The clock drawing test and questionable dementia: reliability and validity

OBJECTIVES: In order to evaluate the suitability of the clock drawing test (CDT) for the detection of questionable dementia (QD), we assessed the inter-rater reliabilities and intercorrelations of four common scoring methods of the CDT in a sample of non-demented subjects and determined the concurrent validity. METHODS: The study sample consisted of 253 discharged general hospital patients, aged between 65 and 85 years. Subjects were screened for cognitive impairment during their hospital stay. Four to six weeks after discharge each non-demented patient was visited at home and interviewed by a trained psychologist. The interview procedure included a cognitive test battery incorporating the CDT, the Mini-Mental State Examination (MMSE), the Syndrome Short Test (SKT), and a verbal fluency test (VF). The criteria of the Clinical Dementia Rating (CDR) were used to differentiate between cognitively normal subjects and those with QD. Clock drawings were scored independently and blindly by two raters according to four different methods. The agreement between raters was assessed, as well as the agreement between the different scoring methods. The association of gender, education, age, test performance and CDR-rating with CDT scores was examined. Accuracy of the CDT for the detection of QD was calculated. RESULTS: Inter-rater reliabilities were high for all four scoring methods. However, substantial differences among the scoring methods were observed, the proportion of abnormal test results varying between 9% and 50%. The CDT correlated significantly with MMSE, SKT and VF, but correlation coefficients were low (r = 0.13 to r = 0.32). Furthermore, CDT scores were influenced by age, gender, and education. Sensitivity of the CDT for QD was 66%, specificity was 65%; the negative predictive value was 73%, the positive predictive value 58%. CONCLUSION: In a sample of non-demented elderly, the reliability of the CDT was sufficiently high, but the different scoring methods were not equivalent. When established cut-off scores were used, the proportion of abnormal CDTs were significantly different. Concurrent validity with other common cognitive tests was unsatisfactory. The CDT lacks sufficient sensitivity and specificity for the identification of QD and should not be used alone to screen for possible prodromal stages of dementing illnesses. The association of age, gender and level of education with CDT scores should be taken into account by clinicians using the CDT.     

Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events

Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events.     

Evaluation of downstaging in the detection of cervical neoplasia in Kolkata,India

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30-64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia.     

Impact of videotaped information on frequency and confidence of breast self-examination

Background Videotaped education materials to teach breast self-examination (BSE) are used worldwide. However, evaluation of videotaped BSE instructions is lacking. Methods Premenopausal women (mean age 33.4±11.2 years) without history of breast cancer were approached to participate in this experimental study and randomly assigned to a video intervention group (VG; n=130; length of the video=15 min) or non-video comparison group (NVG; n=121). All participants answered a questionnaire on BSE behavior and health beliefs. No additional training was given. The total duration of the session including completion of the questionnaire was 15min for the NVG and 30min for the VG. Three months later, changes in BSE behavior were compared in the two groups. The influence of health beliefs on actual BSE behavior was investigated as well. Results Women of both the VG and NVG performed BSE significantly more frequently at follow-up than at baseline. Analysis of covariance, using the baseline BSE-frequency as co-variate and the follow-up BSE frequency as the dependent variable, revealed that women in the VG (adjusted mean=7.9 times per year, 95%CI=6.5–9.4) performed BSE more frequently than women of the NVG (adjusted mean=6.1 times per year, 95%CI=4.6–7.5) (F=4.2, df=2, p=0.02). Among motivational predictors, having an example of a role model (modeling) was shown by regression analysis to explain the greatest amount of variance (13%) in BSE frequency. Conclusion Use of an educational videotape increased the frequency of BSE among premenopausal women.     

Invasive aspergillosis: results of an 8-year study

We analysed retrospectively 90 cases of invasive aspergillosis (IA) which occurred at the University Hospital and the Thoraxklinik gGmbH Heidelberg between 1991 and 1998. 71 cases were histologically proven, 19 were probable diseases. There were 49 male and 41 female patients, with a mean age of 51.5 years (range 16 days to 80 years). Underlying diseases were: hematological malignancies in 52% (n = 47; 24 with acute leukemia), solid organ transplantation (n = 11; 9 liver, 1 kidney, 1 heart), solid cancer (n = 10), others (n = 21), and in one case no underlying disease was diagnosed. Only 54 cases (60%) were correctly diagnosed as IA during lifetime of the patients. In 59 cases (65%) only the lung was affected, 25 patients suffered from disseminated IA, in 6 patients only extrapulmonary lesions were present. 11 patients underwent lung surgery, 63 patients received antimycotic drugs (44 amphotericin B, 15 fluconazole, 4 itraconazole), 21 were not treated antimycotically. 68 patients (71%) died, from these 30 (36%) due to IA during remission of the underlying disease. The laboratory methods showed the following sensitivities, respectively: microscopy by calcofluor white staining 17%, culture 69%, Aspergillus-PCR from respiratory tract samples and biopsies 95%, galactomannan antigen detection by latex agglutination 28%, by enzyme immunoassay 59%, Aspergillus antibody detection 23%.     

Advanced rhythm discrimination for implantable cardioverter defibrillators using electrogram vector timing and correlation

INTRODUCTION: Discrimination of ventricular and supraventricular arrhythmias remains one of the major challenges for appropriate implantable defibrillator (ICD) therapy delivery. The electrogram vector timing and correlation (VTC) algorithm was developed for such rhythm discrimination. The VTC algorithm differentiates normally conducted supraventricular beats from abnormally conducted ventricular beats by comparing the timing and correlation of rate and shock channel electrograms. METHODS AND RESULTS: Rate and shock channel electrograms of sinus rhythm and induced arrhythmias were collected from 93 patients during ICD placement. The algorithm was developed using data from 50 patients and prospectively tested in a software model with the remaining 43 patients. A sinus rhythm reference was formed by averaging complexes of the shock channel signal aligned by the peak amplitude of the rate channel. Eight features measuring the amplitude and timing of shock channel signal characteristics were extracted from the reference for comparison. When a high-rate rhythm was detected, the VTC algorithm computed the correlation of the arrhythmia complex features with the reference. Rhythms with a sufficient number of uncorrelated beats were classified as ventricular tachycardia (VT). In a dual-chamber implementation, the VTC algorithm is integrated with ventricular and atrial rate comparison (V>A) and stability above an atrial fibrillation rate threshold. The test set consisted of 117 arrhythmias. Dual-chamber sensitivity was 100% (81/81 VT) and specificity was 97% (35/36 supraventricular tachycardia). Single-chamber analysis demonstrated 99% sensitivity and 97% specificity. CONCLUSION: The VTC algorithm demonstrated high sensitivity and specificity in discriminating between ventricular and supraventricular arrhythmias.     

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background The aim of this study was to search for mutations in the humanmutS homolog 2 (hMSH2) and humanmutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). Methods The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. ThehMLH1 gene had a higher mutation detection rate thanhMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in thehMLH1 gene and four in thehMSH2 gene. Conclusions ThehMLH1 gene had a higher mutation detection rate thanhMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.     

双引物聚合酶链反应同时快速检测梅毒螺旋体和单纯疱疹病毒Ⅱ型

目的 建立双引物聚舍酶链反应（PCR）用于同时快速检测梅毒螺旋体和单纯疱疹病毒Ⅱ型。方法 基于单纯疱疹病毒Ⅱ型（HSV-2）的DNA聚合酶基因以及梅毒螺旋体47KD膜蛋白基因序列，自行设计2对特异性寡核苷酸引物，建立了同时检测上速2种痛原体的双引物PCR。结果 各特异性引物仅扩增相应的病原体DNA，即单纯疱疹病毒Ⅱ型扩增产物为202bp以及梅毒螺旋体扩增产物为252bp。其他11种生殖道常见微生物及正常人基因组DNA不被扩增。检测了51例临床标本，梅毒螺旋体暗视野显微镜检查阳性检出率为15．7％，双引物PCR阳性检出率为19．6％；二种方法检测结果间比较差异均无统计学意义（P〉0．05）。HSV阳性培养率23．6％，双引物PCR阳性率47．1％，双引物PCR阳性检出率显著高于HSV培养且差异有统计学意义（P=0．019）；上速临床标本分别进行了2种痛原体的单引物PCR，与双引物PCR对照结果完全一致。结论 我们建立的双引物PCR一次可同时检测2种病原体，且有快速、敏感、特异以及简便的特点。     

高效液相色谱荧光检测法测定人体内血浆中氟伐他汀的浓度

目的:建立一种简便、快速的高效液相色谱(HPLC)荧光检测法测定人体内血浆中氟伐他汀的浓度。方法:采用Kromasil C18柱(4.6mm×150mm,5μm),柱温40℃,流动相为13mmol·L-1澳化四丁基铵-乙腈(51:49,V/V),流速为1.0mL·min-1,荧光检测激发波长305nm,发射波长405nm。结果:氟伐他汀在1-1000μg·L-1范围内线性关系良好(r=0.9994)。日内和日间RSD均低于10％。结论:该方法灵敏度高、快速、简便、无杂质干扰,适合于氟伐他汀的体内分析和人体药动学研究。