Biomedical subjects

L A Smith

Publications and source records attributed to L A Smith.

At least 37 records · Page 2Linked to original sources

PubMed2002

Linear and non-linear methods for automatic seizure detection in scalp electro-encephalogram recordings.

The electro-encephalogram is a time-varying signal that measures electrical activity in the brain. A conceptually intuitive non-linear technique, multi-dimensional probability evolution (MDPE), is introduced. It is based on the time evolution of the probability density function within a multi-dimensional state space. A synthetic recording is employed to illustrate why MDPE is capable of detecting changes in the underlying dynamics that are invisible to linear statistics. If a non-linear statistic cannot outperform a simple linear statistic such as variance, then there is no reason to advocate its use. Both variance and MDPE were able to detect the seizure in each of the ten scalp EEG recordings investigated. Although MDPE produced fewer false positives, there is no firm evidence to suggest that MDPE, or any other non-linear statistic considered, outperforms variance-based methods at identifying seizures.

Electroencephalography↗

PubMed2002

The actions of a D-1 agonist in MPTP treated primates show dependence on both D-1 and D-2 receptor function and tolerance on repeated administration.

The potent and long acting D-1 receptor agonist, A-77636 reverses motor deficits in MPTP treated common marmosets following subcutaneous or oral administration. We now explore the effects of acute versus repeated administration of A-77636 and the relative roles of D-1 and D-2 receptor involvement in its antiparkinsonian actions. Acute oral administration (0.18-9.0 mg/kg) or subcutaneous administration (0.036-1.08 mg/kg) of A-77636 produced well co-ordinated bouts of discontinuous locomotor activity. There was no evidence of repetitive or stereotyped movements. However, oral administration of A-77636 (1.44 mg/kg) on alternate days for 10 days produced tolerance to the increase in locomotor activity and improvement of disability. Pretreatment with the D-1 antagonist SCH 23390 (0.625, 2.5 or 5.0 mg/kg, intraperitoneally), produced a dose dependent reduction in locomotor activity and antagonised the reduction in disability scores following administration of A-77636 (0.36 mg/kg, subcutaneously). The inhibitory effects of SCH 23390 lasted for some 2-5 hours after which the activity of A-77636 was gradually restored. Unexpectedly, pretreatment with the D-2 antagonist raclopride (1.25, 5.0 or 20.0 mg/kg, intraperitoneally), dramatically diminished the antiparkinsonian effects of A-77636 (0.36 mg/kg, subcutaneously) in a dose dependent manner. The dependence of the antiparkinsonian activity of A-77636 on intact D-2 receptor function, suggests a need for endogenous D-2 receptor tone to express D-1 mediated locomotor activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2001

Preliminary assessments of spatial influences in the Ambos Nogales region of the US-Mexican border.

Ambient air measurements collected from 1994 to 1995 were used in a preliminary assessment of potential source and spatial influences in the Ambos Nogales border region (Nogales, Arizona, USA and Nogales, Sonora, Mexico). In this assessment, volatile organic compounds (VOC) and particulate matter (PM) species were used from four sites, two on either side of the border. An examination of median levels and principal component analysis indicated the dominance of soil dusts and mobile sources. Pairwise comparisons of sites for VOCs associated with mobile sources revealed statistically significant differences between sites in the central Nogales area vs. the two sites furthest from the border. Particulate lead at Mexican sites was higher and significantly different vs. US sites. Although further analyses are necessary, findings suggest that local and immediate mobile/other anthropogenic and soil dust influences are present throughout Nogales, with particulate lead from leaded motor vehicle exhaust or soldering operations being a possible influence on the Mexican side.

Air Movements↗

PubMed2001

Techniques to assess cross-border air pollution and application to a US-Mexico border region.

A year-long assessment of cross-border air pollution was conducted in the eastmost section of the US-Mexico border region, known as the Lower Rio Grande Valley, in South Texas. Measurements were conducted on the US side and included fine particle mass (PM2.5) and elemental composition, volatile organic compounds (VOCs) and meteorology. Wind sector analyses of chemical tracers and diagnostic ratios, in addition to principal component analysis (PCA), were initially applied to assess cross-border and overall air shed influences. Linear-angular correlation statistics [Biometrika, 63, (1976), 403-405] and nonparametric multiple comparisons between wind sectors were computed with the particle element data using principal component scores from PCA to determine the direction of source classes. Findings suggest crustal particles and salts carried or stirred by sea breeze winds from a southerly and southeasterly direction from the Gulf of Mexico heavily influenced the elemental composition of the particulate samples. Pair-wise comparisons of wind directions for the principal component scores suggest possible oil combustion influences from utilities or boilers coming from the south and possible coal combustion influences from the north and northwest. The techniques discussed can provide a methodology to assess future ambient levels and cross-border influences in the Valley as conditions change.

Air Movements↗

PubMed2001

Systematic review of the use of honey as a wound dressing.

OBJECTIVE: To investigate topical honey in superficial burns and wounds though a systematic review of randomised controlled trials. DATA SOURCES: Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and databases were used to seek randomised controlled trials. Seven randomised trials involved superficial burns, partial thickness burns, moderate to severe burns that included full thickness injury, and infected postoperative wounds. REVIEW METHODS: Studies were randomised trials using honey, published papers, with a comparator. Main outcomes were relative benefit and number-needed-to-treat to prevent an outcome relating to wound healing time or infection rate. RESULTS: One study in infected postoperative wounds compared honey with antiseptics plus systemic antibiotics. The number needed to treat with honey for good wound healing compared with antiseptic was 2.9 (95% confidence interval 1.7 to 9.7). Five studies in patients with partial thickness or superficial burns involved less than 40% of the body surface. Comparators were polyurethane film, amniotic membrane, potato peel and silver sulphadiazine. The number needed to treat for seven days with honey to produce one patient with a healed burn was 2.6 (2.1 to 3.4) compared with any other treatment and 2.7 (2.0 to 4.1) compared with potato and amniotic membrane. For some or all outcomes honey was superior to all these treatments. Time for healing was significantly shorter for honey than all these treatments. The quality of studies was low. CONCLUSION: Confidence in a conclusion that honey is a useful treatment for superficial wounds or burns is low. There is biological plausibility.

Anti-Bacterial Agents↗

PubMed2001

Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.

BACKGROUND: Meta-analysis usually restricts the information pooled, for instance using only randomised, double-blind, placebo-controlled trials. This neglects other types of high quality information. This review explores using different information for the combination of paracetamol 1000 mg and codeine 60 mg in acute postoperative pain. RESULTS: Randomised, double-blind, placebo-controlled trials of paracetamol 1000 mg and codeine 60 mg had an NNT of 2.2 (95% confidence interval 1.7 to 2.9) for at least 50% pain relief over four to six hours in three trials with 197 patients. Computer simulation of randomised trials demonstrated 92% confidence that the simulated NNT was within +/- 0.5 of the underlying value of 2.2 with this number of patients. The result was supported a rational dose-response relationship for different doses of paracetamol and codeine in 17 additional trials with 1,195 patients. Three controlled trials lacking a placebo and with 117 patients treated with of paracetamol 1000 mg and codeine 60 mg had 73% (95%CI 56% to 81%) of patients with at least 50% pain relief, compared with 57% (48% to 66%) in placebo controlled trials. Six trials in acute pain were omitted because of design issues, like the use of different pain measures or multiple dosing regimens. In each paracetamol 1000 mg and codeine 60 mg was shown to be better than placebo or comparators for at least one measure. CONCLUSIONS: Different designs of high quality trials can be used to support limited information used in meta-analysis without recourse to low quality trials that might be biased.

Acetaminophen↗

PubMed2001

Rizatriptan for acute migraine.

BACKGROUND: There are a number of different drug treatments for acute migraine, including currently four triptans, with several more likely to become available in the future. There is a need for evidence-based information to help determine the balance of benefit and harm for acute migraine treatment. OBJECTIVES: To quantitatively assess the efficacy of a single dose of rizatriptan (Maxalt) for treating a single migraine attack using the outcomes of headache response and pain-free response at half-an-hour, one hour, two hours, and sustained relief over 24 hours. To express efficacy in terms of numbers-needed-to-treat (NNTs). SEARCH STRATEGY: Trials were identified by searching MEDLINE (1966-July 2000), EMBASE (1980-June 2000), the Cochrane Library (Issue 3, 2000) and the Oxford Pain Relief Database (1950-1994). Date of last search: July 2000. SELECTION CRITERIA: The inclusion criteria were randomised, placebo-controlled trials of rizatriptan for acute migraine; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a four-point standardised rating scale; dichotomous or percentage data for at least one of the main efficacy outcomes; and full journal publication. DATA COLLECTION AND ANALYSIS: Main outcomes considered were i) headache response at two hours, ii) headache response at one hour, iii) pain-free response at two hours, iv) sustained relief over 24 hours, v) pain-free response at 24 hours and vi) adverse effects. Minor outcomes were headache response and pain-free response at half-an-hour and four hours, and pain-free response at one hour. Dichotomous or percentage data were extracted and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for each outcome. MAIN RESULTS: Seven trials met our inclusion criteria, with 2626 patients given rizatriptan and 902 given placebo. Significant benefit of rizatriptan over placebo was shown for both doses of rizatriptan (5 mg and 10 mg) for all five main efficacy outcomes (ranging from one to 24 hours). A dose response was seen for the main outcomes. It was not possible to analyse adverse effects information in a meaningful way. REVIEWER'S CONCLUSIONS: Rizatriptan 5 mg and 10 mg are effective in treating acute migraine, with a dose-related increase in efficacy.

Acute Disease↗

PubMed2001

Eletriptan for acute migraine.

BACKGROUND: Eletriptan (Relpax) is a new triptan soon to be made available by prescription for the treatment of acute migraine. Currently five triptans are available by prescription and more are under development. In light of the many drugs for treating acute migraine, there is a need for evidence-based assessments to help determine the relative efficacy and harm of these treatments. OBJECTIVES: To determine the efficacy of eletriptan for treating a single migraine attack using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4 hours, and sustained relief over 24 hours. To express efficacy in terms of number-needed-to-treat (NNT). To determine the adverse effects of a single dose of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow for the comparison of the efficacy of eletriptan with other migraine treatments evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase III randomised placebo-controlled trials were made available by the manufacturer, Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant to this review in a published or unpublished form; thus, searches of electronic databases for further trials of eletriptan were not conducted. SELECTION CRITERIA: Trials of eletriptan for acute migraine; randomised allocation to treatment groups, including a placebo group; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a 4-point standardised rating scale (0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain); and dichotomous or percentage data for at least one of the main efficacy outcomes. DATA COLLECTION AND ANALYSIS: Trials were scored for quality and data extracted by two independent reviewers. Dichotomous or percentage data were extracted and pooled to calculate the relative benefit (RB) or relative risk (RR) and NNTs or NNHs for a number of outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main outcomes considered were headache response at 1 and 2 hours, pain-free response at 2 hours, sustained relief over 24 hours and adverse effects. Minor outcomes considered were headache response at 0.5 and 4 hours, and pain-free response at 0.5, 1 and 4 hours. MAIN RESULTS: Six trials met the inclusion criteria. Significant benefit of eletriptan over placebo was shown for eletriptan 20 mg, 40 mg and 80 mg for the primary efficacy outcomes of headache response and pain-free response at 2 hours. For headache response at 2 hours, the NNTs (with 95% confidence intervals) were 4.4 (3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to 3.0) for eletriptan 20 mg, 40 mg and 80 mg, respectively. For pain-free response at 2 hours, the NNTs were 9.9 (6.9 to 18), 4.5 (4.0 to 5.1) and 3.7 (3.4 to 4.2), for eletriptan 20 mg, 40 and 80 mg, respectively. There was no significant difference in the incidence of major adverse effects between any dose of eletriptan and placebo. The incidence of minor adverse effects was significantly higher for all eletriptan doses than for placebo, with NNHs of 11 (95% confidence interval, 6.2 to 39), 7.0 (5.2 to 11) and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 40 mg and 80 mg, respectively. REVIEWER'S CONCLUSIONS: Eletriptan 20 mg, 40 mg and 80 mg are effective for the treatment of an acute migraine attack. Effectiveness is dose-related, with statistically significant differences between doses for pain-free response and 24-hour outcomes. Eletriptan compares well with other triptans available for outcomes measured up to 2 hours and provides meaningful relief for 24 hours. Taken as a single dose, eletriptan was well tolerated and caused no major harm. The incidence of minor harm was dose-dependent, with 80 mg giving significantly more adverse effects than 40 mg.

Acute Disease↗

PubMed2001

Seeking a simple measure of analgesia for mega-trials: is a single global assessment good enough?

We sought to investigate the potential of using a simple global estimation ('How effective do you think the treatment was?') as a measure of efficacy by comparing it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief) in acute pain studies. One hundred and fifty randomized, double-blind trials included in 11 systematic reviews of single dose, oral analgesics for postoperative pain were used as a source of data. The relationship between the proportion of patients reporting the top two or three values on a five-point global scale and the proportion with at least 50%maxTOTPAR was investigated. Twenty-six trials provided data on the proportion reporting the top two categories (very good or excellent) and 27 gave data on the top three categories (good, very good or excellent). The relationship between the percentage of patients recording the top two categories on a five-point global scale and the proportion with at least 50%maxTOTPAR was fair (r(2)=0.67). That for the top three categories was less good (r(2)=0.57). Similar numbers-needed-to-treat were calculated for aspirin 600/650 mg and ibuprofen 400 mg using at least 50%maxTOTPAR and the top two categories. No real difference was seen in the correlation for standard wording compared to non-standard wording. Individual patient data were also used from four randomized, placebo-controlled, double-blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was plotted for patients reporting each of the five categories on the global scale. A global assessment provides similar measures of analgesic efficacy as TOTPAR derived from hourly measurements, but the effects of adverse effects have yet to be understood.

Analgesia↗

PubMed2001

Enzymatic autocatalysis of botulinum A neurotoxin light chain.

Highly purified recombinant zinc-endopeptidase light chain of the botulinum neurotoxin serotype A underwent autocatalytic proteolytic processing and fragmentation. In the absence of added zinc, initially 10-28 residues were cleaved from the C-terminal end of the 448-residue protein followed by the appearance of an SDS-stable dimer and finally fragmentation near the middle of the molecule. In the presence of added zinc, the rate of fragmentation was accelerated but the specificity of the cleavable bond changed, suggesting a structural role for zinc in the light chain. The C-terminal proteolytic processing was reduced, and fragmentation near the middle of the molecule was prevented by adding the metal chelator TPEN to the light chain. Similarly, adding a competitive peptide inhibitor (CRATKML) of the light-chain catalytic activity also greatly reduced the proteolysis. With these results, for the first time, we provide clear evidence that the loss of C-terminal peptides and fragmentation of the light chain are enzymatic and autocatalytic. By isolating both the large and small peptides, we sequenced them by Edman degradation and ESIMS-MS, and mapped the sites of proteolysis. We also found that proteolysis occurred at F266-G267, F419-T420, F423-E424, R432-G433, and C430-V431 bonds in addition to the previously reported Y250-Y251 and K438-T439 bonds.

Amino Acid Sequence↗

PubMed2001

Children's understanding of the physical, cognitive and social consequences of impairments.

The present study explored typically developing children's (n = 77) understanding of physical, cognitive and social competencies of children with impairments. Children in each of four age groups (4-5 years, 6-7 years, 9-10 years and 11-12 years) were interviewed to explore their ideas about the abilities of children with physical impairments (minor: missing thumb; major: wheel-chair bound), sensory impairments (vision and hearing), learning disabilities (non-specific and Down's syndrome) and emotional/behavioural difficulties (attention deficit hyperactivity disorder and lack of social skills). Significant age differences were found in children's judgements of the capabilities of children with impairments. Furthermore, children's understanding of the consequences of impairments varied as a function of disability type. Findings are discussed in relation to previous research on children's disability concepts and implications for inclusive education practices.

Activities of Daily Living↗

PubMed2001

Integration of the Aedes aegypti mosquito genetic linkage and physical maps.

Two approaches were used to correlate the Aedes aegypti genetic linkage map to the physical map. STS markers were developed for previously mapped RFLP-based genetic markers so that large genomic clones from cosmid libraries could be found and placed to the metaphase chromosome physical maps using standard FISH methods. Eight cosmids were identified that contained eight RFLP marker sequences, and these cosmids were located on the metaphase chromosomes. Twenty-one cDNAs were mapped directly to metaphase chromosomes using a FISH amplification procedure. The chromosome numbering schemes of the genetic linkage and physical maps corresponded directly and the orientations of the genetic linkage maps for chromosomes 2 and 3 were inverted relative to the physical maps. While the chromosome 2 linkage map represented essentially 100% of chromosome 2, approximately 65% of the chromosome 1 linkage map mapped to only 36% of the short p-arm and 83% of the chromosome 3 physical map contained the complete genetic linkage map. Since the genetic linkage map is a RFLP cDNA-based map, these data also provide a minimal estimate for the size of the euchromatic regions. The implications of these findings on positional cloning in A. aegypti are discussed.

Aedes↗

PubMed2001

Clostridium perfringens iota-toxin: mapping of receptor binding and Ia docking domains on Ib.

Clostridium perfringens iota-toxin is a binary toxin consisting of iota a (Ia), an ADP-ribosyltransferase that modifies actin, and iota b (Ib), which binds to a cell surface protein and translocates Ia into a target cell. Fusion proteins of recombinant Ib and truncated variants were tested for binding to Vero cells and docking with Ia via fluorescence-activated cytometry and cytotoxicity experiments. C-terminal residues (656 to 665) of Ib were critical for cell surface binding, and truncated Ib variants containing > or = 200 amino acids of the C terminus were effective Ib competitors and prevented iota cytotoxicity. The N-terminal domain (residues 1 to 106) of Ib was important for Ia docking, yet this region was not an effective competitor of iota cytotoxicity. Further studies showed that Ib lacking just the N-terminal 27 residues did not facilitate Ia entry into a target cell and subsequent cytotoxicity. Five monoclonal antibodies against Ib were also tested with each truncated Ib variant for epitope and structural mapping by surface plasmon resonance and an enzyme-linked immunosorbent assay. Each antibody bound to a linear epitope within the N terminus (residues 28 to 66) or the C terminus (residues 632 to 655). Antibodies that target the C terminus neutralized in vitro cytotoxicity and delayed the lethal effects of iota-toxin in mice.

ADP Ribose Transferases↗

PubMed2001

Candidate vaccine against botulinum neurotoxin serotype A derived from a Venezuelan equine encephalitis virus vector system.

A candidate vaccine against botulinum neurotoxin serotype A (BoNT/A) was developed by using a Venezuelan equine encephalitis (VEE) virus replicon vector. This vaccine vector is composed of a self-replicating RNA containing all of the VEE nonstructural genes and cis-acting elements and also a heterologous immunogen gene placed downstream of the subgenomic 26S promoter in place of the viral structural genes. In this study, the nontoxic 50-kDa carboxy-terminal fragment (H(C)) of the BoNT/A heavy chain was cloned into the replicon vector (H(C)-replicon). Cotransfection of BHK cells in vitro with the H(C)-replicon and two helper RNA molecules, the latter encoding all of the VEE structural proteins, resulted in the assembly and release of propagation-deficient, H(C) VEE replicon particles (H(C)-VRP). Cells infected with H(C)-VRP efficiently expressed this protein when analyzed by either immunofluorescence or by Western blot. To evaluate the immunogenicity of H(C)-VRP, mice were vaccinated with various doses of H(C)-VRP at different intervals. Mice inoculated subcutaneously with H(C)-VRP were protected from an intraperitoneal challenge of up to 100,000 50% lethal dose units of BoNT/A. Protection correlated directly with serum enzyme-linked immunosorbent assay titers to BoNT/A. The duration of the immunity achieved was tested at 6 months and at 1 year postvaccination, and mice challenged at these times remained refractory to challenge with BoNT/A.

Animals↗

PubMed2001

Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation.

UNLABELLED: Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC, 20 microM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 +/- 0.4 to 21 +/- 2 min (P < 0.01, n = 14). The magnitude of the ARNA response was unaffected by L-SMTC. Similar effects were produced by N(omega)-nitro-L-arginine methyl ester (L-NAME) but not D-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during L-SMTC, from 5.9 +/- 1.4 to 13.6 +/- 4.2 pg/min before and from 4.9 +/- to 12.6 +/- 2.7 pg/min during L-SMTC. L-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 microM) from 1.2 +/- 0.2 to 5.6 +/- 1.1 min (P < 0.01, n = 9) without affecting the magnitude of the ARNA response. IN CONCLUSION: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.

Animals↗

PubMed2001

Hypercholesterolemia impairs endothelium-dependent relaxations in common carotid arteries of apolipoprotein e-deficient mice.

BACKGROUND AND PURPOSE: The effects of Western-type fat diet on endothelium-dependent relaxations and vascular structure in carotid arteries from a mouse model of human atherosclerosis are not known. Our objective was to characterize the mechanisms underlying endothelial dysfunction in apoE-deficient mice. METHODS: C57BL/6J and apoE-deficient mice were fed for 26 weeks with a lipid-rich Western-type diet. Changes in the intraluminal diameter of pressurized common carotid arteries (ID 450 micrometer) were measured in vitro with a video dimension analyzer. Endothelial NO synthase protein content was evaluated by Western blotting. Intracellular cGMP and cAMP levels were determined by radioimmunoassay. RESULTS: No morphological changes were observed in the carotid arteries of apoE-deficient mice. However, endothelium-dependent relaxations to acetylcholine (10(-9) to 10(-5) mol/L) were impaired (maximal relaxation 52+/-7% versus 83+/-5% for control mice, P<0.05). Treatment of arteries with NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester inhibited relaxations to acetylcholine to the same extent in apoE-deficient mice as in control mice. Preincubation of carotid arteries with cell-permeable superoxide dismutase mimetic Mn(III) tetra(4-benzoic acid)porphyrin chloride almost normalized NO-mediated relaxations to acetylcholine (75+/-5%, P<0.05). Endothelium-dependent relaxations to calcium ionophore and endothelium-independent relaxations to NO donor diethylammonium(Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate were unchanged in apoE-deficient mice. In addition, no changes in endothelial NO synthase protein expression and cGMP/cAMP levels were found in carotid arteries of apoE-deficient mice. CONCLUSIONS: In carotid arteries of apoE-deficient mice, hypercholesterolemia causes impairment of receptor-mediated activation of eNOS. Increased superoxide anion production in endothelial cells appears to be coupled to activation of cholinergic receptors and is responsible for hypercholesterolemia-induced endothelial dysfunction. The apoE-deficient mouse carotid artery is a valuable new experimental model of endothelial dysfunction.

Animals↗

PubMed2001

Hematopoietic stem cell transplantation.

Hematopoietic stem cells have been shown to provide the best chance for long term patient engraftment in bone marrow transplantation, peripheral blood stem cell transplantation, and umbilical cord blood transplantation. Characteristics of these cells include the ability to divide without differentiating; presence in bone marrow, peripheral blood, and cord blood; and negativity for all lineage CD markers. Autologous, syngeneic, and allogeneic transplantations have all been performed and patients respond well. Complications include graft rejection or failure and graft-versus-host disease; however, such complications can be minimized and treated. Hematopoietic stem cell transplantation holds promise for the treatment of many malignancies and metabolic diseases that have not responded to other forms of treatment.

Graft Rejection↗

PubMed2001

Complications and risks in hematopoietic stem cell transplant patients.

Hematopoietic stem cell transplantation is a recognized treatment for hematological diseases such as leukemia and lymphoma, certain solid organ tumors, and a limited number of immunologic disorders. The major risks associated with this procedure are infections and development of graft-vs-host disease. Bacterial or viral agents are the most common cause of infections, but fungal and protozoan organisms may also be isolated. Bacterial infections occur most frequently in the first 30 days after transplant, whereas the onset of viral infections usually occurs later during the first three months posttransplant. Studies have demonstrated that there are a variety of predisposing factors that influence the type of infection a patient develops. These include underlying disease, type of chemotherapy regimen, type of antimicrobial and antiviral regimen, presence of graft-vs-host disease, and period of severe neutropenia posttransplant. Of these, the period of neutropenia appears to be the most significant. Graft-vs-host disease is seen in those patients who have received allogeneic hematopoietic stem cell transplants. New antimicrobial and antiviral agents and manipulation of the hematopoietic stem cell transplant to select specific cell types for infusion have provided some methods to prevent or decrease the number and severity of infections or to prevent/control graft-vs-host disease.

Bacterial Infections↗