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Biomedical subjects

A Paul

Publications and source records attributed to A Paul.

At least 91 records · Page 5Linked to original sources
PubMed2001

Adults with learning disabilities and epilepsy: knowledge about epilepsy before and after an educational package.

The understanding individuals have about their epilepsy may influence the success with which that individual copes with his/her epilepsy. This paper presents the first evaluation of a video-assisted brief educational package for adults with mild learning disabilities and epilepsy ("Epilepsy and You"; Paul, 1996 21). Utilizing a deferred entry to treatment design to evaluate intervention effects eighteen subjects participated in the study. Their knowledge about epilepsy before and after training was assessed using a checklist of knowledge and the Epilepsy Knowledge Questionnaire-Revised for use with people with learning disabilities. Results demonstrated significant gains in knowledge which were durable over a short follow-up period (1 month). "Epilepsy and You" was found to be suitable for use with a wide range of individuals and subjects' opinions demonstrated they enjoyed taking part. This study is a preliminary investigation from which other research can develop. Therefore, criticisms and suggestions for further research have been made.

Adult↗
PubMed2001

Cost-effective reduction of NOx emissions from electricity generation.

This paper analyzes the benefits and costs of policies to reduce NOx emissions from electricity generation in the United States. Because emissions of NO contribute to the high concentration of atmospheric ozone in the eastern states associated with health hazards, the U.S. Environmental Protection Agency (EPA) has called on eastern states to formulate state implementation plans (SIPs) for reducing NOx emissions. Our analysis considers three NOx reduction scenarios: a summer seasonal cap in the eastern states covered by EPA's NOx SIP Call, an annual cap in the same SIP Call region, and a national annual cap. All scenarios allow for emissions trading. Although EPA's current policy is to implement a seasonal cap in the SIP Call region, this analysis indicates that an annual cap in the SIP Call region would yield about $400 million more in net benefits (benefits less costs) than would a seasonal policy, based on particulate-related health effects only. An annual cap in the SIP Call region is also the policy that is most likely to achieve benefits in excess of costs. Consideration of omissions from this accounting, including the potential benefits from reductions in ozone concentrations, strengthens the finding that an annual program offers greater net benefits than does a seasonal program.

Air Pollution↗
PubMed2001

Calpain inhibitor I reduces the activation of nuclear factor-kappaB and organ injury/dysfunction in hemorrhagic shock.

There is limited evidence that inhibition of the activity of the cytosolic cysteine protease calpain reduces ischemia/reperfusion injury. The multiple organ injury associated with hemorrhagic shock is due at least in part to ischemia (during hemorrhage) and reperfusion (during resuscitation) of target organs. Here we investigate the effects of calpain inhibitor I on the organ injury (kidney, liver, pancreas, lung, intestine) and dysfunction (kidney) associated with hemorrhagic shock in the anesthetized rat. Hemorrhage and resuscitation with shed blood resulted in an increase in calpain activity (heart), activation of NF-kappaB (kidney), expression of iNOS and COX-2 (kidney), and the development of multiple organ injury and dysfunction, all of which were attenuated by calpain inhibitor I (10 mg/kg i.p.), administered 30 min prior to hemorrhage. Chymostatin, a serine protease inhibitor that does not prevent the activation of NF-kappaB, had no effect on the organ injury/failure caused by hemorrhagic shock. Pretreatment (for 1 h) of murine macrophages or rat aortic smooth muscle cells (activated with endotoxin) with calpain inhibitor I attenuated the binding of activated NF-kappaB to DNA and the degradation of IkappaBalpha, IkappaBbeta, and IkappaBvarepsilon. Selective inhibition of iNOS activity with L-NIL reduced the circulatory failure and liver injury, while selective inhibition of COX-2 activity with SC58635 reduced the renal dysfunction and liver injury caused by hemorrhagic shock. Thus, we provide evidence that the mechanisms by which calpain inhibitor I reduces the circulatory failure as well as the organ injury and dysfunction in hemorrhagic shock include 1) inhibition of calpain activity, 2) inhibition of the activation of NF-kappaB and thus prevention of the expression of NFkappaB-dependent genes, 3) prevention of the expression of iNOS, and 4) prevention of the expression of COX-2. Inhibition of calpain activity may represent a novel therapeutic approach for the therapy of hemorrhagic shock.

Animals↗
PubMed2001

Uremic sera contain inhibitors that block digitoxin-valproic acid interaction.

BACKGROUND: Digitoxin and valproic acid show strong binding to serum albumin. Thus, when present simultaneously in serum, digitoxin and valproic acid compete for binding sites. We studied digitoxin-valproic acid interaction in normal and uremic sera. METHODS: Fluorescence polarization immunoassays were used for measuring total digitoxin and total valproic acid concentrations. We used a modified protocol of improved sensitivity to measure free digitoxin concentrations. We supplemented 2 normal and 2 uremic pools with digitoxin and then aliquots of these pools were further supplemented with various concentrations of valproic acid. After incubation at 37 degrees C for 2 hours in a water bath, specimens were allowed to re-equilibrate at room temperature for 20 minutes. Free digitoxin concentrations were measured. We also investigated digoxin-valproic acid interaction using 1 normal and 1 uremic serum pool. RESULTS: We observed significant increases in free digitoxin concentrations in normal sera in the presence of valproic acid. In contrast, we observed a slight decline in free digitoxin concentration in the presence of valproic acid in uremic sera. We speculated that uremic sera contained inhibitors that block digitoxin-valproic acid interaction and identified indoxyl sulfate as an inhibitor. However, another uremic compound, hippuric acid showed no inhibitory effect. Interestingly, we observed no significant interaction between digoxin and valproic acid in either normal or uremic serum pool. This is probably because of poor protein binding of digoxin. CONCLUSION: We conclude that valproic acid significantly displaces digitoxin from protein binding sites in normal serum. However, uremic sera contain inhibitors that block digitoxin-valproic acid interaction.

Anticonvulsants↗
PubMed2001

Instability of lipoprotein(a) in plasma stored at -70 degrees C: effects of concentration, apolipoprotein(a) genotype, and donor cardiovascular disease.

BACKGROUND: There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered. METHODS: Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting. RESULTS: Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the largest isoform. All patients and controls were heterozygotes. During storage, mean Lp(a) decreased significantly in samples from patients (-23%; P <0.001) but not in samples from controls (-9%; P, not significant). This was not related to the kringle number and was limited to samples with initial plasma Lp(a) concentrations between 41 and 345 mg/L. CONCLUSIONS: Plasma Lp(a) from patients is less stable than Lp(a) from controls, and the difference is not related to distribution of apo(a) genotypes but may be concentration-dependent. Differential sample stability may complicate the interpretation of several studies.

Adult↗
PubMed2000

The continuous administration of aspirin attenuates atherosclerosis in apolipoprotein E-deficient mice.

Aspirin reduces the incidence of thrombotic occlusive events. Classically this has been thought to be due to the platelet inhibitory action of aspirin but it has recently been shown that inflammation plays a predominant role in the initiation and progression of lesions in atherosclerosis. In humans, treatment with aspirin reduces cardiovascular risk and slows carotid plaque growth in a dose-dependent fashion. We have explored this issue in Apo E-deficient mice on a high-fat, high cholesterol diet which provided these animals with a continuous administration of 500 microg/day of acetylsalicylic acid in the drinking water. After 10 weeks of treatment, the size of the atherosclerotic lesion at the aortic sinus had reduced by 35%. At the end of the trial there were no significant changes in either plasma lipids or in the quantitative distribution among lipoproteins. Likewise, the total antioxidant status and the resistance of plasma to oxidation in vitro was similar and there was no change in the distribution of iron deposits and in the relative composition of plasma pro-oxidants and antioxidants, or in the concentration of plasma in ferritin. Therefore, it is our hypothesis that the antiinflammatory effect is responsible for the reduction in lesion size. We propose that antiinflammatory molecules which do not cause gastrointestinal complications should be tested in humans to determine long-term efficacy in the attenuation of atherosclerosis.

Animals↗
PubMed2000

Physical and functional interaction between two pluripotent proteins, the Y-box DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF.

CTCF is a unique, highly conserved, and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple DNA site specificities. It is able to bind to varying target sequences to perform different regulatory roles, including promoter activation or repression, creating hormone-responsive gene silencing elements, and functional block of enhancer-promoter interactions. Because different sets of ZFs are utilized to recognize different CTCF target DNA sites, each of the diverse DNA.CTCF complexes might engage different essential protein partners to define distinct functional readouts. To identify such proteins, we developed an affinity chromatography method based on matrix-immobilized purified recombinant CTCF. This approach resulted in isolation of several CTCF protein partners. One of these was identified as the multifunctional Y-box DNA/RNA-binding factor, YB-1, known to be involved in transcription, replication, and RNA processing. We examined CTCF/YB-1 interaction by reciprocal immunoprecipitation experiments with anti-CTCF and anti-YB-1 antibodies, and found that CTCF and YB-1 form complexes in vivo. We show that the bacterially expressed ZF domain of CTCF is fully sufficient to retain YB-1 in vitro. To assess possible functional significance of CTCF/YB-1 binding, we employed the very first identified by us, negatively regulated, target for CTCF (c-myc oncogene promoter) as a model in co-transfection assays with both CTCF and YB-1 expression vectors. Although expression of YB-1 alone had no effect, co-expression with CTCF resulted in a marked enhancement of CTCF-driven c-myc transcriptional repression. Thus our findings demonstrate, for the first time, the biological relevance of the CTCF/YB-1 interaction.

Base Sequence↗
PubMed2000

P2Y receptor-mediated inhibition of tumor necrosis factor alpha -stimulated stress-activated protein kinase activity in EAhy926 endothelial cells.

In the EAhy926 endothelial cell line, UTP, ATP, and forskolin, but not UDP and epidermal growth factor, inhibited tumor necrosis factor alpha (TNFalpha)- and sorbitol stimulation of the stress-activated protein kinases, JNK, and p38 mitogen-activated protein (MAP) kinase, and MAPKAP kinase-2, the downstream target of p38 MAP kinase. In NCT2544 keratinocytes, UTP and a proteinase-activated receptor-2 agonist caused similar inhibition, but in 13121N1 cells, transfected with the human P2Y(2) or P2Y(4) receptor, UTP stimulated JNK and p38 MAP kinase activities. This suggests that the effects mediated by P2Y receptors are cell-specific. The inhibitory effects of UTP were not due to induction of MAP kinase phosphatase-1, but were manifest upstream in the pathway at the level of MEK-4. The inhibitory effect of UTP was insensitive to the MEK-1 inhibitor PD 098059, changes in intracellular Ca(2+) levels, or pertussis toxin. Acute phorbol 12-myristate 13-acetate pretreatment also inhibited TNFalpha-stimulated SAP kinase activity, while chronic pretreatment reversed the effects of UTP. Furthermore, the protein kinase C inhibitors Ro318220 and Go6983 reversed the inhibitory action of UTP, but GF109203X was ineffective. These results indicate a novel mechanism of cross-talk regulation between P2Y receptors and TNFalpha-stimulated SAP kinase pathways in endothelial cells, mediated by Ca(2+)-independent isoforms of protein kinase C.

Cell Line↗
PubMed2000

Examination of intrafascicular muscle fiber terminations: implications for tension delivery in series-fibered muscles.

Mammalian skeletal muscles with long fascicle lengths are predominantly composed of short muscle fibers that terminate midbelly with no direct connection to the muscle origin or insertion. The manner in which these short fibers terminate and transmit tension through the muscle to their tendons is poorly understood. We made an extensive morphological study of a series-fibered muscle, the guinea pig sternomastoid, in order to define the full range of structural specializations for tension transmission from short fibers within this muscle. Terminations were examined in single fibers, teased small bundles of fibers, and in sections at both the light and electron microscopic level. In many cases, sites of fiber termination were defined by reactivity for the enzyme acetylcholinesterase, which also marks myotendinous junctions. Additionally, transport of the lipophilic fluorescent dye, DiI, or injection of Lucifer Yellow were used to visualize undisturbed fiber terminations in whole muscles using confocal and fluorescence microscopy. At the light microscopic level, we find that intrafascicularly terminating fibers end about equally often in either a long progressive taper, or in a series of small or larger blunt steps. Combinations of these two morphologies are also seen. However, when analyzed at higher resolution with confocal or electron microscopy, the apparently smooth progressive tapers appear also to be predominantly composed of a series of fine stepped terminations. Stepwise terminations in most cases join face-to-face with complementary endings of neighboring muscle fibers, some via an extended collagenous bridge and others at close interdigitating myomyonal junctions. These muscle-to-muscle junctions show many of the features of myotendinous junctions, including dense subsarcolemmal plaques in regions of myofibrillar termination and we suggest that they serve to pass tension from fiber to fiber along the longitudinal axis of the muscle. In addition, we observe regions of apparent side-to-side adhesion between neighboring fibers at sites where there is no apparent fiber tapering or structural specialization typical of myofibril termination. These sites show acetylcholinesterase reactivity, and large numbers of collagen fibers passing laterally from fiber to fiber. These latter connections seem most likely to be involved in lateral transmission of tension, either from fiber to fiber, or from fiber to endomysium. Overall, our results suggest that tension from intrafascicularly terminating fibers is likely to be passed along the muscle to the tendon using both in-series and in-parallel arrangements. The results are discussed in light of current theories of tension delivery within the series-fibered muscles typical of large, nonprimate mammals.

Acetylcholinesterase↗
PubMed2000

Measurement of radon and radon progenies at the German radon reference chamber.

The activity concentration of radon in the environment can vary over five orders of magnitude. Radon and its progenies thus concern all people involved in radiation protection as well as in low-level experiments. In the German radon reference chamber at the PTB, radon and its progenies are measured with different systems for alpha- and gamma-spectrometry with the full set of environmental parameters, e.g. temperature, humidity and aerosol concentration being controlled. Control of air pressure is also possible by use of an extention chamber. The sampling and measuring technique for radon and its short-lived progenies at the German radon reference chamber are the basis for fundamental studies with regard to the understanding of the equilibrium factor and the unattached fraction of progenies. The facility also serves for the calibration of radon progeny detectors.

Environmental Monitoring↗
PubMed2000

Species-specific prevalence of vaginal candidiasis among patients with diabetes mellitus and its relation to their glycaemic status.

OBJECTIVES: Non- C. albicans Candida species are increasingly being recognized as the cause of vulvo-vaginal candidiasis. These species are often less susceptible to antifungal agents. Patients with diabetes mellitus are at risk for vulvo-vaginal candidasis. We assessed the species-specific prevalence rate and risk of candidiasis in patients with diabetes mellitus and healthy controls. METHODS: Genital tract examination, direct microscopy and fungal cultures of discharge collected by high vaginal swab were undertaken among 78 consecutive patients with diabetes mellitus (mean (+/-sd) age 32+/-12 years and body mass index (BMI) 22.3+/-5.5kg/m(2)) and 88 age- and BMI-matched healthy females. Glycaemic control in the diabetic cohort was assessed by measuring total glycosylated haemoglobin. RESULTS: Candida species were isolated in 36 of 78 (46%) subjects with diabetes mellitus and in 21 of 88 (23%) healthy subjects (Chi-squared 9.11, P=0.0025). The predominant Candida species isolated in diabetics with vulvo-vaginal candidiasis were Candida glabrata (39%), C. albicans (26%) and C. tropicalis (17%). In contrast, in the control group, C. albicans, C. glabrata and C. hemulonii comprised 30% each, with none having C. tropicalis infection (for C. tropicalis: diabetic vs. control; 17% vs. nil, P=0. 05). Among the diabetic group, subjects with vulvo-vaginal candidiasis had significantly higher mean HbA1 when compared to those who had no such infection (12.8+/-2.6% vs. 9.7+/-1.7% respectively, P=0.001). The overall accuracy of direct microscopy and clinical examination for predicting vulvo-vaginal candidiasis was only 77% and 51%, respectively, in the diabetic group, and 83% and 65% in the control group. CONCLUSIONS: Patients with diabetes mellitus had a high prevalence rate (46%) of vulvo-vaginal candidiasis with relative risk of 2.45. The non- C. albicans species such as C. glabrata and C. tropicalis were the predominant species isolated among them. There seems to be a significant link between hyperglycaemia and vulvo-vaginal candidiasis.

Adult↗
PubMed2000

Prospective double-blind randomised study of a new regimen of pre-emptive analgesia for inguinal hernia repair: evaluation of postoperative pain course.

OBJECTIVE: To evaluate the effectiveness of a new regimen of pre-emptive analgesia on the development of postoperative pain after inguinal hernia repair. DESIGN: Prospective, double-blind, randomised study. SETTING: University Hospital, Germany. SUBJECTS: 70 consecutive patients who had primary unilateral inguinal hernia repairs. INTERVENTIONS: A new regimen of pre-emptive analgesia with bupivacaine that was infiltrated preoperatively, intraoperatively, and postoperatively was tested. The control group were given saline infiltrations at the same times. Pain was measured up to postoperative day 30 using the visual analogue scale (VAS), the verbal rating scale (VRS), and by recording patient-controlled use of ibuprofen suppositories. RESULTS: Pain was significantly less in the pre-emptive analgesia group than in the control group during the first 10 days postoperatively as assessed by VAS and VRS (p < 0.05). Analgesic consumption was also significantly reduced in the pre-emptive analgesia group (p < 0.05). Multivariate analysis showed that bupivacaine infiltration (pre-emptive analgesia) was associated with significantly less postoperative pain (p < 0.0001). CONCLUSION: This regimen of pre-emptive analgesia is an effective and safe method of reducing postoperative pain and analgesic consumption after inguinal hernia repair.

Adult↗
PubMed2000

Stereospecificity of antibody: quinine, the optical isomer of quinidine and anti-malarial drug chloroquine do not cross-react with quinidine immunoassays.

Quinine is an optical isomer of quinidine. Both quinine and chloroquine (an aminoquinoline derivative) are used in treating malaria. The authors studied cross-reactivity of quinine and chloroquine with the quinidine immunoassays using the TDx and AxSYM analyzers (Abbott Laboratories, Abbott Park, IL). The authors observed no cross-reactivity of chloroquine with quinidine immunoassays (TDx and AXSYM) even when drug-free serum was supplemented with 1000 microg/mL chloriquine. The authors observed no cross-reactivity of quinine up to a concentration of 250 microg/mL. At higher concentrations, the authors observed a small cross-reactivity. The cross-reactivity of a substance should be studied in the presence of the primary analyte. When serum pools prepared from patients receiving quinidine were supplemented with various concentrations of quinine or chloroquine, the authors observed statistically significant declines in quinidine concentrations with higher concentrations of both quinine and chloroquine. The authors observed significant cross-reactivity of L-amphetamine with the amphetamine immunoassay also marketed by Abbott Laboratories and run on the AxSYM analyzer. The authors conclude that although the antibody used in the quinidine assay is stereospecific, the antibody used in the amphetamine assay by the same manufacturer is not stereospecific.

Antibodies↗
PubMed2000

Brucellosis associated with thrombocytopenia.

Brucellosis is a zoonotic disease and is endemic in Saudi Arabia. Many hematological complications have been reported. We report a case of selective thrombocytopenia in an expatriate from Bangladesh. Patient responded well to antibrucella and steroid treatment.

Adult↗
PubMed2000

Neurobrucellosis.

Brucellosis, which is endemic in Saudi Arabia, can present as a disease with multisystem involvement. Occasionally the organisms invade the central nervous system producing varied neurological manifestations. Often the clinical diagnosis of neurobrucellosis is not straight forward and is obscure. Certain criteria have to be fulfilled for the definitive diagnosis of neurobrucellosis. We report 2 cases of neurobrucellosis which were encountered for the first time during the past 10 years at this hospital.

Adult↗