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The recent discovery of a mutational variant in the CEP290 gene (CEP290: IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence, frequency and clinical consequence of rdAc. The rdAc allele displayed widespread distribution, observed in 16/43 (37%) breeds, exhibiting a high allele frequency (∼33%) in North American and European Siamese populations. Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.1E-6), with clinical disease similar to affected Abyssinians/Somalis. This retinal degeneration has not been reported in breeds other than the Abyssinian/Somali and poses a significant health risk particularly in the Siamese breed group. Alertness of the veterinary community and the present availability of commercial diagnostic testing could synergistically enable breeders to reduce the incidence of rdAc blindness in pure-bred cat populations.

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The karyotypic relationships of skunks (Mephitidae) with other major clades of carnivores are not yet established. Here, multi-directional chromosome painting was used to reveal the karyological relationships among skunks and between Mephitidae (skunks) and Procyonidae (raccoons). Representative species from three genera of Mephitidae (Mephitis mephitis, 2n = 50; Mephitis macroura, 2n = 50; Conepatus leuconotus, 2n = 46; Spilogale gracilis, 2n = 60) and one species of Procyonidae (Procyon lotor, 2n = 38) were studied. Chromosomal homology was mapped by hybridization of five sets of whole-chromosome paints derived from stone marten (Martes foina, 2n = 38), cat, skunks (M. mephitis; M. macroura) and human. The karyotype of the raccoon is highly conserved and identical to the hypothetical ancestral musteloid karyotype, suggesting that procyonids have a particular importance for establishing the karyological evolution within the caniforms. Ten fission events and five fusion events are necessary to generate the ancestral skunk karyotype from the ancestral carnivore karyotype. Our results show that Mephitidae joins Canidae and Ursidae as the third family of carnivores that are characterized by a high rate of karyotype evolution. Shared derived chromosomal fusion of stone marten chromosomes 6 and 14 phylogenetically links the American hog-nosed skunk and eastern spotted skunk.

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With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species.

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Feline immunodeficiency virus (FIV) is a lentivirus related to human immunodeficiency virus (HIV) that causes feline AIDS in the domestic cat (Felis catus). Serological surveys indicate that at least 25 other species of cat possess antibodies that cross-react with domestic cat FIV. Most infected nondomestic cat species are without major symptoms of disease. Long-term studies of FIV genome variation and pathogenesis reveal patterns consistent with coadaptation of virus and host in free-ranging FIV-Ple-infected African lions (Panthera leo) and FIV-Pco-infected pumas (Puma concolor) populations. This report examined correlates of immunodeficiency in wild and captive lions and pumas by quantifying CD5(+), CD4(+), and CD8(+) T-cell subsets. Free-ranging FIV-Ple-infected lions had immunofluorescence flow cytometry (IFC) profiles marked by a dramatic decline in CD4(+) subsets, a reduction of the CD4(+)/CD8(+) ratio, reduction of CD8(+)beta(high) cells, and expansion of the CD8(+)beta(low) subset relative to uninfected lions. An overall significant depletion in CD5(+) T-cells in seropositive lions was linked with a compensatory increase in total CD5(-) lymphocytes. The IFC profiles were altered significantly in 50% of the seropositive individuals examined. The FIV-Pco-infected pumas had a more generalized response of lymphopenia expressed as a significant decline in total lymphocytes, CD5(+) T-cells, and CD5(-) lymphocytes as well as a significant reduction in CD4(+) T-cells. Like lions, seropositive pumas had a significant decline in CD8(+)beta(high) cells but differed by not having compensatory expansion of CD8(+)beta(low) cells relative to controls. Results from FIV-infected lions and pumas parallel human and Asian monkey CD4(+) diminution in HIV and SIV infection, respectively, and suggest there may be unrecognized immunological consequences of FIV infection in these two species of large cats.

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This study documents the seroprevalence of feline immunodeficiency virus (FIV) and puma lentivirus (PLV) in free-ranging and captive Florida panthers (Puma concolor coryi) (n = 51) and translocated Texas cougars (P. concolor stanleyana) (n = 10) from 1985 to 1998. The sera were tested for anti-FIV antibodies by enzyme-linked immunosorbent assay (ELISA) and Western blot tests. The ELISAs were read kinetically (KELA) and the sera were retrospectively examined by PLV peptide ELISA. Eleven panthers and one cougar were positive by KELA; 4 panthers and 4 cougars were equivocal; 35 panthers and 5 cougars were negative; and 1 panther had no data. Seven of the 11 KELA-positive panthers were also positive by Western blot tests and all but one were positive by PLV peptide ELISA. Ten KELA-negative and Western blot-negative cats, were positive by PLV peptide ELISA. KELA results varied within cats from one sample period to the next, but PLV peptide ELISA results were consistent. Territorial sympatry and mating behaviour, noted from radiotelemetry location data on the cats, may have contributed to viral transmission between seropositive animals. These findings suggest that Florida panthers and the introduced Texas cougars have been exposed to FIV and/or PLV.

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We report construction of second-generation integrated genetic linkage and radiation hybrid (RH) maps in the domestic cat (Felis catus) that exhibit a high level of marker concordance and provide near-full genome coverage. A total of 864 markers, including 585 coding loci (type I markers) and 279 polymorphic microsatellite loci (type II markers), are now mapped in the cat genome. We generated the genetic linkage map utilizing a multigeneration interspecies backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis). Eighty-one type I markers were integrated with 247 type II markers from a first-generation map to generate a map of 328 loci (320 autosomal and 8 X-linked) distributed in 47 linkage groups, with an average intermarker spacing of 8 cM. Genome coverage spans approximately 2,650 cM, allowing an estimate for the genetic length of the sex-averaged map as 3,300 cM. The 834-locus second-generation domestic cat RH map was generated from the incorporation of 579 type I and 255 type II loci. Type I markers were added using targeted selection to cover either genomic regions underrepresented in the first-generation map or to refine breakpoints in human/feline synteny. The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications.

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Removing entrapped pacing and defibrillator leads has been greatly simplified by making use of the excimer laser extractor. Sixty-two leads were successfully removed, although where appropriate, portions of the lead remained in place in 10 cases. There were two serious complications, one tear of the superior vena cava during an ICD extraction and one tear of the atrium during an atrial lead extraction. Both were controlled successfully through emergency sternotomy. Although extracting entrapped leads has been much simplified by making use of the laser extractor, the process is not free of serious complications. Those involved in explanting leads should be aware of the outcomes and be prepared for emergent management.

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In addition to its beneficial effect on patient survival, the implanted cardioverter defibrillator (ICD) changes a patient's life physically, socially, and psychologically. For improved patient management, it is important to understand the quality-of-life changes that accompany this mode of treatment. To this end, 119 patients were surveyed retrospectively and interviewed concurrently regarding their emotional, physical, and behavioral responses to ICD shocks and to the device itself. Most (55%) correctly estimated the total number of shocks they had received within a 10% margin. They found the shocks severe, 79% assigning a score between 3 and 5 on a scale of 1-5. Common descriptions of the shock sensation were a blow to the body or a spasm causing the entire body to jump. Most patients tolerated the shocks as lifesaving, but 23% dreaded shocks and 5% even said they would rather be without the ICD and take their chances. After a shock, 50% of patients called their physician and 42% continued their daily routine. Thirty percent went to a hospital emergency room or called a rescue service. Sixty-five percent had no preshock prodromes. Fifty-four percent were interested in the programmable option of a warning signal prior to a shock, while 31% preferred no warning. Of the 74% who were advised not to drive after implantation, 29% drove anyway. Five patients were shocked while driving with no resulting accidents. We conclude that most patients find ICD shocks moderately uncomfortable, but they tolerate them because of the lifesaving protection provided by the device.

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The purpose of this study was to determine whether serial measurements of helical screw pacemaker lead impedance could reliably confirm electrode fixation in the right atrium and right ventricle. Fixation is generally assessed fluoroscopically, which can be misleading because the myocardium is radiolucent. Alternatively, because the electrical conductivity of blood is greater than that of myocardium, serial measurements of the lead impedance might be expected to show an impedance increase with appropriate fixation of the pacemaker electrode when the electrode becomes embedded in myocardial tissue. Impedance measurements were made during the placement of 23 atrial and 28 ventricular active fixation electrodes in 31 consecutive patients. Impedance measurements were recorded in unipolar and bipolar electrode configurations with the electrode free floating in the chamber, unfixed (with exposed screws) but touching the endocardial surface, and after fixation. No significant impedance differences were found between free-floating and unfixed electrode positions. With fixation, the lead impedance increased significantly in the ventricle (P = 0.0001, unipolar and bipolar) and the atrium (P = 0.0069 unipolar and 0.0052 bipolar). Typical increases, reflected by median values, were 197 ohms unipolar and 203 ohms bipolar in the ventricle and 47 ohms unipolar and 53 ohms bipolar in the atrium for electrodes with permanently exposed or retractable screw designs. Comparing serial measurements of lead impedance before and after electrode fixation is a valid electrical method of confirming appropriate fixation of helical screw electrodes.

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OBJECTIVE: The purpose of this study was to determine the ability of a visual-perception assessment tool, the Motor-Free Visual Perception Test, to predict on-road driving outcome in subjects with stroke. DESIGN: This was a retrospective study of 269 individuals with stroke who completed visual-perception testing and an on-road driving evaluation. Driving evaluators from six evaluation sites in Canada and the United States participated. Visual-perception was assessed using the Motor-Free Visual Perception Test. Scores range from 0 to 36, with a higher score indicating better visual perception. A structured on-road driving evaluation was performed to determine fitness to drive. Based on driving behaviors, a pass or fail outcome was determined by the examiner. RESULTS: The results indicated that, using a score on the Motor-Free Visual Perception Test of < or =30 to indicate poor visual-perception and >30 to indicate good visual perception, the positive predictive value of the Motor-Free Visual Perception Test in identifying those who would fail the on-road test was 60.9% (n = 67/110). The corresponding negative predictive value was 64.2% (n = 102/159). Univariate logistic regression analyses revealed that older age, low Motor-Free Visual Perception Test scores and a right hemisphere lesion contributed significantly to identifying those who failed the on-road test. CONCLUSIONS: The predictive validity of the Motor-Free Visual Perception Test is not sufficiently high to warrant its use as the sole screening tool in identifying those who are unfit to undergo an on-road evaluation.

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Since 1994, 611 patients with atrial Accufix leads have been followed. Consideration was given to explanting these leads based on the presence or absence of fractures of the retention wire. All leads were followed according to a protocol proposed by the manufacturer, chiefly by regular 6-month high quality X rays and fluoroscopic evaluation. The impact of various conditions on the incidence of fracture was evaluated, such as the shape and location of the lead, prior open heart surgery, and the implantation route. The only factor related to the frequency of fractures was the shape of the lead, fractures occurring statistically more frequently if the leads were pulled from their normal J shape into an L or straightened configuration. The frequency of fractures has plateaued at 6 through 9 years with no further occurrence of Class III or IV fractures (protrusion of the fractured segment). Altogether there were nine (1.5%) Class III and Class IV fractures at the 9-year follow-up. Actuarial survival, in Class I or II, was 97%. We concluded, that the frequency of retention wire fractures has plateaued. This information coupled with the knowledge that the Accufix lead extraction can be difficult and dangerous, suggests that the remaining leads are best left in place.

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In female pacemaker recipients undergoing screening mammography, the impact of a pulse generator placed in the pectoral region has yet to be reviewed. We evaluated mammograms from 74 female pacemaker patients aged 40 years and older. The pulse generator obscured a portion of the mammogram in 7 patients (12%). During pacemaker implantation in women, the potential for the pulse generator to interfere with screening mammography should be considered. Baseline mammography should be obtained or reviewed; in high risk patients a nonconventional location for the pulse generator may be appropriate.

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Transvenous atrial defibrillation with multiple atrial lead systems has been shown to be effective in models without the potential for ventricular arrhythmias. The specific aim of this study was to evaluate the efficacy and safety of transvenous single lead atrial defibrillation in a canine model of ischemic cardiomyopathy. Ten dogs had ischemic cardiomyopathy induced by repeated intracoronary microsphere injections. The mean LV ejection fraction decreased from 71% +/- 9% to 38% +/- 14% (P = 0.003). Spontaneous atrial fibrillation (AF) developed in four dogs, and in six AF was induced electrically. Atrial defibrillation thresholds (ADFTs) were determined with synchronous low energy shocks using a transvenous tripolar lead with two defibrillation coils (right ventricle, superior vena cava) and an integrated sensing lead (RV coil vs electrode tip). The ADFTs derived by logistic regression were compared at 50% and 90% probability of success (ED50, ED90): ED50 was 2.4 +/- 1.7 J and 2.9 +/- 2.1 J, respectively, for 5- and 10-ms monophasic shocks, and 1.8 +/- 0.9 J, respectively, for 5- and 10-ms biphasic shocks. Immediately after 3 of 2,179 (0.1%) synchronized shocks, ventricular fibrillation (VF) developed. VF was induced in 3 of 1,062 (0.3%) shocks with integrated sensing (RV coil vs electrode tip) compared to 0 of 1,117 shocks when a separate bipolar RV sensing electrode was used for synchronization. In our canine model of ischemic cardiomyopathy, low energy atrial defibrillation via a transvenous single lead system was highly effective. However, there was a small but definite risk of VF induction, which seemed to be greater when an integrated as opposed to a true bipolar RV sensing was used.

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