Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Serum and tissue trace elements in Iranian camels (Camelus dromedarius)

There were 26 male and female (nonpregnant and nonlactating) apparently healthy adult (5 to 10 years) field camels (Camelus dromedarius) studied to provide data regarding the normal values of trace elements in serum and different tissues. Blood samples were collected by jugular venepuncture and serum was separated by centrifugation. Tissue samples (liver, heart, striated muscle, spleen, kidney, and hair) were collected during postmortem examinations. All the samples were digested and analyzed for copper, iron, cobalt, and molybdenum using atomic absorption spectrophotometry. The results showed that the highest concentration of iron was present in the spleen and that the concentrations of this element in the liver and kidney were higher than those in the heart, striated muscle, serum, and hair (p<0.05). The lowest mean iron concentration was observed in the serum (p<0.05). The mean copper concentration was highest in liver in comparison to other tissues (p<0.05). No significant differences in cobalt concentrations were detected among different compartments. The mean molybdenum concentration of striated muscle, heart, kidney, spleen, and liver were significantly higher than those of serum and hair (p<0.05). No difference due to sex was detected in different tissue and serum concentrations of trace elements.     

Serum creatine kinase B subunit levels in neurogenic atrophies

Summary This study is an attempt to determine the creatine kinase B (CK-B) subunit levels in neurogenic atrophies. A group of 69 patients was studied and the results were compared with those in a group of 32 patients with muscle disease. The results showed that the CK-B levels are considerably higher in patients with amyotrophic lateral sclerosis (P<0.001) and peroneal muscular atrophy (P<0.001). Further studies in the various subgroups of neurogenic atrophies showed that, regardless of the nosological entity, the CK-B activity is considerably higher: (1) in the widespread as opposed to limited forms (P<0.001); (2) in the chronic than in the acute neurogenic atrophies (P<0.001); and (3) in the active as opposed to residual forms (P<0.02). It is suggested that the increase of CK-B in neurogenic atrophies is a strong indication of an active regeneration process in the denervated muscle.     

A double-blind study on the effect of discontinuation of gold therapy in patients with rheumatoid arthritis

Summary To assess the benefit of further gold treatment of rheumatoid arthritis (RA) patients who had already received more than 6 g of this metal, 24 such patients were included in a double-blind trial. Besides this gold group comprising 11 patients who received gold (Auromyose^®) in the same dosage schedule as before the study, the trial included a placebo group comprising 13 patients who received gold in a suspension diluted 1/100. In either group clinical, laboratory, and radiological data did not differ after 6 and 24 months in relation to the results at entry except for the serum gold concentrations, which were lower in the placebo group. We conclude that discontinuation of the treatment in RA patients who have received more than 6 g gold is not harmful to the patients for at least two years after withdrawal.     

Growth,regression and cell death in rat liver as related to tissue levels of the hepatomitogen cyproterone acetate

Previous studies have shown that xenobiotic compounds such as the environmental pollutant -hexa-chlorocyclohexane (-HCH) and the synthetic sex steroid cyproterone acetate (CPA) induce growth of rat liver by hypertrophy and hyperplasia. After withdrawal of the growth stimuli, liver hypertrophy was usually found to be readily reversible. Conflicting observations were made concerning the fate of liver hyperplasia: hepatic hyperplasia persisted when induced by -HCH but was found to be partially reversible when induced by CPA. The present study confirms the reversibility of hepatic hyperplasia induced by CPA in rats: about 30% of liver DNA present at maximal liver enlargement disappeared within 6 days after cessation of CPA treatment. Simultaneously, a dramatic increase in the rate of cell elimination by apoptosis was found. Glutamate-pyruvate transaminase and alkaline phosphatase in serum did not show major increases, suggesting that cell death was not due to lytic membrane damage. Furthermore, if treatment with CPA was continued or resumed, the enhanced DNA content persisted and the number of apoptotic bodies was greatly reduced. These observations suggest that the occurrence of cell death is due to withdrawal of the growth stimulus CPA. It may reflect a regulatory phenomenon serving to maintain homeostasis of cell number.Further studies showed that CPA is rapidly eliminated from rat liver and serum: t 1/2 in the liver is about 11 h. In contrast, -HCH was previously found to be eliminated more slowly: t 1/2 approximately 144 h. The present study revealed that -HCH, CPA and nafenopin lower the number of apoptotic bodies. This suggests that inducers of liver growth can inhibit hepatocellular death by apoptosis. It is concluded that the regression of hyperplasia after CPA withdrawal may be due to its rapid elimination. On the other hand the relatively long persistence of -HCH may result in inhibition of cell death and thereby stabilize hepatic hyperplasia.Abbreviations CPA cyproterone acetate - -HCH -hexachlorocyclohexane - PB phenobarbital - NAF nafenopin - AB apoptotic body - b.w. body weight - p. admin. post-administration - GPT glutamate-pyruvate transaminase - ALP alkaline phosphatase Dedicated to Professor W. Koransky on the occasion of his 65th birthday     

Determination of free fractions of tricyclic antidepressants

Summary The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment.The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible.Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to ₁-acid glycoprotein and for total binding in serum. For ₁-acid glycoprotein, the k-values ranged from 1·10⁵ to 8·10⁵ M^–1, and for pooled serum from 0.4·10⁵ to 8·10⁵ M^–1. The determined number of binding sites on the ₁-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2–14 times the concentration of ₁-acid glycoprotein.     

Perioperative Cefamandolprophylaxe bei aortocoronaren Bypass-Operationen Serumkonzentrationsverlauf während der extrakorporalen Zirkulation

Zusammenfassung Eine perioperative antibiotische Kurzprophylaxe mit 2 g Cefamandol intravenös bei Narkoseeinleitung wurde bei 12 Patienten während coronarchirurgischer Eingriffe unter Verwendung der Herz-Lungen-Maschine durchgeführt. Bei Beginn der extrakorporalen Zirkulation (= EKZ) kam es infolge Hämodilution zu einem Absinken der Serumkonzentrationen von 110,96 ± 40,29 mcg/ml auf 70,89 ± 34,65 g/ml innerhalb von 10 min. Im weiteren Verlauf der EKZ war der Abfall der Serumspiegel gleich schnell wie davor und danach. Nach 240 min fanden sich noch Serumspiegel von 16,80 ± 9,32 g/ml. Als Ursache für das Versagen einer antibiotischen Prophylaxe kommt bei einer Operationsdauer von mehr als 4 h das Absinken der Serumspiegel unter die minimale Hemmkonzentration der entsprechenden Keime in Frage.

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Perioperative cefamandole prophylaxis in aortocoronary bypass operations: Course of serum concentration during extracorporeal circulation

Summary Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 ± 40.29 mcg/ml to 70.89 ± 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 ± 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.

     

气相色谱-串联质谱法测定血清中的16种多环芳烃

目的 建立血清中16种多环芳烃的气相色谱-串联质谱测定方法。方法 血清样经甲醇沉淀蛋白,加入正己烷与二氯甲烷混合溶剂萃取,萃取物氮吹至近干后,正己烷和二氯甲烷混合溶剂复溶,取1 μl上清液进样分析。16种待测多环芳烃经DB-5色谱柱(30 m×0.25 mm,0.25 μm)分离,多反应监测模式监测,内标法定量。结果 本法在1.0 μg/L～2.0×10² μg/L范围内线性良好,方法检出限为4.20×10^-2 μg/L～0.27 μg/L,加标回收率为79.7%～108.0%,精密度为2.57%～6.76%。结论 本方法具有灵敏、快速、回收率和重复性好等优点,满足人血清中多种多环芳烃测定的要求。     

腺样体肥大患儿血清炎症介质和淋巴细胞亚群表达特征及与患儿预后的相关性

目的研究腺样体肥大患儿血清炎症介质、淋巴细胞亚群表达特征及其与患儿预后的相关性。方法选取浙江中医药大学附属第三医院收治的86例腺样体肥大患儿(观察组)和86例健康儿童(对照组)作为研究对象,采集血液标本测定血清炎症介质及淋巴细胞亚群相关指标,对比两组儿童的测定结果。分析腺样体肥大患儿的肥大程度、腺样体再增生情况,对比不同肥大程度患儿的血清指标,并分析各指标与患儿病情程度及预后(腺样体再增生)的关系。结果观察组患儿肿瘤坏死因子-α(TNF-α)、可溶性白细胞介素-2受体(sIL-2R)及白细胞介素-6(IL-6)水平分别为(492.44±50.56)mg/L、(420.48±61.79)U/ml及(33.65±4.51)pg/ml,对照组儿童分别为(301.22±41.65)mg/L、(236.55±57.90)U/ml及(16.25±3.27)pg/ml,差异均有统计学意义(t=16.004,P<0.05;t=20.311,P<0.05;t=8.995,P<0.05)。观察组CD4⁺、CD8⁺及CD4⁺/CD8⁺水平分别为(35.75±7.05)、(16.22±2.69)及(1.46±0.67),对照组分别为(34.25±4.53)、(17.62±2.35)及(1.40±0.62),差异均无统计学意义(t=1.036,P>0.05;t=0.905,P>0.05;t=0.823,P>0.05)。相比腺样体中度肥大患儿,重度肥大患儿的TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平明显更高(P<0.05)。相比未增生患儿,腺样体再增生患儿的TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平明显更高(P<0.05)。相关分析显示,患儿腺样体肥大程度与TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平均呈正相关(P<0.05)。患儿腺体再增生与TNF-α、sIL-2R、IL-6、CD4⁺及CD4⁺/CD8⁺水平也呈正相关(P<0.05)。结论腺样体肥大患儿的血清炎症介质及部分T淋巴细胞亚群表达显著升高,其与腺样体肥大程度、患儿预后密切相关。     

超高效液相色谱-串联质谱法同时快速检测微量血清中6种脂溶性维生素

目的 建立超高效液相色谱-串联质谱法（UPLC-MS/MS）同时快速检测微量血清中维生素A、维生素D（25-OH-VD2 、25-OH-VD3 ）、维生素E（α-、β-和γ-生育酚）的方法。方法 血清中脂溶性维生素经甲醇-乙腈（50:50, v/v)沉淀蛋白、正己烷萃取,以Phenomenex Kinetex F5色谱柱为分离柱,2.5 mmol/L甲酸铵-0.1%甲酸水溶液和甲醇为流动相,梯度洗脱,电喷雾电离（ESI+ ）、多反应监测（MRM）模式下检测,同位素内标法定量。结果 血清中6种脂溶性维生素线性范围内线性关系良好,相关系数 r >0.995;6种脂溶性维生素的检测限为0.20~1.25 ng/ml,定量限为0.39~3.88 ng/ml;加标回收率为86.6%~107.7%,日内精密度<9.6%,日间精密度<9.3%。NIST标准参照品SRM 968f验证方法准确度,结果偏差均在5%以内。结论 本方法准确度高、重现性好、用血量少,适于婴幼儿等采血困难者微量血样中多种脂溶性维生素的同时快速检测。