Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lessions from epidemiological studies. The Clinical Trial Group for Neurosurgery of the University of California San Diego (UCSD) is involved in epidemiological studies and trials of new pharmacological agents in traumatic brain injury. A great number (> 10,000) of patients has been prospectively analyzed forming an integrated database for further purposes. The development of these databases is based on earlier work by the European Neurosurgeons Jennett and Braakmann and the US-Traumatic Coma Data Bank Study. These studies allowed for the development of sophisticated data collection instruments which were used in the international Tirilizad Trials which enrolled over 1,100 patients. A major observation from that trial was that pretreatment hypotension or hypoxia could be unbalanced even in a large two arm blinded study. Another issue of the tirilazad trial was the influence of gender affecting not only outcome but also drug metabolism. Similar experiences were gathered with the phase-III trial on the competitive NMDA-receptor antagonist selfotel, which interferes with the excitotoxic amino acid glutamate as mediator of secondary brain damage, as ischemia-induced neuronal degeneration. Unfortunately, the trial, already underway, had to be prematurely aborted, since concurrent stroke studies with enrollment of nonintubated patients on low-dose selfotel revealed an increased number of deaths and other adverse events. A retrospective analysis did not confirm that Selfotel was associated with an increased mortality in TBI, but there was also no evidence that the drug was efficacious. A problem here was that a major portion of patients did not have intracranial mass lesions (contusion, subdural haematoma) on CT, questioning whether these had a treatment responsive brain injury. Both studies on tirilazad or selfotel underscore the significance of well designed and conducted phase-I and -II trials to characterize the pharmacokinetics of the agent, to confirm availability of drug in the brain, and to identify a sufficient number of patients with lesions responding to the drug. A major issue is the blood-brain barrier permeability of the agent under study. Further, the phenomenon of secondary deterioration - neurological worsening - turned out as a powerful predictor of poor outcome. The findings and conclusions of both clinical trials (tirilazad, selfotel) were utilized for a subsequent patient study on CP101-606 in consultation with the Pfizer company, the US Brain Injury Consortium, and the San Diego Clinical Trial Group. The patient population was a priori selected towards responsiveness of the brain lesions to the treatment. The major conclusions are: I Development of therapeutic regimens targeted towards the mechanisms of brain injury. II Availability of adequate preclinical data. III Directing treatment towards an appropriate patient population. IV Central gathering and interpretation of the neuroradiological findings. V Monitoring of trial center performance. VI Stratification and pre-trial prognostic analysis for identification of subgroups.
 ...
PMID:Lessons from epidemiologic studies in clinical trials of traumatic brain injury. 1533 8

The aim of the present study was to ascertain whether the possible occurrence of overproduction of inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) in the brain and inflammatory cytokines in the peripheral blood exhibited during heat stroke can be reduced by prior administration of Shengmai San, a Chinese herbal medicine. Aminoguanidine, an iNOS inhibitor, was evaluated at the same time as a reference (positive control). Urethane-anesthetized rats were exposed to heat stress (ambient temperature of 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were all significantly lower than in control rats. However, cerebral iNOS immunoreactivity and NO levels were all greater after the onset of heat stroke. The serum levels of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were all increased after the onset of heat stroke. Shengmai San (1.2 g/ml per rat) or aminoguanidine (30 micromol/ml per rat) was administered orally, daily, and consecutively for 7 days before the initiation of heat stress; and this significantly attenuated the heat stress-induced arterial hypotension, cerebral ischemia, and increased levels of brain iNOS-dependent NO production and serum cytokines formation. Shengmai San shared with the aminoguanidine almost the same efficacy in reducing iNOS-dependent NO and cytokines overproduction during heat stroke. These results suggest that Shengmai San or aminoguanidine protects against heat stroke-induced arterial hypotension and cerebral ischemia by inhibition of iNOS-dependent NO overproduction in the brain and excessive accumulation of several inflammatory cytokines in the peripheral blood stream.
 ...
PMID:Shengmai San, a Chinese herbal medicine protects against rat heat stroke by reducing inflammatory cytokines and nitric oxide formation. 1587 82

Older Mexican Americans (MAs) have consistently scored lower on the Folstein Mini-Mental State Examination (MMSE) than older European Americans (EAs). These lower scores may arise from factors other than those traditionally posited (age and education). Thus, this study examined the association between acculturation and structural assimilation and MMSE-assessed cognitive impairment, taking into account education, income, and other contextual factors. Subjects were participants in the San Antonio Longitudinal Study of Aging, a community-based study of chronic disease and functional status in 457 older MAs and 376 older EAs. Scales were used to measure two dimensions of acculturation: (family attitude, cultural values) and structural assimilation (functional integration into the broader American society). Logistic regression was used to examine the association between age, sex, acculturation, and structural assimilation and MMSE scores suggestive of cognitive impairment (<24). After adjusting for contextual factors (age, sex, education and household income), diseases (diabetes mellitus, stroke, and hypertension), and sensory impairments (hearing and vision), structural assimilation, but neither dimension of acculturation, was significantly and negatively associated with MMSE-assessed cognitive impairment. Older MAs in the lowest structural assimilation stratum were 1.89 times as likely to have MMSE-assessed cognitive impairment as those in the highest. Age, education, and visual impairment were also independently associated with cognitive impairment. These findings highlight the need for geriatricians to take contextual factors (including age, education, and structural assimilation) into account when interpreting MMSE scores of MA patients.
 ...
PMID:Association between acculturation and structural assimilation and mini-mental state examination-assessed cognitive impairment in older Mexican Americans: findings from the San Antonio Longitudinal Study of Aging. 1610 45

Factors were examined that might explain reported ethnic differences in leisure time physical activity (LTPA) between Mexican Americans (MAs) and European Americans (EAs). Data were from a random sample of 749 community-dwelling MAs and EAs, aged 65 and older, who participated in the San Antonio Longitudinal Study of Aging (SALSA) baseline examination. Variables examined included LTPA measured as kilocalories of energy expended per week, contextual variables (age, sex, socioeconomic status (SES), acculturation/structural assimilation), psychosocial measures (self-esteem, mastery, perceived health control), lifestyle variables (fat avoidance, current alcohol drinker, years smoking, body mass index (BMI)), and presence of chronic diseases (diabetes mellitus, angina pectoris, myocardial infarction, stroke, hypertension, arthritis, chronic obstructive pulmonary disease, depression, mild cognitive impairment). Hierarchical multiple regression was used to examine potential mediators of the ethnic group-LTPA association. EAs expended almost 300 kcal/wk more energy than did MAs (1,287 kcal/wk vs 1,001 kcal/wk). SES and psychosocial (self-esteem), lifestyle (fat avoidance, smoking, BMI), and disease (depression) factors that vary by SES explained this ethnic difference. In MAs, structural assimilation, but not acculturation, was significantly associated with LTPA independent of SES. Self-esteem, BMI, and depression explained this association. Psychosocial resources, lifestyle behaviors, and depression explain differences in LTPA between older MAs and EAs. Interventions to increase LTPA in both ethnic groups should be targeted especially at women and persons who have low self-esteem, smoke, and are obese or depressed. In MAs, additional emphasis should be focused on those who are less structurally assimilated into the broader American society.
 ...
PMID:Potential mediators of ethnic differences in physical activity in older Mexican Americans and European Americans: results from the San Antonio Longitudinal Study of Aging. 1610 46

The present study aimed to determine the long-term safety and efficacy of chimeric anti-CD 20 antibody rituxan (rituximab, Biogen IDEC, San Diego, CA, USA; Genentech, South San Francisco, CA, USA) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in previously untreated patients with aggressive non-Hodgkin's lymphoma (NHL). Thirty-three patients with previously untreated aggressive B-cell NHL received six infusions of rituximab (375 mg/m(2) per dose) on day 1 of each cycle of CHOP chemotherapy, given on day 3 of each cycle of therapy. Currently, the patients now have a median follow-up of 63 months (range 34 - 82 months). The overall response (OR) rate was 94% and the complete response (CR) rate was 61% at the end of therapy. Of the 33 patients, 2 patients experienced disease progression and subsequently died of their disease, 2 patients experienced disease progression but were alive at last follow-up following additional therapy, and 2 patients died without experiencing disease progression: one due to a cerebral vascular accident at 9 months after therapy and a second patient due to small cell lung carcinoma at 55 months. The 5-year survival rate was 88% (95% confidence interval (CI) 72 - 97) and the 5-year progression-free survival was 82% (95% CI 64 - 93). There were no long-term adverse events noted directly related to the rituximab. The long-term follow-up of patients in this phase II trial of rituximab with CHOP chemotherapy for previously untreated aggressive NHL demonstrates a high response rate, which remains very durable with high 5-year overall and progression-free survivals.
 ...
PMID:Long-term update of a phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. 1623 11

In 2001, the incidence of primary and secondary syphilis increased in the United States for the first time in a decade. Increasing rates of early syphilis among men who have sex with men have been reported in many American cities, with similar outbreaks noted in Canada and Europe. In San Francisco, the increase has been particularly sharp and accompanied by an increase in the incidence of neurosyphilis. Early neurosyphilis develops within weeks to years of primary infection and primarily involves the meninges. Syndromes include syphilitic meningitis (often accompanied by cranial neuropathies), meningovascular syphilis (with associated ischemic stroke), or asymptomatic neurosyphilis. Late neurosyphilis occurs years to decades after exposure as cerebral or spinal gummatous disease or the classic parenchymal forms affecting the brain (general paresis or syphilitic encephalitis) or spinal cord and nerve roots (tabes dorsalis). Treponema pallidum, the causative agent, cannot be cultured in vitro, and microscopic techniques are laborious. Thus, diagnosis depends on serologic tests and cerebrospinal fluid (CSF) examination. The suboptimal sensitivity and specificity of these tests complicate diagnosis, particularly among patients coinfected with HIV. CSF examination should be performed to evaluate for neurosyphilis in all patients with positive serum syphilis serology and neurologic, ophthalmic, or tertiary disease, or in those who have failed therapy, and in HIV-infected patients with late latent syphilis or syphilis of unknown duration. Intravenous penicillin G is the recommended treatment for all forms of neurosyphilis and for syphilitic eye disease. An outpatient alternative, if adherence can be assured, is intramuscular benzathine penicillin with oral probenecid. Newer drugs that penetrate CSF, such as ceftriaxone or azithromycin, have not yet been adequately tested for neurosyphilis. Syphilis facilitates transmission of HIV (and vice versa), and thus all patients diagnosed with syphilis should be offered HIV testing.
 ...
PMID:Treatment of neurosyphilis. 1656 77

Shengmai San (SMS) is a traditional Chinese medicine (TCM) comprising three different herbal components, Panax ginseng, Ohiopogon japonicus and Fructus schisandrae and has been used for treating coronary heart diseases (Bensky and Barolet, 1990). It was shown that SMS effectively prevented cerebral oxidative injury in rats when it administered into the duodenum before cerebral ischemia-reperfusion. In the present study, we examined whether post-ischemic administration of SMS can ameliorate cerebral ischemia-reperfusion injury in rats as well. Results showed that SMS injected immediately after ischemia also prevented the ischemia-reperfusion injury, when the effect was evaluated by the formation of protein carbonyl and thiobarbituric acid reactive substance (TBARS), and the loss of glutathione peroxidase (GPX). The preventative potential of SMS was decreased rapidly dependent on the time lag until SMS was injected after ischemia. However, it was noted that intravenously administered SMS protected the oxidative injury approximately 30% even after 60 min of reperfusion in terms of protein carbonyl formation. It is thus suggested that SMS injection might be useful for preventing the progression of injury in cerebral infarction after stroke.
 ...
PMID:Prevention of cerebral oxidative injury by post-ischemic intravenous administration of Shengmai San. 1688 30

We report changes in cardiac troponin-T (TnT) and a new plasma stroke biomarker panel (D-dimer, B-natriuretic peptide [BNP], matrix metalloproteinase-9 [MMP-9], S-100 b, Biosite Diagnostics, San Diego, CA) in 30 nonprofessional marathon runners before and immediately after the 2005 Boston Marathon. Following competition, there was a statistically significant increase in MMP-9 (P < .001) and D dimer (P < .001). Nonsignificant changes in S-100 b and BNP were observed. Premarathon and postmarathon values for a multimarker stroke index increased from 0.97 (normal) to 3.5 (low risk or more; P < .001). Two subjects had index values more than the high-risk cutoff value. Mean TnT premarathon and postmarathon levels increased (from <0.01 to 0.03 ng/mL; P < .0001). After the marathon, with a cutoff value of 0.05 ng/mL, 7 runners (23%) had values above the manufacturer's recommended cutoff for myocardial damage. Although biochemical evidence of myocardial damage following strenuous exercise may reflect myocardial stunning or subclinical ischemia, the changes in the stroke index and values for individual stroke markers may reflect a systemic inflammatory response to exertional rhabdomyolysis which is common, but the possibility of subclinical central nervous system damage cannot be excluded.
 ...
PMID:Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston marathon. 1689 Nov 91

Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease and cancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause-specific death rates from year 2000 to 2004 in mainland and the San Blas islands where only Kuna live. Our hypothesis was that if the high flavanoid intake and consequent nitric oxide system activation were important the result would be a reduction in the frequency of ischemic heart disease, stroke, diabetes mellitus, and cancer--all nitric oxide sensitive processes. There were 77,375 deaths in mainland Panama and 558 deaths in the San Blas. In mainland Panama, as anticipated, cardiovascular disease was the leading cause of death (83.4 +/- 0.70 age adjusted deaths/100,000) and cancer was second (68.4 +/- 1.6). In contrast, the rate of CVD and cancer among island-dwelling Kuna was much lower (9.2 +/- 3.1) and (4.4 +/- 4.4) respectively. Similarly deaths due to diabetes mellitus were much more common in the mainland (24.1 +/- 0.74) than in the San Blas (6.6 +/- 1.94). This comparatively lower risk among Kuna in the San Blas from the most common causes of morbidity and mortality in much of the world, possibly reflects a very high flavanol intake and sustained nitric oxide synthesis activation. However, there are many risk factors and an observational study cannot provide definitive evidence.
 ...
PMID:Does flavanol intake influence mortality from nitric oxide-dependent processes? Ischemic heart disease, stroke, diabetes mellitus, and cancer in Panama. 1729 79

The California Institute for Regenerative Medicine (CIRM) was established in 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Initiative. The statewide ballot measure, which provided US$3 billion in funding for stem cell research at California universities and research institutions, was approved by California voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities and other vital research opportunities. Here, Dr Zach Hall, Interim President of the CIRM, outlines the ethos and aspirations of the CIRM to Regenerative Medicine. Dr Hall trained as a basic neuroscientist and became a faculty member and department chair at the University of California, San Francisco. In 1994, he was appointed Director of National Institute of Neurological Disorders and Stroke within the National Institutes of Health, and was responsible for a research program that awarded more than US$500 million a year in grants and contracts. Since that time, he has held senior positions in research administration within both the University of California, San Francisco, where he was Executive Vice Chancellor, and the University of Southern California. Full information about the CIRM can be found at www.cirm.ca.gov.
 ...
PMID:California dreaming? A new start for regenerative medicine in the Golden State. Interview with Dr. Zach Hall. 1746 72


<< Previous 1 2 3 4 5 6 7 8 9 Next >>