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Biomedical subjects

B Smith

Publications and source records attributed to B Smith.

At least 37 records · Page 2Linked to original sources
PubMed2004

Pragmatic 'real world' study of the effect of audit of asthma on clinical outcome.

AIMS: To test whether participation in clinical audit is associated with improved care of a long-term health condition. METHODS: 'Real world' study comparing 1339 patients of all ages and severity of asthma managed by 77 self-selected highly motivated general practices in Scotland with 9617 patients from 319 practices from a national sample. RESULTS: Patients managed by 'audit' practices had more structured clinical reviews by nurses [817 (61%) versus 4301 (45%) OR 0.52, 95% CI 0.46-0.58] and less acute GP contacts [440 (33%) v 4161 (43%) OR 1.56, CI 1.38-1.56]. Consequently they experienced more checking of inhaler technique, use of peak flow meters and self- management plans. 'Audit' patients had more symptom free days [365 (42%) v 2216 (23%) OR 0.80, CI 0.70-0.91], and fewer asthma attacks [217 (16%) v 1938 (20%) OR 1.30, CI 1.12-1.53]. They made less use of hospital services including A&E [30 (2%) v 326 (3%) OR 1.53, CI 1.03-2.28] and outpatients [42 (3%) v 459 (5%) OR 1.55, CI 1.11-2.16]. CONCLUSIONS: Patients with asthma benefit from being managed by a practice involved in a programme of audit.

Journal Article↗
PubMed2004

Sparing of the penile bulb and proximal penile structures with intensity-modulated radiation therapy for prostate cancer.

Quality of life is an important consideration in the treatment of early prostate cancer. Laboratory and clinical data suggest that higher radiation doses delivered to the bulb of penis and proximal penile structures correlates with higher rates of post-radiation impotence. The goal of this investigation was to determine if intensity-modulated radiation therapy (IMRT) spares dose to the penile bulb while maintaining coverage of the prostate. 10 consecutive patients with clinically organ confined prostate cancer were planned with 3D conformal radiation therapy (3D-CRT) or IMRT to give a dose of 74 Gy without specifically constraining the plans to spare the penile bulb. All 10 patients were ultimately treated with IMRT. Dose-volume histograms were evaluated and the doses to prostate, rectum, bladder and penile bulb were compared. IMRT reduced the mean penile bulb doses compared with 3D-CRT (33.2 Gy vs 48.9 Gy, p<0.001), the percentage of penile bulb receiving over 40 Gy (37.7% vs 67.2%, p<0.001) and the dose received by >95% of penile bulb (5.3 Gy vs 11.7 Gy, p=0.003). Maximum penile bulb doses were higher with IMRT (81.2 Gy vs 73.1 Gy, p<0.001) although the volume of this high dose region was small. Both methods resulted in similar coverage of the prostate. The volume of rectum receiving 70 Gy was significantly reduced with IMRT (18.4% vs 21.9%, p=0.003) but the volumes of bladder receiving 70 Gy were similar (p=0.3). IMRT may potentially reduce long term sexual morbidity by reducing the dose to the majority of the penile bulb.

Dose-Response Relationship, Radiation↗
PubMed2003

Effect of antibodies to intercellular adhesion molecule type 1 on the protection of distant organs during reperfusion syndrome in rats.

We investigated kidney and lung alterations caused by intercellular adhesion molecule type 1 (ICAM-1) blockade after ischemia and reperfusion of hind limb skeletal muscles. Rats were submitted to ligature of the infrarenal aorta for 6 h. The animals were randomized into three groups of 6 rats each: group I, sacrificed after ischemia; group II, reperfusion for 24 h, and group III, reperfusion for 24 h after receiving monoclonal anti-ICAM-1 antibodies. At the end of the experiment, blood samples were collected for creatinine, lactate dehydrogenase, creatine phosphokinase, potassium, pH and leukocyte counts. Samples were taken from the muscles of the hind limbs and from the kidneys and lungs for histological analysis and measurement of the neutrophil infiltrate by myeloperoxidase staining. The groups did not differ significantly with regard to the laboratory tests. There were no major histological alterations in the kidneys. An intense neutrophil infiltrate in the lungs, similar in all groups, was detected. Myeloperoxidase determination showed that after reperfusion there was significantly less retention of polymorphonuclear neutrophils in the muscles (352 +/- 70 vs 1451 +/- 235 x 10(2) neutrophils/mg; P<0.01) and in the kidneys (526 +/- 89 vs 852 +/- 73 10(2) neutrophils/mg; P<0.01) of the animals that received anti-ICAM-1 before perfusion compared to the group that did not. The use of anti-ICAM-1 antibodies in this experimental model minimized neutrophil influx, thus reducing the inflammatory process, in the muscles and kidneys after ischemia and reperfusion of the hind limbs.

Animals↗
PubMed2003

Reversed latissimus dorsi muscle flap for repair of recurrent congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Neonates with large congenital diaphragmatic hernias (CDH) require prosthetic patch closure of the defect because of the paucity of native diaphragmatic tissue. As the child grows, patch separation can occur necessitating reoperation. Use of vascularized autologous tissue may decrease the incidence of reherniation as tissue incorporation and growth may be improved. The authors report our early experience using a local muscle advancement flap with microneural anastomosis for those children in whom reherniation develops after prosthetic patch placement. METHODS: Seven patients with CDH (6 left and 1 right) whose synthetic diaphragmatic patch separated from the chest wall resulting in a clinically significant recurrent hernia were followed up with prospectively. After dissecting the ipsilateral latissimus dorsi off the chest wall and dividing the thoracodorsal neurovascular bundle (based on its lumbar blood supply), the synthetic patch was removed via an eighth intercostal incision. The muscle flap was placed into the hemithorax through the bed of the tenth rib and sutured in place over a Vicryl mesh scaffold. The thoracodorsal nerve was anastomosed to the phrenic nerve. Functional analysis of the flap was performed in 4 patients. RESULTS: Age at placement of the muscle graft ranged from 2 months to 48 months (median, 24 months). There has been no evidence of reherniation after placement of the muscle graft. Long-term outcome and functional analysis of the flap was available in 4 patients (mean, 19 months). Two infants had fluoroscopic and sonographic evidence of nonparadoxical neodiaphragmatic motion. In one of these, electromyographic evidence of function was documented with a phrenic nerve conduction velocity of 22 meters per second. The third infant showed no evidence of neodiaphragmatic motion, and the fourth infant had paradoxical motion. CONCLUSIONS: This is the first direct documentation of phrenic nerve function in an infant with CDH. An innervated reversed latissimus dorsi (RLD) flap reconstruction for recurrent CDH provides an alternative to prosthetic patch repair. This technique offers the advantages of autologous vascularized tissue with potential phrenic nerve innervation and physiologic neodiaphragmatic motion.

Female↗
PubMed2003

Shoot meristem: an ideal explant for Zea mays L. transformation.

We report on a rapid high-frequency somatic embryogenesis and plant regeneration protocol for Zea mays. Maize plants were regenerated from complete shoot meristem (3-4 mm) explants via organogenesis and somatic embryogenesis. In organogenesis, the shoot meristems were directly cultured on a high-cytokinin medium comprising 5-10 mg x L(-1) 6-benzylaminopurine (BAP). The number of multiple shoots produced per meristem varied from six to eight Plantlet regeneration through organogenesis resulted in just four weeks. Callus was induced in five days of incubation on an auxin-modified Murashige and Skoog (MS) medium. Prolific callus, with numerous somatic embryos, developed within 3-4 weeks when cultured on an auxin medium containing 5 mg 2,4-dichlorophenoxyacetic acid x L(-1). The number of multiple shoots varied from three to six per callus. Using R23 (Pioneer, Hi-Bred, Johnston, Iowa), the frequency of callus induction was consistently in excess of 80% and plant regeneration ranged between 47 and 64%. All regenerated plantlets survived in the greenhouse and produced normal plants. Each transgenic plant produced leaves, glumes, and anthers that uniformly expressed green fluorescent protein (GFP). The GFP gene segregated in the pollen. Based on this data it is concluded that the transgenics arose from single-cell somatic embryos. The rate of transfer DNA (T-DNA) transfer to complete shoot meristems of Zea mays was high on the auxin medium and was independent of using super-virulent strains of Agrobacterium.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2003

Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis.

Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.

Cell Death↗
PubMed2002

The enhancement of hydration of fluidized bed combustion ash by sonication.

The use of limestone to control SO2 emissions in fluidized bed combustors (FBC) results in high CaO content in the ashes. This presents challenges for their disposal including significant exothermic behavior and uncontrolled expansion in the landfill. Hydration of the ashes is required to convert the CaO, but the current two-step hydration process is not very effective. In the present work a new technique using ultrasound to promote the hydration was examined. Initial work was done using an ultrasonic bath and subsequently an ultrasonic probe. Hydration levels greater than 80% in 20-40 min with amplitudes of 40% or more were achieved with residues containing high levels of CaO. This is about twice what can be achieved using conventional hydration technique. Similar results were obtained using FBC ashes from four utility/industrial scale and one pilot plant scale FBC units. The mechanism for the promotion of hydration bythe ultrasound is also explored.

Air Pollutants↗
PubMed2002

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Journal Article↗
PubMed2002

Analogy in moral deliberation: the role of imagination and theory in ethics.

This paper develops themes addressed in an article by Eric Wiland in the Journal of Medical Ethics 2000;26:466-8, where he aims to contribute to the debate concerning the moral status of abortion, and to emphasise the importance of analogies in moral argument. In the present paper I try to secure more firmly a novel understanding of why analogy is an essential component in the attempt to justify moral beliefs. I seek to show how analogical argument both encapsulates and exercises the notions of rationality and imagination and that the construction, development, and comparison of analogies fundamentally underpins ethical argument. In so doing, it enables us to adopt imaginative and ethically illuminating perspectives but in a manner that does not relinquish any claims to intellectual rigour. I present a critique of a brand of "moral particularism" by showing how it cannot, if construed in a certain way, adequately conceive of how we use analogies and imaginary cases in ethics. Although such a particularism is thus impotent with regard to ethical debate, I show that the wider motivation behind particularism that can be extracted is of clear relevance and importance to medical practitioners.

Abortion, Induced↗
PubMed2001

Tension-induced straightening transition of self-assembled helical ribbons.

Helical ribbons with pitch angles of either 11 degrees or 54 degrees self-assemble in a wide variety of quaternary surfactant-phospholipid/fatty acid-sterol-water systems. By elastically deforming these helices, we examined their response to uniaxial forces. Under sufficient tension, a low pitch helix reversibly separates into a straight domain with a pitch angle of 90 degrees and a helical domain with a pitch angle of 16.5 degrees. Using a newly developed continuum elastic free energy model, we have shown that this phenomenon can be understood as a first order mechanical phase transition.

DNA↗
PubMed2001

Removal of the pro-domain does not affect the conformation of the procaspase-3 dimer.

We have investigated the oligomeric properties of procaspase-3 and a mutant that lacks the pro-domain (called pro-less variant). In addition, we have examined the interactions of the 28 amino acid pro-peptide when added in trans to the pro-less variant. By sedimentation equilibrium studies, we have found that procapase-3 is a stable dimer in solution at 25 degrees C and pH 7.2, and we estimate an upper limit for the equilibrium dissociation constant of approximately 50 nM. Considering the expression levels of caspase-3 in Jurkat cells, we predict that procaspase-3 exists as a dimer in vivo. The pro-less variant is also a dimer, with little apparent change in the equilibrium dissociation constant. Thus, in contrast with the long pro-domain caspases, the pro-peptide of caspase-3 does not appear to be involved in dimerization. Results from circular dichroism, fluorescence anisotropy, and FTIR studies demonstrate that the pro-domain interacts weakly with the pro-less variant. The data suggest that the pro-peptide adopts a beta-structure when in contact with the protein, but it is a random coil when free in solution. In addition, when added in trans, the pro-peptide does not inhibit the activity of the mature caspase-3 heterotetramer. On the other hand, the active caspase-3 does not efficiently hydrolyze the pro-domain at the NSVD(9) sequence as occurs when the pro-peptide is in cis to the protease domain. Based on these results, we propose a model for maturation of the procaspase-3 dimer.

Caspase 3↗
PubMed2001

Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo.

The formation of heparan sulfate occurs within the lumen of the endoplasmic reticulum-Golgi complex-trans-Golgi network by the concerted action of several glycosyltransferases, an epimerase, and multiple sulfotransferases. In this report, we have examined the location and interaction of tagged forms of five of the biosynthetic enzymes: galactosyltransferase I and glucuronosyltransferase I, required for the formation of the linkage region, and GlcNAc N-deacetylase/N-sulfotransferase 1, uronosyl 5-epimerase, and uronosyl 2-O-sulfotransferase, the first three enzymes involved in the modification of the chains. All of the enzymes colocalized with the medial-Golgi marker alpha-mannosidase II. To study whether any of these enzymes interacted with each other, they were relocated to the endoplasmic reticulum (ER) by replacing their cytoplasmic N-terminal tails with an ER retention signal derived from the cytoplasmic domain of human invariant chain (p33). Relocating either galactosyltransferase I or glucuronosyltransferase I had no effect on the other's location or activity. However, relocating the epimerase to the ER caused a parallel redistribution of the 2-O-sulfotransferase. Transfected epimerase was also located in the ER in a cell mutant lacking the 2-O-sulfotransferase, but moved to the Golgi when the cells were transfected with 2-O-sulfotransferase cDNA. Epimerase activity was depressed in the mutant, but increased upon restoration of 2-O-sulfotransferase, suggesting that their physical association was required for both epimerase stability and translocation to the Golgi. These findings provide in vivo evidence for the formation of complexes among enzymes involved in heparan sulfate biosynthesis. The functional significance of these complexes may relate to the rapidity of heparan sulfate formation.

Animals↗
PubMed2001

SuperStar: comparison of CSD and PDB-based interaction fields as a basis for the prediction of protein-ligand interactions.

SuperStar is an empirical method for identifying interaction sites in proteins, based entirely on the experimental information about non-bonded interactions, present in the IsoStar database. The interaction information in IsoStar is contained in scatterplots, which show the distribution of a chosen probe around structure fragments. SuperStar breaks a template molecule (e.g. a protein binding site) into structural fragments which correspond to those in the scatterplots. The scatterplots are then superimposed on the corresponding parts of the template and converted into a composite propensity map. The original version of SuperStar was based entirely on scatterplots from the CSD. Here, scatterplots based on protein-ligand interactions are implemented in SuperStar, and validated on a test set of 122 X-ray structures of protein-ligand complexes. In this validation, propensity maps are compared with the experimentally observed positions of ligand atoms of comparable types. Although non-bonded interaction geometries in small molecule structures are similar to those found in protein-ligand complexes, their relative frequencies of occurrence are different. Polar interactions are more common in the first class of structures, while interactions between hydrophobic groups are more common in protein crystals. In general, PDB and CSD-based SuperStar maps appear equally successful in the prediction of protein-ligand interactions. PDB-based maps are more suitable to identify hydrophobic pockets, and inherently take into account the experimental uncertainties of protein atomic positions. If the protonation state of a histidine, aspartate or glutamate protein side-chain is known, specific CSD-based maps for that protonation state are preferred over PDB-based maps which represent an ensemble of protonation states.

Databases, Factual↗
PubMed2001

Pertussis is a frequent cause of prolonged cough illness in adults and adolescents.

Although pertussis is increasingly recognized as a cause of prolonged cough illness in adolescents and adults, its prevalence is not well established. We evaluated pertussis infection in 442 adolescents and adults > or = 12 years old (mean age, 41.3 years) who had a cough-related illness of 7--56 days' duration. For 4 patients (0.9%), results of nasopharyngeal culture or PCR were positive for Bordetella pertussis; for 10 patients (2.3%), either results of culture or PCR were positive or pertussis antibody titers increased 4-fold. Eighty-eight patients (19.9%) had either laboratory-confirmed pertussis or laboratory evidence of pertussis. These patients had significantly longer duration of cough than did patients without laboratory evidence of pertussis (56 days vs. 46 days), and more of them had vomiting with cough (45.5% vs. 28.5%, respectively). Pertussis is a common cause of prolonged cough illness in adolescents and adults and is frequently associated with other symptoms of whooping cough.

Adolescent↗
PubMed2001

Azepanone-based inhibitors of human and rat cathepsin K.

The synthesis, in vitro activities, and pharmacokinetics of a series of azepanone-based inhibitors of the cysteine protease cathepsin K (EC 3.4.22.38) are described. These compounds show improved configurational stability of the C-4 diastereomeric center relative to the previously published five- and six-membered ring ketone-based inhibitor series. Studies in this series have led to the identification of 20, a potent, selective inhibitor of human cathepsin K (K(i) = 0.16 nM) as well as 24, a potent inhibitor of both human (K(i) = 0.0048 nM) and rat (K(i,app) = 4.8 nM) cathepsin K. Small-molecule X-ray crystallographic analysis of 20 established the C-4 S stereochemistry as being critical for potent inhibition and that unbound 20 adopted the expected equatorial conformation for the C-4 substituent. Molecular modeling studies predicted the higher energy axial orientation at C-4 of 20 when bound within the active site of cathepsin K, a feature subsequently confirmed by X-ray crystallography. Pharmacokinetic studies in the rat show 20 to be 42% orally bioavailable. Comparison of the transport of the cyclic and acyclic analogues through CaCo-2 cells suggests that oral bioavailability of the acyclic derivatives is limited by a P-glycoprotein-mediated efflux mechanism. It is concluded that the introduction of a conformational constraint has served the dual purpose of increasing inhibitor potency by locking in a bioactive conformation as well as locking out available conformations which may serve as substrates for enzyme systems that limit oral bioavailability.

Administration, Oral↗
PubMed2001

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis.

BACKGROUND: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. METHODS: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. RESULTS: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. CONCLUSION: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Acetates↗
PubMed2001

State SCHIP design and the right to coverage.

This Policy Brief is the first in a series of reports examining the design of state SCHIP programs as they near full implementation status. It explores, whether states in their enabling legislation establishing separate SCHIP programs confer upon eligible children an individual legal right to health insurance benefits (i.e., an individual entitlement) under state law, similar to the entitlement that Medicaid eligible children enjoy under federal law. The question of whether states guarantee necessary health coverage for low-income children through the creation of an individual entitlement is fundamental to the study of state policy making under SCHIP.

Child↗