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Predictive value of 6-month decline in ADAS-cog for survival without severe Alzheimer's disease.

BACKGROUND/AIMS: To determine the predictive value of the 6-month evolution of the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD) patients on the risk of death or severe dementia (MMSE <10) within 2 years. METHODS: Cognition was assessed every 6 months using the ADAS-cog scale in the Real.fr study, a cohort of AD patients. Six classes of ADAS-cog evolution were distinguished, from the severest deterioration (decline >or=7 points) to the greatest cognitive improvement (gain >or=4 points). RESULTS: Among 536 AD patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with the severest deterioration was significantly associated with the risk of severe dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval, CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at least 4 points were also at greater risk of severe dementia. CONCLUSION: These results confirm the value of the ADAS-cog scale as a judgement criterion in clinical trials since it is a good surrogate marker of long-term prognosis. The proportion of fast decliners on the ADAS-cog could be a helpful judgement criterion for future trials in AD.

Aged↗

[Chronic diarrhea--value of function tests in diagnosis].

The D-xylose-adsorption test yields information about small intestinal absorptive function. To investigate ileal absorptive function the Schilling test is performed. The standard diagnostic test for hypolactasia is the oral lactose tolerance test with lactose breath hydrogen testing. Various radioactive and nonradioactive breath tests have been proposed as noninvasive tests for small intestinal bacterial overgrowth. Intubation tests for pancreatic function testing are time-honored and direct, but limited by several technical difficulties. Measurement of pancreatic enzymes in stool has received a high degree of acceptance.

Breath Tests↗

Correlation between nerve conduction studies and clinical scores in diabetic neuropathy.

Polyneuropathy, a frequent complication of diabetes, can be assessed clinically and electrophysiologically. Neurological examination can be quantified by validated scores, e.g., the neuropathy symptom score (NSS) or the neuropathy disability score (NDS). Such scores exclude electrophysiological aspects of the neuropathy. A software tool was designed to convert electrophysiological data into one single index of polyneuropathy (IPN). This index was calibrated to grade the severity of a polyneuropathy from 0.00 to 1.00. In a series of 38 diabetic patients, we have calculated NSS, NDS, and IPN. We found correlations between these variables, NDS and IPN exhibiting the more significant association. The use of IPN allowed us to demonstrate that nerve conduction values correlated with clinical scores in diabetic polyneuropathy. Such a software tool, by providing a single electrophysiological index, may facilitate clinico-electrophysiological assessment in large descriptive studies or therapeutic trials of diabetic polyneuropathy.

Adolescent↗

Acute cholecystitis. Frequency of stones in the common duct and predictive value of liver function tests.

Two hundred and forty-three patients aged under 75 years with acute calculous cholecystitis treated by early surgery were studied with a view to investigating the frequency of choledocholithiasis and the predictive value of routine liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase). 7% had stones in the common duct, but 33% had hyperbilirubinaemia. In less than 10% of the latter could be hyperbilirubinaemia be attributed to common bile duct stones. It was concluded that the frequency of common bile duct stones in acute cholecystitis was low, and that patients often had signs of impaired liver function which was of no help in diagnosing the presence of stones in the common duct.

Adult↗

In vitro testing of Aspergillus fumigatus clinical isolates for susceptibility to voriconazole, amphotericin B and itraconazole: comparison of sensititre versus NCCLS M38-A using two different inocula.

Voriconazole, amphotericin B and itraconazole were tested in vitro against 18 strains of Aspergillus fumigatus isolated from cystic fibrosis patients. Susceptibility was tested with the broth microdilution method (M38-A protocol-NCCLS). Results of this reference method were compared with those of an experimental commercial microdilution broth method (Sensititre). Two different inocula, prepared from 2- and 7-day cultures, were used. Minimum inhibitory concentrations (MICs) of the reference method ranged from 0.25 to 2 microg/ml for voriconazole, 0.06 to 1 microg/ml for amphotericin B, 0.016 to >16 microg/ml for itraconazole. There were no significant differences in the MIC ranges or MIC90 values obtained with the two testing methods or with the two types of inocula. These findings confirm the good in vitro activity of voriconazole, itraconazole and amphotericin B against A. fumigatus. They also indicate that reliable susceptibility data can be generated more rapidly by commercial systems and use of 2-day cultures for inoculum preparation.

Amphotericin B↗

Should we ignore dimensional risk factors in prevention of schizophrenia? Signposts to prevention.

OBJECTIVE: The objective was to outline the development of the concept of allusive thinking as a genetic marker of predisposition to schizophrenia and relate this to other cognitive markers of this predisposition. METHOD: Publications were reviewed which were considered relevant to the objective. RESULTS: Allusive thinking as detected clinically could be measured objectively from subjects' performance on an Object Sorting Test. Using this test it was shown that parents, both of patients with schizophrenia and of university students with allusive thinking, themselves showed allusive thinking, indicating it was familially transmitted. Subjects with allusive thinking showed reduced cortical evoked brain P300 potentials, suggesting the transmission was genetic. The hypothesis that allusive thinking was associated with weaker cortical inhibitory processes was supported by the finding that subjects with such thinking chose more remote word associations. It was suggested that reasons allusive thinking has not been used as a marker in intervention studies is that as a dimension of abstract thinking, marked allusive thinking is not associated with a high risk of developing schizophrenia, and that administration of the Object Sorting Test is time-consuming. Other dimensional cognitive factors, such as psychoticism and perceptual anhedonia and aberration, are independent of allusive thinking and are also associated with a low risk of developing schizophrenia. Genetic transmission of schizophrenia would appear to involve a number of predisposing factors distributed dimensionally in the population with the contribution of each factor being small. CONCLUSIONS: As they are associated with only a low risk of predisposition to schizophrenia, cognitive markers may not be of immediate value in the prevention of schizophrenia when compared with the less specific markers used for this purpose. However, it would seem that their study will be necessary if the nature of the genetic transmission of the illness is to be understood. This understanding could be expected to ultimately lead to more effective prevention.

Genetic Markers↗

IQ in childhood psychiatric attendees predicts outcome of later schizophrenia at 21 year follow-up.

OBJECTIVE: Preschizophrenic children who merit psychiatric referral are claimed to have a particularly malevolent illness when the psychosis develops later. The 21 years outcome of a sample of such children was investigated. METHOD: Fifty-one children who attended psychiatric services, and were later diagnosed as having schizophrenia, were followed up a mean of 21 years later. Baseline childhood demographic, clinical and putative aetiological characteristics were identified from the case notes. Follow-up assessment evaluated clinical symptoms, social functioning and service utilization. The predictive value of baseline factors on outcome was examined. RESULTS: Outcome was poor, and seven (14%) of the subjects were deceased. Childhood IQ was strongly predictive of social outcome (F=5.1, P=0.01) and service utilization (F=5.2, P=0.01), but not clinical symptoms. No other factors predicted outcome. CONCLUSION: Low childhood IQ had an unfavourable impact on social outcome and service utilization once schizophrenia developed.

Age of Onset↗

Arthrometric evaluation of posterior cruciate ligament injuries.

We reviewed the clinical examinations and knee arthrometry evaluations of 40 patients: 10 with posterior cruciate ligament injuries, 10 with combination anterior and posterior cruciate ligament injuries, 10 with anterior cruciate ligament injuries alone, and 10 with no history of knee injury. Using a 3-mm side-to-side difference as the minimal limit for detection of posterior cruciate ligament injury, the sensitivity of the arthrometer at 40 pounds of posterior force was 90%, the specificity was 100%, the predictive value of a positive test was 100%, and the predictive value of a negative test was 91%. When total anterior-posterior translation was assessed, the sensitivity was 100%, the specificity was 85%, the predictive value of a positive test was 87%, and the predictive value of a negative test was 100%. The overall accuracy of arthrometry for detection of posterior cruciate ligament injury was 96% for 40 pounds of posterior force and 94% for total anterior-posterior translation at 40 pounds. Grade 1 posterior cruciate ligament injuries had significantly greater arthrometric posterior translation compared with grade 0 (normal) knees. Regression analysis showed arthrometric laxity measurements correlated well with the clinical grade of the posterior drawer test. Finally, the accuracy of the arthrometer was not affected by concomitant anterior cruciate ligament injury.

Adolescent↗

Antibiotic susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: comparative (NCCLS criteria) evaluation of antimicrobial drugs with the agar dilution and the agar disk diffusion (Bauer-Kirby) tests.

Ninety-six clinical isolates of Stenotrophomonas maltophilia were examined with the agar dilution method for susceptibility to 19 antimicrobial drugs. Doxycycline, cotrimoxazole, timentin, ofloxacin, fosfomycin, and piperacillin + tazobactam, in that order, inhibited the majority of strains. All isolates were resistant to nitrofurantoin. Concurrent disk susceptibility (Bauer-Kirby method) testing, using currently valid NCCLS interpretative criteria for Pseudomonas aeruginosa, uncovered a significant incidence of very major (category I), major (category II), and minor (categories III and IV) discrepancies for aminoglycosides, cephalosporins, chloramphenicol, and piperacillin + tazobactam and ticarcillin + clavulanic acid. Therefore, new interpretative criteria indicative of intermediate (I) susceptibility of S. maltophilia to these various antibiotics were proposed. In addition, new intermediate susceptibility criteria were proposed for the two beta-lactam-beta-lactamase inhibitor combinations. It was recommended to exclude ciprofloxacin from test batteries against this microorganism due to the wide scatter of minimal inhibitory concentration values and diameters of inhibition zones; the same was true for polymyxin B. It is hoped that the proposed modified, species-specific criteria will improve the clinical utility of laboratory-generated disk antibiograms with respect to the inherently multiple antibiotic-resistant, opportunistic pathogen S. maltophilia.

Anti-Bacterial Agents↗

Tissue transglutaminase auto-antibodies in cord blood from children to become celiacs.

BACKGROUND: Determination of tissue transglutaminase auto-antibodies (tTGAA) has been shown to be a sensitive and specific diagnostic tool for large-scale screening for celiac disease. The purpose of this study was to measure tissue tTGAA in cord blood in infants that later developed celiac disease to evaluate if this assay could serve as a predictive tool for later development of celiac disease. METHODS: IgG tTGAA were analyzed in cord blood through immunoprecipitation from 51 future celiac patients and 102 age-matched controls. Cut-off level was set at 0.040. RESULTS: No difference in tTGAA levels was found between cord blood from infants who later developed celiac disease and controls (P = 0.746). 2/51 future celiac patients (3.9%) had levels above cut-off-value in cord blood, while 3/102 controls were positive (2.9%) (P = 1.000). tTGAA levels were higher in the 1980s and at the beginning of the 1990s than they have been in recent years (P = 0.003). CONCLUSIONS: Determination of tissue tTGAA in cord blood does not predict future celiac disease in children. tTGAA levels vary with time, which should be considered in retrospective studies analyzing tTGAA.

Autoantibodies↗

The role of atopy patch tests in the diagnosis of allergy in atopic dermatitis.

PURPOSE OF REVIEW: Recent literature on the atopy patch test, published since 2004, is reviewed to evaluate whether the pathomechanism of the test has become more evident and whether previous studies require standardization. RECENT FINDINGS: There is evidence accumulating that a smaller subset of patients with atopic dermatitis show only atopy patch test positivity while specific IgE to the same allergen remains negative. It is possible that local IgE-mediated reactions occur in the skin. New data bring us a step forward in understanding the role of the atopy patch test in diagnosis of allergy in atopic dermatitis but no comprehensive studies were published during the period reviewed. SUMMARY: Despite recent advances in determining the value and indication for use of the atopy patch test in atopic dermatitis, more objective studies are needed. The atopy patch test may be useful in understanding the mechanisms of atopic allergy, and in defining the clinical relevance of the airborne allergens in eliciting dermatitis. Regarding food allergy, the atopy patch test still requires standardization. To date, methodology differs in all published papers; even the gold standard, the challenge test itself, is not appropriately standardized, which makes the interpretation of results less reliable.

Bronchial Provocation Tests↗

Prenatal evaluation of fetal renal function based on serum beta(2)-microglobulin assessment.

The relationship between fetal renal function (FRF) and fetal serum beta(2)-microglobulin (B2MG) was investigated by comparing its value in 112 unaffected fetuses with that of 23 fetuses presenting with urinary tract malformations (UTM). Fetal serum level of B2MG was totally unrelated to gestational age; its value increased in cases of severe impairment of FRF but was similar to controls in all mild uropathies (p<0.05). Evaluating serum B2MG could be beneficial in fetuses with severe renal damage, but is of no use in unilateral UTM since only the global FRF is tested and not the function of each single kidney.

Case-Control Studies↗

Validation study of the three-objects-three-places test: a screening test for Alzheimer's disease.

The aim of the present study was to validate a short, ecological test of episodic memory for the screening of Alzheimer's disease (AD). The validation was performed by computing intrarater reliability, homogeneity, internal coherence, convergent, discriminant and known group validities in the performance of normal subjects (N = 65), mild cognitive impairment (MCI) patients (N = 114), and AD (N = 44) and non-AD demented (N = 39) patients. Intrarater reliability was 0.88, homogeneity ranged from 0.81 to 0.97, and internal coherence was 0.87. With respect to convergent and discriminant validities, the test loaded strongly on memory factor (value = 0.64) and weakly on other nonmemory factors. The known group validity showed a specificity between 87% and 91% and a sensitivity between 92% and 100% in correctly identifying AD in age classes ranging from 50 to 65 and 66 to 80 years. The test is a valid instrument for the screening of AD.

Aged↗

Rapid differentiation of subarachnoid hemorrhage from traumatic lumbar puncture using the D-dimer assay.

The D-dimer assay of 40 cerebral spinal fluid (CSF) samples accurately differentiated subarachnoid hemorrhage (SAH) from traumatic lumbar puncture. The D-dimer assay was positive in all six patients with subarachnoid hemorrhage. Negative D-dimer values were obtained in control groups of 14 patients with hemorrhagic CSF secondary to traumatic lumbar puncture (LP) and in 20 patients with normal CSF. The D-dimer assay proved to be a better test than xanthochromia or the decline in erythrocyte count in sequentially collected tubes in differentiating subarachnoid hemorrhage from traumatic LP.

Antibodies, Monoclonal↗

[In vitro testing for allergic contact dermatitis].

Patch testing is the standard method to identify allergic contact dermatitis. Simple, safe and accurate in vitro methods identifying contact allergies would offer both theoretical and practical advantages. Using the lymphocyte transformation test (LTT), allergen-specific lymphocytes central to the pathogenesis of Type IV allergies can be identified. Various studies have assessed the value of LTT in the diagnosis of contact allergies. The current assessment is that the test can be helpful in distinguishing between irritant and allergic reactions. LTT is especially useful in demonstrating drug allergies and can also be employed to prove sensitization to gases or toxic substances. At the present time, it is not an alternative for patch testing in daily practice.

Allergens↗

Evaluation of carbohydrate-deficient transferrin for detection of alcohol abuse in patients with liver dysfunction.

The determination of carbohydrate-deficient transferrin (CDT) in serum has been suggested as a marker of alcohol abuse. We evaluated serum CDT in 199 patients admitted to our Department of Medicine using a commercially available radioimmunoassay kit for CDT. A history of alcohol consumption was obtained quantitatively by a self-administered questionnaire and qualitatively by the Munich Alcoholism Test. Using a cut-off level of 60 g ethanol per day according to the information from the questionnaire. CDT had a sensitivity of 70% and a specificity of 84%. False-positive values were primarily encountered in cases of hepatic malignoma, primary biliary cirrhosis and chronic hepatitis C. The sensitivity and specificity of CDT was superior to two other markers of chronic ethanol consumption, serum gamma-glutamyltransferase and mean cell volume, and thus proved to be the best single laboratory test for the detection of alcohol abuse.

Biomarkers↗

Ultrasound in the diagnosis of hepatocellular carcinoma associated with cirrhosis.

A total of 100 cirrhotic patients with clinically suspected neoplastic transformation was assessed prospectively with ultrasound. Ultrasound was diagnostic in 27/30 patients who had a final diagnosis of hepatocellular carcinoma (sensitivity 90%); there were five false-positive examinations (specificity 93%). The positive predictive value of the test was 84.4%; negative predictive value was 95%. Three different ultrasound patterns were observed in hepatocellular carcinoma: increased reflectivity, decreased reflectivity, and mixed echo pattern. Ultrasound can be used as a safe, effective first-line screening test for cirrhotic patients with clinically suspected neoplastic transformation.

Carcinoma, Hepatocellular↗

Predictive value of drug levels, HIV genotyping, and the genotypic inhibitory quotient (GIQ) on response to saquinavir/ritonavir in antiretroviral-experienced HIV-infected patients.

Plasma levels of HIV protease inhibitors (PI) are often close to IC50 values of wild-type viruses when administered without ritonavir boosting. The impact of drug levels, resistance mutations, and the genotypic inhibitory quotient (GIQ) were examined on the response to saquinavir/ritonavir (SQV/r)-based salvage therapy. Patients with prior exposure to PI other than SQV and currently failing virologically were recruited prospectively in a multicenter trial. All patients began SQV/r 1000/100 mg bid plus another two antiretrovirals. A total of 139 patients was enrolled. At month 12, virological response (VR), defined as plasma HIV-RNA decline >1 log, was recorded in 68.2% of patients on treatment (41.7% in the intent-to-treat analysis). The median baseline number of protease resistance mutations was three. The VR was significantly lower in patients with >5 protease resistance mutations and in those with plasma SQV Cmin<0.1 microg/ml. At week 48, the VR was seen in 77.1% of patients with a GIQ>0.04 compared to 18.2% of those with a lower GIQ (P=0.001). In the multivariate analysis, 0.1 microg/ml were independently associated with VR. Interestingly, drug levels had their highest predictive value of the VR at week 12, since low SQV plasma levels often permitted ruling out poorly adherent patients. In contrast, the number of protease resistance mutations had the highest impact on the VR at week 24, suggesting that for those taking the drugs, the VR is highly dependent of the presence of resistance mutations. At any time, nevertheless, the GIQ provided the most accurate prediction of the VR.

Antiretroviral Therapy, Highly Active↗