Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis

Context  Cholinesterase inhibitors are the primary treatment for the cognitive symptoms of Alzheimer disease (AD). Cholinergic dysfunction is also associated with neuropsychiatric and functional deficits, but results from randomized controlled trials of cholinesterase inhibitors are conflicting. Objective  To conduct a systematic review and meta-analysis to quantify the efficacy of cholinesterase inhibitors for neuropsychiatric and functional outcomes in patients with mild to moderate AD. Data Sources  We performed a literature search of trials using MEDLINE (January 1966–December 2001), Dissertations Abstracts On-line, PSYCHINFO, BIOSIS, PubMed, and the Cochrane Controlled Trials Register. We retrieved English- and non–English-language articles for review and collected references from bibliographies of reviews, original research articles, and other articles of interest. We searched for both published and unpublished trials, contacting researchers and pharmaceutical companies. Study Selection  We included 29 parallel-group or crossover randomized, double-blind, placebo-controlled trials of outpatients who were diagnosed as having mild to moderate probable AD and were treated for at least 1 month with a cholinesterase inhibitor. Sixteen trials included neuropsychiatric and 18 included functional measures. Data Extraction  Two investigators (N.H.T. and J.H.) independently extracted study methods, sources of bias, and outcomes. Neuropsychiatric outcomes were measured with the Neuropsychiatric Inventory (NPI, 0-120 points) and the Alzheimer Disease Assessment Scale, noncognitive (ADAS-noncog, 0-50 points) and were analyzed with the weighted mean difference method. Functional outcomes were measured with several activities of daily living (ADL) and instrumental activities of daily living (IADL) scales and analyzed with the standardized mean difference method. Data Synthesis  For neuropsychiatric outcomes, 10 trials included the ADAS-noncog and 6 included the NPI. Compared with placebo, patients randomized to cholinesterase inhibitors improved 1.72 points on the NPI (95% confidence interval [CI], 0.87-2.57 points), and 0.03 points on the ADAS-noncog (95% CI, 0.00-0.05 points). For functional outcomes, 14 trials used ADL and 13 trials used IADL scales. Compared with placebo, patients randomized to cholinesterase inhibitors improved 0.1 SDs on ADL scales (95% CI, 0.00-0.19 SDs), and 0.09 SDs on IADL scales (95% CI, 0.01 to 0.17 SDs). There was no difference in efficacy among various cholinesterase inhibitors. Conclusions  These results indicate that cholinesterase inhibitors have a modest beneficial impact on neuropsychiatric and functional outcomes for patients with AD. Future research should focus on how such improvements translate into long-term outcomes such as patient quality of life, institutionalization, and caregiver burden.      

The timing of spinal fusion in adolescent idiopathic scoliosis

102 cases of idiopathic adolescent scoliosis seen over a period of 5 years were studied. 59 patients who were treated surgically and followed up for a minimum of 48 months, fell into one of two groups: Group I - those operated on within 3 years following the adolescent growth spurt, and Group II - those who were operated on at or after skeletal maturity. 35 patients were treated by Harrington instrumentation and posterior fusion and 24 by Harrington instrumentation, segmental sublaminar wiring and posterior fusion. In 7 patients anterior release was performed initially. In Group I, the extent of deformity correction and elimination of the rib hump were better, and complications such as neurological deficit, hook dislodgement and implant breakage were encountered less frequently. Harrington instrumentation, segmental sublaminar wiring and posterior fusion gave better results than instrumentation and fusion. Our results suggest that surgical correction should be done within 3 years following growth spurt, i.e. 14 to 16 years of age.     

Retroperitonial atypical lipomatous tumour--a case report

We report a case of atypical lipomatous tumor-sclerosing type, a rare retroperitoneal soft tissue liposarcoma, presented with vague musculoskeletal symptoms. Patient was managed with complete resection of the tumor mass with adjuvant chemotherapy. The patient is doing well, with no evidence of recurrence 22 months after the treatment.     

Accelerated transplant coronary artery disease and massive silent acute myocardial infarction in a heart transplant patient--a case report and brief review of literature

This case report describes an aggressive form of accelerated atherosclerosis predicted early after transplant by dobutamine stress echocardiography in a patient who died of massive myocardial infarction 32 months after transplantation. The main objective finding of this event was markedly increased cardiac filling pressures during an elective cardiac catheterization and coronary angiography. The literature is briefly reviewed.     

Diagnosis of superficial mycoses by direct microscopy - A statistical evaluation

A mycological study was undertaken in 250 cases of superficial mycotic infections, which included 210 cases of dermatophytosis, 18 cases of cutaneous candidiasis and 22 cases of tinea versicolor. The scrapings from all the cases were subjected to direct microscopic examination in 10% KOH solution and culture was done in case of candidiasis and dermatophytosis. Out of 250 cases direct microscopy was positive (KOH +ve) in 88 cases of dermatophytosis, 11 cases of candidiasis and all cases of tinea versicolor. Culture for dermatophytes and candida species in SDA medium were positive in 76 and 9 cases respectively. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and the overall efficiency of the direct microscopy in the diagnosis of superficial mycotic infections were calculated to be 89.41%, 83.90%, 76.76%, 93.02% and 85.96% respectively.     

Determination of soil, sand and ore primordial radionuclide concentrations by full-spectrum analyses of high-purity germanium detector spectra

The full-spectrum analysis (FSA) method was used to determine primordial activity concentrations (ACs) in soil, sand and ore samples, in conjunction with a HPGe detector. FSA involves the least-squares fitting of sample spectra by linear combinations of ²³⁸U, ²³²Th and ⁴⁰K standard spectra. The differences between the FSA results and those from traditional windows analyses (using regions-of-interest around selected photopeaks) are less than 10% for all samples except zircon ore, where FSA yielded an unphysical ⁴⁰K AC.     

ECG beat classification using empirical mode decomposition and mixture of features

Computer-aided analysis is useful in predicting arrhythmia conditions of the heart by analysing the recorded ECG signals. In this work, we proposed a method to detect, extract informative features to classify six types of heartbeat of ECG signals obtained from the MIT-BIH Arrhythmia database. The powerful discrete wavelet transform (DWT) is used to eliminate different sources of noises. Empirical mode decomposition (EMD) with adaptive thresholding has been used to detect precise R-peaks and QRS complex. The significant features consists of temporal, morphological and statistical were extracted from the processed ECG signals and combined to form a set of features. This feature set is classified with probabilistic neural network (PNN) and radial basis function neural network (RBF-NN) to recognise the arrhythmia beats. The process achieved better result with sensitivity of 99.96%, and positive predictivity of 99.81 with error rate of 0.23% in detecting the QRS complex. In class-oriented scheme, the arrhythmia conditions are classified with accuracy of 99.54%, 99.89% using PNN and RBF-NN classifier respectively. The obtained result confirms the superiority of the proposed scheme compared to other published results cited in literature.     

Glanzmann's thrombasthenia: updated

Glanzmann's thrombasthenia is an autosomal recessive disorder, rare in a global context, but a relatively more common platelet function defect in communities where consanguineous marriages are more frequent. On clinical grounds alone, it cannot be distinguished from other congenital platelet function defects. Epistaxis, gum bleeding, menorrhagia are the common clinical manifestations, whereas large muscle hematoma or hemarthrosis seldom occur in these patients. Essential diagnostic features are a normal platelet count and morphology, a greatly prolonged bleeding time, absence of platelet aggregation in response to ADP, collagen, epinephrine, thrombin and to all aggregating agents which ultimately depend on fibrinogen binding to platelets for this effect, flow cytometry, studies of GPIIb-IIIa receptors on the platelet membrane surface using monoclonal antibodies. The present review describes some of the uncommon features of the disorders and the currently available options which the treating physicians should be aware of during the management of these patients. Although by definition all patients with Glanzmann's thrombasthenia have a virtually complete failure of platelet aggregation, a number of variant forms of GT have been described in which the glycoproteins are present in normal or near normal amounts but are functionally defective. Understanding the pathophysiology of the disorder by the treating physicians is of utmost importance. Presence of high affinity platelet receptors resulting in thrombasthennia-like phenotype may require an antagonistic treatment atypical of classical GT management. It has now been established that different genetic mutations of either GPIIb or IIIa genes results in such a heterogeneity of thrombasthenia phenotype. Glanzmann's thrombasthenia is a paradigm for treating coronary artery disease patients with GPIIb-IIIa antibody and inhibitors. By using these medicines we create a temporary GT-like situation. Hence, understanding this disease is of utmost importance to the practicing cardiologist. As mutations for different variant forms of GT become known, our understanding of how GPIIb-IIIa molecules can be activated to act as a receptor for fibrinogen molecules will be increased. Such understanding undoubtedly will help us to devise better drugs with GPIIb-IIIa inhibitors. Molecular biology techniques have enabled us to equivocally detect heterozygote carriers who are clinically asymptomatic. However, there may be several laboratories in the developing world, which have no access to molecular biology techniques. Development of more robust techniques of quantitation of platelet receptors has enabled an accurate diagnosis of heterozygote carriers or an unborn fetus in the second trimester. The importance of the GPIIb-IIIa polymorphisms in carrier and prenatal diagnosis has not been properly studied. Nowadays the less direct method of PLA1 typing (determination of the levels of platelet antigen) of the foetal platelets as early as 16 weeks of intrauterine life can be used for prenatal diagnosis of GT.     

Pyruvate inhibits galactosemic changes in cultured cat lens epithelial cells

An attempt was made to maintain cat lens epithelial cells (CLEC) in culture and study the morphology, growth and survival of these cells in vitro. The influence of incorporation of galactose (30 mM) into the culture medium on the morphology and biochemistry of CLEC in the primary culture was then investigated. To establish the effect of galactose on CLEC, various biochemical parameters associated with galactosemic cataract such as aldose reductase (AR), Na+K+ATPase, glutathione, polyol and soluble/insoluble proteins were estimated after 24 h of incubation. The effect of pyruvate (5 mM), a 'physiological antioxidant', on the changes induced by galactose in CLEC was studied. CLEC in culture showed regular hexagonal cells with prominent nuclei. The CLEC culture attained confluency in 11 days during primary culture and semiconfluency in 14 days in two subsequent passages. Vacuolization and significantly raised AR activity, polyol levels and insoluble protein contents were observed; they had no effect on Na+K+ATPase and soluble protein after 24 h of incubation in the culture medium with galactose. Supplementation of pyruvate (5 mM) resulted in a lesser number of vacuoles together with a positive modulation of these parameters.