Virpi Ahola

Citalopram as an adjuvant in chronic schizophrenia: a double‐blind placebo‐controlled study

The effects of citalopram — the most selective serotonin reuptake inhibitor on the market — on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication. Outpatients suffering from schizophrenic disorder (DSM‐III‐R) with Positive and Negative Symptom Scale (PANSS) scores higher than 50 were included in a double‐blind placebo‐controlled add‐on study. The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period. A total of 90 patients (45 patients receiving citalopram and 45 receiving placebo) completed the 12‐week trial. There were no changes in neuroleptic plasma levels during the trial. There was a significant decrease in total PANNS scores during the trial, although no statistically significant differences between the citalopram group and the placebo group were revealed. The number of responders in terms of severity of illness (CGI) was higher and the increase in subjective well‐being (VAS) was greater in patients on citalopram than in those receiving placebo. There were no significant differences in the occurrence of side‐effects. It is concluded that, in chronic schizophrenic out‐patients, citalopram has no clear effect on the psychopathological symptoms; it may improve the general clinical condition, and it appears to increase the subjective well‐being of these patients. Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment.

Smoking and cognitive deficits in schizophrenia: a pilot study

The cross-sectional study assessed the associations among smoking status, number of cigarettes smoked per day, and psychiatric symptoms in 88 chronic schizophrenic outpatients with a stable psychic condition. Among the 49 smokers, the number of cigarettes smoked per day was associated with the severity of cognitive symptoms of the Positive and Negative Syndrome Scale. The authors suggest that smoking may alleviate cognitive deficits in schizophrenia by increasing dopaminergic neurotransmission in the prefrontal areas of the brain.

Effect of smoking on neuroleptics in schizophrenia.

OBJECTIVE The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. METHODS 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. RESULTS Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. CONCLUSIONS Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

A statistical score for assessing the quality of multiple sequence alignments.

BackgroundMultiple sequence alignment is the foundation of many important applications in bioinformatics that aim at detecting functionally important regions, predicting protein structures, building phylogenetic trees etc. Although the automatic construction of a multiple sequence alignment for a set of remotely related sequences cause a very challenging and error-prone task, many downstream analyses still rely heavily on the accuracy of the alignments.ResultsTo address the need for an objective evaluation framework, we introduce a statistical score that assesses the quality of a given multiple sequence alignment. The quality assessment is based on counting the number of significantly conserved positions in the alignment using importance sampling method in conjunction with statistical profile analysis framework. We first evaluate a novel objective function used in the alignment quality score for measuring the positional conservation. The results for the Src homology 2 (SH2) domain, Ras-like proteins, peptidase M13, subtilase and β-lactamase families demonstrate that the score can distinguish sequence patterns with different degrees of conservation. Secondly, we evaluate the quality of the alignments produced by several widely used multiple sequence alignment programs using a novel alignment quality score and a commonly used sum of pairs method. According to these results, the Mafft strategy L-INS-i outperforms the other methods, although the difference between the Probcons, TCoffee and Muscle is mostly insignificant. The novel alignment quality score provides similar results than the sum of pairs method.ConclusionThe results indicate that the proposed statistical score is useful in assessing the quality of multiple sequence alignments.

Comparison of topical 0.7% dexamethasone–cyclodextrin with 0.1% dexamethasone sodium phosphate for postcataract inflammation

BackgroundTo compare 0.7% dexamethasone–cyclodextrin aqueous eye drop solution applied once daily with 0.1% dexamethasone sodium phosphate eye drops applied three times a day for the control of postoperative inflammation after cataract surgery.MethodsTwenty cataract patients who underwent phacoemulsification and intraocular lens implantation were randomly divided into two postoperative treatment groups. Postoperative medication in group I included 0.1% dexamethasone sodium phosphate eye drops three times daily and in group II 0.7% dexamethasone–cyclodextrin eye drop solution once daily. Testing of visual acuity, biomicroscopic examination, applanation tonometry and laser flare cell meter (LFCM) examination were carried out before operation and days 1, 3, 7 and 21 after surgery.ResultsPreoperative and postoperative visual acuity, aqueous flare and cells in biomicroscopic examination, and the mean intraocular pressure did not show any statistically significant differences between the treatment groups. LFCM examination showed that the mean postoperative photon count values (P=0.032) and the median cell count values on the 1st (P=0.014), 3rd (P=0.031), 7th (P=0.034), and 21st (P=0.0097) postoperative days in group I were more elevated than in group II.Conclusions0.7% dexamethasone–cyclodextrin eye drops applied once daily is a more effective postoperative anti-inflammatory medication than 0.1% dexamethasone sodium phosphate applied three times a day. In both groups, 3 weeks after the operation the mean visual acuity was normal and intraocular pressure significantly lower than before operation. The use of 0.7% dexamethasone–cyclodextrin eye drops may be useful especially in elderly people who cannot apply themselves the eye drops onto the eye.

Endophthalmitis following cataract surgery in southwest Finland from 1987 to 2000.

PurposeTo investigate the incidence, causes, prevention, treatment and outcome of postoperative endophthalmitis (POE) following cataract surgery in south-west Finland from 1987 to 2000.MethodsWe reviewed the medical records of all patients with POE following cataract surgery treated in the hospital district of Southwest Finland from 1 January 1987 to 31 December 2000. Population-based annual incidence rates of cataract extractions and POE were calculated using the corrected population statistics of the hospital district.ResultsThere were 29,350 cataract procedures during the 14-year period. POE developed in 47 patients. The annual incidence of cataract operations increased more than fivefold from 1987 (155 per 100,000 population) to the maximum in 1999 (930 per 100,000 population), whereas the annual incidence of postcataract endophthalmitis decreased from the maximum of 11.1 per 1,000 cataract extractions (1.91 per 100,000 population) in 1988 to the minimum of 0–0.6 per 1,000 cataract extractions in 1999 and 2000. POE occurred statistically significantly more frequently after extracapsular cataract extraction (ECCE) than after phacoemulsification (Phaco) (P=0.0006). Gram-positive bacteria were the most frequent cause of acute POE and Propionibacterium acnes was the most frequent reason for delayed-onset POE. The complications of POE after cataract surgery included visual loss to below 0.05 (25.5% of affected eyes), opacification of the cornea (21.3%), secondary cataract (40.4%), increase in intraocular pressure (29.8%), vitreous clouding (63.8%), and retinal detachment (6.4%). Nearly one half of the eyes achieved final visual acuity of 0.5 or better.ConclusionsDuring the 14-year study period there was a shift from ECCE to Phaco, a fivefold increase in cataract extractions, and a decrease in the annual incidence of POE from 5.5–11.1 to 0–0.6 per 1,000 operations. Phaco was associated with a lower risk of POE than ECCE.

Model-based prediction of sequence alignment quality

MOTIVATION Multiple sequence alignment (MSA) is an essential prerequisite for many sequence analysis methods and valuable tool itself for describing relationships between protein sequences. Since the success of the sequence analysis is highly dependent on the reliability of alignments, measures for assessing the quality of alignments are highly requisite. RESULTS We present a statistical model-based alignment quality score. Unlike other quality scores, it does not require several parallel alignments for the same set of sequences or additional structural information. Our quality score is based on measuring the conservation level of reference alignments in Homstrad. Reference sequences were realigned with the Mafft, Muscle and Probcons alignment programs, and a sum-of-pairs (SP) score was used to measure the quality of the realignments. Statistical modelling of the SP score as a function of conservation level and other alignment characteristics makes it possible to predict the SP score for any global MSA. The predicted SP scores are highly correlated with the correct SP scores, when tested on the Homstrad and SABmark databases. The results are comparable to that of multiple overlap score (MOS) and better than those of normalized mean distance (NorMD) and normalized iRMSD (NiRMSD) alignment quality criteria. Furthermore, the predicted SP score is able to detect alignments with badly aligned or unrelated sequences. AVAILABILITY The method is freely available at http://www.mtt.fi/AlignmentQuality/.

Prediction of positive placebo response among chronic schizophrenic outpatients.

We undertook this study to determine whether predictors of positive placebo response in chronic schizophrenic outpatients could be identified. Twelve placebo responders and 33 placebo nonresponders who participated in a parallel-group, double-blind, 12-week clinical drug trial were compared. No significant differences between the groups were found with regard to 16 anamnestic and symptom variables. To investigate further which variables at baseline predicted positive placebo response, a stepwise linear regression model was created. Of the seven variables entered into the model, only high scores in the positive domain of the Positive and Negative Syndrome Scale (delusions, unusual thought content, grandiosity, and suspiciousness/persecution) at baseline predicted significantly positive placebo response (p = .0047). Because the onset of placebo response was gradual, the authors hypothesize that placebo response in chronic schizophrenia consists mainly of two ingredients: nonspecific psychotherapeutic effect caused by the several assessments carried out during the study, and regression toward the mean.

Statistical Methods for Identifying Conserved Residues in Multiple Sequence Alignment

The assessment of residue conservation in a multiple sequence alignment is a central issue in bioinformatics. Conserved residues and regions are used to determine structural and functional motifs or evolutionary relationships between the sequences of a multiple sequence alignment. For this reason, residue conservation is a valuable measure for database and motif search or for estimating the quality of alignments. In this paper, we present statistical methods for identifying conserved residues in multiple sequence alignments. While most earlier studies examine the positional conservation of the alignment, we focus on the detection of individual conserved residues at a position. The major advantages of multiple comparison methods originate from their ability to select conserved residues simultaneously and to consider the variability of the residue estimates. Large-scale simulations were used for the comparative analysis of the methods. Practical performance was studied by comparing the structurally and functionally important residues of Src homology 2 (SH2) domains to the assignments of the conservation indices. The applicability of the indices was also compared in three additional protein families comprising different degrees of entropy and variability in alignment positions. The results indicate that statistical multiple comparison methods are sensitive and reliable in identifying conserved residues.

Efficient estimation of emission probabilities in profile hidden Markov models.

MOTIVATION Profile hidden Markov models provide a sensitive method for performing sequence database search and aligning multiple sequences. One of the drawbacks of the hidden Markov model is that the conserved amino acids are not emphasized, but signal and noise are treated equally. For this reason, the number of estimated emission parameters is often enormous. Focusing the analysis on conserved residues only should increase the accuracy of sequence database search. RESULTS We address this issue with a new method for efficient emission probability (EEP) estimation, in which amino acids are divided into effective and ineffective residues at each conserved alignment position. A practical study with 20 protein families demonstrated that the EEP method is capable of detecting family members from other proteins with sensitivity of 98% and specificity of 99% on the average, even if the number of free emission parameters was decreased to 15% of the original. In the database search for TIM barrel sequences, EEP recognizes the family members nearly as accurately as HMMER or Blast, but the number of false positive sequences was significantly less than that obtained with the other methods. AVAILABILITY The algorithms written in C language are available on request from the authors.