische Adenosin-3,5monophosphat im Liquor von Patienten mit multipler Sklerose untersucht. Bei einem Teil der Patienten wurden auch die Vergleichswerte im Blutplasma bestimmt. Es zeigte sich bei mehr als der Hälfte der Patienten eine Verminderung der cAMP-Konzentration im Liquor bei normalem Plasmaspiegel. Diese cAMP-Verminderung erwies sich als signifikant abhängig von dem Schweregrad der Erkrankung bzw. der Erkrankungsprogredienz und ist besonders in frühen Erkrankungsfällen als prognostisch ungünstiges Zeichen anzusehen. Es fand sich kein Zusammenhang mit dem Krankheitsstadium, d.h. Schub bzw. Intervall, und mit der Erkrankungsdauer. Eine ACTH-Behandlung vermochte diese Verminderung der Werte nicht auszugleichen. Es wird die Wertigkeit dieser Befunde diskutiert.

     

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy

Summary In this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into good and poor responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.     

单磷酸阿糖腺苷治疗慢性乙型肝炎32例研究

目的 研究单磷酸阿糖腺苷在慢性乙型肝炎中的应用情况。方法 62例慢性乙型肝炎患者随机分为A、B两组，A组采用还原性各胱甘肽、甘草酸二胺等治疗2个月，B组在此基础上加用单磷酸阿糖腺苷治疗28d，病程2个月时监测血清TBiL、DBiL、ALT、AST、HBeAg、HBV DNA。结果 B组TBiL、ALT、AST、HBeAg、HBV DNA较A组明显下降。结论 单磷酸阿糖腺苷可较好地治疗慢性乙型肝炎。     

维生素B_1和维生素C联合应用对铅染毒小鼠睾丸某些生化和形态指标的影响

目的探讨维生素B1、C联合应用对铅染毒小鼠睾丸某些生化和形态指标的影响。方法75只雄性小鼠随机分为空白对照组,0.2%染铅组和维生素高、中、低干预组,每组各15只。并分别在第2、4、6周处死每组各5只小鼠,取其睾丸组织,用免疫组化检测各组小鼠睾丸转化生长因子β1(TGFβ1)、半胱天冬酶3(Caspase-3)的表达;DNA片段原位末段标记技术(TUNEL法)检测睾丸细胞凋亡;单细胞凝胶电泳(彗星实验)检测细胞DNA的损伤。结果染铅组小鼠睾丸TGFβ1、Caspase-3表达增强,凋亡指数增加。与空白对照组相比,差异有统计学意义(P<0.01)。低、中剂量维生素B1、C联合干预后,睾丸细胞DNA损伤降低,凋亡细胞减少,光镜下可见损伤的组织明显改善。与0.2%染铅组比较,差异有统计学意义(P<0.05)。但在高剂量组,维生素联合作用则促进了小鼠睾丸TGFβ1、Caspase-3的表达,使细胞凋亡指数增高,但彗星尾长和拖尾率则显著降低。结论维生素B1、C联合作用可拮抗铅的某些睾丸毒性作用。     

Visual Loss Due to Wernicke Syndrome Following Gastric Bypass

Purpose: To report a case of Wernicke encephalopathy after gastric bypass surgery resulting in vision loss, ophthalmoplegia, and ataxia, all of which reversed with a single dose of IV thiamine. Methods: Observational case report. Results: A 34-year-old woman presented with decreased vision and intermittent diplopia after gastric bypass surgery. She was found to have bilateral limitation of horizontal gaze, decreased vision with bilateral central scotoma and mild disc edema OU. Her cranial magnetic resonance imaging (MRI) was normal. A presumptive diagnosis of Wernicke encephalopathy was made. The patient was admitted, and a single dose of IV thiamine reversed the ophthalmoplegia and vision loss within 24 hours. Conclusion: Wernicke encephalopathy should be considered in patients with vision loss after gastric bypass surgery. The classic triad of confusion, ataxia, and ophthalmoplegia may not be present and, although uncommon, the findings of optic disc edema and vision loss should not deter the clinician from making the diagnosis. Replacement thiamine if given promptly may rapidly reverse the findings.