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Biomedical subjects

R A Curtis

Publications and source records attributed to R A Curtis.

At least 19 recordsLinked to original sources

Protein-protein interactions in concentrated electrolyte solutions.

Protein-protein interactions were measured for ovalbumin and for lysozyme in aqueous salt solutions. Protein-protein interactions are correlated with a proposed potential of mean force equal to the free energy to desolvate the protein surface that is made inaccessible to the solvent due to the protein-protein interaction. This energy is calculated from the surface free energy of the protein that is determined from protein-salt preferential-interaction parameter measurements. In classical salting-out behavior, the protein-salt preferential interaction is unfavorable. Because addition of salt raises the surface free energy of the protein according to the surface-tension increment of the salt, protein-protein attraction increases, leading to a reduction in solubility. When the surface chemistry of proteins is altered by binding of a specific ion, salting-in is observed when the interactions between (kosmotrope) ion-protein complexes are more repulsive than those between the uncomplexed proteins. However, salting-out is observed when interactions between (chaotrope) ion-protein complexes are more attractive than those of the uncomplexed proteins.

Computer Simulation↗

Hydrophobic forces between protein molecules in aqueous solutions of concentrated electrolyte.

Protein-protein interactions have been measured for a mutant (D101F) lysozyme and for native lysozyme in concentrated solutions of ammonium sulfate at pH 7 and sodium chloride at pH 4.5. In the mutant lysozyme, a surface aspartate residue has been replaced with a hydrophobic phenylalanine residue. The protein-protein interactions of D101F lysozyme are more attractive than those of native lysozyme for all conditions studied. The salt-induced attraction is correlated with a solvation potential of mean force given by the work required to desolvate the part of the protein surfaces that is buried by the protein-protein interaction. This work is proportional to the aqueous surface-tension increment of the salt and the fractional non-polar surface coverage of the protein. Experimental measurements of osmotic second virial coefficients validate a proposed potential of mean force that ascribes the salt-induced attraction between protein molecules to an enhancement of the hydrophobic attraction. This model provides a first approximation for predicting the protein-protein potential of mean force in concentrated aqueous electrolyte solutions; this potential is useful for determining solution conditions favorable for protein crystallization.

Chemical Precipitation↗

Locomotion evaluation for racing in thoroughbreds.

The potential racing and locomotory profile of a Thoroughbred yearling should be taken into account for its training programme and racing career. A gait test has been designed to assist the trainer in this task. The aim of this study was to investigate the temporal and kinetic locomotory variables of Thoroughbreds at the gallop, in relationship to their racing ability. Thirty Thoroughbred horses in race training were tested at maximal speed during a training session. The training exercise consisted of a warming-up session at trot and canter for 10 min followed by a gallop session at increasing speed on a dirt track 1942 m long. The maximal speed was measured for the last 800 m before the finishing post. An acclerometric device attached to the girth provided quantitative information about the kinetic and temporal variables of the gallop such as: stride length (SL), stride frequency (SF), times elapsed between each hoof midstance phase (HIND, DIAGO, FORE), regularity of the strides (REG), mean vector of propulsion (VPROP), energy of propulsion (EPROP) and energy of loading (ELOAD). The performance records (number of wins, placings and average earning/start [PERF]) were used to analyse the relationship with the gait measurements. The mean maximum speed was 15.26 m/s. Several locomotory variables were significantly (P < 0.05) correlated to the gallop speed: SL (0.90), SF (0.75), DIAGO (0.42), REG (-0.47), VPROP (0.52), ELOAD (0.56) and EPROP (0.65). There were significant correlations between PERF and the following gait variables: REG (0.79), DIAGO (0.43), SF (0.42), SL (-0.32) and ELOAD (-0.40). The horses that won short distance races (< 1400 m) had a larger relative ground contact duration and higher stride frequency than horses that won in longer distance races. The gait test was easy to perform and provided useful locomotory variables that may be used to evaluate the racing ability of the Thoroughbreds in training.

Acceleration↗

Protein-protein and protein-salt interactions in aqueous protein solutions containing concentrated electrolytes.

Protein-protein and protein-salt interactions have been obtained for ovalbumin in solutions of ammonium sulfate and for lysozyme in solutions of ammonium sulfate, sodium chloride, potassium isothiocyanate, and potassium chloride. The two-body interactions between ovalbumin molecules in concentrated ammonium-sulfate solutions can be described by the DLVO potentials plus a potential that accounts for the decrease in free volume available to the protein due to the presence of the salt ions. The interaction between ovalbumin and ammonium sulfate is unfavorable, reflecting the kosmotropic nature of sulfate anions. Lysozyme-lysozyme interactions cannot be described by the above potentials because anion binding to lysozyme alters these interactions. Lysozyme-isothiocyanate complexes are strongly attractive due to electrostatic interactions resulting from bridging by the isothiocyanate ion. Lysozyme-lysozyme interactions in sulfate solutions are more repulsive than expected, possibly resulting from a larger excluded volume of a lysozyme-sulfate bound complex or perhaps, hydration forces between the lysozyme-sulfate complexes.

Animals↗

Human tumor models in the severe combined immune deficient (scid) mouse.

PURPOSE: To test a number of established human tumor cell lines and early passage breast cancer (UACC2150) and melanoma cells (UACC1273) for growth in the scid mouse and the tumors' response to conventional chemotherapeutic drugs. METHODS: Established melanoma (A375, C81-61), colon (SW480), lung (A549), lymphomoblastoid leukemia (LCL-B), promyelocytic leukemia (HL60), prostate (PC-3, DU145), and breast (MCF7) cell lines were injected at subcutaneous (s.c.), intraperitoneal (i.p.), or mammary fat pad (MFP) sites. Tumor volume growth curves and survival curves were established for the various tumor cell lines. Carmustine (BCNU), cisplatin (CDDP), cyclophosphamide (CPA), doxorubicin, dacarbazine (DTIC), tamoxifen and vincristine were injected s.c. or i.p.. The chemotherapeutic drug effects on tumor volumes and survival were determined. RESULTS: Tumor growth occurred with each cell type. After i.p. injection, 90% mortality occurred within 26 to 60 days except for the early passage melanoma cell line UACC1273 with which mortality occurred within approximately 90 days. In the MCF7 breast model, treatment with tamoxifen (P < 0.001) and CPA (P < 0.0001) resulted in significant tumor growth delay compared with control groups. BCNU and CDDP resulted in significant tumor growth delays relative to control in SW480 colon cancer (P < 0.0014) and A375 melanoma (P < 0.0001) models, respectively. CPA and doxorubicin improved survival in the HL60 leukemia model (P = 0.0018). CONCLUSIONS: These scid mouse human tumor models appear to reflect the clinical situation in that clinically active chemotherapeutic drugs are similarly active in the scid mouse models. Therefore, the scid mouse models may be useful for testing new chemotherapeutic agents against various human cancer types.

Animals↗

Aspects of the epidemiology of nematode infections in a cow-calf herd in Ontario.

On May 29, 1980, 108 cows and calves were placed on a 20 hectare pasture until October 26, except that from September 18 to October 2 they were in a barn. Every two weeks during the total period, fecal samples were taken from 17 cows and 14 calves and herbage samples were collected from the pasture. Parasite fecal egg counts were estimated using the Cornell-Wisconsin centrifugation technique and herbage infective larvae by a modified Sandwich technique. Daily maximum and minimum air temperature and precipitation were recorded. The principal parasite egg found was the trichostrongyle-strongyle morulate, oval-shaped egg referred to as a gastrointestinal nematode (GIN) egg. The mean GIN egg/g of feces for cows varied from 14.2 to 23.9 and for calves it rose from 0.2 in the spring to 134.8 in the fall. Nematodirus, Trichuris, Strongyloides, Moniezia and coccidia were also found. Larvae were recovered first in July, with the greatest number, over 2000/kg of dry weight of herbage, in September and were primarily Cooperia and Ostertagia.

Animals↗

Effect of prepartum energy, body condition, and sodium bicarbonate on health and blood metabolites of holstein cows in early lactation.

Effects of prepartum energy and of postpartum sodium bicarbonate (0, .75% DM) on health were studied in two trials. In trial 1, 36 cows consumed either 102, 131, or 162% of their energy requirement in the dry period. Postpartum glucose and D(-)-3-hydroxybutyrate levels indicated that 131% group (between wk 1 and 2) and 162% group (over the first 4 wk) were closer to a ketotic state than treatment groups at other times. Displaced abomasums occurred more frequently in the 162% group than either the 102 or 131 group. Sodium bicarbonate did not alter the health. In trial 2, 40 cows were used to evaluate the effects of prepartum energy for a longer period. Energy treatments imposed in late lactation and in the dry period were 1) cows fed to requirement in both periods; 2) cows overfed in the first and underfed in the second period; 3) cows fed to requirement in the first and overfed in the second; 4) cows overfed in both periods. Blood metabolites and health measures were not affected by energy or sodium bicarbonate treatments. Overconsumption of energy by prepartum cows should be avoided; however, for a short period, overconsumption did not produce major health problems.

Animals↗

Clinical pharmacy on-call program in the emergency department.

This is a descriptive and evaluative report regarding a clinical pharmacy residency in-house on-call program that facilitates the provision of 24-hour clinical pharmacy consultative services within the emergency department. During the two-year evaluation period, clinical pharmacy residents completed 3.1 consultations per 14-hour call period. Additionally, greater than 90% of the clinical pharmacy recommendations were accepted and completely followed by physician cohorts. These consultations were usually solicited by internal medicine physicians within the emergency department, involved patient-specific drug therapy recommendations, and required about 100 minutes (mean per consultation) of the clinical pharmacist's time. Thus, clinical pharmacy consultative services can be a useful addition to health care within the emergency department in teaching hospitals.

Chicago↗

Effect of empiric dosing on blood levels of theophylline and phenytoin.

To evaluate empiric dosing guidelines for aminophylline and phenytoin in the management of acute exacerbations of obstructive lung disease and seizure disorders, we utilized an emergency department (ED)-based EMIT system to measure stat plasma theophylline and phenytoin levels in patients intended to receive these drugs. Plasma drug level results were available prior to initiation of therapy. Of the patients evaluated, 45 of 163 (27.6%) aminophylline patients and 21 of 73 (28.7%) phenytoin patients were projected to have plasma concentrations below the recommended therapeutic range if empiric dosing schedules were employed. In addition, 39 of 163 (23.9%) aminophylline and 10 of 73 (13.7%) phenytoin patients, had they received these drugs empirically, would have had plasma theophylline and phenytoin levels in excess of the recommended therapeutic range using empiric dosing. We conclude that the use of empiric dosing guidelines for aminophylline and phenytoin in the ED do not reliably produce therapeutic plasma concentrations. The development of a stat drug analysis laboratory in the hospital or within the ED would improve the effectiveness and safety of these acutely used drugs with narrow therapeutic ranges.

Critical Care↗

Volume of distribution of theophylline in acute exacerbations of reversible airway disease. Effect of body weight.

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.

Adolescent↗

A survey of sheep diseases in Canada.

A mail survey of disease occurrence in Canadian sheep flocks was conducted. The survey, which covered the period from September 1982 to August 1983, utilized flocks on the Record of Performance (ROP) sheep program and relatively complete data were available from 116 flocks. Data about lambing rates, incidence of a variety of lamb and ewe diseases and reasons for culling were obtained. At the same time a retrospective evaluation of records of diagnoses of sheep diseases recorded at diagnostic laboratories across the country was performed. Data from the years 1978 to 1982 were obtained and summarized. A lambing percentage of 153% (1.53 lambs live born per ewe lambing) was observed and an additional 0.05 lambs were stillborn. The major identified causes of mortality amongst lambs were starvation, pneumonia, scours and accidents. Pasteurella spp. were the etiological agents most commonly associated with pneumonia in lambs and Escherichia coli had the same predominant position with regards to nonparasitic scours. A large discrepancy existed between the proportional mortality rates for internal parasites and coccidiosis as determined from the farm survey data compared to diagnostic laboratory data. This suggests that clinical parasitism may not be adequately recognized at the farm level. Abortions in ewes occurred in approximately half the flocks, but generally at a low level and no severe abortion storms occurred. Pneumonia was the most commonly identified cause of mortality in ewes and although Pasteurella spp. appear to be the most important etiological agents, regional differences were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Veterinary↗

Fatal maprotiline intoxication.

We report a fatal case of drug toxicity associated with torsade de pointes following an overdose of the tetracyclic antidepressant, maprotiline (Ludiomil). Tissue and plasma levels were obtained at autopsy and are noted. In addition, the cardiovascular effects, pharmacokinetics, and toxicity of maprotiline are reviewed and compared with that of tricyclic antidepressants.

Adult↗

Efficacy of ipecac and activated charcoal/cathartic. Prevention of salicylate absorption in a simulated overdose.

Twelve adult volunteers were given 24 81-mg aspirin tablets and were randomly assigned into the following treatment groups: (1) control aspirin, (2) 30 mL of ipecac repeated if vomiting not induced, (3) 60 g of activated charcoal per 15 g of magnesium sulfate (MgSO4), and (4) ipecac repeated if needed, followed by activated charcoal/MgSO4 given 1 1/2 hours after the last vomiting episode. All treatments began 60 minutes following aspirin ingestion. Urine was collected for 48 hours for percent total salicylate excretion. Mean +/- SD recovery of salicylate from urine was as follows: aspirin, 96.3% +/- 7.5%; ipecac 70.3% +/- 11.8%, activated charcoal/MgSO4, 56.4% +/- 12%; and ipecac and activated charcoal/MgSO4, 72.4% +/- 14.1%. Ten subjects completed the study. In group 4, eight of ten subjects vomited the activated charcoal/MgSO4 immediately, making statistical analysis impossible. Analysis revealed that activated charcoal/MgSO4 significantly lowered the absorption of aspirin compared with the control and ipecac-treated groups. Furthermore, ipecac significantly lowered aspirin absorption compared with the control group. We conclude that activated charcoal/MgSO4 used alone is superior to the other treatment modalities at inhibiting the absorption of multiple aspirin tablets.

Adult↗

Effects of gonadotrophin releasing hormone on reproductive performance of dairy cows with retained placenta.

The effects of gonadotrophin releasing hormone (GnRH) on the reproductive performance of dairy cows with retained placenta were studied. Three hundred and seventy-eight cows diagnosed as having retained placenta received intramuscular injections of either 2 mL sterile water or 200 micrograms of GnRH in 2 mL sterile water between day 8 and day 14 postpartum. Rectal palpation was performed at the time of treatment and ten to 20 days after treatment in order to determine the rate of uterine involution. Thereafter, monthly rectal examinations were carried out until insemination. Pregnancy diagnosis was made by rectal palpation at 40 days or more after breeding. Using the entire experimental population, there were no significant differences between GnRH-treated and control cows for the rate of uterine involution, the occurrence of reproductive problems, the interval from parturition to first observed estrus, the interval from parturition to first insemination, the interval from parturition to conception, the number of services per conception, the total number of services per cow regardless of conception and the incidence of culling for infertility. When the data for herds in which breeding began earlier in the postpartum period (herds having a mean less than or equal to 80 days from parturition to first service for retained placenta cows) were considered, the GnRH treatment resulted in a significantly shorter (p less than or equal to 0.01) calving to conception interval as compared to control cows. Also, there was a significant reduction (p less than or equal to 0.05) in the total number of services per cow regardless of conception and a significant reduction in the interval from parturition to first service.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antimicrobial use in feedlot calves: its association with culture rates and antimicrobial susceptibility.

Data were collected on anti-microbial usage and health problems, in beef feedlot calves. Although the association between them was not significant, many feedlot owners did not use recommended dosages or duration of treatment and this may have led to a reduced recovery rate.Injectable tetracyclines were the most frequent antimicrobial for primary treatment of sick calves; whereas chloramphenicol was selected most frequently when the primary treatment appeared to be ineffective. Treatment with anti-microbials reduced the likelihood of isolating both Pasteurella multocida and Haemophilus somnus. Chloramphenicol therapy reduced the likelihood of isolating Pasteurella haemolytica. Therapy with a particular antimicrobial, in the week prior to death, increased the level of resistance in P. haemolytica to that antimicrobial. Treatment with other antimicrobials also increased the level of resistance to that antimicrobial; although to a lesser degree. The lowest levels of resistance were observed in Pasteurella isolated from nontreated cattle. After adjustment for antimicrobial exposure, resistance to penicillin, tetracyclines and chloramphenicol occurred together more frequently than expected by chance alone.

Animal Husbandry↗