Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.     

Evaluation ofin vitro drug screening leads using experimental models of human ovarian cancer

Summary Five compounds which were identified as potential new anticancer drugs inin vitro screening with the human tumor colony forming assay were selected for further evaluation usingin vitro andin vivo models of human ovarian cancer. Three of five compounds were found to inhibitin vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing.     

Radioiodinated tracers for the evaluation of dopamine receptors in the neonatal rat brain after hypoxic-ischemic injury

In order to evaluate in vivo single-photon emission tomography (SPET) method of assessing cerebral function after hypoxic-ischemic injury in human neonates, we studied D₁ and D₂ dopamine receptors in a rat model. Seven-day-old rats underwent permanent unilateral common carotid ligation followed by exposure to 8% O₂. Two weeks later, in brains with no visible loss of hemispheric volume, striatal dopaminergic receptors were studied, with [¹²⁵I]TISCH and [1251]IBZM for the D₁ and D₂ dopamine receptors, respectively. Using [¹²⁵I]TISCH, we observed no modifications of D₁ receptors, but in contrast, ex vivo and in vitro autoradiographic experiments showed a 40% decrease in the striatal binding of [¹²⁵I]IBZM on both the ipsilateral and the contralateral side to the carotid ligation. These alterations were detected with IBZM, a D₂ dopamine receptor ligand usable for SPET imaging. Therefore, exploration of D₂ receptors by SPET in human neonates suffering from perinatal hypoxia-ischemia may be valuable for the diagnosis and follow-up of cerebral function damages. Correspondence to: D. Guilloteau     

Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Summary: Some of the properties of 4–bromobenzalde-hyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of γ-aminobu-tyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 μM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABA_A receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.     

Rhizomelic Bone Dysplasia with Club-like Femora (Case report and confirmation of a syndrome)

A newborn with rhizomelic bone dysplasia with club-like femora is reported. This is the fourth case Of this easily recognizable, recently reported, congenital bone disease. Maroteaux et al recently reported two patients with rhizomelic bone dysplasia and club-like femora as a distinctive new bone dysplasia. Their observation was confirmed by Gugliantini et al (2) who reported another case. This paper reports a fourth patient with this easily recognisable disorder.     

Prevalence of juvenile periodontitis in a circumpubertal population

A cross-sectional radiographic screening was performed on bite-wing pairs (BW) from 1872 10-12 year old schoolchildren in the Greater Worcester, Massachusetts area to assess the prevalence of juvenile periodontitis (JP). The 3-stage screening process entailed: (1) visual identification of possible cases based upon a visual assessment of BW for interproximal crestal bone levels greater than or equal to 2 mm from the cemento-enamel junction (CEJ) on greater than or equal to 1 permanent first molar; (2) identification of probable cases based upon BW from possible cases measured with a transparent ruler calibrated in millimeters; (3) finally, clinical confirmation of JP in consenting probable cases. A total of 1038 subjects were eligible to be included in the study (greater than or equal to 3 mesial sites readable). Of the 1038 eligible subjects, 117 possible and 103 probable cases were identified in stage 1 and stage 2, respectively. A total of 99 probable cases could be contacted and 43 were examined clinically. Two cases of JP were confirmed clinically in stage 3, yielding a prevalence rate of 4.6/1000. Specifically, this report defines a rate of JP in 10-12 year-old schoolchildren for the first time. In addition, these results indicate that BW can be used to identify children with JP from large data sets. However, further studies including complete clinical and radiographic examinations are necessary to determine whether this method is adequate for large epidemiologic studies.     

新生大鼠反复惊厥对NMDA受体表达的长期影响

目的：研究反复惊厥对大鼠脑内N-甲基-D-天门冬氨酸(NMDA)受体表达，以及成年期认知功能和惊厥阈的长期影响。方法：生后6d(用P6表示，下同)的Wistar大鼠随机分成两组，每组6只，惊厥组每日吸入三氟乙醚诱导惊厥发作1次，每次持续30min，连续6d；对照组同样操作但不吸入三氟乙醚。两组大鼠于P60-P65行Morris水迷宫实验，检测大鼠的学习记忆功能。于P75时给予大鼠腹腔注射戊四唑(PTZ)测定大鼠的惊厥阈。随即断头处死大鼠，分离大脑皮质和海马，匀浆提取细胞膜蛋白，应用免疫印记法测定NMDA受体亚基l(NRl)和NR2A-2D表达的变化。结果：从P6l至P65，两组大鼠寻找平台时间均逐渐缩短，惊厥组大鼠在P65的平均寻找平台时间较对照组显著延长。惊厥组大鼠注射PTZ后发生惊厥的潜伏期与对照组比较差异无显著性。在大脑皮层，惊厥组大鼠较对照组NRl和NR2B表达水平明显下调，在海马这两种亚基表达水平无明显改变，在大脑皮层和海马区，惊厥组较对照组NR2A表达水平明显下调，NR2C表达水平明显上调。两组在皮层和海马均无NR2D表达。结论；新生大鼠反复惊厥可导致远期认知障碍，同时伴有NMDA受体的数量和结构上的长期改变，NMDA受体表达的这种改变可能在发育期惊厥导致的脑长期认知功能损害中起重要作用。     

Simple screening test for risk of falls in the elderly

Background:   The aim of this study is to construct a simple screening test for the risk of falls in community-dwelling elder persons.
Methods:   A total of 1378 community-dwelling people aged 65 years and older in five different communities in Japan were asked to answer a self rated questionnaire including 22 items covering physical, cognitive, emotional and social aspects of functioning and environmental factors. At a six-month follow-up, the outcome of fall occurrence and the number of falls was ascertained by social workers, health visitors or nurses.
Results:   Five out of 22 items were selected using a logistic regression model. Using this five-item version, a screening test was constructed, and at the best cut-off point, the sensitivity and specificity were 68% and 70%, respectively. The validity of this scale was tested on persons with cognitive dysfunction.
Conclusion:   The simplicity and the predictive validity of the screening test support the use of this test in health check ups or general outpatient facilities.     

Routinely collected general practice data aids identification of people with hyperglycaemia and metabolic syndrome.

AIMS: To assess the performance of a risk score comprising data routinely available in general practice records (age, gender, body mass index, family history of diabetes, smoking habits and prescribed anti-hypertensive drugs or steroids) in detecting diabetes, impaired glucose tolerance and metabolic syndrome. METHODS: In a population-based, cross-sectional study in a semi-rural general practice in Jutland, Denmark, Cambridge Risk Scores were calculated for 1355 patients without known diabetes (69% response rate) who completed questionnaires and underwent anthropometric measurement and an oral glucose tolerance test. RESULTS: Prevalences of diabetes, impaired glucose tolerance and metabolic syndrome were 2.29% (95% CI: 1.56-3.23), 6.64% (95% CI: 5.38-8.10) and 13.4% (95% CI: 11.5-15.2), respectively. Area under the ROC curve for the risk score and diabetes was 83.8% (75.9-91.7) and for metabolic syndrome [European Group for the Study of Insulin Resistance (EGIR)] was 78.1% (74.6-81.6). Twenty per cent of the population had a risk score above 0.246; at this threshold the sensitivity to detect diabetes was 71.0% (53.4-83.9), the specificity 81.2% (79.0-83.2), positive predictive value 8.1% (6.6-10.0) and likelihood ratio 3.77 (2.94-4.85). For metabolic syndrome (EGIR) corresponding values for sensitivity were 50.3% (43.1-57.5), specificity 84.7% (82.5-85.6), positive predictive value 33.6% (28.2-39.4), and likelihood ratio 3.28 (2.69-4.00). CONCLUSIONS: Undiagnosed hyperglycaemia and metabolic syndrome are common. The Cambridge Risk Score is a practical first step in a screening procedure to identify individuals with these disorders who might benefit from diagnostic testing or to direct preventive interventions.     

噬菌体抗体库固相筛选条件的初步研究

目的:探讨噬菌体抗体库的固相筛选条件,为筛选方案的设计提供实验依据。方法:利用多种针对HEVNE2蛋白的特异性噬菌体人源抗体和非特异性噬菌体人源抗体,对噬菌体抗体与抗原的结合时间、抗原包被的浓度、洗涤强度和洗脱方式等多种筛选的条件进行初步探索。结果:阳性噬菌体抗体与抗原反应1min,就可较好结合,洗涤次数为20～30次、洗涤液的pH为5时,筛选得到的阳性率最高。包被抗原的浓度对筛选的阳性率没有明显影响,用10mg/L抗原竞争洗脱60min,可得到较高的阳性率。结论:噬菌体抗体库的筛选是一个非常复杂的过程,其中的各个条件之间有着密切的联系,应该根据具体情况进行调整。