Saphenous vein graft aneurysm fistula formation causing right heart failure: an unusual presentation.

Saphenous vein graft aneurysm (SVG) formation after coronary artery bypass grafting is a rare complication of the surgery. We present a case of a 68-year-old man with an unusual presentation of such an aneurysm. Thirty-four years after his initial bypass surgery, the patient presented with a fistula formation into his right atrium from a vein graft aneurysm. Late aneurysm formation is thought to occur secondary to atherosclerotic degeneration of the SVG with background hypertension and dyslipidaemia accelerating the process. Diagnostic modalities used to investigate SVG aneurysms include computed tomography, transthoracic echocardiogram, magnetic resonance imaging and cardiac catheterisation. Aneurysms with fistula formation historically require aggressive surgical intervention. Resection of the aneurysm with subsequent revascularisation if required is the surgical norm. SVG aneurysm with fistula formation into a cardiac chamber is a rare complication of coronary artery bypass grafting (CABG), which can occur with atypical presenting symptoms. Physicians should keep in mind the possibility of this occurring in post-CABG patients presenting with heart failure and a new murmur.

Neuro-embolic protection during percutaneous balloon mitral valvuloplasty.

This report describes the management of a patient with severe symptomatic mitral stenosis and a large mobile thrombus extending from the left atrial appendage that was resistant to warfarin therapy. Percutaneous balloon mitral valvuloplasty was performed with cerebral protection using bilateral internal carotid artery filters to minimize the risk of embolic stroke.

Thrombotic risk in patients with aortic bioprostheses.

Thrombosis of Mosaic aortic valve bioprostheses occurring at more than one month after surgery occurs in 0.8% (95% CI 0.33-1.67%) of patients. In the two cases reported here, each patient had risk factors for thrombus formation, namely severe left ventricular impairment in one patient, while the other patient was heterozygous for prothrombin variant G20210A. The cases were treated successfully, by thrombolytic therapy with streptokinase in the first case, and by repeat aortic valve replacement in the second case. Thrombosis of bioprosthetic valves in the aortic position is rare, and a period of anticoagulation postoperatively does not invariably protect against this serious complication. In conclusion, patients with risk factors for thrombus formation should be considered for long-term anticoagulation.

Financing medical office buildings.

This article discusses financing medical office buildings. In particular, financing and ownership options from a not-for-profit health care system perspective are reviewed, including use of tax-exempt debt, taxable debt, limited partnerships, sale, and real estate investment trusts (REITs).

Immunoassay detection of drugs in racing horses: detection of ethacrynic acid and bumetanide in equine urine by ELISA.

We have raised antibodies and developed one-step enzyme-linked immunosorbent assays (ELISA) for the diuretics ethacrynic acid and bumetanide as part of a panel of pre- and post-race tests for high potency drugs in racing horses. These ELISA tests are rapid (completed within one hour), sensitive, and can be read by eye. The ELISA detects ethacrynic acid at a drug concentration for half-maximal inhibition (I-50) of about 2.5 ng/mL for the parent drug. After dosing horses intravenously with 5 mg ethacrynic acid per horse, the parent drug or its metabolites are detectable in urine for at least 8 hours. The bumetanide ELISA has an I-50 for the parent drug of about 2.0 ng/mL and will detect bumetanide or its metabolites for about 8 hours in urine after intravenous administration of a 1.7-mg dose per horse. Both antibodies are relatively specific for each drug and do not cross-react with other commonly used diuretics or other acidic compounds often found in post-race equine urine samples. Ethacrynic acid and bumetanide are potent diuretics suspected of being illegally substituted for furosemide in certain racing jurisdictions. Development of these rapid, sensitive, and simple tests for these agents will allow more effective pre- and post-race control of the use of these agents in racing horses. Both tests have recently uncovered several "positives" for these medications in a midwestern racing jurisdiction.

Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse.

Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. These effects were transient, and the animals appeared normal within 30 mins of dosing. Treated horses were tested in a variable interval responding apparatus 30 mins after dosing and no residual stimulation or depressant effects of hordenine were apparent. Animals dosed orally with 2.0 mg/kg bwt of hordenine showed no changes in heart rate, respiratory rate, basal body temperature or behaviour. After iv injection of hordenine, (2.0 mg/kg bwt) plasma reached a maximum value of about 1.0 micrograms/ml, and declined thereafter in a biexponential fashion. Kinetics of plasma concentration satisfied the concept of a two compartment open system, with an alpha-phase half-life of about 3 mins, and a beta-phase half-life of about 35 mins. Total urinary concentrations of hordenine (free and conjugated) peaked at about 400 micrograms/ml, and then declined exponentially to background levels by 24 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulfotransferase-mediated chlorination of 1-hydroxymethylpyrene to a mutagen capable of penetrating indicator cells.

Methylated polycyclic aromatic hydrocarbons are common in the human environment. Many of them are stronger carcinogens than their purely aromatic congeners. They may be metabolized to benzylic alcohols. We report here on biochemical and toxicological characteristics of 1-hydroxymethylpyrene (HMP), a typical representative of this class of compounds. Rat liver cytosol, fortified with 3'-phosphoadenosine-5'-phosphosulfate, converted HMP into its sulfate ester (HMPS), HMPS bound covalently to isolated DNA. In physiological buffer at 37 degrees C, HMPS had a half-life of 2 min, the major decomposition product being HMP. Thus, cyclic activation is possible. When Cl- anions were present at physiological concentrations, an additional reaction product of HMPS, 1-chloromethylpyrene (ClMP), could be identified on the basis of its chromatographic properties and its mass spectrum, using the authentic standard for comparison. ClMP was shorter-lived in buffer than HMPS. ClMP reacted with DNA, the adduct pattern in the 32P-postlabeling analysis being similar, or identical, to that of HMPS. ClMP proved to be a very potent mutagen in Salmonella typhimurium, whereas HMPS, and HMP in the presence of a sulfate-conjugating system, showed strong mutagenicity only when Cl- or Br- ions were present in the exposure buffer. It is concluded that HMPS is capable of reacting with DNA, but is hampered in its distribution by membrane barriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Equine urine pH: normal population distributions and methods of acidification.

Our investigation of the urine of grazing horses at the University of Kentucky shows that the mean pH level is about 7.9, and if their diet is supplemented with grain, it is about 7.4. There appears to be no significant effect of time of day or year on urine pH levels in horses. However, horses taken from pasture and supplemented with grain in a stalled environment show a slight decrease in urine pH. Additionally, we investigated the effects of storage on pH levels. Equine urine samples appear to be quite stable with regard to pH for 48h, but then show a marked increase. Urine pH can have a great effect on the urine concentration of some drugs and therefore, uncertainties can arise when data generated in grazing horses are compared or extrapolated to racing horses whose urine pH can be quite low. In an effort to simulate the drop in urine pH seen in some racing horses, we examined the effects of ammonium chloride, ascorbic acid, lactic acid and methionine on urine pH in research horses. Both oral and intravenous routes of administration were used. Although all agents tested showed varying degrees of efficacy, oral administration of ascorbic acid proved to be the safest and most effective agent to model the rapid acidification of urine seen in post race samples.

Pharmacologic effects and detection methods of methylated analogs of fentanyl in horses.

Pharmacologic effects of alpha-methylfentanyl and 3-methylfentanyl, analogs of fentanyl, were investigated in mares. The ability of an 125I-labeled fentanyl radioimmunoassay (125I-RIA) to detect these methylated fentanyl analogs in individual and pooled urine samples from horses was evaluated. Also, the ability of 7 fentanyl antibodies to react with fentanyl and fentanyl derivatives (sufentanil, alfentanil, and carfentanil) was investigated. Mares were studied in a locomotor test to determine the amount of stimulation methylated fentanyl analogs might induce. Two mares each were given alpha-methylfentanyl at 1, 2, 4, 8, or 13 micrograms/kg of body weight, IV, or 3-methylfentanyl at 0.4, 0.7, or 1 microgram/kg IV. The cross-reactivity of sufentanil, alfentanil, carfentanil, alpha-methylfentanyl, and 3-methylfentanyl with 7 fentanyl antibodies was studied, using the 125I-RIA. All fentanyl analogs, with the exception of alfentanil, cross-reacted well with a C1 antibody raised to fentanyl. Less satisfactory cross-reactivity was determined with 6 other antibodies raised to fentanyl derivatives. When the C1 antibody was combined with an iodinated analog to fentanyl, good detectability of alpha-methylfentanyl and 3-methylfentanyl, in terms of fentanyl equivalents, was obtained from urine samples of dosed mares. The ability of the 125I-RIA to detect methylated fentanyl analogs in forensic urine samples pooled in groups of up to 20 samples was evaluated. When these methylated analogs were administered to mares in doses that induced measurable locomotor stimulation, the analog's presence was readily detected in individual or pooled samples.

Left ventricular response to exercise and autonomic control mechanisms in end-stage renal disease.

Left ventricular (LV) function during rest and during exercise was evaluated in patients with end-stage renal disease (ESRD) in whom other causes of LV dysfunction were eliminated through rigid selection criteria. Autonomic function was also assessed in these patients with Valsalva's maneuver and plasma catecholamine determinations. Echocardiography and radionuclide ventriculography in the group with ESRD revealed no abnormalities of LV wall motion or ejection fraction. During graded exercise, patients with ESRD achieved 85% of age-predicted heart rate, and no differences in exercise tolerance or LV function were observed. Valsalva's response was abnormal in patients with ESRD, and post exercise the norepinephrine level was markedly increased (12.5 +/- 1.43 vs 8.28 +/- 0.82 nmol/L). Our results fail to indicate an independent adverse effect of ESRD on LV function.

Metabolism of 3-methylcholanthrene in rat liver cytosol.

The present study investigates the metabolism of the potent carcinogen 3-methylcholanthrene in rat liver cytosol preparations. Three metabolites of 3-methylcholanthrene were characterized by HPLC and GC/MS analysis. These metabolites were identified as 1-hydroxy-3-methylcholanthrene, 1-keto-3-methylcholanthrene and cholanthrene. The results of the present study, taken together with earlier studies, suggests that the first step in the metabolic activation of 3-methylcholanthrene is hydroxylation at the 1-position, the most easily oxidized reactive center in the molecule.

Narcotic analgesics, their detection and pain measurement in the horse: a review.

Narcotic analgesics produce pharmacological effects by interacting with specific opiate receptors. At least five major types of opiate receptors have been recognised. These include mu (morphine) and kappa (ethylketazocine) receptor types. Narcotic analgesics which interact with mu receptors produce locomotor and autonomic stimulation at doses that produce little or no analgesia. Therefore, use of these drugs as analgesics in equine medicine has not been very satisfactory. Theoretical considerations suggested that the role of kappa agonists in equine analgesia be investigated. Using a pure kappa agonist, U-50, 488H, good analgesia was produced in the horse with little or no locomotor stimulation or autonomic effects. These data suggest that kappa agonists may be superior analgesics for clinical use in the horse. On the other hand, the locomotor stimulant effects of mu agonist analgesics enable their use as illegal medications. Specifically, these agents produce a good running response, signs of central nervous stimulation and analgesia, all potentially useful effects in a racehorse. Regulatory control of most narcotic analgesics can be obtained by high performance thin layer chromatographic screening. However, effective screening for the fentanyls and small doses of etorphine can only be achieved by use of immunoassay.

Polymorphic ventricular tachycardia.

The case of a patient with torsade de pointes in the setting of congenital complete heart block is described. Lack of recognition of this polymorphic ventricular tachycardia resulted in therapy that potentiated the dysrhythmia. After correct recognition, and directed therapy, the patient responded appropriately. The clinical settings, recognition, and management options available for torsade de pointes are discussed to familiarize the emergency physician with this important and unique dysrhythmia.

Non-isotopic immunoassay drug tests in racing horses: a review of their application to pre- and post-race testing, drug quantitation, and human drug testing.

We have introduced large scale non-isotopic immunoassay testing into pre- and post-race drug testing in racehorses. The technologies utilized are Particle Concentration Fluorescence Immuno Assay (PCFIA) and the one-step Enzyme Linked Immuno Sorbent Assay (ELISA). These technologies are rapid, inexpensive, and highly effective. On introduction into post-race testing in the Western United States, these ELISA tests exposed several previously undetected patterns of drug abuse. The drugs detected were buprenorphine, oxymorphone, mazindol, sufentanil and cocaine. This led to the suspension of a large number of trainers and exposed the high false negative rate of thin layer chromatography (TLC) based testing. More recently, we have introduced both PCFIA and ELISA assays into pre- and post-race testing in Illinois. Within days, our pre-race PCFIA tests detected signs of acepromazine abuse. Directed searches of post-race urines from these horses showed evidence for acepromazine metabolites in the urine of these horses. Examination of frozen samples from associated horses yielded about 70 ELISA "positives" for acepromazine. To date, about 25 of these ELISA "positives" have been confirmed by mass spectrometry. We have also raised antibodies to phenylbutazone and furosemide to enable rapid and inexpensive quantitation of these permitted medications. Furosemide is a particular problem since its use requires a pre-race detention barn. For furosemide, we have developed a regulatory schedule based on our immunoassay test that allows elimination of the detention barn. For phenylbutazone, we have developed a similar immunoassay that allows rapid and inexpensive quantitation of this drug in blood. To enable racing authorities to test jockeys and other racetrack personnel, we have adapted PCFIA technology to human drug testing, and a full range of very sensitive tests for human drugs of abuse is available. These immunoassays are sufficiently sensitive to control abuse of the most potent drugs available to horsemen. In principle, an immunoassay can be raised to any drug within about six months, and made available worldwide at competitive rates. It appears clear that these non-isotopic immunoassays provide racing with the only technological basis that is sufficiently sensitive to detect the most potent abused drugs pre- and post-race, and has the flexibility to be readily adaptable to different drugs. Because of the high false negative rate generated by TLC, credible pre- and post-race testing programs cannot be based on TLC alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunoassay detection of drugs in racing horses. VI. Detection of furosemide (Lasix) in equine blood by a one step ELISA and PCFIA.

A one step enzyme-linked immunosorbent assay (ELISA) and a particle concentration fluorescent immunoassay (PCFIA) test for furosemide were evaluated as part of a panel of pre- and post-race tests for illegal medication of racing horses. These tests are very sensitive to furosemide with an I-50 for furosemide of about 20 ng/ml. The test is also rapid; an average pre-race complement of 10 samples can be analyzed in 90 minutes or less. The ELISA test results can be read with an inexpensive spectrophotometer, or even by eye. Both the PCFIA test and the ELISA test readily detect the presence of furosemide in equine blood for up to five hours after administration of the recommended therapeutic dose of this agent. The principal utility of these tests lies in rapid screening of samples for compliance with regulations governing the use of furosemide. Thus these tests can be used pre-race to determine whether horsemen have treated their horses with furosemide, and post-race to perform an initial evaluation of whether certain blood concentrations of furosemide have been exceeded. Pilot trials with these systems in Kentucky and Illinois suggest that these tests are economical and effective, and can form part of an analytical approach to substitute for the detention barn system of monitoring furosemide administration.

Immunoassay detection of drugs in racing horses. IV. Detection of fentanyl and its congeners in equine blood and urine by a one step ELISA assay.

We have developed and evaluated a one step enzyme-linked immunosorbent assay (ELISA) test for fentanyl as part of a panel of pre- and post-race tests for narcotic analgesics in racing horses. This ELISA test detects fentanyl with an I-50 of about 100 pg/ml. The test is economical in that it can be read with an inexpensive spectrophotometer, or even by eye. The test is rapid, and ten samples, a normal pre-race complement, can be analyzed in about twenty minutes. The test readily detects the presence of fentanyl or its metabolites in equine blood and urine from two and twenty-four hours respectively after administration of sub-therapeutic doses. The two antibodies evaluated also cross-react with the methylated analogs of fentanyl, sufetanil and carfentanil and the test detected these drugs shortly after their administration to horses. When introduced into routine screening, this test, in combination with another immunoassay test previously described, yielded 10 sufentanil positives. As such this test is capable of both improving the quality and reducing the cost of pre-race and post-race testing for fentanyl and a number of its congeners in racing horses.

Bioalkylation and biooxidation of anthracene, in vitro and in vivo.

Anthracene undergoes biomethylation in rat liver cytosol preparations in vitro and in rat subcutaneous tissue, in vivo. The in vitro reaction is dependent on cytosol preparations fortified by the addition of S-adenosyl-L-methionine. The products of the reaction are the meso-anthracenic or L-region derivatives 9-methylanthracene and 9,10-dimethylanthracene. The latter compound may be the simplest polynuclear aromatic hydrocarbon carcinogen known. These reactive methylated metabolites are readily oxidized in cytosol preparations and in subcutaneous tissue, in vivo, to hydroxymethyl and formyl derivatives. Oxidation takes place mainly on the methyl groups since ring oxidized products were not detected.

The detection, pharmacokinetics and behavioral effects of diisopropylamine dichloroacetate (DADA) in the horse: a preliminary report.

1. Drug administration studies using diisopropylamine dichloroacetate (DADA) and diisopropylamine (DIPA) were conducted in Thoroughbred and Standardbred horses to assess physiological effects and develop detection methods. 2. Four horses received 0.08 mg DADA/kg body wt and showed no changes in heart and respiratory rates or body temperature as measured over a 1-hr period after administration. A transient diuretic effect was found to occur in 2 mares dosed with 0.80 mg DADA/kg body wt. 3. A qualitative detection method using thin-layer chromatography was developed to detect DIPA, the major metabolite of DADA in equine urine. A quantitative detection method (lower limit of detection 0.5 micrograms/ml urine) for this metabolite was also developed using gas chromatography. 4. Neither DADA or the free base, DIPA, were detectable in equine blood samples using the above-mentioned methodologies.

Effects of phenylbutazone and oxyphenbutazone on acidic drug detection in high performance thin layer chromatographic systems.

Interference or "masking" in thin layer chromatography occurs when the presence of one drug on a thin layer plate physically obscures or interferes with the detection of another drug. We investigated the ability of phenylbutazone and oxyphenbutazone to mask or interfere with the detection of acidic drugs of high performance thin layer chromatography. Of 20 acidic drugs called "positive" since 1981 by laboratories affiliated with the Association of Official Racing Chemists, 16 did not comigrate with phenylbutazone or oxyphenbutazone and could not, therefore, be masked by these agents. Three medications (diclofenac, fenoprofen, ibuprofen) were potentially masked by phenylbutazone and one (sulindac) was potentially masked by oxyphenbutazone. These agents were therefore administered to horses to determine whether or not their metabolites would allow their detection. In each case, metabolites of these agents were detectable for at least 24 hr after drug administration and detection was not interfered with by phenylbutazone or oxyphenbutazone. These results suggest that these 20 acidic drugs should be readily detectable in postrace urines of horses in the presence of phenylbutazone either as the parent drug or by virtue of the easily distinguishable metabolites that each agent possesses. There is, therefore, no reason to believe that the agents tested in this study can be effectively masked or interfered with by phenylbutazone or its metabolites in equine urine.

High-sensitivity radioimmunoassay screening method for fentanyl.

A radioiodinated analog of fentanyl was synthesized for use with a commercially available radioimmunoassay for fentanyl. The sensitivity of the modified assay was at least 100 times greater than that of the original assay. Using this modified assay, concentrations of fentanyl as low as 1 pg/ml of fentanyl or fentanyl equivalents in equine urine were detected. Doses of fentanyl 100 times smaller than the minimum dose for a pharmacologic effect were detectable and a pharmacologically effective dose of fentanyl was detectable for up to 96 hours or more. The high sensitivity of the assay indicated that large numbers of urine samples (ie, 10 to 20) probably could be pooled and screened simultaneously, which would result in an economical analysis for fentanyl in the urine of horses after a race. Sufentanil and its metabolites also were detectable, using this assay, but at only about 1% of the efficiency at which fentanyl was detectable.