The application of molecular biology to the prenatal diagnosis of renal disease

The rapid development of new techniques in molecular biology is leading to identification of the genes responsible for a wide variety of diseases. Several renal conditions are caused by gene defects and are amenable to this approach. The process of gene mapping is discussed and the current position regarding prenatal diagnosis and carrier testing for genetic renal disease is reviewed.     

The significance of simultaneous estimation of serum creatine kinase and myoglobin in neuromuscular diseases

Summary Serum creatine kinase (CK) and myoglobin (Mb) levels were measured in patients with different neuromuscular diseases, carriers of X-linked Duchenne-type muscular dystrophy and normal volunteers. The highest levels were found in Duchenne dystrophy and both values decreased in parallel with age. In patients suffering from limb-girdle dystrophy the increases in CK activity and Mb concentration were also pronounced. However, there were families with normal and others with elevated CK and Mb levels in facioscapulohumeral dystrophy. In neurogenic atrophies both CK and Mb levels generally increased only slightly. Serum Mb and CK levels have similar values as indicators of muscle damage in primary and secondary skeletal muscle disorders. The serum Mb level helps in the detection of carriers but is not more sensitive than CK measurement.     

Quantitative electromyography in the detection of the carriers in duchenne type muscular dystrophy

Summary The quantitative EMG technique was used to detect Duchenne muscular dystrophy carriers. The tests were carried out, measuring the parameters of M.U. potentials (the duration, the phase, and the Ø index according to Van den Bosch, modified by Gardner-Medwin), and using the Willison analyzer, in a group of carriers and normal subjects. Ten M.U. potentials from the deltoid, biceps brachii and quadriceps muscles were photographed and measured in each subject, and the right and the left biceps were examined with the Willison analyzer. An high detection rate was obtained by manual EMG, measuring traditional values such as mean number of phases, A.P. duration and Ø index. The Willison analyzer was significant in 2 known carriers. The total EMG detection rate was higher than the CPK tests both in the known carriers and in the possible carriers. It is concluded that the quantitative EMG technique is an useful and specific test to detect carriers of the gene of Duchenne muscular dystrophy.

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Zusammenfassung Die quantitative EMG-Technik wurde zur Erfassung von Konduktorinnen der Duchenneschen Muskeldystrophie angewendet. Bei einer Gruppe von Konduktorinnen und von Normalpersonen wurden sowohl die Parameter der motorischen Einheiten gemessen (Dauer, Anzahl Phasen, Ø Index nach Van den Bosch, modifiziert nach Gardner-Medwin) als auch unter Anwendung des Willison-Analysators. Es wurden 10 Potentiale motorischer Einheiten aus dem Deltoides, dem Biceps brachii und dem Quadriceps bei jeder Versuchsperson fotografiert und ausgemessen und sowohl der rechte wie der linke Biceps wurden mit dem Willison-Analysator untersucht. Eine hohe Erfassungsrate wurde bei Anwendung der manuellen EMG-Techniken mit Messung der konventionellen Werte erreicht. Bei 2 Konduktorinnen war der Willison-Analysator entscheidend. Gesamthaft war der Prozentsatz der positiven EMG-Befunde höher als derjenige der Kreatinphosphokinasebestimmungen, sowohl bei den sicheren Konduktorinnen als bei den möglichen Konduktorinnen. Es wird gefolgert, daß die quantitative EMG-Technik ein nützliches Instrument zum Nachweis der Konduktorinnen einer Duchenneschen Muskeldystrophie darstellt.

     

Air classifier technology (ACT) in dry powder inhalation Part 4. Performance of air classifier technology in the Novolizer multi-dose dry powder inhaler

In this study, the in vitro fine particle deposition from a multi dose dry powder inhaler (Novolizer) with air classifier technology has been investigated. It is shown that different target values for the fine particle fraction (fpf<5 microm) of the same drug can be achieved in a well-controlled way. This is particularly relevant to the application of generic formulations in the inhaler. The well-controlled and predictable fpf is achieved through dispersion of different types of formulations in exactly the same classifier concept. On the other hand, it is shown that air classifier-based inhalers are less sensitive to the carrier surface and bulk properties than competitive inhalers like the Diskus. For 10 randomly selected lactose carriers for inhalation from four different suppliers, the budesonide fpf (at 4 kPa) from the Novolizer varied between 30 and 46% (of the measured dose; R.S.D.=14.2%), whereas the extremes in fpf from the Diskus dpi were 7 and 44% (R.S.D.=56.2%) for the same formulations. The fpf from a classifier-based inhaler appears to be less dependent of the amount of lactose (carrier) fines (<15 microm) in the mixture too. Classifier-based inhalers perform best with coarse carriers that have relatively wide size distributions (e.g. 50-350 microm) and surface discontinuities inside which drug particles can find shelter from press-on forces during mixing. Coarse carrier fractions have good flow properties, which increases the dose measuring accuracy and reproducibility. The fpf from the Novolizer increases with increasing pressure drop across the device. On theoretical grounds, it can be argued that this yields a more reproducible therapy, because it compensates for a shift in deposition to larger airways when the flow rate is increased. Support for this reasoning based on lung deposition modelling studies has been found in a scintigraphic study with the Novolizer. Finally, it is shown that this inhaler produces a finer aerosol than competitor devices, within the fpf<5 microm, subfractions of particles (e.g. <1, 1-2, 2-3, 3-4 and 4-5 microm) are higher.     

Quantitative EMG and histological carrier detection of duchenne muscular dystrophy

Summary Seventy-nine women known as, or suspected to be, carriers of the Duchenne type of muscular dystrophy were examined. The 15 known carriers had an estimation of the CPK serum level and a manual quantitative EMG, which gave the high detection rate of 93%. The 64 suspected carriers had CPK determination and quantitative EMG, or CPK and muscle biopsy, and the value of each technic is discussed. The problem of giving a reassuring answer to women considered to be possible carriers on genetic criteria, but who are not really carriers, is solved if the results of all three tests are negative.

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Zusammenfassung 13 sichere und 56 mögliche Konduktorinnen einer Duchenne'schen Muskeldystrophie wurden untersucht. Bei sicheren Konduktorinnen wurde mittels CPK-Bestimmung im Serum und manueller quantitativer EMG-Technik eine positive Nachweisrate von 93% erreicht. Bei 64 möglichen Konduktorinnen wurde entweder durch CPK-Bestimmung und quantitative EMG-Untersuchung oder durch CPK-Bestimmung und Muskelbiopsie untersucht. Es wird der Wert der einzelnen Untersuchungstechniken besprochen. Es wird auf die Notwendigkeit hingewiesen, die möglichen Konduktorinnen, die jedoch mittels der durchgeführten Untersuchungen nicht als solche gesichert werden konnten, richtig zu orientieren.

     

An algorithm based on one or two nasal samples is accurate to identify persistent nasal carriers of Staphylococcus aureus

Persistent Staphylococcus aureus nasal carriers are at high risk of S. aureus infection. The present study delineates a simple strategy aimed at identifying rapidly and accurately this subset of subjects for clinical or epidemiological purposes. Ninety healthy volunteers were each identified as persistent, intermittent or non-nasal carriers of S. aureus by using seven specimens sampled over a 5-week period. By reference to this so-called reference standard, six other strategies aimed at simplifying and speeding the identification of persistent carriers and based on the qualitative or quantitative detection of S. aureus in one to three nasal samples were evaluated by the measure of the area under the curve of receiver operating characteristic diagrams. Among strategies using qualitative results, there was no statistical difference between protocols using seven and three samples. A threshold of 10³ CFU of S. aureus per swab was found capable of defining persistent nasal carriage with a sensitivity of 83.1% and a specificity of 95.6%. These figures reached 95.5% and 94.9%, respectively, by using an algorithm including one or two nasal specimens according to the threshold of 10³ CFU of S. aureus in the first swab. The latter two strategies were shown to be costly equivalents. The proposed algorithm-based strategy proved to be relevant to identify properly and consistently persistent nasal carriers of S. aureus. However, as it was built from data of healthy volunteers, it needs to be confirmed prospectively on patients potentially at risk for S. aureus infection.     

荧光光度法研究不同药物载体制成5-FU纳米粒的靶向性

目的：研究抗癌药物五氟尿嘧啶用不同的药物载体制成的纳米粒在小鼠体内的靶向性分布。方法：应用荧光分光光度法测定包裹钙黄绿素的纳米粒的钙黄绿素量,选择激发波长和发射波长分别为365nm,513nm,测定小鼠组织中的钙黄绿素荧光强度。结果：线性回归方程为：C=0．4935I＋0．9879（R^2=0．9998）,浓度在1×10^-7mol／L-1×10^-6mol／L范围内线性良好。结论：抗癌药物的靶向载体叶酸偶联白蛋白靶向性优于白蛋白。     

Influenza A virus derived from persistently virus-infected cells shows attenuated cytotoxicity in cultured cells but virulent pathogenicity in mice

The IVpi-43 strain of influenza A virus, a progeny virus derived from persistently virus-infected Madin-Darby canine kidney (MDCK) cells, showed a more attenuated nature in cytopathology in cultured cells than the parental wild-type influenza virus (IVwt) that was used for establishment of the virus carrier culture. Upon infection of MDCK cells, growth of the IVpi-43 virus was restrained with an impaired synthesis of virus structural proteins in the cells. Apoptosis induced by IVpi-43 virus was confined at a low level. The IVpi-43 virus was able to easily cause persistent infection in fresh MDCK cells. In contrast to the in vitro phenotype, the IVpi-43 virus proved highly virulent in mice, with massive and broadly disseminated virus multiplication in the lungs. It was suggested that impaired activity of the neuraminidase molecule of the IVpi-43 virus was responsible for the delayed and faint appearance of apoptosis in the IVpi-43 virus-infected respiratory cells, which made it possible for the virus to replicate for a longer period and to spread to a broader area of the lungs and that abundant numbers of the virus-infected lung cells were killed within a short period by the subsequently established virus-specific immune responses, leading to unrecoverable serious pneumonia.     

Clinical Characteristics of Patients in Their 40s With HCV Antibody-Positive Hepatocellular Carcinoma

Background: We investigated the clinical characteristics of hepatitis C virus (HCV) antibody-positive hepatocellular carcinoma (HCC) patients who developed HCC at a relatively young age. Methods: Clinical characteristics of patients in their 40s were investigated and were compared with those of patients 50 years and older. The subjects were 648 HCC patients, 469 men (72%) and 179 women (28%), who were treated at our hospital between 1991 and 1997. Results: No patient was under 40 years of age. Eighteen patients (3%) were in their 40s, 137 patients (21%) were in their 50s, 338 patients (52%) were in their 60s, 143 patients (22%) were in their 70s, and 12 patients (2%) were in their 80s. Fifteen of the patients (83%) in their 40s were male. The proportion of men in their 40s was higher than that of all men. Eight of the 15 men in their 40s (53%) were heavy drinkers, and 2 (14%) were habitual drinkers. Three of the 15 men (20%) were HBV carriers, and these 3 HBV carriers were not drinkers. The proportion of heavy drinkers and HBV carriers was significantly higher among the patients in their 40s than in the 60 patients randomly sampled from the patients 50 years of age and older. The mean ages of male patients with HCC who were heavy drinkers, habitual drinkers, occasional drinkers, or nondrinkers were 52.3, 58.9, 62.0, and 61.7 years, respectively. HCC occurred significantly earlier in heavy drinkers than in the other 3 groups. We compared laboratory data of the patients in their 40s with data of all of the patients of 50 years and older. Serum total bilirubin, prothrombin time, and platelet counts were significantly worse in the patients in their 40s. Conclusions: Logistic regression analysis revealed that heavy drinking and presence of HBV infection were independently related to HCV antibody-positive HCC development at a younger age.     

肺炎链球菌耐药性和血清型分布及隐匿性耐药克隆株的研究

目的 了解儿童肺炎链球菌携带者耐药菌株的流行情况,比较携带者菌株血清型与肺炎链球菌结合疫苗血清型的符合率,寻找单个患儿同时携带第三和耐药菌株的可能性。方法 （１）对１９９７年１１月～１２月在北京儿童医院普通门诊登记的３个月～５岁儿童进行问卷调查;（２）采集鼻咽拭子和尿标本,培养、分离和鉴定肺炎链球菌,并测定尿标本中的抗生素活性;（３）根据ＮＣＣＬＳ方法使用微量稀释法测定肺炎链球菌对青霉素、头孢呋新