PubMed Health⌕ Search

Biomedical subjects

R Boston

Publications and source records attributed to R Boston.

16 recordsLinked to original sources
PubMed2001

Simultaneous determination of etoposide and its catechol metabolite in the plasma of pediatric patients by liquid chromatography/tandem mass spectrometry.

The anticancer drug etoposide is associated with leukemias with MLL gene translocations and other translocations as a treatment complication. The genotype of cytochrome P450 3A4 (CYP3A4), which converts etoposide to its catechol metabolite, influences the risk. In order to perform pharmacokinetic studies aimed at further elucidation of the translocation mechanism, we have developed and validated a liquid chromatography/electrospray/tandem mass spectrometry assay for the simultaneous analysis of etoposide and its catechol metabolite in human plasma. The etoposide analog teniposide was used as the internal standard. Liquid chromatography was performed on a YMC ODS-AQ column. Simultaneous determination of etoposide and its catechol metabolite was achieved using a small volume of plasma, so that the method is suitable for pediatric patients. The limits of detection were 200 ng ml(-1) etoposide and 10 ng ml(-1) catechol metabolite in human plasma and 25 ng ml(-1) etoposide and 2.5 ng ml(-1) catechol metabolite in protein-free plasma, respectively. Acceptable precision and accuracy were obtained for concentrations in the calibration curve ranges 0.2--100 microg ml(-1) etoposide and 10--5000 ng ml(-1) catechol metabolite in human plasma. Acceptable precision and accuracy for protein-free human plasma in the range 25--15 000 ng ml(-1) etoposide and 2.5--1500 ng ml(-1) etoposide catechol were also achieved. This method was selective and sensitive enough for the simultaneous quantitation of etoposide and its catechol as a total and protein-free fraction in small plasma volumes from pediatric cancer patients receiving etoposide chemotherapy. A pharmacokinetic model has been developed for future studies in large populations.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Ancylostoma caninum: the finger cell neurons mediate thermotactic behavior by infective larvae of the dog hookworm.

Bhopale, V. M., Kupprion, E. K., Ashton, F. T., Boston, R., and Schad, G. A. 2001. Ancylostoma caninum: The finger cell neurons mediate thermotactic behavior by infective larvae of the dog hookworm. Experimental Parasitology 97, 70-76. In the amphids (anteriorly positioned, paired sensilla) of the free-living nematode Caenorhabditis elegans, the so-called finger cells (AFD), a pair of neurons, each of which ends in a cluster of microvilli-like projections, are known to be the primary thermoreceptors. A similar neuron pair in the amphids of the parasitic nematode Haemonchus contortus is also known to be thermoreceptive. The hookworm of dogs, Ancylostoma caninum, has apparent structural homologs of finger cells in its amphids. The neuroanatomy of the amphids of A. caninum and H. contortus is strikingly similar, and the amphidial cell bodies in the lateral ganglia of the latter nematode have been identified and mapped. When the lateral ganglia of first-stage larvae (L1) of A. caninum are examined with differential interference contrast microscopy, positional homologs of the recognized amphidial cell bodies in the lateral ganglia of H. contortus L1 are readily identified in A. caninum. The amphidial neurons in A. caninum were consequently given the same names as those of their apparent homologs in H. contortus. It was hypothesized that the finger cell neurons (AFD) might mediate thermotaxis by the skin-penetrating infective larvae (L3) of A. caninum. Laser microbeam ablation experiments with A. caninum were conducted, using the H. contortus L1 neuronal map as a guide. A. caninum L1 were anesthetized and the paired AFD class neurons were ablated. The larvae were then cultured to L3 and assayed for thermotaxis on a thermal gradient. L3 with ablated AFD-class neuron pairs showed significantly reduced thermotaxis compared to control groups. The thermoreceptive function of the AFD-class neurons associates this neuron pair with the host-finding process of the A. caninum infective larva and shows functional homology with the neurons of class AFD in C. elegans and in H. contortus.

Ancylostoma↗
PubMed2001

Evaluation of a tapered-sleeve transcortical pin to reduce stress at the bone-pin interface in metacarpal bones obtained from horses.

OBJECTIVE: To evaluate stiffness and bone-pin interface stress for a transcortical tapered-sleeve pin (TSP) that incorporates bilateral tapered sleeves over a transcortical pin. SAMPLE POPULATION: 14 third metacarpal bones (MCIII) collected from adult horses of various breeds. PROCEDURE: Each MCIII was cut in half to provide 2 test specimens. Pins (conventional and TSP) of 3 diameters (6.35, 7.94, and 9.50 mm) were inserted in specimens (3 specimens for each diameter and each type of pin). The test fixture simulated a typical sidebar-span skeletal fixation device for horses. Single cycle load-deflection tests were performed. Cyclic fatigue tests of TSP were performed to evaluate fatigue characteristics and stress conditions at the bone-pin interface. Maximum stress and strain were calculated, and results were compared with existing data on fatigue characteristics of bone. RESULTS: Significant increases in stiffness (load-deflection) and higher loads at yield point were detected for the TSP (stiffness for conventional 9.50mm pins, 4,500 N/mm; stiffness for TSP, 19,988 N/mm). Results of cyclic tests revealed a close correlation with existing data on fatigue characteristics. CONCLUSIONS AND CLINICAL RELEVANCE: The TSP described here is stiffer than conventional transcortical pins, and stress across the bone-pin interface is more evenly distributed. Use of this TSP should minimize major problems encountered during external fixation associated with the transcortical pin and bone-pin interface (ie, bone necrosis, infection of the pin track, pin loosening, and bone failure).

Animals↗
PubMed2000

Thermotaxis and thermosensory neurons in infective larvae of Haemonchus contortus, a passively ingested nematode parasite.

As a basis for studies of thermal behavior of infective larvae (L3) of Haemonchus contortus resulting from ablation of amphidial neurons, the locations of the amphidial cell bodies in the hatchling larva (L1) were compared with their locations in the L3. We sought to verify that killing each targeted cell body in L1 destroys the putative corresponding dendrite of the L3. These comparisons confirmed the predicted cell body-to-dendrite connections, as well as similarities in the general amphidial structure of the two stages. We then conducted a series of studies using laser microbeam ablation of amphidial cell bodies in the L1 to determine the role of specific neurons in the thermal behavior of the L3. In a thermal gradient, normal L3 of H. contortus migrate to the temperature at which they were cultured and/or maintained. Larvae grown at 16 degrees or 26 degrees C migrate appropriately to either of these temperatures. Larvae grown to the L3 stage at 16 degrees C and then moved to 26 degrees C become acclimated to this temperature and thereafter migrate to it. However, when the putative thermosensory neurons, the finger cell neurons (AFD), were ablated in hatchling larvae with a laser microbeam, and these were grown to the L3 stage and tested on a radial thermal gradient, they failed to migrate to their culture temperature. Instead, they moved actively and continuously over much of the assay plate surface, with no obviously oriented cryo- or thermotactic movement. Ablation-control larvae, those in which putatively chemosensory neuron classes ASE or AWC were killed, migrated normally to their culture temperature. When the RIA interneurons (identified by positional homology with those of Caenorhabditis elegans) were ablated, the operated larvae moved actively, but circled near the initial placement point; control larvae, in which other nonamphidial neurons were killed, migrated normally. These results indicate that the finger cell neurons (AFD) are the primary thermosensory class in H. contortus. The RIA-class neurons integrate thermal responses in H. contortus, as do their putative structural homologs in C. elegans, but the behavior of H. contortus subsequent to RIA ablation is strikingly different.

Animals↗
PubMed2000

The neurons of class ALD mediate thermotaxis in the parasitic nematode, Strongyloides stercoralis.

Strongyloides stercoralis, a skin-penetrating nematode parasite of homeotherms, migrates to warmth. In nematodes, the amphids, anteriorly positioned, paired sensilla, each contain a bundle of sensory neurons. In the amphids of the free-living nematode Caenorhabditis elegans, a pair of neurons, each of which ends in a cluster of microvilli-like projections, are known to be the primary thermoreceptors, and have been named the finger cells (class AFD). A similar neuron pair in the amphids of the parasite Haemonchus contortus is also known to be thermosensory. Strongyloides stercoralis lacks finger cells but, in its amphids, it has a pair of neurons whose dendrites end in a multi-layered complex of lamellae, the so-called lamellar cells (class ALD). Consequently, it was hypothesised that these lamellar cells might mediate thermotaxis by the skin-penetrating infective larva of this species. To investigate this, first stage S. stercoralis larvae were anaesthetised and the paired ALD class neurons were ablated with a laser microbeam. The larvae were then cultured to the infective third stage (L3) and assayed for thermotaxis on a thermal gradient. L3 with ablated ALD class neuron pairs showed significantly reduced thermotaxis compared with control groups. The thermoreceptive function of the ALD class neurons (i) associates this neuron pair with the host-finding process of S. stercoralis and (ii) demonstrates a functional similarity with the neurons of class AFD in C. elegans. The structural and positional characteristics of the ALD neurons suggest that these neurons may, in fact, be homologous with one pair of flattened dendritic processes known as wing cells (AWC) in C. elegans, while their florid development and thermosensory function suggest homology with the finger cells (AFD) of that nematode.

Animals↗
PubMed1998

Balancing needs, efficiency, and functionality in the provision of modeling software: a perspective of the NIH WinSAAM Project.

The development of new software or the refinement of existing software for new operating environments each calls for judicious balancing. On the one hand, we strive for simplicity, predictability, and operational protection as it is well recognized that software with these attributes will attract an audience of satisfied users. But, on the other hand, these attributes do not conjure a sense of power, efficiency, or flexibility, and these other properties are also appreciated by users, albeit a somewhat different group of users. The goal is to achieve a blend which isolates critical functionality, flexible control, and user support while meeting the needs of the broadest collection of serious users. In this chapter, we discuss the issues impacting the migration of SAAM to the Windows environment, the NIH WinSAAM Project, and we outline the steps taken to ensure its feasibility. In addition, we describe a new paradigm for software development and use which ensures the durability of the software for modeling.

Computer Simulation↗
PubMed1998

Hemodynamic factors affecting uterine artery Doppler waveform pulsatility in sheep.

Quantitative analysis of vascular resistance from the Doppler time-velocity waveform relies on measuring arterial pulsatility. However, input pressure waveform pulsatility, impedance, and resistance have all been found to effect artery flow waveform pulsatility in circulatory mathematic models and in umbilical sheep preparations in vivo. The present study used an in vivo sheep preparation to determine that embolization of the uteroplacental circulation and maternal angiotensin II administration caused changes in the uterine Doppler time-velocity waveform pulsatility that were dependent on input pressure waveform pulsatility, fundamental impedance, and resistance changes. Uteroplacental vascular embolization increased vascular resistance and the uterine artery Doppler waveform resistive index; the mean component of flow (mean pressure/resistance) decreased. Decreased uterine artery Doppler resistive index occurred despite angiotensin II-induced vasoconstriction and increased vascular resistance because the pulse component of flow (pulse pressure/impedance) decreased.

Angiotensin II↗
PubMed1997

Glucose metabolism in severe malaria: minimal model analysis of the intravenous glucose tolerance test incorporating a stable glucose label.

Basal plasma glucose is usually increased in uncomplicated malaria, implying insulin resistance. If the infection progresses, the risk of hypoglycemia will increase as host glucose production becomes insufficient for host/parasite demand. To assess the relative contribution of insulin-mediated and non-insulin-mediated glucose disposal to plasma glucose levels in severe malaria, we studied six healthy controls (two males and four females; mean age, 38 years) and eight patients with complicated falciparum malaria (five males and three females; mean age, 31 years) who had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in which 10% of the dextrose bolus was 6,6-D2-glucose. The minimal model was applied to native and labeled plasma glucose and serum insulin profiles over 4 hours postinjection. Basal plasma glucose concentrations in the patients were significantly greater than in the controls (median [range], 6.1 [2.1 to 8.5] v 4.3 [3.9 to 4.7] mmol/L, P = .03). Malaria-associated insulin resistance was confirmed by a lower insulin sensitivity index (SI) in patients (5.6 [2.4 to 17.4] v 16.0 [2.5 to 22.3] x 10(-4).min-1 per microU/mL in controls, P = .026). Glucose effectiveness ([SG] the ability of glucose to reduce its own plasma concentration) was higher in the patients (0.015 [0.006 to 0.024] v 0.008 [0.007 to 0.010] min-1 in controls, p = .019). Glucose disappearance at basal concentration was increased by a median of 42% in severe malaria patients, with the insulin-independent component comprising 81%, versus 67% in controls. Indices of beta-cell function were normal in malaria patients. These data demonstrate that basal plasma glucose utilization is increased approximately 50% in severe malaria, consistent with previously published isotope-turnover studies. Altered SG plays a major role. Prevention and treatment of early hypoglycemia should be based on adequate glucose replacement. Strategies that reduce insulin secretion or effects appear to be of minor importance.

Adolescent↗
PubMed1997

Using models to explore whole-body metabolism and accessing models through a model library.

A model is a mathematical representation of a system that can be used to explore the system in a number of ways: to determine the system's internal connections, to calculate properties of the system such as flow rates and pool sizes, and to make predictions about the system's behavior under different conditions. The use of modeling to explore whole-body metabolism is demonstrated using a compartmental model of zinc kinetics as an example. Because models are useful tools for exploring systems, a facility called a "model library" is being established on the Internet to provide access to working versions of published models.

Animals↗
PubMed1997

Passive transfer of immune serum reduces the L1/adult ratio of worms recovered from the intestines of Strongyloides stercoralis-infected gerbils.

In Strongyloides stercoralis-infected gerbils it had been observed previously that the ratio of first-stage larvae to adult worms decreases after 3 wk of infection. Serum obtained from gerbils after this decrease in fecundity, but before worms were expelled, was transferred passively to other infected gerbils during the peak of worm fecundity. The immune serum caused a significant decrease in the L1/adult ratio but had no effect on the number of uterine eggs, the length, or the intestinal and ovarian ultrastructure of adult worms. Apparently a factor(s) in the immune serum either killed eggs, after oviposition, or the hatched larvae, without damaging the adult worms.

Animals↗
PubMed1995

Rest potential--cooperative selectivity.

It is often necessary to determine the selectivity and cooperativity constants of ions and other substances which are selectively and cooperatively adsorbed at surface sites of biological cells. A computer program based on the Levenberg-Marquardt method is given to determine the selectivity and cooperativity constants from the non-linear equation for the resting potential.

Adsorption↗
PubMed1992

EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.

Algorithms↗
PubMed1984

Suppression by diets rich in fish oil of very low density lipoprotein production in man.

The highly polyunsaturated fatty acids in fish oils lower the plasma triglyceride concentration. We have studied the effect of a diet rich in fish oil on the rate of production of the triglyceride-transporting very low density lipoprotein (VLDL). Seven subjects, five normal and two with hypertriglyceridemia received up to 30% of daily energy needs from a fish oil preparation that was rich in eicosapentaenoic acid and docosahexaenoic acid, omega-3 fatty acids with five and six double bonds, respectively. Compared with a diet similarly enriched with safflower oil (in which the predominant fatty acid is the omega-6 linoleic acid, with two double bonds), the fish oil diet lowered VLDL lipids and B apoprotein concentrations profoundly. High density lipoprotein lipids and A1 apoprotein were also lowered, but the effect on low density lipoprotein (LDL) concentration was inconsistent. The daily production or flux of VLDL apoprotein B, calculated from reinjected autologous 125I-labeled lipoprotein, was substantially less in six subjects studied after 3 wk of fish oil, compared with after safflower oil. This effect on flux was more consistent than that on the irreversible fractional removal rate, which was increased in the four normolipidemic but inconsistent in the hypertriglyceridemic subjects. This suggests that fish oil reduced primarily the production of VLDL. The daily production of VLDL triglyceride, calculated from the kinetics of the triglyceride specific radioactivity-time curves after [3H]glycerol was injected, also showed very substantial reductions in five subjects studied. The marked suppression in VLDL apoprotein B and VLDL triglyceride formation was found not to be due to diminished plasma total free fatty acid or plasma eicosapentaenoic flux, calculated during constant infusions of [14C]eicosapentaenoic acid and [3H]oleic acid in four subjects. In two subjects there was presumptive evidence for substantial independent influx of LDL during the fish oil diet, based on the precursor-product relationship between the intermediate density lipoprotein and LDL apoprotein B specific radioactivity-time curves.

Adult↗
PubMedDate not supplied

Clinical experiences with axial deviation of the aryepiglottic folds in 52 racehorses.

OBJECTIVE: To describe the clinical findings in 52 racehorses with axial deviation of the aryepiglottic folds (ADAF) and to report outcome in 33 of these horses after either rest or transendoscopic laser excision of aryepiglottic fold tissue. STUDY DESIGN: Retrospective study. ANIMAL OR SAMPLE POPULATION: Racehorses admitted for high-speed treadmill (HST) evaluation of poor performance. METHODS: Medical records and videotapes of resting and exercising videoendoscopic examinations were reviewed. Racing performance records and owner or trainer interviews, at least 1 year after HST examination, were used to compare results after either surgical management or rest in 33 horses with ADAF and no other upper-airway abnormalities. RESULTS: ADAF occurred in 6% of horses evaluated for poor performance. No breed or gender predisposition existed, but horses with ADAF were younger than the overall population evaluated on the HST. Of 52 horses with ADAF, 19 horses had at least one other upper-airway abnormality. There was no apparent association between ADAF and other causes of dynamic upper-respiratory obstruction. Surgical correction was successfully performed in standing or anesthetized horses without complications. When ADAF was the only upper-airway obstruction, 75% of horses that had surgery and 50% of rested horses had objective improvement in performance. Owners and trainers also perceived greater improvement in performance in horses that had surgery. CONCLUSIONS: Whereas surgical management of ADAF is recommended, clinical experience indicated that it is not required to resolve ADAF in all horses. However, owners and trainers of horses that had surgery were more satisfied with outcome than those with horses managed conservatively. CLINICAL RELEVANCE: Diagnosis of ADAF can only be made by videoendoscopic evaluation during high-speed exercise. Transendoscopic laser excision of the collapsing portion of the aryepiglottic folds can be performed safely in standing horses and results in resolution of airway obstruction and rapid return to training.

Airway Obstruction↗