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Biomedical subjects

B P Smith

Publications and source records attributed to B P Smith.

At least 19 recordsLinked to original sources
PubMed2004

Complications associated with traction on the hip during arthroscopy.

We studied 16 hips (eight cadaver specimens) using arthrography, arthroscopy and anatomical dissection, under incremental traction of up to a maximum of 64 kg, to determine the relationship of the portals to nearby neurovascular structures. The distance of each arthroscopic portal (anterior, anterolateral, and posterolateral) to the associated neurovascular structures was measured after the application of 23 kg of traction. Traction of up to 64 kg on the lower limb failed to produce evidence of labral or capsular injury. Furthermore, traction of 23 kg resulted in little change in the position of adjacent neurovascular structures relative to the standard arthroscopic portals.

Arthroscopy↗
PubMed2002

Evidence for biosynthesis of pseudophrynamine alkaloids by an Australian myobatrachid frog (pseudophryne) and for sequestration of dietary pumiliotoxins.

Australian myobatrachid frogs of the genus Pseudophryne have only two classes of alkaloids in skin extracts, pseudophrynamines (PSs) and pumiliotoxins (PTXs). The former are unique to such Australian frogs, while the PTXs occur worldwide in all other genera of frogs/toads that contain lipophilic alkaloids. The major alkaloid of wild-caught frogs from one population of Pseudophryne semimarmorata was PTX 267C, while PSs were only minor or trace alkaloids. Captive-raised frogs from the same parental stock had no PTXs, but had larger amounts of PSs. A PTX fed to captive-raised frogs accumulated into skin along with dihydro and hydroxy metabolites. Thus, Pseudophryne frogs appear to biosynthesize PSs, but to sequester into skin dietary PTXs. In addition, biosynthesis of PSs appears reduced when high levels of dietary PTXs have accumulated into skin. This is the first evidence indicating that certain frogs are capable of synthesizing rather than merely sequestering alkaloids. A wide range of PSs, including many with molecular weights >500, were detected using both GC-mass spectral and LC-mass spectral analysis.

Alkaloids↗
PubMed2001

Monitoring biogenic volatile compounds emitted by Eucalyptus citriodora using SPME.

A procedure to monitor BVOC emitted by living plants using SPME technique is presented. For this purpose, a glass sampling chamber was designed. This device was employed for the characterization of biogenic volatile compounds emitted by leaves of Eucalyptus citriodora. After extraction with SPME fibers coated with PDMS/ DVB, it was possible to identify or detect 33 compounds emitted by this plant. A semiquantitative approach was applied to monitor the behavior of the emitted BVOC during 9 days. Circadian profiles of the variation in the concentration of isoprene were plotted. Using diffusion-based SPME quantitation, a recently introduced analytical approach, with extraction times as short as 15 s, it was possible to quantify subparts-per-billion amounts of isoprene emitted by this plant.

Butadienes↗
PubMed2001

Conventional and surrogate light chains differentially regulate Ig mu and Dmu heavy chain maturation and surface expression.

Positive selection of precursor (pre-) B cells by Ig membrane mu H chains (mum HC) and counterselection mediated by the truncated HC Dmu depend on the ability of each HC to form a pre-B cell receptor (pre-BCR) signaling complex with the surrogate L chain (SLC) components lambda5 and Vpre-B. To better understand how pre-BCR signaling output is determined by its Ig components and the SLC, we investigated the regulation of pre-BCR surface expression and HC secretory maturation in a new nonlymphoid system. We took this approach as a means to distinguish B-lineage-specific effects from pre-BCR-intrinsic properties that may influence these aspects of pre-BCR homeostasis necessary for signaling. As in pre-B cells, the SLC in nonlymphoid cells supported only a limited degree of mum HC maturation and low pre-BCR surface expression levels compared with conventional LCs, indicating that this was due to an intrinsic property of the SLC. We identified the non-Ig region of lambda5 as harboring the restrictive activity responsible for this phenotype. This property of lambda5 was also evident with Dmu, but the overall SLC- and L chain-dependent requirements for Dmu maturation and surface expression were markedly different from those for mum. Surprisingly, Dmu was modified in an unusual manner that was only dependent on Vpre-B. These results establish a novel function of lambda5 in limiting surface pre-BCR levels and reveal biochemical properties of Ig molecules that may underlie the diverse consequences of pre-BCR signaling in vivo by different HCs.

B-Lymphocytes↗
PubMed2001

Virulence factors in Escherichia coli isolated from the blood of bacteremic neonatal calves.

Twenty-five Escherichia coli isolates from the blood of critically ill bacteremic calves sampled in two separate studies on a calf-rearing farm housing over 15,000 calves, in the San Joaquin Valley, California were studied. Isolates were characterized for O serogroups and for pathotypes as determined by the presence of specific virulence factors including heat-labile enterotoxin (LT), heat-stable enterotoxins a and b (STa, STb), verotoxins 1 and 2 (VT1, VT2), cytotoxic necrotizing factor (CNF), aerobactin, intimin Eae and P, F17 and CS31A fimbrial adhesins, and resistance to bactericidal effects of serum. These isolates constituted a heterogeneous group. However, isolates were mostly aerobactin positive and often resistant to the bactericidal effects of serum. Isolates of pathotypes O78 (n=6), O119:CS31a (n=3), and P positive but O non-typeable (n=3) were associated with a high mortality rate. The remaining isolates belonged to diverse pathotypes, often possessing the adhesins P, F17, CS31A and Eae but belonging to O serogroups other than O78 and O119, and were less frequently associated with mortality. Although no virulence factor common to all isolates was identified, the capacity to use iron by the presence of aerobactin which is important to the capture of iron was a predominant factor. Moreover, certain pathotypes appear to be associated with primary colisepticemia whereas other pathotypes may cause a bacteremia without necessarily leading to septicemia.

Adhesins, Bacterial↗
PubMed2001

Arthroscopic and open management of dynamic scaphoid instability.

This article focuses on the pathophysiology and treatment of dynamic scaphoid instability. Cadaver studies suggest that dynamic instability results from isolated injury to the scapholunate interosseous ligament without damage to the dorsal intercarpal and dorsal radial lunotriquetral ligaments. The diagnosis may be made by dynamic fluoroscopic examination, including stress and load views. The role of arthroscopy is twofold: (1) it enables the surgeon to distinguish between a complete, grossly unstable scapholunate interosseous space that requires open treatment and (2) it permits direct visualization of the reduction and percutaneous pinning of the articulation in an effort to stabilize the joint. Operative indications, open and arthroscopic techniques, and results are discussed.

Arthroscopy↗
PubMed2001

Isotype-specific antibody responses of cattle to Salmonella Dublin lipopolysaccharide and porin following Salmonella Dublin vaccination and acute and chronic infection.

Stimulation of different T-cell subsets during antigen presentation influences the antibody isotype response to an antigen. Salmonella infection and Salmonella bacterin vaccination are likely to stimulate different T-cell subtypes. The objective of this study was to determine whether there are differences in the isotype response of cattle to Salmonella antigens following Salmonella infection and Salmonella bacterin vaccination. Sera from Salmonella bacterin-vaccinated, experimentally infected, and chronically infected (carrier) adult cattle collected during previous studies was used to evaluate the IgG1, IgG2, and IgM isotype responses of cows to Salmonella serotype Dublin lipopolysaccharide (LPS) and porin. Following vaccination and experimental oral infection, IgG1 titers to LPS and porin rose more quickly and persisted longer than did IgG2 titers. In contrast to Salmonella infection, bacterin vaccination stimulated a weak response to Salmonella porin. Salmonella infection also induced a higher IgG2:IgG1 titer ratio to LPS than did bacterin vaccination. Chronic Salmonella infection induced the highest LPS and porin IgG2:IgG1 titer ratios and the highest correlation between LPS and porin titers. Response operating characteristic curves for each isotype-specific enzyme-linked immunosorbent assay (ELISA) were determined to evaluate the effect of isotype on the sensitivity and specificity of Salmonella ELISA serology for distinguishing sera of Salmonella carriers from those of vaccinated and acutely infected cows. IgG2 titers to LPS and porin provide a more specific indicator of chronic Salmonella infection status than do IgG1 titers to the same antigens with little to no loss in sensitivity.

Acute Disease↗
PubMed2001

Serological distinction of bovine Salmonella carriers from vaccinated and acutely infected cows.

Identification of Salmonella carriers using lipopolysaccharide (LPS) ELISA serology in a Salmonella-infected herd requires distinction of chronically infected cattle from convalescent and vaccinated cows. Cows responding to Salmonella infection and vaccination produce titers to Salmonella LPS that overlap with the lower titers of some Salmonella carriers. The objective of this study was to determine if the LPS antigen specificity of the bovine humoral immune response to Salmonella LPS antigens differs following vaccination and acute and chronic Salmonella infection. The study focused on the nondiscriminatory area of Salmonella ELISA serology, specifically, peak-titered sera from Salmonella bacterin-vaccinated and experimentally infected cows and low-titered sera from Salmonella carriers. The LPS serogroup specificity of the IgG1 and IgG2 response following acute and chronic Salmonella serotype Dublin infection and Salmonella bacterin vaccination was evaluated using 5 Salmonella serogroup (B, D, E1, C3, and C1) LPS ELISA assays. IgG, titers of carriers, vaccinated, and acutely infected cows were predominantly O antigen specific. Similarly, the IgG2 titers of acutely infected cows were also O antigen specific. In contrast, Salmonella carriers produced an IgG2 response to each of the heterologous LPS antigens (B, E1, C3, and C1) examined. The results of this study indicate that the bovine IgG1 isotype response to Salmonella LPS is serogroup specific. Conversely, production of IgG2 antibodies to core Salmonella LPS antigens shared across Salmonella serogroups is a feature of chronic Salmonella infections.

Animals↗
PubMed2001

Botulinum toxin type a neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial.

BACKGROUND: Focal spasticity of the gastrocnemius-soleus muscles causes equinus gait in children with cerebral palsy (CP). Botulinum toxin type A (BTX-A), a neuromuscular blocking agent, reduces muscle tone/overactivity in dystonia, stroke, and CP. OBJECTIVE: A prospective, open-label, multicenter clinical trial evaluated the long-term safety and efficacy of repeated intramuscular injections of BTX-A on equinus gait in CP children. METHODS: Nine centers enrolled 207 children. BTX-A injections (4 U/Kg) were given approximately every 3 months (maximum dose 200 U per treatment). Outcome measures included a Physician Rating Scale of gait, ankle range of motion measurements, and the incidence and profile of adverse events. RESULTS: One hundred fifty-five (75%) of 207 children completed at least 1 year with a total of 302 patient years of BTX-A treatment. The mean duration of BTX-A exposure was 1.46 years per patient. Dynamic gait pattern on the Physician Rating Scale improved in 46% of patients (86/185) at first follow-up. The response was maintained in 41% to 58% of patients for 2 years. Both gait pattern and ankle position improved at every visit. The most common treatment-related adverse events included increased stumbling, leg cramps, leg weakness, and calf atrophy in 1% to 11% of patients. No treatment-related serious adverse events were reported. Only 6% (7/117) of patients with pre- and postantibody samples had both detectable antibodies and a subsequent treatment failure. CONCLUSION: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait.

Adolescent↗
PubMed2001

Evaluation of an autogenous Salmonella bacterin and a modified live Salmonella serotype Choleraesuis vaccine on a commercial dairy farm.

OBJECTIVE: To compare the efficacy of a Salmonella bacterin and a modified live Salmonella ser. Choleraesuis vaccine on a commercial dairy. ANIMALS: 450 cows in late gestation and 80 calves. PROCEDURE: Group-1 cows (n = 150) were vaccinated once with a modified live S. Choleraesuis (serogroup C1) strain 54 (SC54) vaccine, group-2 cows (150) were vaccinated on enrollment and 30 days later with a Salmonella ser. Montevideo (serogroup C1) bacterin, and group-3 cows (150) served as unvaccinated controls. One gallon of colostrum harvested from the first 80 cows to calve was fed to each calf. Outcome assessments included fecal shedding of Salmonella spp for the first 10 days after parturition (cows) or birth (calves), milk production, involuntary culling rate, mastitis incidence, antimicrobial use, and mortality rate. RESULTS: Salmonellae were isolated from 306 of 309 (99%) cows and 64 of 74 (86.5%) calves. Shedding frequency was less in SC54-vaccinated cows and calves that received colostrum from those cows, compared with the other groups, and vaccination was specifically associated with less shedding of serogroup C1 salmonellae. Production data were similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Vaccination of pregnant cows with an autogenous Salmonella bacterin had no effect on fecal shedding of salmonellae, whereas vaccination with a modified live S. Choleraesuis vaccine reduced the frequency of fecal shedding of serogroup C1 salmonellae during the peripartum period. A commercial S. Choleraesuis vaccine licensed for use in swine may be more efficacious than autogenous Salmonella bacterins on dairies infected with serogroup C1 salmonellae.

Animals↗
PubMed2001

A simple transport system for radiation treatment of specific pathogen-free mice in lifetime studies.

To prevent the introduction of pathogens, specific pathogen-free (SPF) facilities generally have a "once out, never back" policy with respect to animals and materials. In a lifetime study of the long-term effects of ionizing radiation exposure in mice, large numbers of SPF mice needed to be transported from clean-animal barrier labs to a multiuser conventional building for radiation treatment and then back into the animal facility. The conventional building is known to harbor wild mice as well as insects, spiders, and mites, and this situation might potentiate the transfer of wild mouse pathogens to laboratory animals. Introduction of pathogens into the mouse population would jeopardize the entire study, but the radiation treatments were an essential component of the study. These considerations prompted development of a system for transporting individual animals out of and back into the facility without exposure to pathogens. The system consists of reusable transport/treatment vessels and transport protocols designed to minimize the potential for pathogen exposure.

Animals↗
PubMed2000

Prevalence of Salmonella in beef feeder steers as determined by bacterial culture and ELISA serology.

Results are presented for monitoring Salmonella infection by bacteriological culture and immune response (enzyme linked immunosorbent assay (ELISA) and haptoglobin) testing of samples collected from beef cattle at a single feedyard sampled over time. A total of 120 beef steers were examined on entry to the feedyard and at days 30, 60, and at time of slaughter (120-150 days). Isolations of Salmonella decreased over time from 40% of the steers sampled at day 0 to 0% at slaughter, whereas serological results varied by serogroup. Seropositivity increased for Salmonella group B up to day 60, and subsequently decreased to about half of the 60-day positivity rate at the time of slaughter. No significant changes in seropositivity were detected during the course of the study for the four other Salmonella serogroups (C1, C3, D1, and E1). Haptoglobin measurements were not a good indicator of Salmonella infection status. Sequential Salmonella testing either by culture, ELISA, or both could be used to monitor pathogen control practices.

Animal Husbandry↗
PubMed2000

PhRMA perspective on population and individual bioequivalence.

The Food and Drug Administration (FDA) issued a second-draft guidance in August 1999 on the subject of in vivo bioequivalence, which is based on the concepts of individual and population bioequivalence (IBE and PBE, respectively). The intention of this guidance is to replace the 1992 guidance that requires that in vivo bioequivalence be demonstrated by average bioequivalence (ABE). Although the concepts of population and individual bioequivalence are intuitively reasonable, a detailed review of the literature has not uncovered clinical evidence to justify the additional burden to the innovator and generic companies as well as the consumer that the new guidelines would impose. The criteria for bioequivalence described in the draft guidance employ aggregate statistics that combine information about differences in bioavailability between formulation means and differences in bioavailability variation of formulations between and within subjects. The purely technical aspects of the statistical approach are reasonably sound. However, PhRMA believes that important operational issues remain that need to be resolved before any changes to current practice are implemented. PhRMA believes that the ideals of prescribability and switchability are intuitively reasonable, but it is uncertain of the extent to which the proposed guidance can achieve these goals. It is not clear whether the attainment of such goals is necessary in the evaluation of bioequivalence given the role this plays in drug development, and the lack of clinical evidence argues against a pressing need to change current practice. PhRMA is concerned that the trade-off offered by the aggregate criteria may ultimately represent more harm than good to the public interest. PhRMA recommends more rigorous evaluation of methods based on two-way crossover designs before moving to methods that require more complex designs. One such method is identified herein and contains procedures for estimating prescribability and switchability. The possibility of a phase-in or trial period to collect replicate crossover data to further evaluate IBE and PBE and possibly allow market access based on these criteria as they are being evaluated has been proposed. PhRMA believes this is unprecedented and will offer little additional information beyond that which can be obtained by simulation or has already been collected by the FDA. Simulation studies have the advantage of allowing evaluation of the sensitivity of various procedures to represent the data patterns as created within the simulation. Operating characteristics by which proposed criteria can be adequately judged have not yet been defined. The limitations of ABE for highly variable drugs and narrow therapeutic drugs are well appreciated and may be addressed by means other than a wholesale change in the current criteria.

Humans↗
PubMed2000

Confidence interval criteria for assessment of dose proportionality.

PURPOSE: The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. METHODS: Statistical estimation is used to derive a (1-alpha)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = beta0 x Dose(beta1); however, the logic holds for other functional forms. RESULTS: It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (rho1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (rho2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. CONCLUSION: The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.

Analysis of Variance↗
PubMed2000

Differences in the skin peptides of the male and female Australian tree frog Litoria splendida. The discovery of the aquatic male sex pheromone splendipherin, together with phe8 caerulein and a new antibiotic peptide caerin 1.10.

The skin secretions of female and male Litoria splendida have been monitored monthly over a three-year period using HPLC and electrospray mass spectrometry. Two minor peptides are present only in the skin secretion of the male. The first of these is the female-attracting aquatic male sex pheromone that we have named splendipherin, a 25 amino acid peptide (GLVSSIGKALGGLLADVVKSKGQPA-OH). This pheromone constitutes about 1% of the total skin peptides during the breeding season (January to March), dropping to about 0.1% during the period June to November. Splendipherin attracts the female in water at a concentration of 10-11-10-9 M, and is species specific. The second peptide is a wide-spectrum antibiotic of the caerin 1 group, a 25 residue peptide (GLLSVLGSVAKHVLPHVVPVIAEKL-NH2) named caerin 1.10. The neuropeptides of L. splendida are also seasonally variable, the change identical for both the female and male. During the period October to March, the sole neuropeptide present in skin secretions is caerulein [pEQDY(SO3)TGWMDF-NH2]; this is active on smooth muscle and is also an analgaesic. During the southern winter (June to September), more than half of the caerulein is hydrolysed to [pEQDYTGWMDF-NH2], a peptide that shows no smooth muscle activity. In place of caerulein, a new peptide, Phe8 caerulein [pEQDY(SO3)TGWFDF-NH2], becomes a major component of the skin secretion. Perhaps this seasonal change is involved in thermoregulation, that is, with the initiation and maintenance of the inactive (hibernation) phase of the animal.

Amino Acid Sequence↗
PubMed2000

Arterial reconstruction for radial artery occlusion.

This study was designed to detail the history and symptoms of symptomatic radial artery vaso-occlusive disease and to evaluate the results of radial artery reconstruction. Thirteen patients with symptomatic vaso-occlusive disease of the radial artery unresponsive to management by nonoperative modalities were managed with arterial reconstruction. All cases were treated with reversed interpositional vein grafting from the radial artery in the forearm (end-to-side) to the deep arch distally (end-to-end). Patients completed preoperative and postoperative assessments of symptoms and function, cold sensitivity (cold intolerance), and digital microvascular perfusion (isolated cold stress test evaluation with laser Doppler fluxmetry). At the follow-up examination all vascular grafts were patent, as determined by Allen's testing and Doppler ultrasound. The patients reported symptoms and functional status that demonstrated significant improvement following reconstruction. Microvascular evaluations demonstrated a significant improvement in digital microvascular perfusion as assessed by laser Doppler fluxmetry and digital temperature recordings with a resultant resolution of ischemic pain, numbness, and ulceration.

Adolescent↗