QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

The electrocardiography (ECG) QT interval is influenced by fluctuations in heart rate (HR) what may lead to misinterpretation of its length. Considering that alterations in QT interval length reflect abnormalities of the ventricular repolarisation which predispose to occurrence of arrhythmias, this variable must be properly evaluated. The aim of this work is to determine which method of correcting the QT interval is the most appropriate for dogs regarding different ranges of normal HR (different breeds). Healthy adult dogs (n=130; German Shepherd, Boxer, Pit Bull Terrier, and Poodle) were submitted to ECG examination and QT intervals were determined in triplicates from the bipolar limb II lead and corrected for the effects of HR through the application of three published formulae involving quadratic, cubic or linear regression. The mean corrected QT values (QTc) obtained using the diverse formulae were significantly different (ρ<0.05), while those derived according to the equation QTcV = QT + 0.087(1- RR) were the most consistent (linear regression). QTcV values were strongly correlated (r=0.83) with the QT interval and showed a coefficient of variation of 8.37% and a 95% confidence interval of 0.22-0.23 s. Owing to its simplicity and reliability, the QTcV was considered the most appropriate to be used for the correction of QT interval in dogs.

A 37-kb restriction map of the human immunoglobulin lambda variable locus, VB cluster, harboring four functional genes and two non-coding Vl sequences

The human immunoglobulin lambda variable locus (IGLV) is mapped at chromosome 22 band q11.1-q11.2. The 30 functional germline v-lambda genes sequenced untill now have been subgrouped into 10 families (Vl1 to Vl10). The number of Vl genes has been estimated at approximately 70. This locus is formed by three gene clusters (VA, VB and VC) that encompass the variable coding genes (V) responsible for the synthesis of lambda-type Ig light chains, and the Jl-Cl cluster with the joining segments and the constant genes. Recently the entire variable lambda gene locus was mapped by contig methodology and its one- megabase DNA totally sequenced. All the known functional V-lambda genes and pseudogenes were located. We screened a human genomic DNA cosmid library and isolated a clone with an insert of 37 kb (cosmid 8.3) encompassing four functional genes (IGLV7S1, IGLV1S1, IGLV1S2 and IGLV5a), a pseudogene (VlA) and a vestigial sequence (vg1) to study in detail the positions of the restriction sites surrounding the Vl genes. We generated a high resolution restriction map, locating 31 restriction sites in 37 kb of the VB cluster, a region rich in functional Vl genes. This mapping information opens the perspective for further RFLP studies and sequencing

Genomic characterization of Brazilian hepatitis C virus genotypes 1a and 1b

Parts of 5' non-coding (5' NC) and of E1 envelope regions of the hepatitis C virus (HCV) genome were amplified from sera of 26 Brazilian anti-HCV antibody-positive patients using the reverse transcription-polymerase chain reaction (RT-PCR). Fourteen samples were PCR positive with primers from the 5' NC region and 8 of them were also positive with primers from the E1 region. A genomic segment of 176 bp from the E1 region of 7 isolates was directly sequenced from PCR products. The sequences were compared with those of HCV strains isolated in other countries and the Brazilian isolates were classified by phylogenetic analysis into genotypes 1a and 1b. This could have a clinical importance since it has been shown that individuals infected with type 1 viruses are less likely to respond to treatment with interferon than individuals infected with types 2 and 3 viruses. Two quasispecies isolated from the same patient with an interval of 13 months differed by two base substitutions (1.1%). The sequence of another isolate presented a three-nucleotide deletion at codon 329

A novel polymorphism in the coding region of the vasopressin type 2 receptor gene

Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R)) gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R) gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R) gene have also been reported. In the present study, we analyzed exon 3 of the V2(R) gene in 20 unrelated individuals by direct sequencing. A C®T alteration in the third position of codon 331 (AGC®AGT), which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome

Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary artery disease

Parasympathetic dysfunction is an independent risk factor in patients with coronary artery disease; thus, cholinergic stimulation is a potential therapeutic measure that may be protective by acting on ventricular repolarization. The purpose of the present study was to determine the effects of pyridostigmine bromide (PYR), a reversible anticholinesterase agent, on the electrocardiographic variables, particularly QTc interval, in patients with stable coronary artery disease. In a randomized double-blind crossover placebo-controlled study, simultaneous 12-lead electrocardiographic tracings were obtained at rest from 10 patients with exercise-induced myocardial ischemia before and 2 h after the oral administration of 45 mg PYR or placebo. PYR increased the RR intervals (pre: 921 ± 27 ms vs post: 1127 ± 37 ms; P<0.01) and, in contrast with placebo, decreased the QTc interval (pre: 401 ± 3 ms vs post: 382 ± 3 ms; P<0.01). No other electrocardiographic variables were modified (PR segment, QT interval, QT and QTc dispersions). Cholinergic stimulation with PYR caused bradycardia and reduced the QTc interval without important side effects in patients with coronary disease. These effects, if confirmed in studies over longer periods of administration, may suggest a cardioprotection by cholinergic stimulation with PYR.

Chronic converting enzyme inhibition normalizes QT interval in aging rats

The aim of the present study was to investigate the effects of converting enzyme inhibition by captopril on ECG parameters in aged rats. Four-month-old male rats received captopril dissolved in tap water (0.5 mg/l) or tap water for 2 or 20 months. At the end of treatment, under anesthesia, RR and PR interval, P wave and QRS duration, QT and corrected QT interval were measured in all animals. On the following day, chronic ECG (lead II) recordings were performed to quantify supraventricular (SVPB) or ventricular premature beats (VPB). After sacrifice, the hearts were removed and weighed. RR interval was similar in young and untreated aged rats, but significantly larger in aged rats treated with captopril. P wave and QRS length did not differ among groups. PR interval was significantly larger in old than in young rats and was not affected by captopril. Corrected QT interval was larger in aged than in young rats (117 ± 4 vs 64 ± 6 ms, P<0.05) and was reduced by captopril (71 ± 6 ms, P<0.05). VPB were absent in young rats and highly frequent in untreated old animals (8.4 ± 3.0/30 min). Captopril significantly reduced VPB in old rats (0.3 ± 0.1/30 min, P<0.05). The cardiac hypertrophy found in untreated aged rats was prevented by captopril (3.44 ± 0.14 vs 3.07 ± 0.10 mg/g, P<0.05). The beneficial effects of angiotensin converting enzyme inhibition on the rat heart during the aging process are remarkable.

Comparative sequence analysis of the P-, M- and L-coding region of the measles virus CAM-70 live attenuated vaccine strain

Measles virus is a highly contagious agent which causes a major health problem in developing countries. The viral genomic RNA is single-stranded, nonsegmented and of negative polarity. Many live attenuated vaccines for measles virus have been developed using either the prototype Edmonston strain or other locally isolated measles strains. Despite the diverse geographic origins of the vaccine viruses and the different attenuation methods used, there was remarkable sequence similarity of H, F and N genes among all vaccine strains. CAM-70 is a Japanese measles attenuated vaccine strain widely used in Brazilian children and produced by Bio-Manguinhos since 1982. Previous studies have characterized this vaccine biologically and genomically. Nevertheless, only the F, H and N genes have been sequenced. In the present study we have sequenced the remaining P, M and L genes (approximately 1.6, 1.4 and 6.5 kb, respectively) to complete the genomic characterization of CAM-70 and to assess the extent of genetic relationship between CAM-70 and other current vaccines. These genes were amplified using long-range or standard RT-PCR techniques, and the cDNA was cloned and automatically sequenced using the dideoxy chain-termination method. The sequence analysis comparing previously sequenced genotype A strains with the CAM-70 Bio-Manguinhos strain showed a low divergence among them. However, the CAM-70 strains (CAM-70 Bio-Manguinhos and a recently sequenced CAM-70 submaster seed strain) were assigned to a specific group by phylogenetic analysis using the neighbor-joining method. Information about our product at the genomic level is important for monitoring vaccination campaigns and for future studies of measles virus attenuation.

An analysis of the electrocardiogram QT interval

No reports testing the efficacy of the use of the QT/RR ratio <1/2 for detecting a normal QTc interval were found in the literature. The objective of the present study was to determine if a QT/RR ratio <=1/2 can be considered to be equal to the normal QTc and to compare the QT and QTc measured and calculated clinically and by a computerized electrocardiograph. Ratios (140 QT/RR) of 28 successive electrocardiograms obtained from 28 consecutive patients in a tertiary level teaching hospital were analyzed clinically by 5 independent observers and by a computerized electrocardiograph. The QT/RR ratio provided 56% sensitivity and 78% specificity, with an area under the receiver operator characteristic curve of 75.8% (95%CI: 0.68 to 0.84). The divergence in QT and QTc interval measurements between clinical and computerized evaluation were 0.01 ± 0.03 s (95%CI: 0.04-0.02) and 0.01 ± 0.04 s (95%CI: -0.05-0.03), respectively. The QT and QTc values measured clinically and by a computerized electrocardiograph were similar. The QT/RR ratio <=1/2 was not a satisfactory index for QTc evaluation because it could not predict a normal QTc value.

Cloning, sequence analysis, and expression of cDNA coding for the major house dust mite allergen, Der f 1, in Escherichia coli

Our objective was to clone, express and characterize adult Dermatophagoides farinae group 1 (Der f 1) allergens to further produce recombinant allergens for future clinical applications in order to eliminate side reactions from crude extracts of mites. Based on GenBank data, we designed primers and amplified the cDNA fragment coding for Der f 1 by nested-PCR. After purification and recovery, the cDNA fragment was cloned into the pMD19-T vector. The fragment was then sequenced, subcloned into the plasmid pET28a(+), expressed in Escherichia coli BL21 and identified by Western blotting. The cDNA coding for Der f 1 was cloned, sequenced and expressed successfully. Sequence analysis showed the presence of an open reading frame containing 966 bp that encodes a protein of 321 amino acids. Interestingly, homology analysis showed that the Der p 1 shared more than 87% identity in amino acid sequence with Eur m 1 but only 80% with Der f 1. Furthermore, phylogenetic analyses suggested that D. pteronyssinus was evolutionarily closer to Euroglyphus maynei than to D. farinae, even though D. pteronyssinus and D. farinae belong to the same Dermatophagoides genus. A total of three cysteine peptidase active sites were found in the predicted amino acid sequence, including 127-138 (QGGCGSCWAFSG), 267-277 (NYHAVNIVGYG) and 284-303 (YWIVRNSWDTTWGDSGYGYF). Moreover, secondary structure analysis revealed that Der f 1 contained an a helix (33.96%), an extended strand (17.13%), a ß turn (5.61%), and a random coil (43.30%). A simple three-dimensional model of this protein was constructed using a Swiss-model server. The cDNA coding for Der f 1 was cloned, sequenced and expressed successfully. Alignment and phylogenetic analysis suggests that D. pteronyssinus is evolutionarily more similar to E. maynei than to D. farinae.

Training-related changes in the R-R interval at the onset of passive movements in humans

The aim of the present study was to determine whether training-related alterations in muscle mechanoreflex activation affect cardiac vagal withdrawal at the onset of exercise. Eighteen male volunteers divided into 9 controls (26 ± 1.9 years) and 9 racket players (25 ± 1.9 years) performed 10 s of voluntary and passive movement characterized by the wrist flexion of their dominant and non-dominant limbs. The respiratory cycle was divided into four phases and the phase 4 R-R interval was measured before and immediately following the initiation of either voluntary or passive movement. At the onset of voluntary exercise, the decrease in R-R interval was similar between dominant and non-dominant forearms in both controls (166 ± 20 vs 180 ± 34 ms, respectively; P > 0.05) and racket players (202 ± 29 vs 201 ± 31 ms, respectively; P > 0.05). Following passive movement, the non-dominant forearm of racket players elicited greater changes than the dominant forearm (129 ± 30 vs 77 ± 17 ms; P < 0.05), as well as both the dominant (54 ± 20 ms; P < 0.05) and non-dominant (59 ± 14 ms; P < 0.05) forearms of control subjects. In contrast, changes in R-R interval elicited by the racket players' dominant forearm were similar to that observed in the control group, indicating that changes in R-R interval at the onset of passive exercise were not attenuated in the dominant forearm of racket players. In summary, cardiac vagal withdrawal induced by muscle mechanoreflex stimulation is well-maintained, despite long-term exposure to training.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

Effects of continuous vs interval exercise training on oxygen uptake efficiency slope in patients with coronary artery disease

The oxygen uptake efficiency slope (OUES) is a submaximal index incorporating cardiovascular, peripheral, and pulmonary factors that determine the ventilatory response to exercise. The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease. Thirty-five patients (59.3±1.8 years old; 28 men, 7 women) with coronary artery disease were randomly divided into two groups: continuous exercise training (n=18) and interval exercise training (n=17). All patients performed graded exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold (VAT), respiratory compensation point, and peak oxygen consumption (peak VO2). The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation. After the interventions, both groups showed increased aerobic fitness (P<0.05). In addition, both the continuous exercise and interval exercise training groups demonstrated an increase in OUES (P<0.05). Significant associations were observed in both groups: 1) continuous exercise training (OUES and peak VO2 r=0.57; OUES and VO2 VAT r=0.57); 2) interval exercise training (OUES and peak VO2 r=0.80; OUES and VO2 VAT r=0.67). Continuous and interval exercise training resulted in a similar increase in OUES among patients with coronary artery disease. These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms.

The development of norm-based coding and category-specific face prototypes : an examination of 5- and 8-year-olds' face space

The present set of experiments was designed to investigate the organization and refmement of young children's face space. Past research has demonstrated that adults encode individual faces in reference to a distinct face prototype that represents the average of all faces ever encountered. The prototype is not a static abstracted norm but rather a malleable face average that is continuously updated by experience (Valentine, 1991); for example, following prolonged viewing of faces with compressed features (a technique referred to as adaptation), adults rate similarly distorted faces as more normal and more attractive (simple attractiveness aftereffects). Recent studies have shown that adults possess category-specific face prototypes (e.g., based on race, sex). After viewing faces from two categories (e.g., Caucasian/Chinese) that are distorted in opposite directions, adults' attractiveness ratings simultaneously shift in opposite directions (opposing aftereffects). The current series of studies used a child-friendly method to examine whether, like adults, 5- and 8-year-old children show evidence for category-contingent opposing aftereffects. Participants were shown a computerized storybook in which Caucasian and Chinese children's faces were distorted in opposite directions (expanded and compressed). Both before and after adaptation (i.e., reading the storybook), participants judged the normality/attractiveness of a small number of expanded, compressed, and undistorted Caucasian and Chinese faces. The method was first validated by testing adults (Experiment I ) and was then refined in order to test 8- (Experiment 2) and 5-yearold (Experiment 4a) children. Five-year-olds (our youngest age group) were also tested in a simple aftereffects paradigm (Experiment 3) and with male and female faces distorted in opposite directions (Experiment 4b). The current research is the first to demonstrate evidence for simple attractiveness aftereffects in children as young as 5, thereby indicating that similar to adults, 5-year-olds utilize norm-based coding. Furthermore, this research provides evidence for racecontingent opposing aftereffects in both 5- and 8-year-olds; however, the opposing aftereffects demonstrated by 5-year-olds were driven largely by simple aftereffects for Caucasian faces. The lack of simple aftereffects for Chinese faces in 5-year-olds may be reflective of young children's limited experience with other-race faces and suggests that children's face space undergoes a period of increasing differentiation over time with respect to race. Lastly, we found no evidence for sex -contingent opposing aftereffects in 5-year-olds, which suggests that young children do not rely on a fully adult-like face space even for highly salient face categories (i.e., male/female) with which they have comparable levels of experience.

Sampling Interval and estimated Betas : Implications for the Presence of Transitory Components in Stock Prices

We provide a theoretical framework to explain the empirical finding that the estimated betas are sensitive to the sampling interval even when using continuously compounded returns. We suppose that stock prices have both permanent and transitory components. The permanent component is a standard geometric Brownian motion while the transitory component is a stationary Ornstein-Uhlenbeck process. The discrete time representation of the beta depends on the sampling interval and two components labelled \"permanent and transitory betas\". We show that if no transitory component is present in stock prices, then no sampling interval effect occurs. However, the presence of a transitory component implies that the beta is an increasing (decreasing) function of the sampling interval for more (less) risky assets. In our framework, assets are labelled risky if their \"permanent beta\" is greater than their \"transitory beta\" and vice versa for less risky assets. Simulations show that our theoretical results provide good approximations for the means and standard deviations of estimated betas in small samples. Our results can be perceived as indirect evidence for the presence of a transitory component in stock prices, as proposed by Fama and French (1988) and Poterba and Summers (1988).

PSWT Based Linear Predictive Coding and Development of a Parallel Multiple Subsequence Structure for DWT Computation

During 1990's the Wavelet Transform emerged as an important signal processing tool with potential applications in time-frequency analysis and non-stationary signal processing.Wavelets have gained popularity in broad range of disciplines like signal/image compression, medical diagnostics, boundary value problems, geophysical signal processing, statistical signal processing,pattern recognition,underwater acoustics etc.In 1993, G. Evangelista introduced the Pitch- synchronous Wavelet Transform, which is particularly suited for pseudo-periodic signal processing.The work presented in this thesis mainly concentrates on two interrelated topics in signal processing,viz. the Wavelet Transform based signal compression and the computation of Discrete Wavelet Transform. A new compression scheme is described in which the Pitch-Synchronous Wavelet Transform technique is combined with the popular linear Predictive Coding method for pseudo-periodic signal processing. Subsequently,A novel Parallel Multiple Subsequence structure is presented for the efficient computation of Wavelet Transform. Case studies also presented to highlight the potential applications.