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Biomedical subjects

S Chaturvedi

Publications and source records attributed to S Chaturvedi.

At least 19 recordsLinked to original sources

Toxoplasma gondii ADP-ribosylation factor 1 mediates enhanced release of constitutively secreted dense granule proteins.

Toxoplasma gondii dense granules are morphologically similar to dense matrix granules in specialized secretory cells, yet are secreted in a constitutive, calcium-independent fashion. We previously demonstrated that secretion of dense granule proteins in permeabilized parasites was augmented by the non-hydrolyzable GTP analogue guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) (Chaturvedi, S., Qi, H., Coleman, D. L., Hanson, P., Rodriguez, A., and Joiner, K. A. (1998) J. Biol. Chem. 274, 2424-2431). As now demonstrated by pharmacological and electron microscopic approaches, GTPgammaS enhanced release of dense granule proteins in the permeabilized cell system. To investigate the role of ADP-ribosylation factor 1 (ARF1) in this process, a cDNA encoding T. gondii ARF1 (TgARF1) was isolated. Endogenous and transgenic TgARF1 localized to the Golgi of T. gondii, but not to dense granules. An epitope-tagged mutant of TgARF1 predicted to be impaired in GTP hydrolysis (Q71L) partially dispersed the Golgi signal, with localization to scattered vesicles, whereas a mutant impaired in nucleotide binding (T31N) was cytosolic in location. Both mutants caused partial dispersion of a Golgi/trans-Golgi network marker. TgARF1 mutants inhibited delivery of the secretory reporter, Escherichia coli alkaline phosphatase, to dense granules, precluding an in vivo assessment of the role of TgARF1 in release of intact dense granules. To circumvent this limitation, recombinant TgARF1 was purified using two separate approaches, and used in the permeabilized cell assay. TgARF1 protein purified on a Cibacron G3 column and able to bind GTP stimulated dense granule secretion in the permeabilized cell secretion assay. These results are the first to show that ARF1 can augment release of constitutively secreted vesicles at the target membrane.

ADP-Ribosylation Factor 1↗

Poor prognosis of acute stroke patients denied thrombolysis due to early CT findings.

OBJECTIVES: Whether acute stroke patients with major early infarct signs on computed tomography (CT) should be treated with intravenous (i.v.) thrombolysis remains controversial. The authors sought to define the outcomes in 5 consecutive patients who were not treated with i.v. thrombolysis, according to established guidelines. METHODS: The authors retrospectively analyzed the outcomes of a consecutive series of 5 patients evaluated by an acute stroke team at a university medical center and who were denied i.v. tissue plasminogen activator due to early CT changes. RESULTS: Five patients with a median National Institutes of Health Stroke Scale score of 22 (range 20-28) were evaluated. Despite aggressive care (e.g., hemicraniectomy), 2 patients died owing to herniation, 1 patient died of cardiac causes, and neither of the 2 surviving patients achieved a 3-month Rankin score below 4 (moderately severe disability). CONCLUSIONS: Given the poor prognosis of patients with hemispheric stroke and early CT changes, alternative treatment modalities such as intra-arterial thrombolysis, early hemicraniectomy, and neuroprotective therapy should be vigorously pursued.

Acute Disease↗

Results of carotid endarterectomy with prospective neurologist follow-up.

BACKGROUND: Previous studies have shown that neurologic complications following carotid endarterectomy (CE) are underestimated if patients are not examined by neurologists after surgery. OBJECTIVE: To review the morbidity and mortality in a cohort of patients examined before and after CE in a neurology and stroke clinic. METHODS: This was a prospective case series from an academic medical center; 44 patients were referred for CE during the period June 1995 to April 1999. Mean age was 64.3 years; 70.5% were referred for symptomatic stenosis and 29.5% were asymptomatic. Three neurosurgeons and two vascular surgeons operated on the patients. RESULTS: The 30-day mortality rate was 4.5% and the 30-day stroke or death rate was 11.4%. One patient had a TIA due to thrombus formation at the operative site and a second patient had an asymptomatic intimal flap. CONCLUSIONS: With prospective follow-up by neurologists, the CE complication rate in an academic medical center was significantly higher than the rates reported in controlled clinical trials. The generalizability of data from CE clinical trials is limited and local audits are necessary to better establish the risk/benefit ratio for individual hospitals and surgeons.

Aged↗

Assessment of availability and working components of school health services in Delhi.

A total of 204 schools of different types and geographical zones were surveyed. Principals of the selected schools were interviewed to generate data regarding availability and working components of school health during last one year. School health services were non existent in 56 (27.45%) of the total schools and in another 27%, the visits made by school health team were only three or less during last one year. The situation was much better in NDMC and MCD schools but in Govt. of Delhi group, 40 of the 82 schools did not have any school health services. In most of the schools having some form of school health services (govt. or private), all the essential areas of health appraisal viz. anthropometry, general health check-up, vision testing, ENT check-up and dental examination were covered. In 21.62% of such schools no health education activity was done by the school health team. Even in the schools having some form of school health services, referral-follow up system did not seem to be working well. In this situation health check-ups merely satisfy administrative requirements and end up with some data for storage. School health services in Delhi, like other health services, are administered through multiple agencies with somewhat overlapping areas and responsibilities. This has more disadvantages than benefits. An integration of various school health schemes in Delhi with uniform system and standards should be attempted.

Child↗

Structural and organizational features of school health schemes in Delhi.

The magnitude of work and existence of multiple agencies makes the task of providing school health services to all pupils of the State of Delhi with uniform standards, a very complex job. The present article looks at the matter from the provider's end, illustrates the structural and organizational features of various school health schemes in Delhi and tries to come out with some suggestions for improvement. This study was based on qualitative research methods. Besides the three major agencies involved i.e. Govt. of Delhi, MCD and NDMC, a host of private and other agencies were also contributing significantly in covering a total of approx. 3700 schools with around 19 lakh children. Organizational and other features of school health services varied widely according to the providing agency. There is a need for integration between various school health schemes in Delhi. Since MCD school health scheme appeared to be better organized, its features can be adopted while developing uniform standards. About the components of services, promotive inputs and follow-up of health appraisals are the areas that need to be strengthened. Proper maintenance of cumulative health records, central documentation and timely dissemination of reports are also equally important and need strengthening.

Child↗

Cerebral angioplasty practice at major medical centers in the United States.

Concern has been expressed recently regarding the proliferation of angioplasty and/or stenting of cerebral vessels. However, little is known about the volume of angioplasties being performed or the number of experienced interventionalists. A questionnaire was mailed to directors of accredited radiology residency programs in the United States, to define the level of expertise available at teaching hospitals in terms of angioplasty and/or stenting. Of 200 programs surveyed, 111 responded (56 %). Of 111 program directors 47 (42%) indicated that cerebral angioplasty was being performed at their center. The greatest experience is currently for angioplasty of post-subarachnoid hemorrhage vasospasm (mean 16 procedures performed) and the least experience for dilation of basilar artery atherosclerosis (mean five procedures performed). The reported stroke and/or death rate in centers performing angioplasty of the extracranial carotid system is 1.5 %. Comparisons with other medical specialties (e.g., cardiologists, neurologists, neurosurgeons) are necessary to determine the full scope of extracranial neurovascular procedures being performed and the corresponding complication rates.

Angioplasty, Balloon↗

Carotid endarterectomy: indications for symptomatic and asymptomatic stenosis.

There have been several clinical trials pertaining to carotid endarterectomy in the last two decades. These studies have provided long-awaited information regarding the risks and benefits of surgery for carotid stenosis. This paper outlines the key results for patients with symptomatic and asymptomatic stenosis. A scheme for the identification of patients likely to benefit from surgery, and persistent areas of controversy and uncertainty, are reviewed.

Carotid Stenosis↗

Direct PCR of Cryptococcus neoformans MATalpha and MATa pheromones to determine mating type, ploidy, and variety: a tool for epidemiological and molecular pathogenesis studies.

Cryptococcus neoformans MATalpha and MATa pheromones were amplified by direct PCR. Nucleotide sequence analyses revealed unique restriction enzyme sites. Sixty strains were used to devise a restriction fragment length polymorphism typing scheme that yielded three variety-specific patterns. Additionally, pheromone-specific PCR allowed easier identification of diploid C. neoformans strains than flow cytometry.

Cryptococcosis↗

Long-term clinical and angiographic outcomes in symptomatic patients with 70% to 99% carotid artery stenosis.

BACKGROUND AND PURPOSE: In 1991, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) reported the benefit of carotid endarterectomy for 659 patients with 70% to 99% stenosis. Follow-up continued until 1997. METHODS: The present study examined the risks and causes of ipsilateral stroke in the randomized groups and in those who had delayed endarterectomy or continued on medical therapy and also examined the evolution of carotid disease on follow-up imaging. RESULTS: By on-treatment (efficacy) analysis, the risk of any ipsilateral stroke at 3 years was 28.3% for medically randomized and 8.9% for surgically randomized patients (19.4% absolute risk reduction, P:<0.001). For combined disabling or fatal ipsilateral stroke, the risks were 14.0% and 3.4%, respectively (10. 6% absolute risk reduction). In medical patients, >80% of the first strokes at 3 years were of large-artery origin. After February 1991, 116 suitable medical patients underwent endarterectomy within 6 months, and 115 continued on medical therapy. The 3-year risk of any ipsilateral stroke in the groups of 116 and 115 patients was 7.9% and 15.0%, respectively (7.1% absolute risk reduction). During follow-up, 81 patients had angiograms comparable to the baseline images. Progression by >/=10% occurred in 7 patients; regression, in 8; no change, in 39; and occlusion, in 27. By use of both angiography and ultrasound, 63 (25.5%) of the 247 medically treated patients progressed to occlusion, of whom 31.7% had an ipsilateral stroke before or on the day of occlusion. CONCLUSIONS: Endarterectomy for patients with 70% to 99% stenosis and recent symptoms was efficacious in the long term. Compared with patients who continued on medical therapy, medical patients with delayed endarterectomy experienced a moderate benefit. Medically treated patients experienced a high risk of occlusion.

Aged↗

Attitudes of Canadian and U.S. neurologists regarding carotid endarterectomy for asymptomatic stenosis.

BACKGROUND: The American Heart Association carotid endarterectomy (CE) guidelines endorse CE for asymptomatic carotid stenosis if the procedure can be performed with low morbidity. However, the Canadian Stroke Consortium has published a consensus against CE for asymptomatic stenosis. The views of practicing neurologists in the two countries on this subject are unclear. METHODS: A survey was undertaken of 270 neurologists from either Florida or Indiana and 180 neurologists from either Ontario or Quebec. RESULTS: The survey was returned by 36% of neurologists. Both Florida (65%) and Indiana neurologists (35%) were significantly more likely than Canadian neurologists (11%) to sometimes/often refer patients for surgery(p<0.001). Neurologists from Florida relied more on noninvasive methods of carotid stenosis assessment (36%) than Canadian neurologists (12%, p=0.003), who preferred angiography. Neurologists from Florida more often cited medicolegal concerns as a reason for referring patients for surgery (27%), compared to Canadian neurologists (3%, p=0.0001). CONCLUSIONS: Practices pertaining to carotid stenosis evaluation and management differ both regionally and by country. Canadian neurologists refer fewer asymptomatic patients for CE and rely more on angiography as a preoperative diagnostic tool. The potential of medicolegal liability is a greater force in clinical decision-making for certain U.S. neurologists, compared to their Canadian counterparts. These differences may partly explain the variations in CE utilization in the two countries.

Attitude of Health Personnel↗

Spontaneous rupture of the inferior vena cava: case report and literature review.

Spontaneous rupture of the inferior vena cava is a rare clinical entity. Diagnosis of this condition, in the absence of any relevant history, is usually made at laparotomy. Only one such case has previously been reported in the literature. We report a case of spontaneous rupture of the inferior vena cava which was diagnosed following laparotomy for hypovolaemia and acute abdominal pain. This case highlights the fact that spontaneous rupture of the inferior vena cava may be a cause of massive intra-abdominal bleeding not associated with trauma or rupture of the abdominal aorta.

Aged↗

Measles, immunisation and disease: rapid epidemiological assessment in two trans-Yamuna villages of Delhi.

A community investigation was conducted in 2 villages of east Delhi, having 15,000 population. Ten per cent households were selected from both the villages by systematic random sampling and all the under 3-year children in selected households were included in the study. A total of 126 under 3-year children from 360 households were investigated. Total children immunised against measles were 86. Most of the 86 immunised children were vaccinated between 9 and 11 completed months. Of the 80 children aged 12 months or above, 12(15%) were unimmunised. Main reason behind non-immunisation was parental apathy. Of the total 126 surviving under 3-year children, 12(9.52%) had a history of probable measles. Two of these children had already measles before they could be eligible for measles vaccination as per the current schedule.

Attitude to Health↗

Increased brain serotonin synthesis in migraine.

OBJECTIVE: To measure brain serotonin synthesis with PET using the tracer alpha-[11C]methyl-L-tryptophan in migraine patients. BACKGROUND: Although the cause of migraine remains poorly understood, there is considerable evidence to support a role of the neurotransmitter serotonin in the pathophysiology of migraine. METHODS: We studied 11 women (aged 33+/-7.7 years) with a diagnosis of migraine according to International Headache Society criteria and 8 healthy women (aged 29+/-9.2 years). Five patients were studied before and after chronic treatment with propranolol or nadolol. RESULTS: Serotonin synthesis capacity (K-complex) values in migraine patients were higher than those measured in controls throughout the brain (p = 0.016); mean K-complex for whole brain was 0.0077 + 0.0020 mL/g/min in patients with migraine and 0.0054+/-0.0003 mL/g/min in controls. The regional pattern did not differ between the two groups. However, the K-complex for whole brain in the subgroup of migraine patients with aura (n = 3) did not differ from that of the control group (p = 0.32). In the five patients studied twice (before and after treatment), we found a trend of increased whole-brain K-complex after drug treatment (p = 0.06). CONCLUSIONS: Our findings indicating increased brain serotonin synthesis capacity in migraine patients are consistent with previous reports of systemic alteration of serotonin metabolism in patients without aura. Our results also suggest that the mechanism of action of beta-adrenergic antagonists for migraine prophylaxis may involve regulation of serotonin synthesis.

Adrenergic beta-Antagonists↗

Ischemia in the territory of a hypoplastic vertebrobasilar system.

BACKGROUND: Congenital variations in the configuration and size of the cerebral vessels may predispose to ischemic stroke. OBJECTIVES/METHODS: To illustrate that a hypoplastic basilar artery may lead to posterior circulation ischemia in adults, eight cases are reported from two university medical centers. RESULTS: Five men and three women with a mean age of 49.8 years are reported. Four of the patients had other conventional stroke risk factors. Two patients had brainstem strokes, and six had TIA. All patients had hypoplastic basilar arteries. Seven patients had at least one hypoplastic vertebral artery (bilateral in five cases), and six patients had both posterior cerebral arteries originating from the internal carotid arteries. CONCLUSIONS: A hypoplastic basilar artery is frequently accompanied by vertebral artery hypoplasia, and this can predispose adults to posterior circulation ischemia. This entity can be suspected on the basis of MR angiogram, but conventional angiography will provide definitive diagnosis. Optimal medical and surgical treatment of this condition is unresolved.

Adult↗

Activated protein C resistance in young African American patients with ischemic stroke.

BACKGROUND: It has been proposed that activated protein C resistance (APCR) due to the factor V Leiden (FVL) mutation may be a risk factor for stroke in young adults. However, this may not be the case for all ethnic groups due to variability in the prevalence of the FVL mutation. METHODS: Case series from a university neurology clinic. Patients with an APCR ratio of 2.2 or below were tested for the FVL mutation (nine patients). Patients on warfarin were also tested for the FVL mutation (14 patients). RESULTS: 38 African American patients under age 55 with an arterial stroke were identified. The mean age of the patients is 43.1 years. Five percent had an APCR ratio of 2.0 or below. None of the patients with an APCR ratio of 2.2 or below or the patients directly tested for the FVL mutation had the mutant allele. CONCLUSIONS: Activated protein C resistance due to the FVL mutation does not appear to be a major risk factor for stroke in young African Americans. Other, as yet unidentified, mechanisms leading to activated protein C resistance may be important in a small subset of young African American stroke patients.

Activated Protein C Resistance↗

Constitutive calcium-independent release of Toxoplasma gondii dense granules occurs through the NSF/SNAP/SNARE/Rab machinery.

The signals and the molecular machinery mediating release of dense matrix granules from pathogenic protozoan parasites are unknown. We compared the secretion of the endogenous dense granule marker GRA3 in Toxoplasma gondii with the release of a stably transfected foreign reporter, beta-lactamase, that localizes to parasite dense granules. Both proteins were released constitutively in a calcium-independent fashion, as shown using both intact and streptolysin O-permeabilized parasites. N-Ethylmaleimide and recombinant bovine Rab-guanine dissociation inhibitor inhibited beta-lactamase secretion in permeabilized parasites, whereas recombinant hamster N-ethylmaleimide-sensitive fusion protein and bovine alpha-SNAP augmented release. Guanosine 5'-3-O-(thio)triphosphate, but not cAMP, augmented secretion in the presence but not in the absence of ATP. The T. gondii NSF/SNAP/SNARE/Rab machinery participates in dense granule release using parasite protein components that can interact functionally with their mammalian homologues.

Animals↗