Topical dorzolamide increases pericentral visual function in age-related maculopathy: pilot study findings with short-wavelength automated perimetry

PURPOSE: Numerous studies have confirmed the enhancement of ocular circulation by carbonic anhydrase inhibitors (CAIs). Topical CAI treatment with dorzolamide averts the significant pericentral visual function loss accompanying retinal and choroidal vasoconstriction during acute hyperventilation-induced hypocapnia. This study was designed to discern whether dorzolamide might similarly enhance macular function in patients with age-related maculopathy (ARM). METHODS: In a masked, placebo-controlled study, 40 patients with ARM and acuity > 20/50 were randomized to receive either dorzolamide or placebo for 12 weeks, thrice daily. After pre-study perimetric training, pericentral function (mean sensitivity) was quantified using Humphrey 10-2 short-wavelength automated perimetry (SWAP), before and after 12 weeks of topical therapy. RESULTS: Dorzolamide-treated eyes demonstrated a significant increase in mean sensitivity of + 1.55 dB (p = 0.04); placebo-treated eyes showed no significant change (+ 0.58 dB; p = 0.10). Given the non-significant increase of mean sensitivity in the placebo-treated group, fewer than 100 subjects per group would be required to afford > 70% power to yield a significant direct comparative difference between treatment and placebo in a prospective, randomized study of equally short duration. CONCLUSIONS: This study demonstrated a significant increase in short-wavelength sensitivity in ARM with dorzolamide and the lack thereof with placebo. These encouraging pilot study data suggest a potential role for topical CAIs in ARM patients, and establish objective parameters for prospective studies to further evaluate the effects of dorzolamide in ARM.     

The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression

LAPTM4b (lysosome associated protein transmembrane 4 beta) was recently identified as a gene overexpressed in human hepatocellular carcinoma and belongs to the mammalian LAPTM family. By analysing genome-wide expression profiles of microdissected solid tumour samples by the means of Affymetrix GenChip hybridisation, we found LAPTM4b to be upregulated in 88% (23/26) of lung and in 67% (18/27) of colon carcinoma patients. Northern blots revealed additionally an overexpression of LAPTM4b in the majority of carcinomas of the uterus (30/44), breast (27/53) and ovary (11/16). Other members of the LAPTM family were not overexpressed in the investigated tumour samples according to GeneChip hybridisation data. Northen blot and quantitative RT-PCR on different normal tissues, detected highest levels of LAPTM4b mRNA in uterus, heart and skeletal muscle. Due to sequence analysis of bilaterian LAPTM proteins we suggests the presence of four transmembrane helices per protein, which are probably packed together by hydrophobic forces that are excerted by several evolutionary conserved aromatic residues within the alpha-helices. We discuss an active role for LAPTM4b during disease progression of malignant cells and conclude that its putative dual functional involvement in tumour cell proliferation as well as in multidrug-resistance may represent LAPTM4b as a target suitable for development of novel therapeutic agents.     

Development of functional Haemophilus influenzae type b antibodies after vaccination

Sixteen autologous stem cell transplant recipients received three vaccinations with conjugated haemophilus influenzae type b vaccine. Quantitative and qualitative aspects of the antibody response were studied. The vaccination schedule resulted in high antibody response rates and functional maturation of antibodies, as measured by antibody avidity and phagocytosis-inducing capacity.     

Pronominal reference in sentences about persons or things: an electrophysiological approach

German pronouns (er(MALE/masculine), sie(FEMALE/feminine)) that refer to a person are determined by the biological gender (MALE/FEMALE) and/or syntactic gender (masculine/feminine) of the person. Pronouns (er(masculine), sie(feminine)) that refer to a thing are determined by the syntactic gender of this thing (Garten [garden]masculine, Tasche [hand-bag]feminine). The study aimed to investigate whether semantic integration, syntactic integration, or both are involved in establishing co-reference between pronoun and subject/antecedent in sentences. Here we focused on two event-related potential components: the SPS/P600, related to syntactic violation and reanalysis, and the N400 component, related to semantic integration problems. In one condition, a person was introduced as antecedent and later referred to by a pronoun, which either agreed in biological/syntactic gender or not (biological/syntactic gender violation). In a second condition, a thing was introduced as antecedent and the corresponding pronoun either agreed in syntactic gender or not (syntactic gender violation). Results at critical pronouns showed a P600 effect for incongruent compared with congruent pronouns in both conditions with a centro-parietal maximum. This effect was larger for the person compared to the thing condition. We interpreted this finding as reflecting a syntactic integration process that can be influenced by conceptual/semantic and syntactic information of the antecedent type. Furthermore, at the word following the pronoun, we observed an N400 for the thing but not for the person condition. We suggest, supported by the results of a control experiment, that this effect reflects continuous integration processes for things, whereas for persons the integration seems to be finished at pronoun position.     

Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Results of a multicentre case-control study

From 1998 to 2003, 133 Caucasian women aged 17-40 years (median 29 years) suffering from unexplained recurrent miscarriage (uRM) were consecutively enrolled. In patients and 133 age-matched healthy controls prothrombotic risk factors (factor V (FV) G1691A, factor II (FII) G20210A, MTHFR T677T, 4G/5G plasminogen activator inhibitor (PAI)-1, lipoprotein (Lp) (a), protein C (PC), protein S (PS), antithrombin (AT), antiphospholipid/anticardiolipin (APA/ACA) antibodies) as well as associated environmental conditions (smoking and obesity) were investigated. 70 (52.6%) of the patients had at least one prothrombotic risk factor compared with 26 control women (19.5%; p<0.0001). Body mass index (BMI; p=0.78) and smoking habits (p=0.44) did not differ significantly between the groups investigated. Upon univariate analysis the heterozygous FV mutation, Lp(a) > 30 mg/dL, increased APA/ACA and BMI > 25 kg/m(2) in combination with a prothrombotic risk factor were found to be significantly associated with uRM. In multivariate analysis, increased Lp(a) (odds ratio (OR): 4.7/95% confidence interval (CI): 2.0-10.7), the FV mutation (OR:3.8/CI:1.4-10.7), and increased APA/ACA (OR: 4.5/CI: 1.1-17.7) had independent associations with uRM.     

Measuring the executive functions in schizophrenia: the voluntary allocation of effort

INTRODUCTION: Executive functioning reflects not only what a patient does, but also how he does it or whether he does it at all [Lezak MD. The problem of assessing executive functions. Int. J. Psychol. 17 (1982) 281]. Standard test procedures strongly prompt subjects to certain behavior, so that initiative and the amount of voluntary effort one is willing to invest are therefore not being adequately assessed. METHODS: We developed the Cognitive Effort Test (CET); a test for executive functioning specifically aimed at measuring subject's free initiatives, and the amount of effort they invest voluntarily. It is a complex planning task, and performance is being judged by three subscales: Initiative, Planning, and Workload. 36 schizophrenia patients and 30 healthy controls were tested with the CET, and a battery of other cognitive tests (executive functioning, memory, attention and psychomotor speed) was added to investigate construct and divergent validity. Negative symptoms were also recorded (predictive validity). RESULTS: Patients scored below controls on Planning and Workload, but not on Initiative. The CET was significantly related to other tests for cognition but not to negative symptoms. CET Planning and Workload predicted group membership (patients-controls) better than the other tests for executive functioning combined. CONCLUSION: The CET appears to be a clinically useful test that measures an aspect of schizophrenia that is not being assessed by existing tests, presumably the voluntarily allocation of effort.     

Morphometry of the amygdala in patients with questionable dementia and mild dementia

The volume of the amygdala is reduced in advanced Alzheimer's disease (AD). However, there is controversy whether amygdala atrophy is present in mild AD and in the transitional phase between health and the onset of dementia. The aim of this prospective longitudinal study was to investigate whether amygdala atrophy is present in subjects with questionable dementia and mild dementia and whether amygdala volume is associated with the future rate of cognitive change, that is the annual change in the Mini Mental State Examination (MMSE). At baseline, volumes of the amygdala were measured in 97 participants aged 70-87 years (40 controls, 33 patients with questionable dementia, 24 patients with mild AD) using magnetic resonance imaging. Eighty-six participants were clinically re-examined after 2.3 years on average. At baseline, significant differences in mean amygdala volume were found between controls and participants with mild AD. There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups.     

Neural correlates of visuo-spatial attention during an antisaccade task in schizophrenia: an ERP study

The authors investigated the role of visuo-spatial attention in an antisaccade task using event-related potentials (ERPs) in schizophrenia patients compared to healthy controls. ERPs between 80-130 ms (P100) after stimulus onset showed differences between pro- and antisaccades only for controls and can be related to the suppression of irrelevant stimulus features. Between 150-180 ms (N100), a larger amplitude for anti-compared to prosaccades over centroparietal electrodes showed that processes of visuo-spatial attention seem to be engaged in performance of the antisaccade task. Left temporo-occipitally, this activity was only evident in schizophrenia patients, possibly reflecting additional neuronal recruitment in order to perform the antisaccade task successfully.