Biomedical subjects

A Sahgal

Publications and source records attributed to A Sahgal.

At least 19 recordsLinked to original sources

PubMed2006

Focal stereotactic external beam radiotherapy as a vision-sparing method for the treatment of peripapillary and perimacular retinoblastoma: preliminary results.

AIMS: Chemotherapy with aggressive focal ablative therapy is now the mainstay of retinoblastoma therapy. Our experience presents an evolution from conventional radiotherapy by treating posterior pole tumours with focal stereotactic fractionated radiotherapy (SRT). MATERIALS AND METHODS: A retrospective chart review was conducted of five patients (six eyes) treated with SRT at the Hospital for Sick Children and Princess Margaret Hospital, Toronto, Canada, between 1999 and 2004. The prescribed dose was 40 Gy delivered in 20 fractions once daily using 6 MV photons. RESULTS: Five patients (six eyes) were treated. The median age at the time of SRT was 18 months. The median follow-up was 46.5 months as of September 2004. Four patients were treated for a posterior pole focal tumour by focal SRT, and one patient was treated for vitreous seeding with whole-eye SRT. In patients treated with focal SRT, the median doses to the tumour, optic chiasm and brainstem were 41.92, 0.25 and 0.07 Gy, respectively, and to the ipsilateral optic nerve, globe and lens were 9.98, 19.11 and 3.74 Gy, respectively. The median doses to the ipsilateral and contralateral orbital bone were 6.73 Gy (range 5.99-8.29 Gy) and 2.31 Gy (range 0.88-7.08 Gy), respectively. A complete response (residual inactive scar tissue) was seen in four of the five focal tumours treated, with one tumour responding with a partial response (suspicious residual scar tissue). No acute or late side-effects occurred in patients treated with focal SRT. Only the patient treated with whole-eye SRT developed late effects of cataract and corneal ulceration. One patient suffered recurrence within the radiation field 5 months after focal SRT. Control of this recurrence was successful using chemotherapy and focal therapy. No eye has been enucleated. CONCLUSION: Vision-sparing focal SRT for localised tumour masses in critical locations can control tumours with minimal side-effects and a minimal dose to the surrounding critical normal tissue.

Antineoplastic Agents↗

PubMed2004

Variations in the insecticide-resistance spectrum of Anopheles stephensi after selection with deltamethrin or a deltamethrin-piperonyl-butoxide combination.

When the larvae of Anopheles stephensi, a malaria vector, were selected with deltamethrin for 40 successive generations, there was a 60-fold increase in larval resistance to deltamethrin but no increase in the resistance of the adult mosquitoes. This result, and the observation that deltamethrin selection of adults for 40 generations resulted in only a six-fold increase in adult resistance to deltamethrin, indicated some stage specificity. When F(24) deltamethrin-resistant larvae were selected with 1:5 deltamethrin-piperonyl butoxide (deltamethrin-PBO), instead of deltamethrin alone, for 16 generations, the level of resistance to deltamethrin in the F(40) larvae was reduced by 6%-21%. Similarly, selection with deltamethrin-PBO of adults of the parental strain for 20 generations reduced the speed of the development of resistance to deltamethrin, compared with that seen using selection with deltamethrin alone. Deltamethrin selection appears to select initially a monooxygenase-based mechanism. When the monooxygenase-based mechanism is blocked, by treatment with PBO, selection of a kdr-type mechanism is accelerated, as is evident from increased cross-resistance to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) in the adults selected with deltamethrin-PBO. The implications of these results are discussed in terms of the management of the larval and adult stages of An. stephensi .

Animals↗

PubMed2001

Diameter changes in isolated iliac artery aneurysms 1 to 6 years after endovascular graft repair.

OBJECTIVE: Precise diameter changes in iliac artery aneurysms (IAAs) after endovascular graft (EVG) repair are yet to be determined. This report describes the midterm size changes in isolated IAAs 13 to 72 months after treatment with an EVG. METHODS: From January 1993 to April 1999, 31 patients with 35 true isolated IAAs (32 common iliac and 3 hypogastric) had these lesions treated with EVGs and coil embolization of the hypogastric artery or its branches. The EVG used in this study consisted of a balloon-expandable stent attached to a polytetrafluoroethylene graft. Contrast-enhanced spiral computed tomographic scans were performed at 3- to 6-month intervals to follow the aneurysms for change in diameter and endoleaks. RESULTS: Thirty patients had a decrease in the size of their iliac aneurysms with EVG repair. All EVGs remained patent. All patients, except for one, were followed up for 13 to 72 months (mean, 31 months). The pretreatment aneurysm size ranged from 2.5 to 11.0 cm in diameter (mean, 4.6 +/- 1.62 cm). After EVG treatment, the aneurysms ranged from 2.0 to 8.0 cm in diameter (mean, 3.8 +/- 1.36 cm). The change in aneurysm diameter ranged from 0.5 to 3.1 cm (mean, 1.1 +/- 0.62 cm) with an average change of -0.516 +/- 0.01 cm/y for the first year. Five patients died of their intercurrent medical conditions during the follow-up period. One of the patients had a new endoleak and an increase in common iliac aneurysm size 18 months after EVG treatment, despite an early contrast-enhanced computed tomographic scan that showed no endoleak. This patient's aneurysm ruptured, and a standard open surgical repair was successfully performed. Another patient had a decrease in hypogastric aneurysm size after EVG treatment and no radiographic evidence of an endoleak, but eventually the aneurysm ruptured. He was successfully treated with a standard open surgical repair. CONCLUSIONS: EVGs can be an effective treatment for isolated IAAs. Properly treated with EVGs, IAAs decrease in size. The enlargement of an IAA, even if no endoleak can be detected, appears to be an ominous sign suggestive of an impending rupture. IAAs that enlarge should be closely evaluated for an endoleak. If an endoleak is detected, it should be eliminated if possible. If an endoleak cannot be found, open surgical repair should be considered.

Aged↗

PubMed1999

Haloperidol-induced within-session response decrement patterns and catalepsy in rats: behavioural dissociation.

The typical antipsychotic haloperidol is known to induce extra-pyramidal side-effects (EPS). Catalepsy in rats is generally regarded as a valid model for detecting the EPS liability of compounds in humans. Together with its antipsychotic and cataleptogenic actions, haloperidol causes an attenuation of instrumental responding which becomes larger in the course of a session: a within-session response decrement. The present study compared the time-course of haloperidol-induced catalepsy, measured by a bar test, to the haloperidol-induced within-session response decrements, measured by operant behaviour under a fixed ratio 10 schedule of reinforcement. Rats were trained to press a lever on a Fixed Ratio 10 schedule of food reinforcement during sessions of 15 min. When responding was stable, saline or haloperidol in 0.03 mg/kg, 0.1 mg/kg, or 0.3 mg/kg was administered intra-peritoneally either 30, 90 or 180 min prior to behavioural testing. The number of lever presses, food tray visits and latency to press the lever and to visit the food tray were analysed in five successive blocks of 3 min. Catalepsy was tested 30, 60, 90, 120, and 180 min. after injection, by placing a rat with its forepaws on a horizontal bar. The latency to remove both forepaws from the bar was scored. Within-session response decrements were present at 0.1 mg/kg and at 0.3 mg/kg, from 30 min after administration onward. At these doses, latency to press the lever was increased after 30 and 90 min, but not significantly after 180 min. Latency to visit the tray was affected only after 30 min, at 0.3 mg/kg. Haloperidol induced a dose-dependent increase in catalepsy from 60 min onwards, with maximal effect after 120 min. A dissociation between the time-course of occurrence of within-session response decrement and the cataleptogenic action of haloperidol, as well as between the latter and both latency measures, was found. Consequently, the present data suggest that within-session response decrements are not obviously caused by catalepsy-related impairments.

Animals↗

PubMed1998

Recognition memory in rats--I. Concepts and classification.

Recognition is the process by which a subject is aware that a stimulus has been previously experienced. It requires that the characteristics of events are perceived, discriminated, identified and then compared (matched) against a memory of the characteristics of previously experienced events. Understanding recognition memory, its underlying neuronal mechanisms, its dysfunction and alleviation of the latter by putative cognition enhancing drugs is a major research target and has triggered a wealth of animal studies. One of the most widely used animals for this purpose is the rat, and it is the rat's recognition memory which is the focus of this review. In this first part, concepts of recognition memory, stages of mnemonic processing and paradigms for the measurement of the rat's recognition memory will be discussed. In two subsequent articles (parts II and III) we will focus on the neuronal mechanisms underlying recognition memory in rats. Three major points arise from the comparison of paradigms that have in the past been used to assess recognition memory in rats. First, it should be realized that some tasks which, at face value, can all be considered to measure recognition memory in rats, may not assess recognition memory at all but may, for example, be based on recall rather than recognition. Second, it is evident that different types of recognition memory can be distinguished and that tasks differ in the type of recognition memory taxed. Some paradigms, for example, measure familiarity, whereas others assess recency. Furthermore, paradigms differ as to whether spatial stimuli or items are employed. Third, different processes, ranging from stimulus-response learning to the formation of concepts, may be involved to varying extent in different tasks. These are important considerations and question the predictive validity of the results obtained from studies examining, for example, the effects of putative cognition enhancing drugs.

Animals↗

PubMed1998

Recognition memory in rats--II. Neuroanatomical substrates.

A discussion of the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat warrants consideration of different, but not necessarily exclusive concepts. An important concept is the hypothesis that a dichotomy in the neural systems mediating spatial and non-spatial (item) memory exists in the rat. We have adopted a model of recognition memory suggesting that information about previously encountered items is stored in a dynamic pattern of neural activity and not in a localized representation. These patterns are features of distributed neuronal networks and different networks may process different forms of recognition memory. Two parallel-distributed neuronal networks are proposed in the rat. Network 1 is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas. Network 2 comprises the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas, especially the prelimbic cortex, and is suggested to be pivotal for the processing of spatial recognition memory.

Animals↗

PubMed1998

Recognition memory in rats--III. Neurochemical substrates.

In the first part of three overviews on recognition memory in the rat, we discussed the tasks employed to study recognition memory. In the second part, we discussed the neuroanatomical systems thought to be of importance for the mediation of recognition memory in the rat. In particular, we delineated two parallel-distributed neuronal networks, one that is essential for the processing of non-spatial/item recognition memory processes and incorporates the cortical association areas such as TE1, TE2 and TE3, the rhinal cortices, the mediodorsal thalamic nucleus and prefrontal cortical areas (Network 1), the other comprising of the hippocampus, mamillary bodies, anterior thalamic nuclei and medial prefrontal areas (Network 2), suggested to be pivotal for the processing of spatial recognition memory. The next step will progress to the level of the neurotransmitters thought to be involved. Current data suggest that the majority of drugs have non-specific, i.e. delay-independent effects in tasks measuring recognition memory. This may be due to attentional, motivational or motoric changes. Alternatively, delay-independent effects may result from altered acquisition/encoding rather than from altered retention. Furthermore, the neurotransmitter systems affected by these drugs could be important as modulators rather than as mediators of recognition memory per se. It could, of course, also be the case that systemic treatment induces non-specific effects which overshadow any specific, delay-dependent, effect. This possibility receives support from lesion experiments (for example, of the septohippocampal cholinergic system) or studies employing local intracerebral infusion techniques. However, it is evident that those delay-dependent effects are relatively subtle and more readily seen in delayed response paradigms, which tax spatial recognition memory. One interpretation of these results could be that some neurotransmitter systems are more involved in spatial than in item recognition memory processes. However, performance in delayed response tasks can be aided by mediating strategies. Drugs or lesions can alter those strategies, which could equally explain some of the (delay-dependent) drug effects on delayed responding. Thus, it is evident that neither of the neurotransmitter systems reviewed (glutamate, GABA, acetylcholine, serotonin, dopamine and noradrenaline) can be viewed as being directly and exclusively concerned with storage/retention. Rather, our model of recognition memory suggests that information about previously encountered items is differentially processed by distinct neural networks and is not mediated by a single neurotransmitter type.

Animals↗

PubMed1996

Nonverbal visual attention, but not recognition memory of learning, processes are impaired in motor neurone disease.

Pathology outside the motor system is being increasingly recognised in motor neurone disease (MND) and up to 3% of patients may have overt dementia of frontal lobe type; it is not clear whether milder cognitive disturbance is a more frequent feature of the disease. Standard neuropsychological testing can be difficult in MND and we therefore used the microcomputer-controlled Cambridge Neuropsychological Test Automated Battery (CANTAB), which allows accurate assessment in the presence of motor and bulbar dysfunction. The results of subtests evaluating nonverbal visual attention, recognition memory and learning from a large (n = 50) group of patients with MND compared to normal (n = 27) and neurological disease (n = 23) control groups are presented in this report. The MND group showed significant impairment in a focal attention (visual search) task, but no deficits in memory or learning. Inspection of the visual search data showed that up to a quarter of the MND patients scored two or more standard deviations below the mean control score. It is suggested that this reflects pathology in fronto-striatal circuitry.

Attention↗

PubMed1996

The effects of discrete cingulum bundle lesions in the rat on the acquisition and performance of two tests of spatial working memory.

Rats received one of three different surgeries in which radiofrequency lesions were made in the cingulum bundle. These consisted of either: (i) two pairs of bilateral lesions at the mid and posterior levels of the tract (M + PCB, n = 9); (ii) a single pair of bilateral lesions at the posterior level of the tract (PCB, n = 5); or (iii) a single lesion in each hemisphere, one at a posterior level the other at a mid level (CCB, n = 6). Twelve other animals acted as surgical controls (SHAM). None of the groups of animals with cingulum bundle lesions was impaired on either the acquisition or performance of an automated delayed nonmatching-to-position task in an operant chamber. In fact, following combination of the three cingulum bundle groups it was found that the lesions resulted in a small, but significant improvement in performance of this task when compared with the SHAM animals. All three groups with tract lesions were, however, impaired on an alternation task in a T-maze. This double dissociation between the two tests of spatial working memory, coupled with the comparable scores of the three lesion groups, is seen as showing that the cingulum bundle is part of a neuroanatomical circuit subserving aspects of allocentric spatial memory. The relative mildness of the alternation deficit in the present study also suggests that the bundle must be completely destroyed bilaterally to produce a pronounced deficit.

Animals↗

PubMed1996

Further developments in the measurement of working memory in rodents.

This article reviews automated test procedures that can be used to study memory for discrete/trial-unique events in rodents and other animals. A distinction is made between delayed response tasks, i.e. those tasks for which all information necessary to determine the correct response is available prior to the retention interval, and delayed comparison tasks, i.e. tasks in which the subject must compare stimuli presented prior to and after the retention interval in order to determine the correct response. Delayed comparison procedures potentially provide a purer estimate of the subject's memory capacities, but have also been more difficult for rodents to acquire. Suggestions are offered for potential directions for improved delayed comparison tasks.

Animals↗

PubMed1995

Psychopharmacological studies in rats responding at touch-sensitive devices.

A multiple choice serial reaction time task was used to investigate visual attention in rats. The intelligence panel consisted of a transparent touch-sensitive device, placed directly in front of a video monitor. Amphetamine (0.2-1.6 mg/kg IP) increased errors of omission and decreased latency to respond, but had no effect on accuracy. The 5-HT agonist quipazine (0.6-2.4 mg/kg IP) increased errors of omission, but did not affect other parameters. ICV administration of hemicholinium-3 (1-4 micrograms) had no effect upon performance. Thus, psychopharmacological manipulations can reliably alter performance in the touch window box, suggesting potential new avenues for rat cognitive testing.

Amphetamine↗

PubMed1995

The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour.

Cholinergic systems have been linked to cognitive processes such as attention, learning and mnemonic function. However, other neurotransmitter systems, such as the serotonergic one, which may have only minor effects on cognitive function on their own, interact with cholinergic function and their combined effects may have marked behavioural actions. Some studies have dealt with serotonergic-cholinergic interactions, but it is unclear whether both systems affect cognition directly or whether interactions at a behavioural level result from additional alterations in non-cognitive factors. This distinction is difficult, since it is possible that the diverse cholinergic and serotonergic systems serve different roles in the mediation of cognitive processes, both at the neuroanatomical and neurochemical level. Nevertheless, it is possible that cholinergic systems primarily alter accuracy in cognitive tasks, whereas serotonergic neurotransmission modulates behaviour by altering bias (motivation, motor processes). Whether serotonin alters accuracy or bias, however, may also depend on the cognitive process under investigation: it is suggested that attention, stimulus processing and/or arousal can be influenced by both cholinergic and serotonergic systems independently from each other. Cholinergic and serotonergic projections to cortex and thalamus may be of importance in the mediation of these cognitive processes. Serotonergic-cholinergic interactions could also be of importance in the mediation of learning processes and trial-by-trial working memory. The data available do not allow an unambiguous conclusion about the role of these interactive processes in the mediation of long-term reference memory. These processes may rely on serotonergic-cholinergic interactions at the hippocampal level. It is concluded that serotonergic-cholinergic interactions play an important role in the mediation of behavioural, including cognitive, performance, but that further studies are necessary in order to elucidate the exact nature of these interactions.

Acetylcholine↗

PubMed1995

Cholinergic lesions by 192 IgG-saporin and short-term recognition memory: role of the septohippocampal projection.

Two experiments examined the effects of cholinergic basal forebrain lesions by intraventricular and intrahippocampal infusions of the immunotoxin 192 IgG-saporin on recognition memory in an operant delayed-non-matching-to-position task in rats. Intraventricular infusions produced extensive reductions in cortical and hippocampal choline acetyltransferase activity in the first experiment. Behaviourally, a mixed delay-dependent/independent accuracy deficit and increased biased responding was observed post-lesioning. Thus, both mnemonic as well as non-mnemonic processes were affected by the lesion. This performance deficit was indistinguishable from the impairment induced by acute intraventricular injections of the choline uptake inhibitor hemicholinium-3, which suggests that cholinergic damage induced by 192 IgG-saporin disrupted performance. In the second experiment more discrete intrahippocampal 192 IgG-saporin lesions were made, which reduced hippocampal choline acetyltransferase activity about 57%, although this reduction was not as extensive as following intraventricular injections. Although intrahippocampal lesions also impaired non-matching accuracy, this effect failed to reach significance during most stages of the experiment. Scopolamine just failed to significantly impair (P = 0.053) performance in hippocampal lesioned rats more than in controls. The nicotinic antagonist mecamylamine did not affect the lesion-induced changes in performance. These results suggest that the cholinergic basal forebrain, including the septohippocampal system, is important for the mediation of recognition memory, and muscarinic receptor-mediated mechanisms may be of greater importance than alterations of nicotinic receptor-mediated processes in the septohippocampal system.

Acetylcholinesterase↗

PubMed1995

Do differences in visuospatial ability between senile dementias of the Alzheimer and Lewy body types reflect differences solely in mnemonic function?

Visuospatial memory was investigated in two groups of patients suffering from senile dementias of the Alzheimer (SDAT) or Lewy body (SDLT) types; a, third, age-matched, healthy control group was also included. The two patient groups were mildly demented and could not be distinguished from each other by traditional tests of cognitive function. A different pattern of performance emerged in the two groups on a computerised test of spatial working memory, which is a self-ordered pointing task requiring the subject to search for hidden tokens. An analysis of the pattern of errors revealed that the SDLT group made more of both possible types of error ("Within Search" and "Between Search") than the SDAT group. Neither patient groups' performance differed from each other when assessed on a computerised Corsi spatial span task. A measure of planning ability was obtained by examining search strategies. Although an index previously developed to measure the subject's use of a particular strategy in the spatial working memory task failed to detect any differences between the three groups, a novel index was calculated which focuses on performance within a search, and this revealed deficits in both demented groups. Since the two patient groups differed from each other in the spatial working memory, but not the Corsi spatial span, task, it is suggested that the differences between the two demented groups are not due to a specific mnemonic impairment, but reflect dysfunctions in non-mnemonic processes mediated by fronto-subcortical circuits, which are more severely damaged in SDLT.

Aged↗

PubMed1995

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions.

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T-maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.

Animals↗

PubMed1994

Lack of effect of lesions in the anterior cingulate cortex and retrosplenial cortex on certain tests of spatial memory in the rat.

The effects of cytotoxic lesions in either the anterior cingulate cortex or the retrosplenial cortex were compared with those of fornix lesions on three tests of spatial memory. Two of the tasks, delayed nonmatching-to-position and spatial reversal learning, were tested in an automated apparatus. The third task, forced alternation, was tested in a T-maze. Neither anterior cingulate nor retrosplenial cortex damage produced any significant impairment on the three tasks. In contrast, rats with fornix lesions (hippocampal system damage) were markedly impaired on all three tasks. The results, which were considered in the light of proposals for a hippocampal--anterior thalamic--cingulate system that is important for spatial memory, suggest that neither of the cingulate regions involved in this study form a critical subcomponent of this proposed system. It is therefore assumed that the cingulate cortices are only critical for certain classes of spatial problem. It is also suggested that in some previous studies the effects of inadvertent damage to the cingulum bundle may have contributed to the apparent effects of cingulate lesions.

Animals↗

PubMed1994

Lesions of the pedunculopontine tegmental nucleus do not alter delayed non-matching to position accuracy.

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem, and part of the reticular formation, has traditionally been linked to motor function, sleep and arousal, but has recently been implicated in cognition. To investigate this possibility, rats with radiofrequency lesions were tested on a delayed non-matching to position task, a test for spatial recognition memory abilities. Data were analysed according to the methods of signal detection theory. Lesions of the pedunculopontine nucleus did not produce marked deficits in accuracy, although there was some evidence to suggest that motivational processes could have been affected.

Acetylcholine↗

PubMed1994

The pedunculopontine tegmental nucleus: a role in cognitive processes?

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem and part of the reticular formation, has been traditionally linked to motor function, arousal and sleep. Its anatomical connections, however, raise the possibility that the pedunculopontine tegmental nucleus is also involved in other aspects of behaviour such as motivation, attention and mnemonic processes. This is of obvious importance, since the pedunculopontine tegmental nucleus undergoes degeneration in human neurodegenerative disorders also characterized by attentional and/or mnemonic deficits. Moreover, recent behavioural animal work suggests that cognitive processes may be represented in the pedunculopontine tegmental nucleus. The difficulty that faces research in this area, however is the possible influence of cognition by other processes, such as arousal state, motivation and motor function. Nevertheless, by reviewing the literature, the pedunculopontine tegmental nucleus seems to be involved in attentional and possibly also in learning processes. These processes could be mediated by influencing cortical function via the thalamus, basal forebrain and basal ganglia. The involvement of the pedunculopontine tegmental nucleus in mechanisms of memory, however, seems to be rather unlikely.

Animals↗