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T Sharma

Publications and source records attributed to T Sharma.

At least 19 recordsLinked to original sources
PubMed2006

Olanzapine and haloperidol in first episode psychosis: two-year data.

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.

Adult↗
PubMed2005

Visual impairment in elderly patients with hip fracture: causes and associations.

AIMS: To evaluate the current visual status and ophthalmic history of a sample of elderly patients with fractured neck of femur and to study the relationship between visual status and demographic factors. METHODS: A four-centre study of all patients admitted to hospital with fractured neck of femur. The setting was two district (Ayr, Dunfermline) and two teaching (Glasgow, Dundee) hospitals in Scotland. The study examined 537 patients aged 65 years and over admitted with acute fractured neck of femur to hospital. RESULTS: Bilateral visual impairment (binocular visual acuity worse than 6/12) was found in 239 of 518 patients (46%). Of this group, the principal causes for visual deficit were untreated cataract (49%), macular degeneration (21%), uncorrected refractive error (17%), and glaucoma (3%). The visually impaired group were more likely to have symptomatic visual complaints (58 vs 26%), however, were less likely to be under optometric care (71 vs 85%). A higher proportion of the group with visual impairment lived in areas of social deprivation (40 vs 26%). CONCLUSIONS: Patients with fractured neck of femur represent a frail elderly group that have poorer vision than that documented in any other elderly population. The visual defect was potentially remediable in the majority of cases but this group of individuals are not generally in touch with the ophthalmic services. Social deprivation appears to be associated with this groups' inability to access ophthalmic care.

Aged↗
PubMed2005

Optometric and ophthalmic contact in elderly hip fracture patients with visual impairment.

AIM: To describe previous contact with optometry and ophthalmic services in a group of elderly patients with and without visual impairment (VI) who had fallen and sustained a fractured neck of femur. METHOD: A cross sectional study of 537 patients aged 65 and over who had undergone hip fracture surgery in four Scottish centres (Glasgow, Ayr, Dundee and Fife). All patients had an in-depth optometric history, ophthalmic history and examination. RESULTS: Three hundred and ninety-three (79%) patients reported optometric contact in the 3 years preceding surgery and 107 (21%) patients had not seen an optometrist for more than 3 years. In the latter group, 64 had VI, which was due to uncorrected refractive error in 17 (27%) and untreated cataract in 20 (31%). VI (best binocular visual acuity of 6/18 or less) was found in 239 (46%) patients. A past ophthalmic history was present in 257 (50%) patients. Only 39 (16%) patients with VI were under ophthalmic care at the time of the study. CONCLUSIONS: There was significantly poor optometric and ophthalmic contact in patients who had VI and had fallen and sustained hip fracture. A proportion of the VI (66%) was due to uncorrected refractive error and untreated cataract. Public health providers should be made aware of the fact that current optometric and ophthalmic care pathways are not accessed by this group of elderly patients with VI and at risk of falling.

Accidental Falls↗
PubMed2005

Cognitive functioning in siblings discordant for schizophrenia.

OBJECTIVE: The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings. METHOD: Cognitive functioning in 25 individuals with schizophrenia, 25 unaffected siblings and 25 unrelated healthy controls, was assessed using neuropsychological tests of sustained attention, memory and learning, executive function, visual-spatial ability and psychomotor performance. RESULTS: Unaffected siblings demonstrated better performance than patients on some measures of memory and learning and executive function. Patients and siblings demonstrated impaired Full Scale IQ and verbal fluency, otherwise siblings performed similarly to healthy controls. Controlling for differences in IQ, the shared deficit in verbal fluency disappeared. CONCLUSION: Patients with schizophrenia and unaffected siblings (without schizotypy personality disorder) shared a neuropsychological deficit in verbal fluency. This deficit appeared to be mediated by IQ. Deficits, which differentiated patients from controls, may not be inherited and perhaps are related to the manifestation or treatment of schizophrenia.

Adult↗
PubMed2004

Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role.

With evolving diagnostic and therapeutic advances, the survival of patients with acute leukaemia has considerably improved. This has led to an increase in the variability of ocular presentations in the form of side effects of the treatment and the ways leukaemic relapses are being first identified as an ocular presentation. Leukaemia may involve many ocular tissues either by direct infiltration, haemorrhage, ischaemia, or toxicity due to various chemotherapeutic agents. Ocular involvement may also be seen in graft-versus-host reaction in patients undergoing allogeneic bone marrow transplantation, or simply as increased susceptibility to infections as a result of immunosuppression that these patients undergo. This can range from simple bacterial conjunctivitis to an endophthalmitis. Leukaemia can present as pathology in the adnexae, conjunctiva, sclera, cornea, anterior chamber, iris, lens, vitreous, retina, choroid, and optic nerve. Recognition of the varied ocular presentations is also important in assessing the course and prognosis of leukaemia. We have presented a systematic approach taking each part of the eye in turn and outlining how leukaemia has been shown to affect it.

Acute Disease↗
PubMed2004

The relationship of sex hormones and cortisol with cognitive functioning in Schizophrenia.

Gonadal as well as stress hormones have recently been implicated in pathophysiology and sex differences in onset, prognosis and treatment of schizophrenia. The present study investigated the effects of serum levels of oestrogen, progesterone, testosterone and cortisol on neuropsychological functioning and psychopathology in a group of 37 patients (17 women, 20 men) with schizophrenia. Neuropsychological measures included tests of attention, verbal abilities, language, memory, executive functioning, motor and speed of information processing. The results showed that oestrogen and age was associated with low positive symptom scores, and within gender, cortisol predicted poor performance on the information processing domain in men. These findings demonstrate that cortisol, in addition to the commonly reported effects of oestrogen, influences neuropsychological functioning in schizophrenia with differential effects on specific domains of cognitive functioning and underscore the need for further investigation of the modulating role of hormones on neuropsychological functioning in schizophrenia.

Adolescent↗
PubMed2003

The functional neuroanatomy of schizophrenic subsyndromes.

BACKGROUND: There is considerable variability between patients in their expression of the diverse range of symptoms encompassed by the syndrome of schizophrenia, which may modulate functional activation to cognitive processing. METHOD: Here we investigate associations between schizophrenic subsyndrome scores, identified by factor analysis, and experimentally controlled brain activation. Five factors were defined by rotated principal components analysis of PANSS rating scale measurements in 100 patients with schizophrenia. A subsample of 30 patients and a group of 27 comparison subjects were studied using functional magnetic resonance imaging (fMRI) during the performance of two periodically designed cognitive activation experiments: verbal working memory and psychomotor sequencing. RESULTS: Factor analysis replicated the five dimensions consistently reported. Within the patient group. power of activation by working memory was negatively associated with global symptom severity in left lingual and temporo-parietal cortices; negatively associated with positive subsyndrome scores in left inferior frontal and superior temporal cortices and basal ganglia; and positively associated with negative subsyndrome scores in lateral and medial premotor cortex. No relationship was observed between subsyndrome scores and functional activation during the motor task. Between-group comparisons demonstrated reduced power of response to the working memory task by patients in bilateral dorsolateral prefrontal and left pre- and post-central cortices. CONCLUSIONS: In this study we observed task-specific modulation of functional response associated with symptom expression in schizophrenia. Our findings are compatible with previous empirical findings and theoretical conceptualization of human brain function, in terms of capacity constraints on activation in the face of competing demands from pathological and task-related cognitive activity.

Adult↗
PubMed2003

Neuroimaging of sexual arousal: research and clinical utility.

The treatment of sexual dysfunction or deviancy requires an understanding of the underlying neural substrates. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. The development of robust paradigms has implications for the assessment and treatment of sexual disorder in men and women.

Adolescent↗
PubMed2003

Differential organization of a LINE-1 family in Indian pygmy field mice.

Southern blot hybridization analysis of genomic DNAs digested with restriction endonuclease EcoR I and Ava II from Mus musculus domesticus, Mus booduga and Mus terricolor with a cloned repetitive DNA fragment of Mus booduga as a probe showed difference in restriction pattern of this DNA in these three species. Further Southern analysis of the BamH I digested genomic DNAs from these species hybridized with cloned DNA fragment as a probe and sequencing of the cloned DNA revealed that this 252 bp cloned DNA fragment is a part of BamHI repeat element of genus Mus and is 87% homologous to the contiguous portion of the Mus musculus domesticus LINE-1 element. The species specific fragment pattern generated by different restriction endonucleases using this DNA as a probe revealed difference in the organization of LINE-1 repetitive element in the three species of genus Mus.

Animals↗
PubMed2002

Multidimensional scaling of integrated neurocognitive function and schizophrenia as a disconnexion disorder.

Multidimensional scaling (MDS) is a multivariate statistical technique that can be used to define subsystems of functionally connected brain regions based on the analysis of functional magnetic resonance imaging (fMRI) data. Here we introduce three-way multidimensional scaling as a method for the analysis of a group of fMRI data, which yields both a generic interregional configuration in low-dimensional space and a measure of each individual's deviation from the generic configuration. The distance between two generic interregional configurations obtained by MDS of two groups of data can be minimized by generalized Procrustes analysis, and the probability under the null hypothesis (that the two groups are sampled from the same population) of any residual group difference in interregional configurations can be assessed by a permutation test. These methods are developed and applied to activated fMRI time series acquired from 19 patients with schizophrenia and 20 normal comparison subjects during the performance of a semantic categorization and subvocal rehearsal task. The first three scaling dimensions are interpretable in terms of the major anatomical or functional subsystems of the activated system: "left-right," "input processing-other," and "subvocal output-other". We found no significant global or local differences between groups in interregional configurations in this 3D space. However, there was significantly greater variability of interregional configurations within the group of patients with schizophrenia. The implications for schizophrenia as a disconnexion disorder are discussed.

Adult↗
PubMed2002

Inducible nitric oxide synthase gene and diabetic retinopathy in Asian Indian patients.

Nitric oxide, a signal transduction molecule, when modulated causes various diseases including diabetic retinopathy. In diabetes, allelic polymorphism of the inducible nitric oxide synthase (iNOS) gene is associated with retinopathy in the Northern Irish population. In the present study we investigated the Asian Indian population. One hundred and ninety-nine unrelated Asian Indian patients with 15 or more years of type 2 diabetes were divided into two groups: (a) diabetic retinopathy (DR) and (b) diabetic nonretinopathy (DNR) subjects. In these groups the pentanucleotide microsatellite repeat located 2.5 kb upstream of the transcription start site of the iNOS gene was amplified by polymerase chain reaction and analyzed. Eleven alleles, 175-225 bp, were identified. Allele 210 bp was significantly associated with retinopathy (p = 0.044). Individuals carrying this allele had twice the risk of developing retinopathy compared with those who did not carry this allele [odds ratio (OR) - 2.03; 95% CI 0.96-4.35]. Alleles 200 and 220 bp were also significantly associated with no retinopathy and no serious retinopathy complications, respectively. In the Asian Indian population, allele 210 bp of the iNOS gene is a high-risk allele for developing retinopathy and alleles 200 and 220 bp protect an individual from developing retinopathy or its complications.

Alleles↗
PubMed2002

Increases and decreases of whole-arm heterochromatin in specific chromosomes: an extraordinary situation in hybrids of the Mus terricolor complex.

The three chromosomal species of Mus terricolor display fixed variations in the short-arm heterochromatin of autosomes 1, 3, and 6. Some laboratory-generated hybrids among the chromosomal species show an unusual increase or decrease in the extent of whole-arm heterochromatin, instead of the expected heterozygosity for the heterochromatic short arms. The whole-arm increase/decrease tends to favor homozygosity for the presence or absence of the heterochromatic short arms. Interestingly, this increase/decrease conforms with the karyotypes of the parental chromosomal species. Although rapid karyotypic changes have been reported in other plant and animal hybrids, the situation observed in the M. terricolor hybrids is unique. The changes are stable and could be a product of the unusual chromosomal organization of recombinogenic telomeric sequences in this species complex. The altered karyological constitution is constant in both somatic and germ cells of each hybrid, suggesting that the changes occurred early in their development. The high frequency and nonrandom recurrence of similar changes in different hybrids seem to reflect a mechanism that might have been instrumental in the fixation of these chromosomal variations in a stable homozygous condition in natural populations.

Animals↗
PubMed2002

Effects of 10 mg and 15 mg oral procyclidine on critical flicker fusion threshold and cardiac functioning in healthy human subjects.

The critical flicker fusion threshold (CFFT) is thought to index alertness and cortical arousal. Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in schizophrenia. This study examined the effects of clinically relevant doses of oral procyclidine administration on CFFT and heart rate in two separate experiments (Experiment 1, drug dose: 10 mg, n = 16; Experiment 2, drug dose: 15 mg, n = 12) involving healthy subjects using a double-blind, placebo-controlled, cross-over design. 10 mg procyclidine had no significant effect on CFFT, heart rate or self-ratings of mood, but the 15 mg dose significantly lowered CFFT at 1 h and 2 h after procyclidine administration, increased drowsiness ratings and produced a drop in heart rate. The effects observed in this study may have implications for treatment compliance of schizophrenic patients, choice of antipsychotics, prescribing to patients with heart disease and monitoring of cardiac function under treatment. Further investigations are required to quantify the effects of procyclidine on CFFT and cardiac function in patients with schizophrenia.

Adult↗
PubMed2002

Impact on cognition of the use of antipsychotics.

Cognitive dysfunction is recognised as one of the more enduring deficits in schizophrenia. The syndrome is associated with impairment of the temporal and frontal regions of the brain that are concerned with cognitve function, as well as subcortical regions that are closely interconnected with them. Cognitive dysfunction may underpin some of the psychopathology of schizophrenia, as well as contribute to the patient's impaired social and vocational functioning. Cognitive deficits are relatively independent of psychotic symptoms in schizophrenia, and are probably central and enduring features of the disorder. It must also be considered that cognitive disability may be rate-limiting to the schizophrenic patient's rehabilitation and impairs quality of life. Although there is a general consensus that neuroleptic drugs are able to improve the psychopathology of schizophrenia, there is continued debate concerning their impact on cognitve function. Chronic treatment with classical neuroleptics has been reported to produce only minimal improvement in, and may actually impair, cognitive function in schizophrenia. In contrast, novel antipsychotics seem to cause less cognitive impairment than classical antipsychotic medication and may improve cognitive function. Whilst in the past research focused on the development of clinically effective antipsychotic drugs with a reduced propensity to cause extrapyramidal symptoms (EPS), it is now being recognised that maintaining and enhancing cognitive function and improving quality of life should be the goal in the treatment of schizophrenia.

Antipsychotic Agents↗
PubMed2001

Neuroimaging correlates of negative priming.

Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

Adult↗
PubMed2001

An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function.

Functional magnetic resonance imaging (fMRI) was used to investigate the hypothesis that schizophrenia is associated with a dysfunction of prefrontal brain regions during motor response inhibition. Generic brain activation of six male medicated patients with schizophrenia was compared to that of seven healthy comparison subjects matched for sex, age, and education level while performing 'stop' and 'go-no-go' tasks. No group differences were observed in task performance. Patients, however, showed reduced BOLD signal response in left anterior cingulate during both inhibition tasks and reduced left rostral dorsolateral prefrontal and increased thalamus and putamen BOLD signal response during stop task performance. Despite good task performance, patients with schizophrenia thus showed abnormal neural network patterns of reduced left prefrontal activation and increased subcortical activation when challenged with motor response inhibition.

Adult↗
PubMed2001

Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects.

BACKGROUND: Local alterations in morphological parameters are poorly characterized in several brain regions widely implicated in schizophrenia neuropathology. METHODS: Surface-based anatomical modeling was applied to magnetic resonance data to obtain three-dimensional (3D) average anatomical maps and measures of location, shape, asymmetry, and volume for the lateral ventricles, hippocampus, amygdala, and superior temporal gyrus in schizophrenic (n = 25; 15 male) and normal subjects (n = 28; 15 male) matched for demographic variables. For all regions, intra-group variability was visualized and group differences assessed statistically to discriminate local alterations in anatomy across sex and diagnosis. RESULTS: Posterior hippocampal volumes, lengths, and widths were reduced in patients. The right amygdala showed volume increases in schizophrenia patients versus controls. Ventricular enlargements, pronounced in the left hemisphere, occurred in the superior and lateral dimensions in patients, and these effects interacted with gender. Superior horn anterior extremes, inferior horn volumes, and hippocampal asymmetries exhibited gender effects. Significant group differences were absent in superior temporal gyrus parameters. Finally, regional variability profiles differed across groups. CONCLUSIONS: Clear morphometric differences of the lateral ventricles, hippocampus, and amygdala indicate regional displacements and shape distortions in several functional systems in schizophrenia. Alterations in these structures as mapped in 3D may provide the foundation for establishing brain abnormalities not previously defined at such a local level.

Adult↗