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Biomedical subjects

S A Brown

Publications and source records attributed to S A Brown.

At least 19 recordsLinked to original sources
PubMed1997

Effects of parathyroidectomy on induced renal failure in dogs.

OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery). PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for a 24-month period of study and monitored for clinical, hematologic, blood biochemical, and organ function status. On development of uremia or after 24 months, dogs were euthanatized, and tissues were examined. RESULTS: Higher survival rate and smaller decrement in renal function (glomerular filtration rate) were observed in PTX dogs, compared with those that had sham surgery, but values did not reach statistical significance. The PTX dogs remained hypocalcemic during the study and had lower serum Ca2+ X P product values. Regardless of parathyroid state, survivors and fatalities could be separated on the basis of serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition of calcium, and renal lesions were poorly correlated with renal cortical calcium concentration. Abnormalities reported in dogs with renal failure, which were attributed to PTH (glucose intolerance, pulmonary hypertension), were not observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL RELEVANCE: PTX had beneficial effects, but these were mediated via changes in mineral homeostasis rather than via direct effects of PTH. Results attributable to PTX were similar to those previously obtained by dietary restriction of phosphate intake.

Acidosis↗
PubMed1996

Leptospira interrogans serovar grippotyphosa infection in dogs.

Leptospirosis attributed to infection with serovar grippotyphosa was diagnosed in 11 dogs. In naturally and experimentally infected dogs, a stereotypic serologic response to infection with Leptospira serovar grippotyphosa was detected. Although the highest serum antibody titers developed against serovar grippotyphosa, most dogs also had lower titers against serovars bratislava and pomona. Acute renal failure was evident in 10 dogs. One dog died prior to initiation of treatment; the remaining 10 dogs were treated with antibiotics and fluids. Two dogs were euthanatized, 2 dogs recovered without clinical or biochemical evidence of residual renal dysfunction, and 6 dogs recovered but had varying degrees of renal insufficiency. Hepatic involvement appeared to be a minor component of the disease in these dogs. Our results indicate that Leptospira serovar grippotyphosa infection is an important problem in dogs and should be considered when evaluating a dog with renal failure.

Acute Kidney Injury↗
PubMed1996

Activator-dependent regulation of transcriptional pausing on nucleosomal templates.

Promoter-proximal pausing during transcriptional elongation is an important way of regulating many diverse genes, including human c-myc and c-fos, some HIV genes, and the Drosophila heat shock loci. To characterize the mechanisms that regulate pausing, we have established an in vitro system using the human hsp7O gene. We demonstrate that nucleosome formation increases by >100-fold the duration of a transcriptional pause on the human hsp7O gene in vitro at the same location as pausing is observed in vivo. Readthrough of this pause is increased by an activator that contains the human heat shock factor 1 (HSF1) transcriptional activation domains. Maximal effect of the activator requires that the system be supplemented with fractions that have hSWI/SNF activity, which has been shown previously to alter nucleosome structure. No significant readthrough is observed in the absence of activator, and neither the activator nor the hSWI/SNF fraction affected elongation on naked DNA; therefore, these results suggest that an activator can cause increased readthrough of promoter-proximal pausing by decreasing the inhibitory effect of nucleosomes on transcriptional elongation.

Base Sequence↗
PubMed1996

Clinical and pathologic findings in ferrets with lymphoma: 60 cases (1982-1994).

OBJECTIVE: To examine clinical and pathologic findings in 60 ferrets with lymphoma. DESIGN: Retrospective case series. ANIMALS: 60 ferrets in which the diagnosis of lymphoma had been confirmed by means of histologic examination of biopsy or necropsy specimens. PROCEDURE: Information including age, sex, coat color, history, clinical signs, clinicopathologic abnormalities, treatment, outcome, and results of histologic examination of biopsy and necropsy specimens were retrieved from medical records of ferrets with spontaneous lymphoma examined between 1982 and 1994 at the Massachusetts institute of Technology or private veterinary practices in 10 states. Classification of lymphoma was assigned according to the National Cancer Institute's working formulation for non-Hodgkin's lymphomas. Chi 2 Trend analysis was used to determine whether age was associated with history, clinical signs, hematologic abnormalities, stage, histologic grade, or outcome. RESULTS: Acute onset, mediastinal mass, lymphocytosis, and multicentric distribution were linked with younger ferrets, and lymphopenia and survival longer than 2 months after diagnosis was associated with older ferrets. Twenty percent of ferrets in this study had cohabitated with another ferret with lymphoma. Chemotherapeutic efficacy was not evaluated. CLINICAL IMPLICATIONS: Clinical and pathologic features linked with age should be considered when evaluating diagnostic and therapeutic options for ferrets with lymphoma.

Animals↗
PubMed1996

Distribution of nickel and cobalt following dermal and systemic administration with in vitro and in vivo studies.

Contact dermatitis following skin contact with ionic metals occurs in about 15% of the human population, but systemic responses are not as common. It is generally believed that skin contact with metal ions leads to different biological processing compared with systemic contact. The purpose of the experiments presented here was to examine elimination of nickel and cobalt salts following skin application and following injection into the deep tissue of hamsters. In addition uptake of the metal by fibroblasts and by keratinocytes was examined in vitro. The data indicate that elimination of nickel and cobalt in the urine following systemic injection was rapid, as expected, but that elimination following skin application was delayed. Much of the metal was retained in the skin. Uptake of the metal by keratinocytes at low doses was greater than the uptake by the fibroblasts. At high doses the differences were not as great. Thus the conclusion is drawn that metal salts are retained in the skin for an extended period of time and could lead to prolonged antigen processing and consequent immune responses in the dermal tissue. Skin application leads to some systemic distribution but the systemic application did not lead to skin accumulation.

3T3 Cells↗
PubMed1996

Effects of mechanical testing device variables on polymer composite femoral stem strains.

Polymer composite femoral stems do not have a well-established in vitro mechanical testing method. The objective of this study was to examine mechanical testing devices for pressfit composite stems, using finite element analysis. The goals were to examine the effects of testing device design variables (geometry, material, interface friction, embedding height and applied load angle) and to reproduce the maximum strains of the stem implanted in a femur. The stem strains were affected by design changes to the testing device. The maximum normal and interlaminar shear strains of the composite stem in the femur were not as well reproduced by the testing device as were the maximum in-plane tensile strains. Decreasing the embedding height increased the stem strains and shifted the stem failure location from the neck to the embedding height. Testing a femoral stem using a testing device with a low embedding height may be inappropriate when trying to induce neck failure, since failure may occur at the embedding height instead of in the neck. A single-material testing device of birchwood, an orthotropic material with a longitudinal stiffness in the range of bone; best simulated a femur in this study.

Aluminum↗
PubMed1996

Does modifying dietary lipids influence the progression of renal failure?

Recent studies have identified important effects of dietary fatty acid composition in animals with chronic renal disease, particularly in dogs. The theoretic basis for these effects provides a rationale for the use of diets enriched with omega-3 (but not omega-6) polyunsaturated fatty acids. A therapeutic trial with a diet enriched with omega-3 polyunsaturated fatty acids should be considered as a maneuver designed to slow the rate of progression of chronic renal disease in dogs.

Animals↗
PubMed1996

Detrusor-sphincter dyssynergia.

Detrusor-sphincter dyssynergia refers to failure of the urethral sphincter to relax during detrusor contraction. The cause is a central nervous system lesion located between the brain stem micturition center and the sacral spinal cord. This is an extremely rare condition in cats. It may be confused with a failure of urethral relaxation due to local urethral causes such as inflammation or edema. This article reviews detrusor-sphincter dyssynergia to allow the reader to distinguish this rare condition from more common conditions that prevent bladder emptying.

Adrenergic alpha-Antagonists↗
PubMed1996

Identification and quantification of regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein.

Oxidation of human LDL is implicated as an initiator of atherosclerosis. Isolated low density lipoprotein (LDL) and high density lipoprotein (HDL2) were exposed to aqueous radicals generated from the thermolabile azo compound 2,2'-azobis(2-amidinopropane) dihydrochloride. The primary nonpolar lipid products formed from the autoxidation of LDL and HDL were the regioisomeric cholesteryl linoleate hydroperoxides. In LDL oxidations, 9- and 13-hydroperoxides with trans,cis conjugated diene were formed as the major oxidation products if endogenous alpha-tocopheral was present in the LDL. After extended oxidation of LDL, at the time when endogenous alpha-tocopherol was consumed, the two trans,cis conjugated diene hydroperoxides began to disappear and the 9- and 13-hydroperoxides with trans,trans conjugated diene appeared. At very long oxidation times, none of the primary products, the conjugated diene hydroperoxides, were present. In HDL2, which has only very low levels of antioxidants, both the 9- and 13-hydroperoxides with trans,cis conjugated diene and the 9- and 13-hydroperoxides with trans,trans conjugated diene were formed at early stages of oxidation. The corresponding alcohols were also formed in the HDL2 oxidations. A mechanistic hypothesis consistent with these observations is presented.

Alcohols↗
PubMed1996

Distribution of cobalt chromium wear and corrosion products and biologic reactions.

Replacement hip arthroplasty with the use of ultrahigh molecular weight polyethylene for the cup articulating with a metal head has provided a low friction arthroplasty with years of success. However, the search for improved materials and designs for articulating surfaces continues. The use of metallic heads articulating with metallic cups is now being reconsidered for total hip replacements. Success will be enhanced if wear and corrosion of the articulating surfaces can be kept below that of the metal on ultrahigh molecular weight polyethylene couple. Concern has been raised about the release, and biologic fate, of metal species from corrosion and wear. Titanium alloys have been shown to have limitations as an articulating surface showing significant wear, and the alloy per se should not be considered for wear couples in total hip replacements. The cobalt chromium alloys are known to have reasonable wear and corrosion properties and continue to be evaluated. The issue of cobalt chromium wear and corrosion products and how this relates to the biologic performance of total hip replacement devices is reviewed. Under the condition of wear as currently experienced at the articulating surfaces of cobalt chromium alloys and ultrahigh molecular weight polyethylene, the amount of metallic products transferred to the tissues is sufficiently low to be well tolerated by the biologic system. Nickel and cobalt ions arc, rapidly transported from the implant site and eliminated in the urine. Chromium is stored in the tissue and eliminated more slowly. The issue of host hypersensitivity to these elements remains of concern. All 3 elements, in ionic form, are known to cause contact dermatitis. Untoward biologic reactions, including hypersensitivity, should be minimized if wear and corrosion phenomena are minimized.

Alloys↗
PubMed1996

Fluoroquinolones in animal health.

The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram-negative bacteria, mycoplasma, and some gram-positive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid-mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight-bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep-seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial therapy.

Administration, Oral↗
PubMed1996

Effects of age on the pharmacokinetics of single dose ceftiofur sodium administered intramuscularly or intravenously to cattle.

The effects of maturation on the intravenous (IV) and intramuscular (IM) pharmacokinetics of ceftiofur sodium following a dose of 2.2 mg ceftiofur equivalents/kg body weight were evaluated in 16 one-day-old Holstein bull calves (33-53 kg body weight initially; Group 1) and 14 six-month-old Holstein steers (217-276 kg body weight initially; Group 2). Group 1 calves were fed unmedicated milk replacer until 30 days of age and were then converted to the same roughag/concentrate diet as Group 2. Groups 1-IV and 2-IV received ceftiofur sodium IV, and Groups 1-IM and 2-IM received ceftiofur sodium IM. Group 1 calves were dosed at 7 days of age and at 1 and 3 months of age; group 2 calves were dosed at 6 and 9 months of age. Blood samples were obtained serially from each calf, and plasma samples were analysed using an HPLC assay that converts ceftiofur and all desfuroylceftiofur metabolites to desfuroylceftiofur acetamide. Cmax values were similar in all calves, and were no higher in younger calves than in older calves. Plasma concentrations remained above 0.150 microgram ceftiofur free acid equivalents/mliter for 72 h in 7-day-old calves, but were less than 0.150 microgram/mliter within 48 h following IV or IM injection for 6- and 9-month-old calves. Intramuscular bioavailability, assessed by comparing the model-derived area under the curve (AUCmod) from IM and IV injection at each age, appeared to be complete. After IV administration, the AUCmod in 7-day-old and 1-month-old calves (126.92 +/- 21.1 micrograms.h/mliter and 135.0 +/- 21.6 micrograms.h/mliter, respectively) was significantly larger than in 3-, 6- and 9-month-old calves (74.0 +/- 10.7 micrograms.h/mliter, 61.0 +/- 17.7 micrograms.h/mliter and 68.5 +/- 12.8 micrograms.h/mliter, respectively; P < 0.0001). The Vd(ss) decreased linearly within the first 3 months of life in cattle (0.345 +/- 0.0616 L/kg, 0.335 +/- 0.919 L/kg and 0.284 +/- 0.0490 L/kg, respectively; P = 0.031), indicative of the decreasing extracellular fluid volume in maturing cattle. The ClB was significantly smaller in 7-day-old and 1-month-old calves (0.0178 +/- 0.00325 L/h.kg and 0.0167 +/- 0.00310 L/h.kg, respectively) than in 3-, 6- and 9-month-old calves (0.0303 +/- 0.0046 L/h.kg, 0.0398 +/- 0.0149 L/h.kg and 0.0330 +/- 0.00552 L/h.kg, respectively; P < or = 0.001). This observation may be indicative of maturation of the metabolism and/or excretion processes for ceftiofur and desfuroylceftiofur metabolites. The approved dosage regimens for ceftiofur sodium of 1.1-2.2 mg/kg administered once daily for up to 5 consecutive days will provide plasma concentrations above the MIC for bovine respiratory disease pathogens for a longer period of time in neonatal calves than in older calves. Peak plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were no higher in neonatal calves than in more mature cattle, highly suggestive that peak tissue concentrations would be no higher in neonatal calves than in more mature cattle.

Aging↗
PubMed1996

Ceftiofur hydrochloride: plasma and tissue distribution in swine following intramuscular administration at various doses.

Twelve mixed-breed swine (26.5-42.5 kg) received three daily intramuscular (i.m.) doses of 14C-ceftiofur hydrochloride. Three males and three females, received 6.76 +/- 0.83 mg of 14C-ceftiofur free acid equivalents (CFAE)/kg body weight (b.w.)/day, while the other group received 4.41 +/- 0.97 mg.CFAE/kg b.w./day. The swine were slaughtered 12 h following the last dose. Total dose accountability for the 6.76 mg dose was 91.44 +/- 16.11% (72.51% in urine; 12.63% in faeces). For the 4.41 mg dose, accountability was 100.35 +/- 20.45% (82.48% in urine; 12.85% in faeces). Within the tissues used for residue monitoring, the highest concentrations were observed in the kidneys (10.68 and 6.33 micrograms.CFAE/g for the 6.76 and 4.41 mg doses, respectively), followed by the injection sites, lungs, liver and muscle. In a separate study, twelve mix-breed swine (23.1-39.7 kg) received 14C-ceftiofur hydrochloride at 3.08 mg.CFAE/kg b.w. once daily for 3 days. Two males and two females were slaughtered at either 12, 72 or 120 h after the last dose. Total dose accountability for the 3.08 mg dose was > 83% (> 68% in urine; > 13% in faeces). In swine slaughtered 12 h after last dose, residue concentrations closest to the safe concentrations were observed in the kidneys (3.62 micrograms.CFAE/g), followed by the injection sites, lungs, liver and muscle.

Animals↗
PubMed1996

Penetration of parenterally administered ceftiofur into sterile vs. Pasteurella haemolytica-infected tissue chambers in cattle.

The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256-290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (10(6) CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non-infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur-equivalent microbiological activity were measured by high-pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and anti-microbial activity in P. haemolytica-infected tissue chambers were significantly higher than those in non-infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected with P. haemolytica. Antibiotic activity-concentration ratios were lower in plasma and infected chamber fluid compared with non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non-infected chamber fluid, suggests that active drug is reversibly bound to proteins. Protein-bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infection in the animal.

Animals↗
PubMed1996

Conduct disorder among adolescent alcohol and drug abusers.

OBJECTIVE: Delinquent behavior is prevalent among adolescents who abuse alcohol and other drugs. The present study examined the extent to which conduct disorder type behavior predates substance use involvement among 166 adolescents in treatment for alcohol and other drug abuse, and the prognostic significance of conduct disorder behaviors for the clinical course of teens during the first 2 years following treatment. METHOD: This was prospective longitudinal study of 166 alcohol and other drug abusing adolescents, 67 girls and 99 boys, averaging 15.9 years of age. Consecutive admissions were recruited from two adolescent inpatient alcohol and drug treatment facilities. Subjects were interviewed during treatment and again at 6 months and 1 and 2 years posttreatment. RESULTS: Whereas the vast majority (95%) of teens entering alcohol and drug abuse treatment programs displayed a history of conduct disorder type behavior, only 47% met DSM-III-R criteria when behaviors directly or indirectly related to alcohol and drug involvement were excluded. Boys displayed a greater number of conduct disorder behaviors than girls, but the relative incidence of these behaviors was comparable across sexes. A history of conduct disorder independent of alcohol and drug involvement was related to both greater posttreatment alcohol involvement and a later diagnosis of antisocial personality disorder. CONCLUSIONS: This study shows that a significant portion of the delinquent behaviors found in adolescents treated for alcohol and drug abuse is secondary to involvement with alcohol and other drugs. A primary diagnosis of conduct disorder was found to be associated with poorer clinical course in the first 2 years following treatment.

Adolescent↗