The combination of cognitive testing and an informant questionnaire in screening for dementia

Aim: A cognitive test and an informant report questionnaire were used together to investigate whether their combined use could improve the accuracy of detecting dementia in a memory clinic, compared with either test used alone. METHOD: The subjects were 323 patients assessed at a memory clinic. The Mini-Mental State Examination and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly were used. A method of combining the test scores developed by Mackinnon and Mulligan [Am J Psychiatry 1998; 155: 1529-35] was used. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria. RESULTS: Logistic regression analysis showed that the combination of the Mini-Mental State Examination and the Informant Questionnaire on Cognitive Decline in the Elderly produced a slightly more accurate prediction of dementia caseness than either test used alone. Using receiver operating characteristic analysis the performance of the combination of the tests according to a weighted sum rule was compared with the performance of either test used alone. This way of combining the tests resulted in a more accurate screening for dementia than when the Informant Questionnaire on Cognitive Decline in the Elderly was used alone. The area under the receiver operating characteristic curve for the Mini-Mental State Examination combined with the Informant Questionnaire on Cognitive Decline in the Elderly was 0.89 compared with 0.82 for the Informant Questionnaire on Cognitive Decline in the Elderly alone (chi-square = 10.63; P = 0.0011). However, there was no improvement in screening performance when the combination of Mini-Mental State Examination and Informant Questionnaire on Cognitive Decline in the Elderly was compared with the Mini-Mental State Examination used alone (area under the receiver operating characteristic curve = 0.89 versus 0.86; chi-square = 3.54; P = 0.060). CONCLUSION: The combination of cognitive testing and an informant report according to a weighted sum rule in this population did not result in any advantage over the use of the Mini-Mental State Examination alone. The mixed results of this study contrast with those of Mackinnon and Mulligan.     

Subclinical hypothyroidism and Down's syndrome; studies on myocardial structure and function

Background: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by L-thyroxine therapy. As SH frequently affects children with Down''s syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. Aims: To establish whether SH influences myocardial structure and function in children with DS. Methods: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. Results: None of the 16 patients had myocardial impairment. Conclusion: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut.     

Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants

Most vaccines are still delivered by injection. Mucosal vaccination would increase compliance and decrease the risk of spread of infectious diseases due to contaminated syringes. However, most vaccines are unable to induce immune responses when administered mucosally, and require the use of strong adjuvant on effective delivery systems. Cholera toxin (CT) and Escherichia coli enterotoxin (LT) are powerful mucosal adjuvants when co-administered with soluble antigens. However, their use in humans is hampered by their extremely high toxicity. During the past few years, site-directed mutagenesis has permitted the generation of LT and CT mutants fully non toxic or with dramatically reduced toxicity, which still retain their strong adjuvanticity at the mucosal level. Among these mutants, are LTK63 (serine-to-lysine substitution at position 63 in the A subunit) and LTR72 (alanine-to-arginine substitution at position 72 in the A subunit). The first is fully non toxic, whereas the latter retains some residual enzymatic activity. Both of them are extremely active as mucosal adjuvants, being able to induce very high titers of antibodies specific for the antigen with which they are co-administered. Both mutants have now been tested as mucosal adjuvants in different animal species using a wide variety of antigens. Interestingly, mucosal delivery (nasal or oral) of antigens together with LTK63 or LTR72 mutants also conferred protection against challenge in appropriate animal models (e.g. tetanus, Helicobacter pylori, pertussis, pneumococci, influenza, etc). In conclusion, these LTK63 and LTR72 mutants are safe adjuvants to enhance the immunogenicity of vaccines at the mucosal level, and will be tested soon in humans.     

Familial occurrence of early-onset childhood absence epilepsy.

Early onset of absence seizures (<3 years) is rare and usually associated with a poor cognitive prognosis. Familial cases have not been reported to date. We observed a family in which two out of three sibs showed early-onset absences and mild mental retardation. Linkage to the ECA1 locus, where one clinical subtype of CAE is mapped, was excluded by haplotype analysis. Direct sequencing of the candidate genes CLCN2 ,GABRG2 and CHRNA4 showed no mutations. We suggest the possibility of a specific epileptic syndrome with a putative AR inheritance. Further report of affected patients might allow a better classification.     

End of the century overview of skin blisters

A wide spectrum of diseases of the skin are manifested as a blistering process. Blistering may occur as a secondary event associated with viral or bacterial infections of the skin, eg, herpes simplex and impetigo, or with local injury of the skin, eg, burns, ischemia, and dermatitis. In other diseases, blistering of the skin occurs as a primary event and is associated with tissue injury and fluid accumulation within a specific layer of the skin: intraepidermal, dermal-epidermal junction, or subepidermal. Blister formation in this latter group of diseases is due to either genetic mutation or an autoimmune response. Genodermatoses associated with blisters are typically manifested in the neonate, whereas the autoimmune blistering disorders are acquired and usually expressed later in life. Recent advances have uncovered the relevance of the keratinocyte cytoskeleton, the desmosome, the hemidesmosome, and extracellular matrix proteins in blister formation. A pathogenetic classification of blistering diseases is presented.     

Non-invasive evaluation with continuous Doppler of the systolic pressure of the right ventricle in patients with tricuspid insufficiency

Tricuspid regurgitation (TR) is detected by Doppler echocardiography in a high proportion of patients with right ventricle pressure or volume overload. Continuous wave Doppler (CW) provides a noninvasive estimation of the transtricuspid systolic pressure gradient, applying the modified Bernoulli formula to the maximum velocity of the TR jet. The purpose of this study was to test the accuracy of the CW prediction of systolic right ventricular pressure (RVPs), obtained adding a clinical estimate of the mean right atrial pressure (RAPm) to the Doppler derived pressure gradient. The study population consisted of 22 adult patients with Doppler proved TR, undergoing right heart catheterization (cath) for mitral valve disease (12 pts), atrial septal defect (8 pts), dilated cardiomyopathy (1 pt) or pulmonary hypertension (1 pt). Two studies were duplicated after nifedipine administration. TR was graded by pulsed Doppler flow mapping as mild in 7, moderate in 11, severe in 4 pts. RAPm was estimated clinically from the inspection of neck veins pulsatility (mmHg = pulsatility cm+5/1.3). At CATH RVPs ranged from 27 to 80 (46 +/- 17) mmHg, RAPm from 0 to 13 (6 +/- 3) mmHg. RVPs Doppler prediction showed a close correlation with CATH (r .97, SEE 4.2 mmHg), with a slight mean underestimation (-2 +/- 4 mmHg) (Fig. 3, Tab. I). The discrepancies between CW and CATH ranged from -9 to +10 mmHg, almost entirely due to inaccuracy of the RAPm clinical estimate (r .48, see 3.8 mmHg) (Fig. 4, Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibody response against heterogeneous circulating influenza virus strains elicited by MF59- and non-adjuvanted vaccines during seasons with good or partial matching between vaccine strain and clinical isolates

MF59 is already known to enhance the breadth of antibody response to mismatched influenza seasonal and avian strains. However, little is known on the effect of MF59 on immunogenicity of influenza vaccines when “apparent” good matching between circulating and vaccine strains exists. To this end, we compared the immune response elicited by MF59-adjuvanted or non-adjuvanted subunit vaccine, containing A/California/7/04(H3N2) strain, against circulating viruses isolated between 2004/2005 and 2006/2007 seasons, belonging to different clades. The advantage offered by MF59 in terms of higher immunogenicity, expressed as higher post-vaccination HI titres, is observable also against viruses showing antigenic and molecular pattern undistinguishable from vaccine strain, but it became even more evident as the antigenic and molecular distance between vaccine and circulating strains grew. These data show that seasonal influenza vaccine adjuvanted with MF59 can offer a stronger benefit as compared to non-adjuvanted vaccine in protecting against a broader range of virus strains circulating during the influenza season.     

Optimized Technique in Needle Biopsy Protocol Shown to Be of Greater Sensitivity and Accuracy Compared to Wedge Biopsy

Background

Kidney biopsy is an important tool in determining allograft suitability for transplantation. Most deceased-donor renal biopsies performed today in the United States are wedge biopsies (WBs), with core needle biopsies being performed only by a minority of organ procurement organizations (OPOs). The lack of a gold standard in tissue sampling and tissue evaluation has prompted our OPO to find a more sensitive biopsy method as well as a more accurate pathology evaluation protocol to reassess expanded-criteria donor kidneys.

Methods

Between the months of March 2007 and June 2008, the New York Organ Donor Network OPO imported 226 kidneys. These kidneys had been previously biopsied by the originating OPOs utilizing the WB method. All 226 kidneys were rebiopsied by our preservation team using the optimized needle biopsy technique (ONBT) and then evaluated by the pathologists of the Transplant Pathology Laboratory of the Mount Sinai Hospital.

Results

Histologic findings from both types of biopsies were compared in the following parameters: glomerular yield, percentage of obsolete glomeruli, tubular interstitial scarring, arterial intimal fibrosis and acute tubular necrosis. Difference in glomerular yield between WB and ONBT was not statistically significant (P = .1736). ONBT detected more tubular interstitial scarring and arterial intimal fibrous narrowing than WB (P = .00). No statistical difference was found between the two biopsy methods in identifying acute tubular necrosis.

Conclusion

The data suggest that there were no statistical differences in sample reliability between ONBT and WB. However, ONBT was found to be significantly more sensitive in identifying allograft tubular interstitial scarring as well as intimal fibrous narrowing. Overall this study provides proof that ONBT is a more reliable and accurate method compared to WB in identifying important parameters of renal allograft.