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Biomedical subjects

R Joseph

Publications and source records attributed to R Joseph.

At least 127 records · Page 7Linked to original sources

Serotonergic hypofunction in migraine: a synthesis of evidence based on platelet dense body dysfunction.

We studied the platelet dense body as a model for serotonergic vesicular function. Headache-free migraine sufferers had increased numbers of dense bodies, decreased dense body secretion, a defective link between cytosolic ionized calcium and platelet activation, an abnormal sensitivity to activation by platelet-activating factor and decreased serotonin metabolism in the presence of an unactivated platelet. These findings are interpreted as evidence for low platelet serotonin turnover. Also an abnormality in coupling of secretion to cytosolic ionized calcium caused by a membranal defect results in reduced platelet secretory function. A similar abnormality is postulated for serotonergic vesicles in central neurons. Central serotonergic hypofunction in migraine sufferers may reduce this normally present inhibitory influence on the intrinsic noradrenergic system, the activation of which may initiate the neuronal mechanisms of migraine.

Blood Platelets↗

Platelet activation and analysis of organelles in migraineurs.

We used transmission electron microscopy to investigate selected aspects of the platelet response (surface activation as well as aggregation) and quantify cytoplasmic organelles within the cytoplasm of platelets obtained from both healthy control women and women diagnosed as having either common or classic migraine. Comparisons between controls and migraineurs showed no differences for: (1) the number of circulating platelets, (2) degree of surface activation, (3) amount of aggregate formation or (4) percent of hyperactive platelet populations. In contrast, platelets of migraine sufferers uniformly contained a significantly greater number of dense bodies compared to control platelets. Although we did not find functional abnormalities for the platelets obtained from migraineurs, we did demonstrate that they were altered structurally.

Adult↗

Platelet norepinephrine and serotonin balance in migraine.

Platelet serotonin (5 hydroxytryptamine, 5-HT) and norepinephrine (NE) were measured in common and classic migraine patients and healthy controls. Common migraine sufferers had high NE levels and a low 5-HT/NE ratio. Classic migraine patients had a high 5-HT level and a high 5-HT/NE ratio. The data suggest disparate NE and 5-HT metabolism between common and classic migraine.

Adolescent↗

A plasmatic factor may cause platelet activation in acute ischemic stroke.

To study the pathogenesis of platelet activation in ischemic stroke, ionized calcium ([Cai2+]) was measured in aequorin-loaded gel-filtered platelets in the basal and stimulated state. Basal [Cai2+] was increased in stroke patients maximally 36-72 hours after onset. The increase in [Cai2+] after stimulation with thrombin, collagen, and platelet-activating factor were also greater in stroke patients, but the profiles of these [Cai2+] changes were parallel to control. Cross incubation of control platelets with plasma from stroke patients resulted in raised basal [Cai2+] and caused the release of serotonin from platelets. These results indicate that the higher platelet basal [Cai2+] in stroke patients represents a lowered threshold for activation and that this may be due to a plasmatic factor rather than a primary platelet defect.

Adult↗

Whole blood platelet function in acute ischemic stroke. Importance of dense body secretion and effects of antithrombotic agents.

We studied platelet function in whole blood, a situation that better reflects the in vivo state, from 85 patients with acute ischemic stroke and from 19 healthy controls. Patients receiving no antithrombotic drugs demonstrated increased platelet dense body secretion without an associated increase in platelet aggregation, thus raising the possibility that dense body secretion may be of separate importance in cerebral infarction. Our results also suggest that dense body secretion may occur independently of aggregation. Heparin and heparin plus warfarin were ineffective in reducing the high level of dense body secretion seen in acute cerebral infarction, whereas treatment with aspirin plus dipyridamole inhibited both dense body secretion and platelet aggregation. It seems worthwhile to investigate the usefulness of antiplatelet drugs in the treatment of acute ischemic stroke wherein clinical outcome is correlated with the extent of suppression of platelet dense body secretion.

Acute Disease↗

Platelet ultrastructure and secretion in acute ischemic stroke.

We used transmission electron microscopy to count the organelles (dense bodies, alpha granules, and mitochondria) contained within platelets from 11 acute ischemic stroke patients and 12 healthy controls. We randomly selected for evaluation 25 platelet profiles in ultrathin sections cut from three separate blocks. Compared with those from controls, platelets from stroke patients contained significantly fewer alpha granules (p less than 0.001) and mitochondria (p less than 0.02) and showed a trend toward fewer dense bodies. Supportive of our previous studies, the amount of adenosine triphosphate secreted following stimulation by collagen also tended to be greater in platelets from stroke patients. These observations support the presence of increased platelet secretion associated with acute cerebral infarction and raise the possibility that platelet secretion may be of separate importance to the mechanical occlusion of blood vessels by platelet aggregates in the pathogenesis of cerebral infarction.

Adenosine Triphosphate↗

Effect of therapy on platelet activating factor-induced aggregation in acute stroke.

Platelet activating factor, a potent inducer of in vivo platelet activation and thrombosis, has been shown to be excessively active in acute ischemic stroke patients. Therefore, we studied the effect of aspirin/dipyridamole therapy in inhibiting platelet activating factor-induced platelet activation in acute ischemic stroke patients, 23 taking aspirin/dipyridamole and 21 untreated. Aspirin/dipyridamole-treated patients failed to show suppression of platelet activating factor-induced platelet aggregation even though collagen-induced activation was inhibited, suggesting that platelet activating factor acts by cyclooxygenase-independent mechanisms. Failure to suppress cyclooxygenase-independent mechanisms of platelet activation may explain the limited usefulness of current antiplatelet therapy, aspirin in particular, in stroke prevention. The role of selective platelet activating factor antagonists both in isolation and combined with aspirin needs to be investigated for their usefulness in the treatment and prevention of ischemic stroke.

Aspirin↗

The right cerebral hemisphere: emotion, music, visual-spatial skills, body-image, dreams, and awareness.

Based on a review of numerous studies conducted on normal, neurosurgical and brain-injured individuals, the right cerebral hemisphere appears to be dominant in the perception and identification of environmental and nonverbal sounds; the analysis of geometric and visual space (e.g., depth perception, visual closure); somesthesis, stereognosis, the maintenance of the body image; the production of dreams during REM sleep; the perception of most aspects of musical stimuli; and the comprehension and expression of prosodic, melodic, visual, facial, and verbal emotion. When the right hemisphere is damaged a variety of cognitive abnormalities may result, including hemi-inattention and neglect, prosopagnosia, constructional apraxia, visual-perceptual disturbances, and agnosia for environmental, musical, and emotional sounds. Similarly, a myriad of affective abnormalities may occur, including indifference, depression, hysteria, gross social-emotional disinhibition, florid manic excitement, childishness, euphoria, impulsivity, and abnormal sexual behavior. Patients may become delusional, engage in the production of bizzare confabulations and experience a host of somatic disturbances such as pain and body-perceptual distortions. Based on studies of normal and "split-brain" functioning, it also appears that the right hemisphere maintains a highly developed social-emotional mental system and can independently perceive, recall and act on certain memories and experiences without the aid or active reflective participation of the left. This leads to situations in which the right and left halves of the brain sometime act in an uncooperative fashion, which gives rise to inter-manual and intra-psychic conflicts.

Aphasia↗

Dual mental functioning in a split-brain patient.

Case studies of two individuals who had undergone complete corpus callosotomies are presented. In addition to anecdotal observations, controlled neurobehavioral and neuropsychological testing indicated that although both parents demonstrated the disconnection syndromes unique to "split-brain" patients, they also differed rather dramatically. For example, 1-C's left hemisphere developed bilateral motor control, whereas 2-C demonstrated the presence of two independent forms of conscious-awareness, one of which resided in the right and the other in the left hemisphere. Hence, 2-C's right brain was capable of gathering, understanding, recalling, and expressing (nonverbally) various forms of information as well as directing independent behavioral activity as manifested by his left extremities. Indeed, 2-C's left arm and leg not only engaged in controlled, directed, and purposeful behavior, but at times performed activities that his left hemisphere found objectionable and annoying. In some instances, physical struggles that involved the right and left extremities of this patient were observed. In contrast, 1-C's right hemisphere appeared to be lacking in higher-level cognitive capabilities. Speculations with regard to mental activity and hemispheric laterality are presented.

Adult↗

Haematolytic disease due to ABO incompatibility: incidence and value of screening in an Asian population.

The population in Singapore is predominantly Asian, with Chinese forming the major ethnic group. The incidence of haemolytic disease of the newborn (HDN) due to Rh incompatibility is very low. The true incidence of HDN due to ABO incompatibility is unknown. Early discharge is practised in Singapore making it important to predict severe HDN due to ABO incompatibility as this would constitute the main cause of haemolysis next to G6PD deficiency. One thousand, six hundred and eight baby-maternal pairs were typed for ABO, Rh, and tested for direct Coombs' test, maternal titre, cord bilirubin and haptoglobin levels. Two hundred and fifty-one were found to be ABO incompatible, with 141 group A and 110 group B babies. The incidence of HDN due to ABO incompatibility was 3.7% of all group O mothers. Coombs' test, maternal antibody titre, cord bilirubin and haptoglobin levels were of low predictive value for severe HDN due to ABO incompatibility. The data further support the notion that it is not cost effective to screen for ABO incompatibility.

ABO Blood-Group System↗