Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

BACKGROUND: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. ANIMALS: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6). METHODS: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. RESULTS: Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 µg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*µg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs.

Investigating the filled gel model in Cheddar cheese through use of Sephadex beads.

Cheese can be modeled as a filled gel whereby milkfat globules are dispersed in a casein gel network. We determined the filler effects using Sephadex beads (GE Healthcare Life Sciences, Pittsburgh, PA) as a model filler particle. Ideally, such a model could be used to test novel filler particles to replace milkfat in low-fat cheese. Low-filler (6% particles), reduced-filler (16%), and full-filler (33%) cheeses were produced using either Sephadex beads of varying sizes (20 to 150 µm diameter) or milkfat. Small- and large-strain rheological tests were run on each treatment at 8, 12, and 18 wk after cheese manufacturing. Differences in rheological properties were caused primarily by the main effects of filler volume and type (milkfat vs. Sephadex), whereas filler size had no obvious effect. All treatments showed a decrease in deformability and an increase in firmness as filler volume increased above 25%, although the beads exhibited a greater reinforcing effect and greater energy recovery than milkfat.

The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs.

Intravenous benzodiazepines are utilized as first-line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3-way crossover design with a 3-day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high-pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 µg/mL (C0) and 0.20 ± 0.06 µg/mL (Cmax), following IV and IM administration, respectively. Time to peak concentration (Tmax ) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.

Association between ABCB1 genotype and seizure outcome in Collies with epilepsy.

BACKGROUND: Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy. HYPOTHESIS: Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy. ANIMALS: Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs). METHODS: Prospective and retrospective cohort study. Dogs were classified as having a good outcome (≤ 1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects. RESULTS: Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1∆ mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014). CONCLUSIONS AND CLINICAL IMPORTANCE: ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes.

Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial.

BACKGROUND: There is little evidence-based information available to guide treatment of refractory epilepsy in dogs. The antiepileptic drug levetiracetam (LEV) is administered to dogs, although its safety and efficacy are unknown. OBJECTIVE: To evaluate the safety and efficacy of LEV as adjunctive therapy for refractory epilepsy in dogs. ANIMALS: Thirty-four client-owned dogs with idiopathic epilepsy. METHODS: Randomized, blinded trial involving dogs resistant to phenobarbital and bromide. Dogs received LEV (20 mg/kg PO q8h) or placebo for 16 weeks, and after a 4-week washout were crossed over to the alternate treatment for 16 weeks. Owners kept records on seizure frequency and adverse events. Hemogram, chemistry profile, urinalysis, and serum antiepileptic drug concentrations were evaluated at established intervals. RESULTS: Twenty-two (65%) dogs completed the study. Weekly seizure frequency during the 1st treatment period decreased significantly during LEV administration relative to baseline (1.9 ± 1.9 to 1.1 ± 1.3, P = .015). The reduction in seizures with LEV was not significant when compared to placebo (1.1 ± 1.3 versus 1.5 ± 1.7, P = .310). The most common adverse event was ataxia, with no difference in incidence between LEV and placebo (45 versus 18%, P = .090). No changes in laboratory parameters were identified and owners reported an improved quality of life (QOL) with LEV compared to placebo (QOL score 32.7 ± 4.3 versus 29.4 ± 4.5, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Adjunctive treatment with LEV appears safe in epileptic dogs. Efficacy of LEV over placebo was not demonstrated, although the power of the study was limited. Further evaluation of LEV as treatment for epilepsy in dogs is warranted.

The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital.

Levetiracetam (LEV) is a commonly used add-on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7-27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0-3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (C(max) ) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half-life (T(1/2) ) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.

Prevalence of urinary tract infection in dogs after surgery for thoracolumbar intervertebral disc extrusion.

BACKGROUND: Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI. OBJECTIVES: Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI. ANIMALS: Twenty-five dogs treated surgically for 26 acute disc extrusions. METHODS: Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors. RESULTS: Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE: There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results.

Total hip replacement in three cats: surgical technique, short-term outcome and comparison to femoral head ostectomy.

OBJECTIVE: To describe the surgical technique and clinical features of total hip replacement (THR) due to hip trauma in cats. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Three client-owned cats that underwent THR to treat capital epiphyseal fractures, and five client-owned cats that underwent femoral head ostectomy (FHO). METHODS: The clinical data included signalment, body weight, body condition score, diagnosis, implant size, surgical technique, intraoperative observations, and postoperative complications. Radiographic evaluation included implant positioning, cement mantle quality, and follow-up examination of the cement-bone interfaces. Orthopaedic examinations and client interviews were used to evaluate limb function. RESULTS: The three cats that underwent THR had a mean body weight of 5.5 kg, a mean body condition score of 6/9, and a mean age of three years at the time of surgery. The average THR follow-up was 11 months. For the five cats that underwent FHO, the mean body weight was 6.3 kg, mean body score was 7/9, and mean age at the time of FHO was 2.5 years. The average FHO follow-up was 22 months. Hip flexion, hip extension, and thigh girth after THR compared favourably to similar measurements made after FHO. The functional outcomes after THR were excellent. The functional outcomes after FHO ranged from poor to excellent. CONCLUSION AND CLINICAL RELEVANCE: The recovery after THR was excellent based on clinical assessment of muscle mass, hip joint passive range of motion, gait, and owner assessment. Further blinded, randomised, and controlled trials of THR in cats are warranted.

Modeling the growth and death kinetics of Salmonella in poultry litter as a function of pH and water activity.

Contaminated poultry litter, serving as a reservoir for Salmonella, can be linked to both food safety concerns when contaminated birds enter processing plants and environmental concerns when used as a fertilizer. Predictive modeling allows for the estimation of microbial growth or inactivation as a function of controlling environmental growth factors. A study was conducted to observe the combined effects of pH and water activity (A(w)) at a constant temperature on Salmonella populations in used turkey litter to predict microbial response over time. Litter, first pH-adjusted and then inoculated with a 3-strain Salmonella serovar cocktail to an initial concentration of approximately 10(7) cfu/g, was placed into individual sealed plastic containers with saturated salt solutions for controlling A(w). A balanced design including 3 A(w) values (0.84, 0.91, 0.96), 3 pH values (4, 7, 9), and a constant temperature of 30 degrees C was used, with litter samples periodically removed and analyzed for Salmonella populations, pH, and A(w). At each combination of environmental factors, the Churchill or exponential inactivation mathematical models were used to describe the growth and death of Salmonella over time. Salmonella populations exhibited growth (approximately 2 log) with little decline up to 42 d in litter environments of pH 7 and 9 and a A(w) of 0.96. As litter A(w) and pH levels were reduced, populations declined, with the most drastic reductions (approximately 5 log in 9 h) occurring in low-pH (4) and low-A(w) (0.84) environments. Generalized models for bacterial growth and death under grouped pH environments were successfully developed to predict Salmonella behavior in litter over time. These findings suggest that the best management practices and litter treatments that lower litter A(w) to < or =0.84 and pH to < or =4 are effective in reducing Salmonella populations. The use of a single equation to predict the growth and decline of Salmonella populations as a function of pH and A(w) has potential application for use in the development of effective pathogen control strategies at the farm level.

Effect of testing temperature on internal egg quality measurements.

The objective of this study was to determine the effect of egg testing temperature on quality measurements of shell eggs. The quality measurements compared included 3 Haugh unit (HU) devices (electronic Haugh, tripod Haugh, and Haugh meter), egg weight, albumen height, albumen width, albumen index, yolk width, yolk height, yolk index, percentage of thin albumen, and vitelline membrane strength at 3 temperatures of 5, 13, and 23 degrees C from 2 strains of laying hens (Hyline W36 and Bovans White) at 2 storage times. The HU measurements averaged 72.44 at time zero and 59.99 at 7 wk. At 7 wk for all devices, HU values decreased 6 units with increased temperature (P < 0.05). The electronic Haugh and tripod Haugh devices gave equal measurements for all testing conditions. The Haugh meter gave equal values at 5 degrees C for fresh eggs but lower HU at higher temperatures and 7 wk storage. Thus, it is recommended that egg testing temperature be reported when HU are measured. Coefficient of variation generally increased for all HU methods with increasing temperature. Although there was a proportionately different amount of thin albumen detected between the strains of laying hens, no significant difference was seen in HU. From the evaluated methods for measuring quality, the electronic Haugh, which electronically measures albumen height and calculates HU, provided the lowest coefficient of variation, was sensitive to quality loss, and gave the highest quality measurement (5 degrees C).

Determination of 5-log pathogen reduction times for heat-processed, acidified vegetable brines.

Recent outbreaks of acid-resistant food pathogens in acid foods, including apple cider and orange juice, have raised concerns about the safety of acidified vegetable products. We determined pasteurization times and temperatures needed to assure a 5-log reduction in the numbers of Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella strains in acidified cucumber pickle brines. Cocktails of five strains of each pathogen were (separately) used for heat-inactivation studies between 50 and 60 degrees C in brines that had an equilibrated pH value of 4.1. Salmonella strains were found to be less heat resistant than E. coli O157:H7 or L. monocytogenes strains. The nonlinear killing curves generated during these studies were modeled using a Weibull function. We found no significant difference in the heat-killing data for E. coli O157:H7 and L. monocytogenes (P = 0.9709). The predicted 5-log reduction times for E. coli O157:H7 and L. monocytogenes were found to fit an exponential decay function. These data were used to estimate minimum pasteurization times and temperatures needed to ensure safe processing of acidified pickle products and show that current industry pasteurization practices offer a significant margin of safety.

Effects of carcass washers on Campylobacter contamination in large broiler processing plants.

Campylobacter, a major foodborne pathogen found in poultry products, remains a serious problem facing poultry processors. Campylobacter research has primarily focused on detection methods, prevalence, and detection on carcasses; limited research has been conducted on intervention. The aim of this study was to assess the effectiveness of carcass washing systems in 4 large broiler-processing plants in removing Campylobacter species. Washing systems evaluated included combinations of inside/outside carcass washers and homemade cabinet washers. Processing aids evaluated were trisodium phosphate (TSP) and acidified sodium chlorite (ASC). The washer systems consisted of 1 to 3 carcass washers and used from 2.16 to 9.73 L of water per carcass. The washer systems used chlorinated water with 25 to 35 ppm of total chlorine. These washer systems on average reduced Campylobacter populations by log 0.5 cfu/mL from log 4.8 cfu/mL to log 4.3 cfu/mL. Washer systems with TSP or ASC reduced Campylobacter populations on average by an additional log 1.03 to log 1.26, respectively. Total average reductions in Campylobacter populations across the washer system and chill tank were log 0.76 cfu/mL. Washer systems that included antimicrobial systems had total average reductions in Campylobacter populations of log 1.53 cfu/mL. These results suggest that carcass washer systems consisting of multiple washers provide minimal reductions in Campylobacter populations found on poultry in processing plants. A more effective treatment of reducing Campylobacter populations is ASC or TSP treatment; however, these reductions, although significant, will not eliminate the organism from raw poultry.

Observations of electron diffusion regions at the subsolar magnetopause.

Electric and magnetic field observations on the Polar satellite at the subsolar magnetopause show that the magnetopause current is often striated. The largest of the resulting current channels are interpreted as electron diffusion regions because their widths are several electron skin depths and the electron flow U(e) within them does not satisfy E-->+U-->(e)xB-->=0. The data suggest that the magnetopause contains many such electron diffusion regions and that they are required because E-->xB-->/B(2) drifting electrons cannot carry the large filamentary currents imposed on the local plasma. The most probable interpretation of E-->+U-->(e)xB--> not equal 0 is that the pressure term on the right side of the generalized Ohm's law balances this inequality.

Extended acclimatization is required to eliminate stress effects of periodic blood-sampling procedures on vasoactive hormones and blood volume in beagle dogs.

Important in all experimental animal studies is the need to control stress stimuli associated with environmental change and experimental procedures. As the stress response involves alterations in levels of vasoactive hormones, ensuing changes in cardiovascular parameters may confound experimental outcomes. Accordingly, we evaluated the duration required for dogs (n = 4) to acclimatized to frequent blood sampling that involved different procedures. On each sampling occasion during a 6-week period, dogs were removed from their pen to a laboratory area and blood was collected either by venepuncture (days 2, 15, 34, 41) for plasma renin activity (PRA), epinephrine (EPI), norepinephrine, aldosterone, insulin, and atrial natriuretic peptide, or by cannulation (dogs restrained in slings; days 1, 8, 14, 22, 30, 33, 37, 40) for determination of haematocrit (HCT) alone (days 1 to 22) or HCT with plasma volume (PV; days 30 to 40). PRA was higher on days 2 and 15 compared with days 34 and 41 and had decreased by up to 48% by the end of the study (day 41 vs day 15; mean/SEM: 1.18/0.27 vs 2.88/0.79 ng ANG I/ml/h, respectively). EPI showed a time-related decrease from days 2 to 34, during which mean values had decreased by 51% (mean/SEM: 279/29 vs 134/20.9 pg/ml for days 2 and 34, respectively), but appeared stable from then on. None of the other hormones showed any significant variability throughout the course of the study. HCT was relatively variable between days 1 to 22 but stabilized from day 30, after which all mean values were approximately 6% lower than those between days 1 and 8. We conclude that an acclimatization period of at least 4 weeks is required to eliminate stress-related effects in dogs associated with periodic blood sampling.

Molecular cloning of trypsin cDNAs and trypsin gene expression in the salmon louse Lepeophtheirus salmonis (Copepoda: Caligidae).

The salmon louse, Lepeophtheirus salmonis, is a marine ectoparasitic copepod that infects salmonid fishes. We are studying the interactions between this parasite and its salmonid hosts, as it is a common cause of disease in both wild and farmed stocks of salmon. In this paper, we report on the cloning and sequencing of seven trypsin-like enzymes from a cDNA library prepared from whole body preadult female and male L. salmonis. The predicted trypsin activation peptides are 23 or 24 residues in length, considerably longer than previously reported activation peptides of other animals. Differences in the putative signal and activation peptide sequences of the trypsin isoforms suggest that these forms differ in their regulation and function. The calculated molecular weights of the trypsins range from 23.6 to 23.7 kDa. There are eight cysteine residues, which suggest the presence of four disulfide bridges. These trypsins are very similar (>or=46% aa identity) to other crustacean trypsins and insect hypodermins. Using in situ hybridization techniques trypsinogen expression could be identified in all three cell types of the midgut.

Effect of intracerebroventricular orexin-B on food intake in sheep.

Orexin is a hypothalamic neuropeptide that regulates feeding behavior in rats. Orexin-B has recently been cloned in pigs and was shown to stimulate food intake after intramuscular injection. This study was designed to determine whether intracerebroventricular (ICV) and intravenous injections of orexin could regulate appetite in sheep. Suffolk wethers were moved to indoor facilities, adapted to diets for 6 wk, and trained to stand in stanchions for 3 to 6 h each day for 2 wk before indwelling ICV cannulas were installed. These sheep were provided water and they consumed feed ad libitum. On the day before an experiment, each sheep was cannulated in a jugular vein. On the day of an experiment, sheep were placed in stanchions and allowed to stand for 1 h before use. Sheep were then monitored over a 2-h control period before i.v. injection with saline or porcine orexin-B (3 micrograms/kg BW) or ICV injection with artificial cerebrospinal fluid (CSF), orexin (0.03, 0.3, or 3 micrograms/kg BW) or in a second experiment with either orexin B (0.03, 0.3, 3 micrograms/kg BW), neuropeptide-Y (NPY; 0.3 microgram/kg BW), or orexin plus NPY. Food intake was monitored for consecutive 2-h periods. The i.v. injections of orexin did not affect food intake or metabolite or hormone concentrations. In ICV sheep, orexin increased food intake at 2 (P < 0.04) and at 4 h (P < 0.02). Food intake was greatest with the 0.3 microgram/kg BW dosage of orexin (P < 0.05). In the first 2 h after injection, orexin had an effect similar to that of NPY (0.23 kg for orexin and 0.2 kg for NPY). The combination of NPY and orexin had a greater effect on food intake (to 0.34 kg) than did either orexin (P < 0.05) or NPY (P < 0.008) alone. Differences were not apparent in the subsequent 2-h interval. No differences were noted in free fatty acid, glucose, growth hormone, luteinizing hormone, or insulin concentrations following orexin injection. There was an effect of ICV orexin treatment on plasma cortisol concentrations (P < 0.002). Cortisol was increased by orexin at the 0- to 2-h (P < 0.008) and in the 2- to 4-h (P < 0.009) intervals after orexin injection. These data indicate that central administration of orexin stimulates feed intake in sheep.

Echocardiographic Doppler evaluation of left ventricular diastolic filling in older, highly trained male endurance athletes.

Previously published data have suggested that endurance training does not retard the normative aging impairment of early left ventricular diastolic filling (LVDF). Those studies, suggesting no effect of exercise training, have not examined highly trained endurance athletes or their LVDF responses after exercise. We therefore compared LVDF characteristics in a group of older highly trained endurance athletes (n = 12, mean age 69 years, range 65-75) and a group of sedentary control subjects (n = 12, mean age 69 years, range 65-73) with no cardiovascular disease. For all subjects, M-mode and Doppler echocardiographic data were obtained at rest. After baseline studies, subjects underwent graded, maximal cardiopulmonary treadmill exercise testing using a modified Balke protocol. Breath-by-breath respiratory gas analysis and peak exercise oxygen consumption (VO(2)max) measurements were obtained. Immediately after exercise and at 3-6 minutes into recovery, repeat Doppler echocardiographic data were obtained for determination of LVDF parameters. VO(2)max (44 +/-6.3 vs 27+/-4.2 ml/kg/min, P<0.001), oxygen consumption at anaerobic threshold (35+/-5.4 vs 24+/-3.8 ml/kg/min, P<0.001), exercise duration (24+/-3 vs 12+/-6 minutes, P<0.001), and left ventricular mass index (61+/-13 vs 51+/-7.8 kg/m(2), P<0.05) were greater in endurance athletes than in sedentary control subjects, whereas body mass index was lower (22+/-1.7 vs 26+/-3.4 kg/m(2), P<0.001). No differences in any of the LVDF characteristics were observed between the groups with the exception of a trend toward a lower atrial filling fraction at rest in the endurance athlete group versus the control subjects (P = 0.07). High-intensity endurance exercise training promotes exceptional peak exercise oxygen consumption and cardiovascular stamina but does not appear to alter normative aging effects on left ventricular diastolic function.

Results of graft patency by immediate angiography in minimally invasive coronary artery surgery.

BACKGROUND: Although minimally invasive direct coronary artery bypass (MIDCAB) is being employed for revascularization of the left anterior descending coronary artery (LAD) with the left internal mammary artery (LIMA), little objective data exist regarding graft patency. Because the procedure is performed on a beating heart through a limited access approach, concerns have been raised regarding the ability to perform as accurate an anastomosis compared with conventional coronary artery bypass (CAB). METHODS: A prospective study of consecutive patients undergoing MIDCAB LIMA to LAD was undertaken. All procedures were performed through a limited anterior thoracotomy incision with a stabilization device. Selective angiography of the LIMA graft was performed intraoperatively or in the immediate postoperative period. RESULTS: One hundred and three patients underwent the MICAB procedure. Angiographic evaluation of the anastomosis was obtained in 100 patients (97%). Angiographic graft patency was 99%, with perfect graft patency (no stenosis greater than 50%) being 91%. Three grafts were revised in the operating room. One patient underwent reoperation and 3 more underwent percutaneous transluminal coronary angioplasty. There were two noncardiac mortalities (1.9%), both with patent grafts. CONCLUSIONS: Immediate graft patency after MIDCAB is acceptable, and comparable with conventional CAB data, although meaningful comparison is difficult. The significance of early angiographic findings and the role for early angiography remain to be defined.

Familial dilated cardiomyopathy locus maps to chromosome 2q31.

BACKGROUND: Inherited gene defects are an important cause of dilated cardiomyopathy. Although the chromosome locations of some defects and 1 disease gene (actin) have been identified, the genetic etiologies of most cases of familial dilated cardiomyopathy remain unknown. METHODS AND RESULTS: We clinically evaluated 3 generations of a kindred with autosomal dominant transmission of dilated cardiomyopathy. Nine surviving and affected individuals had early-onset disease (ventricular chamber dilation during the teenage years and congestive heart failure during the third decade of life). The disease was nonpenetrant in 2 obligate carriers. To identify the causal gene defect, linkage studies were performed. A new dilated cardiomyopathy locus was identified on chromosome 2 between loci GCG and D2S72 (maximum logarithm of odds [LOD] score=4.86 at theta=0). Because the massive gene encoding titin, a cytoskeletal muscle protein, resides in this disease interval, sequences encoding 900 amino acid residues of the cardiac-specific (N2-B) domain were analyzed. Five sequence variants were identified, but none segregated with disease in this family. CONCLUSIONS: A dilated cardiomyopathy locus (designated CMD1G) is located on chromosome 2q31 and causes early-onset congestive heart failure. Although titin remains an intriguing candidate gene for this disorder, a disease-causing mutation is not present in its cardiac-specific N2-B domain.