MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.     

Postnatal onset of craniosynostosis in a case of Saethre-Chotzen syndrome

Saethre-Chotzen syndrome is a craniosynostosis syndrome characterized by facial and limb abnormalities. It is caused by mutations in the TWIST gene on chromosome 7p21. To date, more than 80 different mutations in TWIST have been reported in the literature.Recently, large deletions of chromosome 7p, encompassing the TWIST locus, have been detected in patients with clinical features of Saethre-Chotzen syndrome. Strikingly, all these patients were severely mentally retarded, which is otherwise a rare finding in Saethre-Chotzen syndrome. The authors report a patient with a large TWIST/7p deletion but with normal development. Furthermore, craniosynostosis was not present at birth or at the age of 4 months. However, skull radiographs taken at the age of 14 months showed stenosis of both coronal sutures, as well as of part of the sagittal suture. Reports on postnatal onset of craniosynostosis have been made in Crouzon syndrome but, to the authors' knowledge, never in Saethre-Chotzen syndrome.     

The effects of load on systolic mitral annular velocity by tissue Doppler imaging

Tissue Doppler Imaging (TDI) provides information on systolic function through its systolic mitral annulus velocity wave (Sm), reflecting the peak velocity of shortening of the myocardial fibers oriented in the longitudinal direction. In this study, we evaluated the effect of load changes on Sm. Forty-two cardiac surgical patients with left ventricular ejection fraction >60% were consecutively evaluated. In 24 patients, load was changed with an IV bolus of phenylephrine (50-100 microg) or nitroglycerine (300-500 microg); in 18 patients, preload was changed with a rapid infusion of 500 mL of a gelatin solution. The sample volume of TDI was placed at the lateral side of the mitral annulus in the mid-esophageal 4-chamber view. Changing loading conditions with phenylephrine or nitroglycerine had no effect on Sm; the increase of preload in 18 patients resulted in a statistically significant increase of Sm (baseline, 8.4 +/- 2.6 cm/s; after increase of preload, 9.6 +/- 2.5 cm/s; P = 0.001). We conclude that Sm is dependent on changes in preload obtained by volume loading and cannot be recommended as an index of ventricular contractile performance in critically ill patients where significant changes in ventricular filling occur.     

Performance characteristics of updated INNO-LiPA assays for molecular typing of human leukocyte antigen A (HLA-A), HLA-B, and HLA-DQB1 alleles

We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.     

Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a

PURPOSE: To evaluate visual impairment in Usher syndrome 1b (USH1b) and Usher syndrome 2a (USH2a). METHODS: We carried out a retrospective study of 19 USH1b patients and 40 USH2a patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS) and functional vision score (FVS) related to age were performed. Statistical tests relating to regression lines and Student's t-test were used to compare between (sub)groups of patients. Parts of the available individual longitudinal data were used to obtain individual estimates of progressive deterioration and compare these to those obtained with cross-sectional analysis. Results were compared between subgroups of USH2a patients pertaining to combinations of different types of mutations. RESULTS: Cross-sectional analyses revealed significant deterioration of the FAS (0.7% per year), FFS (1.0% per year) and FVS (1.5% per year) with advancing age in both patient groups, without a significant difference between the USH1b and USH2a patients. Individual estimates of the deterioration rates were substantially and significantly higher than the cross-sectional estimates in some USH2a cases, including values of about 5% per year (or even higher) for the FAS (age 35-50 years), 3-4% per year for the FFS and 4-5% per year for the FVS (age > 20 years). There was no difference in functional vision score behaviour detected between subgroups of patients pertaining to different biallelic combinations of specific types of mutations. CONCLUSIONS: The FAS, FFS and FVS deteriorated significantly by 0.7-1.5% per year according to cross-sectional linear regression analysis in both USH1b and USH2a patients. Higher deterioration rates (3-5% per year) in any of these scores were attained, according to longitudinal data collected from individual USH2a patients. Score behaviour was similar across the patient groups and across different biallelic combinations of various types of mutations. However, more elaborate studies, preferably covering longitudinal data, are needed to obtain conclusive evidence.     

Is the Trachea a Marker of the Type of Environmental Pollution?

OBJECTIVES/HYPOTHESIS: The differentiated character of changes in the mucous relief of the trachea as induced by air containing pollutants from the wastes of nickel-, mercury-, and cement-producing plants and by Candida albicans occurring in the waste disposal site of a large town are identified. The trachea was chosen because it is the entrance gate for the penetration of polluted air into the lungs. Changes on the trachea influence the character and extent of changes in lungs. STUDY DESIGN: Histological study with Viennese grey strain laboratory rabbits and rats caught directly on an investigated site. METHODS: We present new results of the functional morphology of the respiratory system as the results of scanning and transmission electron microscopy studies that can reveal character and range of damage of mucosal relief of trachea relevant to the functional dynamics of mucociliary clearance. Under physiological conditions this mechanism allows that only respirable dust particles enter the deep respiratory tract. RESULTS: In case of a damaged tracheal relief because of exposure to various aerosols, the functional morphology is changed, which aids in understanding the mechanisms damaging to mucociliary clearance induced by living in heavily polluted areas. CONCLUSION: Understanding of these morphological changes on base of detailed electron microscopic findings sheds new light on elaborating novel diagnostic methods for clinical practice.     

Comparison of hexamethylhypericin and tetrabromohypericin to hypericin for their in vivo efficacy as PDT tools

The present study was performed to evaluate the PDT efficacy, the singlet oxygen yield, and the plasma binding profile of the natural photosensitizer hypericin and two hypericin derivatives, hexamethylhypericin and tetrabromohypericin. All compounds exhibited an excellent 1O2 quantum yield, as documented by TEMP spin trapping experiments. The efficacy of PDT with the different compounds using a P388 lymphoma tumour model was clearly dependent on the interval between drug administration and light irradiation of the tumours. The most effective PDT treatment time was obtained with hypericin (5 mg/kg) using a 30-min drug-light interval, whereas a 24-h interval was optimal for a similar dose of tetrabromohypericin. No significant difference in survival between control animals and animals treated with PDT using tetrabromohypericin (5 mg/kg) was noted when a 30-min, 2- or 6-h interval was used. PDT with hexamethylhypericin (5 mg/kg) using different drug-light intervals was unable to prolong the life span of the tumour-bearing mice. In contrast, a dose of 20 mg/kg hexamethylhypericin, especially when administered 30 min prior to light exposure, produced a profound local reduction of tumour mass and a concomitant significant increase in survival time. The binding of the hypericins to human plasma was evaluated using density-gradient ultracentrifugation. It was found that tetrabromohypericin exhibits an affinity for plasma constituents almost similar to hypericin, in contrast to the more hydrophilic hexamethylhypericin that mainly binds to heavy proteins (e.g. albumin). Since the latter compound showed an efficacy profile similar to hypericin, no correlation could be found between the optimal drug-light interval and the plasma protein binding of the compounds.     

Absence of Neisseria meningitidis W-135 electrophoretic Type 37 during the Hajj, 2002

We document the absence of carriage of Neisseria meningitidis W-135 of the sequence type 11 in returning pilgrims after the Hajj 2002. This finding contrasts with the 15% carriage rate we previously reported in pilgrims returning from the Hajj 2001. The epidemiology of carriage may be changing or may have been controlled by vaccination and a policy of administering antibiotics to pilgrims from countries with a high incidence of meningococcal disease.     

Cell death and growth arrest in response to photodynamic therapy with membrane-bound photosensitizers

Photodynamic therapy (PDT) is a treatment for cancer and for certain benign conditions that is based on the use of a photosensitizer and light to produce reactive oxygen species in cells. Many of the photosensitizers currently used in PDT localize in different cell compartments such as mitochondria, lysosomes, endoplasmic reticulum and generate cell death by triggering necrosis and/or apoptosis. Efficient cell death is observed when light, oxygen and the photosensitizer are not limiting ("high dose PDT"). When one of these components is limiting ("low dose PDT"), most of the cells do not immediately undergo apoptosis or necrosis but are growth arrested with several transduction pathways activated. This commentary will review the mechanism of apoptosis and growth arrest mediated by two important PDT agents, i.e. pyropheophorbide and hypericin.