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Biomedical subjects

A Shuaib

Publications and source records attributed to A Shuaib.

At least 91 records · Page 5Linked to original sources
PubMed1995

Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis.

The underlying mechanisms of neuronal dysfunction in head injury are multifactorial and not fully understood. Recent experimental evidence indicates that excitatory amino acids--for example, glutamate--may play a key part in secondary neuronal damage after head injury. A patient with severe head trauma was monitored for extracellular amino acids by intracerebral in vivo microdialysis. Very high concentrations of glutamate, glycine, and gamma-aminobutyric acid were recorded in the microdialysate specimens collected over three hours. In vivo microdialysis in head injury may prove to be a useful tool in understanding the pathogenesis of cell death in head trauma.

Adult↗
PubMed1995

Transcranial Doppler ultrasonography and transesophageal echocardiography in the investigation of pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia presenting with stroke.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is associated with a high incidence of pulmonary arteriovenous malformations (PAVMs), which can be the underlying cause for cerebral ischemia or brain abscess. The diagnosis of these malformations may be difficult, as clinical or radiological findings may be absent. Transcranial Doppler ultrasound (TCD) with saline contrast and transesophageal echocardiography (TEE) with saline contrast are useful in identifying patients with right-to-left shunts and may help identify PAVMs. CASE DESCRIPTION: A 68-year-old woman with HHT presented with two strokes over a 1-year period. After the first stroke, a transthoracic echocardiogram with saline contrast demonstrated significant right-to-left shunt that was interpreted as a patent foramen ovale. After the second stroke, a TCD contrast study confirmed this right-to-left shunt; however, a TEE contrast study discovered an extracardiac shunt. Pulmonary angiography revealed a left lower lobe PAVM and three telangiectasias involving the right lung. The PAVM was subsequently embolized. Postembolization radiographic imaging showed complete occlusion of the feeding vessel to the PAVM. However, repeated contrast TCD and TEE demonstrated persistent right-to-left shunting. CONCLUSIONS: In our patient, stroke may have resulted from peripheral venous emboli passing through the PAVM or from endogenous thromboemboli originating within the PAVM. TCD and TEE contrast studies were helpful in judging the efficacy of catheter embolization therapy of PAVM. TCD and TEE with saline contrast may be clinically useful follow-up examinations for recurrence or development of new PAVMs.

Aged↗
PubMed1995

Intracerebral human microdialysis. In vivo study of an acute focal ischemic model of the human brain.

BACKGROUND AND PURPOSE: In vivo microdialysis was introduced in 1982 as a technique to study cerebral neurochemistry in awake, freely moving animals. In small animals, bilateral carotid occlusion produces a 7- to 10-fold increase in extracellular glutamate concentrations. This rapidly falls with reperfusion. Increase in extracellular glutamate is currently believed to be a major factor in initiating neuronal injury. Glutamate antagonists are currently undergoing clinical trials in acute stroke. Human data on the extracellular levels of glutamate and other amino acids in the normal or ischemic brain are limited. In this communication we wish to report the extracellular concentrations of glutamate, serine, glutamine, glycine, taurine, alanine, and gamma-aminobutyric acid, as monitored by in vivo microdialysis, in the simulated ischemic model of the temporal lobe of the human brain. METHODS: Intracerebral microdialysis was carried out in five patients who underwent resection of the temporal lobe for intractable epilepsy. Surgical excision leads to an acute (from partial to total, ie, from incomplete to complete) ischemic state of the resected brain. This was our model to study the changes in human extracellular fluid during acute focal ischemic conditions. RESULTS: Extracellular glutamate concentrations were 15 to 30 mumol/L in the preischemic samples. This increased to 380.69 +/- 42.14 mumol/L with partial (incomplete) ischemia and reached a peak of 1781.67 +/- 292.34 mumol/L (> 100-fold) with total isolation of the temporal pole (complete ischemia). The levels fell to 394.52 +/- 72.93 mumol/L 20 minutes after resection. Similar trends were observed with the onset of ischemia in the dialysate levels of serine, glutamine, glycine, alanine, taurine, and gamma-aminobutyric acid. CONCLUSIONS: Our results show that there is a significant increase in extracellular glutamate and other neurotransmitters with ischemia in the temporal lobe model of the human brain. This increase is of a higher magnitude than that in small animals.

Amino Acids↗
PubMed1994

Progressive decrease in extracellular GABA concentrations in the post-ischemic period in the striatum: a microdialysis study.

Repetitive cerebral ischemia in gerbils produces delayed neuronal damage in the substantia nigra reticulata (SNr). This damage begins 4 to 5 days after the insult and is severe by day 7. The damage can be attenuated by GABA agonists. There is a prominent GABAergic striatal pathway to the SNr. Damage to this pathway leads to progressive loss of SNr neurons. This loss can be prevented by GABA agonists. We postulate that, ischemia-induced lack of GABAergic inhibitory input from the striatum to the SNr, may be responsible for this delayed neuronal damage. In the present experiment, we have measured striatal extracellular GABA concentrations with or without nipecotic acid, a GABA-reuptake inhibitor, in gerbils exposed to repetitive ischemia. GABA levels were measured on days 1, 3, 5, and 7 after the ischemic insult. Five control animals and a similar number of ischemic animals were monitored on each day. Extracellular fluid was collected using in vivo microdialysis and GABA levels were measured by electrochemical detection with HPLC. The extracellular striatal GABA levels were very low in the initial three specimens collected, both in the control and in the ischemic animals. However, addition of nipecotic acid resulted in an immediate increase of GABA in measurable range. In comparison to the controls, the increase in GABA on day 1 and 3 were significantly higher in animals with repetitive ischemia (two-way ANOVA with repeated measures). Subsequent measurements showed a gradual decrease in GABA levels when compared to controls. The increase in GABA with nipecotic acid was significantly lower on day 7 after the ischemic insults when compared to the controls. The increased GABA responsiveness immediately after the ischemic insults may reflect a protective effect against excitotoxicity. The subsequent decline in GABA levels after the insult may be secondary to progressive loss of striatal GABAergic neurons. This may contribute to the production of delayed neural damage in the SNr by a decrease in the inhibitory striatal input.

Animals↗
PubMed1994

High extracellular GABA levels in hippocampus--as a mechanism of neuronal protection in cerebral ischemia in adrenalectomized gerbils.

Adrenalectomy protects the brain from delayed neuronal damage that occurs following transient forebrain ischemia in gerbils. Gamma-amino butyric acid (GABA) and GABA-mimetic drugs also have a neuro-protective effect. In this study we estimated the extracellular glutamate and GABA levels in the hippocampus during transient forebrain ischemia in adrenelectomized gerbils (n = 8) compared to controls (n = 6). Duration of ischemia was 10 min, and glutamate and GABA levels were measured with in vivo microdialysis. Microdialysis was started 2 h after the placement of a probe (to stabilise baseline) and samples were collected at 10-min intervals. The pattern of glutamate release did not show any difference between adrenelectomized animals and controls. Adrenelectomized animals showed marked increase in GABA levels during ischemia and upto 30 min after ischemia (P = 0.0287, 2-way ANOVA for repeated measurements). The enhanced GABA release may be one of the possible mechanisms of neuronal protection against ischemia in adrenelectomized gerbils.

Adrenalectomy↗
PubMed1994

Comparisons of repetitive-and single-insult ischaemia: effects on regional brain damage and behaviour.

Single- and repetitive-insult ischaemia have been used with the gerbil to model human stroke and the impact of anti-ischaemic agents. It is currently not well-established whether the duration of an ischaemic insult, or single vs repetitive insults may have different behavioural consequences. In this study, groups of gerbils were given either single- or repetitive-insult ischaemia of either 3, 6 or 9 min cumulative duration. As the cumulative duration of ischaemia was increased, the degree of brain damage correspondingly increased and performance in a water maze task was progressively more impaired. However, no behavioural or brain-damage differences were found between groups of animals which received comparable durations of single- or repetitive-insult ischaemia. Significant mortality was observed in the group receiving three 3 min ischaemic insults, suggesting that the repetitive ischaemia technique may be limited to brief periods of occlusion. We conclude that there are no grounds for distinguishing between the single- and repetitive-ischaemia paradigms when employing cumulative durations up to 9 min.

Animals↗
PubMed1994

Mortality in gerbils with repetitive ischemia: CGSGS-19755/hypothermia therapy.

Repetitive ischemia causes more severe damage than a single insult of comparable duration. Gerbils were followed for 1 month postrepetitive ischemia and 100% mortality was demonstrated in the unprotected ischemia group by 12 days postischemia. Significant protection against mortality due to repetitive ischemia was offered by both CGS-19755 and combination CGS-19755-hypothermia treatments. Current practices of sacrificing repetitive ischemia subjects shortly postischemia may lead to an underestimation of the effects of ischemia and/or an overestimation of the protective effects of experimental treatments.

Animals↗
PubMed1994

Pulmonary embolism: an under-recognized yet frequent cause of death in parkinsonism.

There are very few detailed reports on the cause of death in patients with Parkinson syndrome, and most reports lack postmortem verification. Pulmonary embolism has been reported as an infrequent terminal event. We reviewed the results of 60 complete autopsies performed on patients with Parkinson syndrome personally cared for at our institution. Pulmonary embolism was second only to pneumonia as the most common cause of death overall.

Adult↗
PubMed1994

Hypothyroidism protects the brain during transient forebrain ischemia in gerbils.

The mechanisms by which brain cells die after brief episodes of cerebral ischemia are not fully understood. In certain brain regions this damage may not be apparent for days. Hypothyroidism is known to decrease cerebral metabolism. We postulated that this slowing in cerebral metabolism may be neuroprotective after transient cerebral ischemia. To test this hypothesis, a total of 10 gerbils had thyroidectomies performed 2 weeks prior to ischemia. Six gerbils served as euthyroid controls. All animals were exposed to 5 min of transient ischemia and sacrificed 7 days after the insult. Silver degeneration staining was used for histological evaluation. Hippocampal damage [subiculum (P < 0.001), CA1 (P = 0. < .001), CA3 (P < 0.05), and CA4 (P < 0.001)] was significantly less in the hypothyroid animals. There was also significantly less damage in the cerebral cortex (P < 0.05) and thalamus (P < 0.05) in the hypothyroid animals. The exact mechanism of this protection is not fully understood but could be secondary to a decrease in the metabolic activity, or a reduced generation of free radicals (as is seen with protection from ischemia in kidney and liver under hypothyroid conditions). Further studies are required in order to gain a better understanding of the protective effects of hypothyroidism on cerebral ischemia.

Animals↗
PubMed1994

Decreased glutamate release during hypothyroidism may contribute to protection in cerebral ischemia.

Hypothyroidism protects the brain from the effects of transient forebrain ischemia in gerbils. The mechanism for this protection is not fully understood. In this study we looked at the release of glutamate during ischemia in gerbils exposed to surgical hypothyroidism (n = 7), chemical hypothyroidism (n = 8), and surgical hypothyroidism thyroxine-treated (n = 3) and compared them to control euthyroid animals (n = 8). The duration of ischemia was 10 min. Glutamate release was measured with in vivo microdialysis. Microdialysis analysis began 2 h after the placement of the probes (to stabilize the baseline) and collections were obtained in 10-min samples. During ischemia, there was an increase in the release of glutamate that returned to the baseline within 20 min following the insult. In animals made hypothyroid surgically and chemically, the extent of glutamate release was significantly lower than that in the controls. The release of glutamate in the surgically hypothyroid thyroxine-treated animals was similar to that in controls. The attenuated glutamate release could be a mechanism of protection during ischemia in hypothyroid gerbils.

Animals↗
PubMed1994

Superoxide dismutase, catalase, and U78517F attenuate neuronal damage in gerbils with repeated brief ischemic insults.

Repeated ischemic insults at one hour intervals result in more severe neuronal damage than a single similar duration insult. The mechanism for the more severe damage with repetitive ischemia is not fully understood. We hypothesized that the prolonged reperfusion periods between the relatively short ischemic insults may result in a pronounced generation of oxygen free radicals (OFRs). In this study, we tested the protective effects of superoxide dismutase (SOD) and catalase (alone or in combination), and U78517F in a gerbil model of repetitive ischemia. Three episodes (two min each) of bilateral carotid occlusion were used at one hour intervals to produce repetitive ischemia. Superoxide dismutase and catalase were infused via osmotic pumps into the lateral ventricles. Two doses of U78517F were given three times per animal, one half hour prior to each occlusion. Neuronal damage was assessed 7 days later in several brain regions using the silver staining technique. The Mann-Whitney U test was used for statistical comparison. Superoxide dismutase showed significant protection in the hippocampus (CA4), striatum, thalamus and the medial geniculate nucleus (MGN). Catalase showed significant protection in the striatum, hippocampus, thalamus, and MGN and the substantia nigra reticulata. Combination of the two resulted in additional protection in the cerebral cortex. Compared to the controls, there was little protection in a dose of 3 mg/kg of U78517F. There was significant protection with a dose of 10 mg/kg in the hippocampus (CA4), striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Differential effects of amphetamine and haloperidol on recovery after global forebrain ischemia.

Gerbils subjected to sham surgery or to bilateral occlusion of the carotid arteries were given an injection, during the recovery period, of saline, d-amphetamine, or haloperidol. The animals were subsequently tested once daily for 50 days in an eight-arm radial maze. Global forebrain ischemia had no effect on learning to avoid unbaited arms (reference memory), but greatly increased the number of times animals reentered previously visited arms (working memory errors). Gerbils made ischemic and treated with amphetamine reduced working memory errors more rapidly than did saline-treated ischemic gerbils; conversely, animals made ischemic and treated with haloperidol made more working memory errors than the ischemic controls. Although all ischemic animals were hyperactive, the differential radial maze behaviors of the ischemic groups cannot be explained on the basis of increased activity.

Animals↗
PubMed1994

Neuronal protection with superoxide dismutase in repetitive forebrain ischemia in gerbils.

The underlying mechanism for severe damage with repetitive ischemia is not fully understood. Because of prolonged periods of reperfusions between the brief insults, we speculated that the severe damage may be secondary to excessive generation of oxygen free radicals. In this study we tested the efficacy of peg-superoxide dismutase (SOD) in a model of repeated ischemia in gerbils. Superoxide dismutase (SOD) or vehicle (saline) was delivered through osmotic pumps into the lateral ventricles continuously from the onset of the insult until the gerbils were sacrificed 6 days later. Three doses of SOD were used in the experiments (110, 150, and 190 units per microliter). Damage was assessed using a 0-4 point scoring system and statistical comparisons were done using the Mann-Whitney U-test. There was significant protection in the hippocampus (p < 0.05), striatum (p < 0.001), and substantia nigra reticulata (p < 0.05) in the lowest dose SOD-treated group (110 units per microliter). Animals treated with 150 units showed lesser (but significant) protection in the thalamus, medial geniculate nucleus, and striatum. In the animals treated with the higher dose of SOD (190 units per microliter), the extent of damage was no different than vehicle-treated controls in the cortex, striatum, and hippocampus. Compared to controls, neuronal damage was, however, significantly more severe in the medial geniculate nucleus and the thalamus in the high-dose SOD-treated animals (p < 0.05). Our experiments suggest that the SOD may have a small therapeutic window. Higher doses may either have no neuroprotective effects or may be harmful.

Animals↗
PubMed1994

Very brief transient ischemic attack.

TIA is an important risk factor for ischemic stroke. Early diagnosis and management can result in a significant reduction in the risk of subsequent stroke. We report the case of a 54-year-old man who developed a 5-second episode of leg weakness and in whom a tight stenosis of the appropriate carotid artery was found. TIAs can sometimes be brief and have an atypical presentation, requiring a high level of suspicion for early diagnosis.

Carotid Artery, Internal↗
PubMed1994

Stroke in the elderly.

The incidence of stroke increases dramatically with advancing age. Progressive carotid atherosclerosis, cardiac arrhythmia and emboli, and vascular changes all contribute to this increasing incidence of stroke in the elderly. Treatment of hypertension and other risk factors have resulted in a decline in stroke over the last 50 years. The decline has been most prominent in the elderly. In recent years, this decline has slowed down or may even be reversing. Early and effective control of risk factors together with comprehensive management of acute stroke in a specialized unit is needed to further improve prognosis. Such an approach is especially important in the elderly, who may suffer from multiple problems. Treatment of hypertension and other risk factors have resulted in a decrease in an overall decline in the incidence of stroke over the last 50 years. This decline has been most apparent in the elderly. In recent years, however, there has been a slowing or possibly a reversal of this trend. Early and effective management of risk factors, aggressive therapy of patients with transient ischemic attacks and comprehensive management of acute stroke patients in specialized units may be required to further improve prognosis.

Aged↗
PubMed1994

The Saskatchewan Clinical Stroke Prevention Project: design.

The Saskatchewan Clinical Stroke Prevention Project aims to examine the process and impact of incorporating enhanced stroke prevention into the routine clinical practice of family physicians. Twenty-four physicians in three practices in Saskatchewan are participating in a staged series of educational interventions over two years to enhance their management of smoking, transient ischemic attack/stroke, atrial fibrillation and hypertension. The components of each intervention include a seminar, printed materials, a one-to-one case discussion or "academic detailing," a self-documented chart audit and changes to the office system. Patients for whom this intervention is targeted are those 55 to 75 years of age presenting for a periodic health examination with one or more of the four main risk factors for stroke. Intervention will consist of counselling on relevant risk factors by the doctor and nurse teams, supported by appropriate patient education materials. Patient follow-up will be carried out according to clinical indications and will be done at least 3, 6, 12 and 24 months after entry into the study. Evaluation comprises measures of the process of implementing change in preventive practice as well as of the impact of such change. The former includes semi-structured interviews and focus groups with physicians, support staff and patients. The latter includes an assessment of knowledge, attitudes and charted practice before and after intervention.

Adult↗