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Biomedical subjects

M Alexander

Publications and source records attributed to M Alexander.

At least 37 records · Page 2Linked to original sources
PubMed2001

Epilepsy care in six Indian cities: a multicenter study on management and service.

BACKGROUND: Epilepsy care in developing countries is lagging behind than in the developed countries. Precise data on delivery of neurological services for epilepsy is essential to optimize the medical services for epilepsy care with limited resources. OBJECTIVE: This study was carried out in order to examine the management practices and utilization of various medical services for epilepsy in different parts of India. METHODOLOGY: University centers with epilepsy clinics, one each from six states of India, had participated in this study. Demographic data, clinical details, and data on epilepsy care were collected simultaneously on standard proforma. RESULTS: Data on 285 patients with epilepsy (generalized epilepsy: 49.1%, localization-related epilepsy: 49.9%, others: 1%) were included. Mean age of onset of epilepsy was 14.8+11.1 years. Mean delay in diagnosis was 1.5+/-4 years. Mean distance from place of residence to the consulting neurologist was 70+/-82 km. Medical consultations before referral to epilepsy center included general practitioners (54.1%) and specialists (43.3%). Very few patients received services from clinical psychologist or social worker. Investigations included, EEG (63.2%), CT Scan (36.2%). MRI brain (8.5%) and video EEG (2.1%) were limited to a few. Nearly 75.5% were on monotherapy. Newer Anti-Epileptic Drugs (AEDs) were used only in less than 5% patients. CONCLUSION: The services for epilepsy are urban-based and there is underutilization of services, general practitioners and specialists. Newer AEDs (although expensive) are gradually emerging in Indian market. Facilities for epilepsy surgery, therapeutic drug monitoring and services of clinical psychologist or medical social workers are limited.

Anticonvulsants↗
PubMed2001

Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder.

A role for the dopamine transporter (DAT) in bipolar disorder is implicated by several lines of pharmacological evidence, as well as suggestive evidence of linkage at this locus, which we have reported previously. In an attempt to identify functional mutations within DAT contributing a susceptibility to bipolar disorder, we have screened the entire coding region, as well as significant portions of the adjacent non-coding sequence. Though we have not found a definitive functional mutation, we have identified a number of single nucleotide polymorphisms (SNPs) that span the gene from the distal promoter through exon 15. Of the 39 SNPs that are suitable for linkage disequilibrium (LD) studies, 14 have been analyzed by allele-specific PCR in a sample of 50 parent-proband triads with bipolar disorder. A haplotyped marker comprised of five SNPs, spanning the region between exon 9 and exon 15, was constructed for each individual, and transmission/disequilibrium test (TDT) analysis revealed this haplotype to be in linkage disequilibrium with bipolar disorder (allele-wise TDT p = 0.001, genotype-wise TDT p = 0.0004). These data replicate our previous finding of linkage to markers within and near DAT in a largely different family set, and provide further evidence for a role of DAT in bipolar disorder. Published 2001 Wiley-Liss. Inc.

Alleles↗
PubMed2001

Relationship of properties of polycyclic aromatic hydrocarbons to sequestration in soil.

A study was conducted to determine whether the sequestration of 21 polycyclic aromatic hydrocarbons (PAHs) in soil was correlated with their properties. From 22 to 58% of the PAHs was not extracted with n-butanol after their addition to soil. After 28 days of aging, the percentage of the PAHs remaining in the soil increased to 47-77%; however, nearly all of each compound was recovered by Soxhlet extraction. Correlations were based on the amounts of aged compound extracted with butanol. Properties of compounds used in the correlations included Kow, molecular length and molecular-connectivity indices (MCIs). No one property, including log Kow, resulted in an R2 value greater than 0.26. A chain MCI (2 chi vCH) together with log Kow or a first-order MCI (1 chi) resulted in R2 values of 0.49 and 0.54, respectively. The data suggest that the properties tested are not important to predicting the sequestration of PAHs in soil.

Chemical Phenomena↗
PubMed2001

Traumatic bilateral carotid dissection with concomitant cerebral infarction.

A 40-year-old man presented with a major nondominant hemisphere stroke syndrome after a road traffic accident. Cranial computed tomography scan revealed an extensive right hemisphere infarction involving the entire anterior and middle cerebral artery territories. Duplex Doppler ultrasound and cerebral angiography revealed bilateral internal carotid artery dissection with evidence of underlying fibromuscular dysplasia. Anticoagulation with heparin was commenced despite the coexisting large cerebral infarction, with the objective of protecting the uninjured but at-risk left cerebral hemisphere from ischemic injury. Patients with multiple cerebral arterial dissections complicated by cerebral infarction present a significant management dilemma. Our literature review revealed a lack of clear management guidelines for such cases.

Accidents, Traffic↗
PubMed2001

Economic burden of epilepsy in India.

PURPOSE: The economic burden due to epilepsy is not adequately examined in developing countries. Cost estimates are very important in health care planning and delivery of services. We have estimated the direct and some of the indirect costs of epilepsy in India. METHODS: Epilepsy centers attached to University hospitals in six states of India participated in this study. Data on clinical characteristics, utilization of medical services, and costs were collected in a standardized format. RESULTS: There were 285 patients (mean age, 22.6 + 12.5 years) drawn from six centers in this study. The annual cost of epilepsy per patient was INR 13,755 (USD, 344). The direct cost was INR 3,725 (USD, 93), and the indirect cost was INR 10,031 (USD, 251). Direct cost included medical consultations (INR 329), laboratory services (INR 271), hospitalization charges (INR 316), and cost of travel to clinics (INR 659). The indirect cost included the cost of lost productivity due to seizures, its complications, or attendance to clinics. There are approximately 5 million people with epilepsy in India. The economic burden due to epilepsy to the nation is to the tune of INR 68.75 billion (USD, 1.7 billion). CONCLUSIONS: The annual economic burden of epilepsy in India is 88.2% of GNP per capita and 0.5% of the GNP.

Adolescent↗
PubMed2001

An evaluation of the quality of a chemotherapy administration service established by nurses in an oncology day care centre.

Traditionally, chemotherapy administration has been a medical role in Hong Kong. In 1998, two chemotherapy nurses took over part of this role within a major oncology day care centre after completing a course in chemotherapy administration and patient care. The aim of this study was to measure and evaluate the quality of care by using a self-developed audit form and the Worthing Chemotherapy Satisfaction Questionnaire (WSCQ). All records of patients who had had i.v. cannulas inserted by nurses over a period of one year were audited for the accuracy of the i.v. cannulation (n=2217). Also, patient satisfaction was assessed in 50 patients. The results showed that the accuracy of i.v. cannulation was kept constantly above 80% from the eighth month of auditing onwards. It was also found that patients preferred the use of a butterfly needle for the administration of chemotherapy. The study revealed that the level of information received regarding treatment (r=0.36, P=0.011) and satisfaction of practical advice on caring for side effects (r=0.35, P=0.012) were determinants of patients' overall satisfaction. Furthermore, anxiety when patients received chemotherapy could also be associated with overall satisfaction (r=-0.27), although the P value was of borderline significance only (P=0.58). In conclusion, the study reflected a high level of quality of care in relation to this element of nurse-led practice.

Journal Article↗
PubMed2001

Cerebral ischemia and inflammation.

Cerebral ischemia is accompanied by a marked inflammatory reaction that is initiated by ischemia-induced expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. Preclinical studies suggest that interventions that are aimed at attenuating such inflammation reduce the progression of brain damage that occurs during the late stages of cerebral ischemia. In particular, strategies that block the activity of inflammation-related enzymes, such as inducible nitric oxide synthase and cyclo-oxygenase-2, reduce ischemic damage with an extended therapeutic window. Although a clinical trial using murine antibodies against intercellular adhesion molecule-1 did not show benefit in patients with ischemic stroke, recent data indicate that immune activation induced by the heterologous protein may have played an important role in the failure of this trial. Therefore, there is a strong rationale for continuing to explore the efficacy of anti-inflammatory therapies in the treatment of the late stages of cerebral ischemia.

Animals↗
PubMed2001

Design and use of an inducibly activated human immunodeficiency virus type 1 Nef to study immune modulation.

The Nef protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the infectivity of virus particles, downmodulate cell surface proteins, and associate with many intracellular proteins that are thought to facilitate HIV infection. One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells. This has been attributed to effects of Nef on cell proliferation and apoptosis. We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated. It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain (Nef-ER). The Nef-ER is kept in an inactive state due to steric hindrance, and addition of the membrane-permeable drug 4-hydroxytamoxifen (4-HT), which binds to the ER domain, leads to inducible activation of Nef-ER within cells. We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains (lipid rafts) only after activation. Using this inducible Nef, we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line. Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT. In contrast, 50% downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT. These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef. The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion.

Animals↗
PubMed2001

Towards the control of a powered orthosis for people with muscular dystrophy.

The paper describes the development of a passive/active orthosis for people with limited anti-gravity strength in their arms. This is symptomatic of conditions such as muscular dystrophy and spinal muscular atrophy. A passive orthosis was designed and developed using linear elastic elements. The system is being tested with children with disabilities and preliminary results are encouraging. An RT200 robot was also used as a test-bed for an active orthosis. The robot was instrumented with a six-axis force/torque sensor at the end-effector. The force acted as the input to the robot. The robot kinematics and dynamics were modelled. A number of control schemes were implemented on the test-bed including force proportional to velocity and acceleration; these schemes were evaluated with two subjects.

Arm↗
PubMed2001

Hexosamine-induced fibronectin protein synthesis in mesangial cells is associated with increases in cAMP responsive element binding (CREB) phosphorylation and nuclear CREB: the involvement of protein kinases A and C.

Hyperglycemia-induced alterations in mesangial (MES) cell function and extracellular matrix protein accumulation are seen in diabetic glomerulopathy. Recent studies have demonstrated that some of the effects of high glucose (HG) on cellular metabolism are mediated by the hexosamine biosynthesis pathway (HBP), in which fructose-6-phosphate is converted to glucosamine 6-phosphate by the rate-liming enzyme glutamine:fructose-6-phosphate amidotransferase (GFA). In this study, we investigated the role of HBP on HG-stimulated fibronectin protein synthesis, a matrix component, in SV-40-transformed rat kidney MES cells. Treatment of MES cells with 25 mmol/l glucose (HG) for 48 h increases cellular fibronectin levels by two- to threefold on Western blots when compared with low glucose (5 mmol/l). Glucosamine (GlcN; 1.5 mmol/l), which enters the hexosamine pathway distal to GFA action, also increases fibronectin synthesis. Azaserine (AZA; 0.5 micromol/l), an inhibitor of GFA, blocks the HG- but not the GlcN-induced fibronectin synthesis. Fibronectin contains cAMP responsive element (CRE) consensus sequences in its promoter and the phosphorylation of CRE-binding protein (CREB) may regulate its expression. On Western blots, HG and GlcN stimulate two- to threefold the phosphorylation of CREB at Ser 133, whereas CREB protein content was unaltered by either HG or GlcN. In addition, nuclear CREB activity was increased by HG and GlcN on gel-shift assays using (32)P-CRE oligonucleotides. AZA impeded the HG-enhanced CREB phosphorylation and CRE binding but had no effect on GlcN-mediated CREB phosphorylation and CRE binding. Pharmacologic inhibition of protein kinase C (PKC) and protein kinase A (PKA), which are involved in hexosamine-mediated matrix production, blocked the CREB phosphorylation and fibronectin synthesis seen in HG and GlcN conditions. We conclude that the effects of HG on fibronectin synthesis in the mesangium are mediated by the HBP possibly via hexosamine regulation of CREB and PKC/PKA signaling pathways. These results support the hypothesis that the HBP is a sensor and regulator of the actions of glucose in the kidney.

Animals↗
PubMed2000

[Morphological changes in melanocytic nevi induced by exogenous factors].

Malignant melanoma is the most important differential diagnosis in both clinical and histologic examination of melanocytic nevi. UV exposure with an erythemogenic dose and mechanical irritation of melanocytic nevi are able to induce reversible morphologic changes which simulate malignant melanoma. These changes are associated with an increased expression of HMB-45 antigen. In addition, an increased proliferation and repair activity is observed after UV exposure. The increased number of melanocytes located in suprabasal layers of the epidermis is accompanied by a change in keratinocyte adhesion molecule expression. The UV light is also able to influence the adhesive properties of melanocytes in vitro. Therefore, both keratinocyte-derived factors and direct influence of UV on the melanocyte system are probably responsible for the morphologic changes. While these exogenously evoked changes are reversible, the potential biologic relevance--especially a possible role in the initiation of the carcinogenesis cascade--requires clarification.

Adult↗
PubMed2000

Cost-effectiveness and implications of newborn screening for prolongation of QT interval for the prevention of sudden infant death syndrome.

OBJECTIVE: To determine the cost-effectiveness of universal and high-risk neonatal electrocardiographic (ECG) screening for QT prolongation as a predictor of sudden infant death syndrome (SIDS) risk in a theoretical group of neonates. STUDY DESIGN: Incremental cost-effectiveness analysis with decision analytic modeling. A hypothetical cohort of healthy, term infants was modeled, comparing options of no screening, high-risk neonate screening, and universal screening. The high-risk strategy is speculative, because no currently accepted methodology is known for identifying infants at high risk for SIDS. Given the uncertain mechanisms of association between prolonged corrected QT interval (QTc) and SIDS, analyses were repeated under different assumptions. Sensitivity analyses were also performed on all input variables for both costs and effectiveness. RESULTS: Under the assumption that neonatal electrocardiographic screening detects long QT syndrome responsive to conventional therapy, the cost-effectiveness of high-risk screening was $3403 per life year gained, whereas universal screening cost $18,465 per additional life year gained. However, if the effectiveness of SIDS therapy falls below 10%, the cost-effectiveness deteriorates to $28,376 per life year saved for the high-risk strategy and $118,900 for universal screening. The analyses were robust to a broad array of sensitivity analyses. CONCLUSIONS: The acceptability of the cost-effectiveness of neonatal electrocardiographic screening is heavily dependent on the pathophysiologic mechanism of SIDS and on the efficacy of monitoring and antiarrhythmic treatment. The nature of this association must be elucidated before routine neonatal electrocardiographic screening is warranted.

Cost-Benefit Analysis↗
PubMed2000

Plant-promoted pyrene degradation in soil.

A study was conducted to investigate the capability of nine plant species to promote the degradation of pyrene in soil. The test method allowed for analysis of the entire sample of soil. More pyrene was degraded in the presence of roots of all nine species than in unplanted soil. Within approximately 8 weeks, as much as 74% of the pyrene disappeared from vegetated soil compared to 40% or less from unplanted soil. The data suggest that some of the test species may be especially useful for phytoremediation of soils contaminated with PAHs.

Biodegradation, Environmental↗