Homozygosity for the transthyretin-Met30-gene in seven individuals with familial amyloidosis with polyneuropathy detected by restriction enzyme analysis of amplified genomic DNA sequences

Familial amyloidotic polyneuropathy (FAP) with a mutation in position 30 of transthyretin (TTR) (previously called prealbumin) is an autosomal dominant inherited disorder characterized by varying degrees of peripheral neuropathy, nephropathy, gastrointestinal problems, and vitreous amyloid. We have earlier diagnosed homozygosity for the TTR-Met30-gene using Southern analysis in four Swedish individuals. We have found it possible to detect homozygosity for the Met-30 mutation by amplifying discrete regions of the TTR-gene using polymerase chain reaction (PCR), and the amplification products restricted with NsiI analysed by gel electrophoresis. Clinical data on seven homozygous individuals, including three new cases, are presented.     

甘草甜素和甘草酸单铵促进IL-2增强NK活性的研究

本实验采用乳酸脱氢酶释放法研究甘草甜素和甘草酸单铵对人外周血NK细胞活性的影响。结果表明,甘草甜素和甘草酸单铵本身无增强NK细胞活性的作用,但可明显促进IL-2增强NK活性,这种增强作用与甘草甜素和甘草酸单铵的浓度有关。     

Axial tissue diffusion can account for the disparity between current models of hepatic elimination for lipophilic drugs

An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances.This study was supported by the National Health and Medical Research Council of Australia.     

A Series of Serological Tests for the Detection of Antigens and Specific Antibodies in Deep-Seated Candidosis: Experimental Aspects/Eine Gruppe von Antigen- und Antikörpertests zur Serodiagnose von tieflokalisierten Candida-Mykosen: Experimentelle Aspekte

Summary: We describe a series of six serological tests for the diagnosis of deep-seated candidosis. The array comprises two commercial tests (antigen test, Ramco Inc., and antibody test, Roche), as well as four enzyme immunoassays which have been developed in this laboratory: an antigen test for detection of Candida-proteinase, the corresponding assays for monitoring of anti-proteinase antibodies, and two assays for monitoring of IgG and IgM against heterogenous metabolic antigens of C. albicans. The highly sensitive and specific proteinase antigen-test tolerates samples with high concentration of serum proteins. Proteinase antigen was detected in 10 out of 11 normal mice after intravenous infection with C. albicans blastospores. The proteinase antigen peaked between the second and fourth day after infection. A rise in corresponding antibodies was observed in all animals. No proteinase antigen was detected in sera of healthy human individuals; anti-proteinase antibody titers in these sera amounted up to 1:8000. In related ELISAs, using metabolic fungal antigens, titer values of specific IgG and IgM amounted to 5120 and 1280, respectively. The six tests were carried out in an comparative study under diagnostic conditions, the results of which are the subject of a forthcoming communication. Zusammenfassung: Ein Satz von sechs serologischen Tests für die Diagnostik der tiefen Candida-Mykosen wird vorgestellt. Die Gruppe schließt zwei kommerziell vertriebene Testbestecke ein (Latex-Agglutinationstest zum Antigennachweis, Ramco Inc., und Hämagglutinationstest zum Antikörpernachweis, Roche). Vier weitere Enzymimmuntests wurden von uns entwickelt: Ein Antigentest zum Nachweis von sekretorischer Candida-Protease, ein entsprechender Test zum Nachweis von Antikörpem gegen Candida-Protease, und zwei Assays zum Nachweis von IgG-bzw. IgM-Antikörpem gegen heterogene metabolische Antigene von C. albicans. Der empfindliche spezifische Protease-Antigentest toleriert hohe Konzentrationen unspezifischer Serumproteine und kann deshalb auf Serumproben in geringer Verdünnung (z. B. 1:20) angewandt werden. Protease-Antigen war in 200 fach verdünnten Seren von 10 aus 11 intravenös infizierten NWNI-Mäusen nachweisbar. Die höchste Antigen-Konzentration trat zwischen dem 2. und 4. Tag nach Infektion auf; die Serum-Halbwertszeit von gereinigter Protease in der Maus betrug etwa 60 nun. Ein Anstieg korrespondierender Antikörper war in alien infizierten Tieren zu beobachten. Auch im Serum gesunder Probanden waren Antiprotease-Antikörper bis zu einem Titer von 1:8000 nachweisbar; der Protease-Antigentest fiel hingegen immer negativ aus. Die Titer von Antikörpern gegen metabolische Candida-Antigene erreichten in derselben Gruppe von Seren Werte von 1:5120 bzw. 1:1280. Die sechs Tests wurden unter diagnostischen Bedingungen verglichen; Ergebnisse dieser Studie sind Gegenstand einer weiteren Mitteilung.     

A 3-month double-blind cross-over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure.

The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post-infarction (6-24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double-blind cross-over design with 3-month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure.     

肝病患者血清中总胆汁酸测定的意义

采用全自动酶法分析法 ,测定 32 1例各种肝病患者血清总胆汁酸 (TBA)。结果表明 :血清总胆汁酸是一种较灵敏的肝功能指标。在各类肝病中 ,尤其是急性肝炎、肝硬化、肝癌患者的总胆汁酸 (TBA)浓度均明显高于正常对照组 (P<0 .0 1) ,并在肝功能常规指标改变不明显时对肝脏疾病的诊断有一定的价值     

ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE

1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin-(1–9) to bradykinin-(1–7) and bradykinin-(1–7) to bradykinin-(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors. 2. ACE inhibitors increase vascular levels of both bradykinin-(1–9) and its ACE cleavage product bradykinin-(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non-ACE kininase which cleaves both kinin peptides; this non-ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues. 3. In support of this proposal, ACE inhibitors potentiate bradykinin-(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE-resistant kinin analogues, which may be susceptible to metabolism by a non-ACE kininase. 4. Identification and characterization of the putative non-ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue-specific modulation of kinin levels.     

Quality of life on enalapril after acute myocardial infarction

Quality of life was assessed 4–6 months after an acutemyocardial infarction in a randomized double-blind study ofenalapril versus placebo. Quality of life was evaluated usingthe Nottingham Health Profile (NHP), the Physical Symptoms DistressIndex (PSDI), the Work Performance Scale (WPS) and the LifeSatisfaction Index (LSI). The study comprised 36 women (aged46–85 years, mean 68) and 96 males (aged 39–81 years,mean 62). Quality of life did not differ significantly between patientstreated with enalapril versus placebo. The scores were (enalaprilvs placebo, mean± SE): average NHP 15.4 ± 2.3vs 17.1 ± 2.3; PSDI 9.5± 1.0 vs 10.8 ±0.9; WPS 19.8 ± 2.0 vs 19.4 ± 1.4; LSI 24.1 ±1.0 vs 22.5 ±1.4. Men reported a better quality of lifethan women on most assessments, and non-smokers and ex-smokersbetter than smokers. Patients with moderate or severe anginapectoris had a worse quality of life measured by PSDI and NHPthan patients with minimal or no angina pectoris. Patients withcongestive heart failure had a higher PSDI than those without(13.6 ± 1.7 vs 9.4 ± 0.7, P<0.05), while nosignificant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril andplacebo- treated patients after an acute myocardial infarction.However, it was reduced in patients with angina pectoris orheart failure and in those who continued smoking.     

罗比卡因与布比卡因硬膜外麻醉剖宫产术时心电图及心肌酶的变化

目的　比较硬膜外麻醉剖宫产术时罗比卡因和布比卡因对心电图及心肌酶的影响。方法　择期剖宫产手术病人 30例 ,硬膜外麻醉时Ⅰ组 (15例 )用 0 5 %罗比卡因 ,Ⅱ组 (15例 )用0 5 %布比卡因。观察麻醉手术期间心电图P R、QRS波间期以及肌酸磷酸激酶 (CK)和同工酶 (CK MB)的变化 ,同时观察麻醉镇痛、肌松效果和不良反应。结果　两组病人P R、QRS波间期均在正常范围内 (P >0 0 5 )。两组病人CK术后 2 4h值明显高于术前 (P <0 0 5 ) ,但反映心肌受损特异性较高的CK MB则无明显变化 (P >0 0 5 ) ,两组间亦无差异 (P >0 0 5 )。麻醉效果及不良反应两组间无差异。结论　硬膜外麻醉时罗比卡因与布比卡因对心电图及心肌酶影响无明显差异