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1.
H. Ronald Zielke Marian J. Jackson J. Tyson Tildon Stephen R. Max 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1993,19(3):219-233
The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations. 相似文献
2.
Hershel Jick M.D. Marian Wald Myers P.A.-C. Alan D. Dean M.B. B.S. 《Pharmacotherapy》1995,15(2):176-181
Sulfasalazine (SASP) has often been reported to cause serious blood disorders, particularly agranulocytosis; however, little quantitative information is available to estimate the risk or to identify possible modifiers of the risk. We used comprehensive clinical information recorded on office computers by selected general practitioners in Britain to conduct a follow-up study of some 10,000 users of SASP and some 4000 users of mesalazine to estimate the risk of blood disorders associated with these drugs. Overall, the frequency of blood disorders attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who were treated for arthritic disorders (6.1/1000 users) was some 10 times higher than that for users who were treated for inflammatory bowel disease (0.6/1000 users). There were no cases of blood disorders in users of mesalazine. 相似文献
3.
Lillian L. L. Leong Marian J. Sturm Yahya Ismail Charlene J. Stephens Roger R. Taylor 《Clinical and experimental pharmacology & physiology》1992,19(2):113-118
1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain. 相似文献
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The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice 总被引:1,自引:0,他引:1
Hans-Peter R. Bootsma †Albert P. Aldenkamp Leonie Diepman Jacques Hulsman Danielle Lambrechts Loes Leenen Marian Majoie Ad Schellekens †Marc de Krom 《Epilepsia》2006,47(S2):24-27
Summary: Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV. 相似文献
7.
ABSTRACT: Background: The percentage of United States’ births delivered by cesarean section has increased rapidly in recent years, even for women considered to be at low risk for a cesarean section. The purpose of this paper is to examine infant and neonatal mortality risks associated with primary cesarean section compared with vaginal delivery for singleton full‐term (37–41 weeks’ gestation) women with no indicated medical risks or complications. Methods: National linked birth and infant death data for the 1998–2001 birth cohorts (5,762,037 live births and 11,897 infant deaths) were analyzed to assess the risk of infant and neonatal mortality for women with no indicated risk by method of delivery and cause of death. Multivariable logistic regression was used to model neonatal survival probabilities as a function of delivery method, and sociodemographic and medical risk factors. Results: Neonatal mortality rates were higher among infants delivered by cesarean section (1.77 per 1,000 live births) than for those delivered vaginally (0.62). The magnitude of this difference was reduced only moderately on statistical adjustment for demographic and medical factors, and when deaths due to congenital malformations and events with Apgar scores less than 4 were excluded. The cesarean/vaginal mortality differential was widespread, and not confined to a few causes of death. Conclusions: Understanding the causes of these differentials is important, given the rapid growth in the number of primary cesareans without a reported medical indication. (BIRTH 33:3 September 2006) 相似文献
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This pilot study compared abdominal massage with laxative treatment in the management of constipation in 32 profoundly disabled, institutionalised adults. A randomised cross-over design was used. After an initial 16-day baseline measurement phase without any treatment, there followed two seven-week treatment phases separated by a one-week washout period. Each subject received seven weeks of massage and seven weeks on his or her previous laxative regimen. Primary outcome measures were gastro-intestinal and segmental transit times, measured at the end of the baseline phase and of each treatment phase. Secondary measures included stool frequency, size and consistency, the requirement for enemas and an assessment of patient well-being.The median value of total colonic transit time was 183 hours for the baseline phase and 159 hours for all treatment phases. There was no evidence of any statistically significant treatment differences between laxative and massage therapy for right, left or rectosigmoid segments either separately or in total. Analysis of secondary outcome measures also failed to find any treatment preferences.These results reveal the grossly abnormal colonic transit times of the study population at all times. The effects of laxative and massage therapy within this environment were not demonstrably different. 相似文献
10.
Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption 总被引:5,自引:0,他引:5
Melly S. Oitzl E. Ron de Kloet Marian Joëls Wolfgang Schmid Timothy J. Cole 《The European journal of neuroscience》1997,9(11):2284-2296
Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor. 相似文献