Gestation length and racing performance in 115 Thoroughbred foals with incomplete tarsal ossification.

BACKGROUND: Incomplete ossification of the cuboidal bones of the carpus and tarsus in foals has the potential for significant consequences including chronic lameness and decreased athletic ability. OBJECTIVES: To determine if the degree of ossification of the cuboidal bones is associated with gestational length and if the diagnosis of incomplete ossification is a predictor of performance in Thoroughbred racehorses. STUDY DESIGN: Retrospective cohort study. METHODS: The medical records of Thoroughbred foals less than 90 days of age from 1994 to 2011 were examined and records containing tarsal radiographs identified. Radiographs of the tarsus were examined for signs of incomplete ossification and those that were incompletely ossified graded on a scale of 1-4 using a modification of a previously reported index, with Grade 1 being the least ossified and Grade 4 being the most. Gestational length was determined by examining breeding records and foaling dates reported to the Jockey Club. Race records for 2- and 3-year-old affected foals and their maternal siblings were obtained and compared. RESULTS: Foals with Grades 1 and 2 ossification were usually premature (gestation length <325 days), but Grades 3 and 4 were not. Foals with Grades 2 and 3 ossification were significantly less likely to race than their maternal siblings and Grades 1, 2, 3 and 4 foals earned less money. MAIN LIMITATIONS: A larger sample size of foals with Grade 1 ossification would increase the power of the study. Foals radiographed at an older age may have had lower ossification scores if radiographed earlier. CONCLUSIONS: Incomplete ossification, especially Grades 1 and 2, is associated with a short gestation length. Foals with Grades 2 and 3 incomplete ossification were less likely to race and Grades 1, 2 and 3 earned around $30,000 less than their maternal siblings.

Correlation of racing performance with radiographic changes in the proximal sesamoid bones of 487 Thoroughbred yearlings.

REASONS FOR PERFORMING STUDY: Proximal sesamoiditis has been a common and confusing radiographic diagnosis in Thoroughbred yearling surveys. This study categorised the radiographic appearance of yearling proximal sesamoid bones and determined their effect on the number of races started and earning potential for racing at ages 2 and 3 years. HYPOTHESIS: Yearlings with moderate to severe proximal sesamoiditis have decreased performance at age 2 and 3 years. METHODS: Survey radiographs of 487 Thoroughbred yearlings were reviewed. Proximal sesamoid bones were examined and findings placed into 7 categories, 5 of which measured size, shape, and number of vascular canals, and 2 examined the radiographic shape of the sesamoid abaxial surface. Records of horses age 2 and 3 years were reviewed to obtain the number of races completed and money won in those races. RESULTS: Vascular canals with parallel sides < 2 mm in width in any number were normal. Yearlings with 1 or 2 abnormally conformed vascular canals (nonparallel sides and > 2 mm in width) had a decrease in number of race starts at age 2 years when compared to normal horses. This same change in the fore- or hindlimbs was associated with decreases in starts and earnings at age 2 years. If uniformly present in both fore- and hindlimbs there was no difference from normal horses. Yearlings with > 2 irregular vascular canals had a decrease in number of race starts and earnings at age 2 and 3 years. Changes in proximal sesamoid bone contour did not affect performance. CONCLUSIONS: Horses with enlarged vascular canals, within their sesamoids as yearlings, start fewer races and earn less prize money than horses with normal vascular canals. POTENTIAL RELEVANCE: One or two enlarged canals affected horses as 2-year-olds. Three or more enlarged vascular canals affected horses at ages 2 and 3 years, which should be taken into account when examining radiographs for potential purchase of young horses.

Behavioral treatment of attentional dysfunction in chronic, treatment-refractory schizophrenia.

Attentional impairment is both a core characteristic of schizophrenia and a factor in producing poor outcomes in rehabilitative treatment. While cognitive rehabilitation interventions have demonstrated some success, the severity of some patients' attentional impairment is such that they cannot attend to material in these treatments, leading to unsatisfactory outcomes. In this paper, we report on the results of a behavioral intervention designed to increase attention span in the lowest functioning group of schizophrenia patients on a long-term inpatient unit. The treatment is based on social-learning procedures, especially the principle of shaping. Results indicate that chronic, treatment refractory patients with severe attentional impairment, including those with IQs near or within the mentally retarded range, can improve their attention spans to over 45 minutes with this treatment.

Variation in late potentials and the reproducibility of their measurement.

The usefulness of a test depends on its reproducibility. This determines how closely the test result indicates the actual pathophysiologic state, how well it will predict that state in the future, and if interventions or further pathologic changes are reflected by the test. There is a variation in the parameters of the signal-averaged ECG, more so with spectral than with time domain measurements. These must be accounted for when estimating risk. If one presumes that risk is proportional to the extent of abnormality, then the variation in measurements simply means that only borderline cases can potentially be miscategorized. More important, the lack of reproducibility of measurements made from the signal-averaged ECG indicates that changes noted in an individual after an intervention, such as a surgical intervention, must be viewed with a jaundiced eye. Group changes are perhaps meaningful, and indicate a physiologic effect, but clinical decisions cannot be made unless the changes observed in an individual patient exceed the confidence limits of expected variation. There has been debate as to the usefulness of measurements made from the signal-averaged ECG in predicting antiarrhythmic drug effects (the effect of drugs is discussed elsewhere in this symposium). Here an analogy must be made to the suppression of asymptomatic ventricular ectopy. First, we cannot make a statement that there has been a drug effect unless the parameter measured changes beyond the confidence limits of normal variation or reproducibility. Second, we cannot translate a change in a measurement into a change in risk for arrhythmic events without subjecting that hypothesized relationship to a long-term placebo-controlled clinical trial, albeit acute electrophysiologic trials correlating changes in the signal-averaged ECG to ventricular tachycardia induction provide some insight. And perhaps the relationship must be tested independently for each drug assessed. In the same regard, there is much excitement about the benefits of thrombolytic therapy, but when diagnosing benefit to the individual patient we have to remember the lack of reproducibility of the measurements and also keep in mind that an improved signal-averaged ECG cannot be translated into an improved prognosis without long-term controlled studies. In summarizing the variation and reproducibility of measurements made from the signal-averaged ECG we avoided providing more than a sense of the extent of variation expected because precise confidence intervals depend on the particular techniques used to make the measurements.(ABSTRACT TRUNCATED AT 400 WORDS)

Reproducibility of the signal-averaged electrocardiogram.

Variation in measurements made from signal-averaged electrocardiograms was examined. Averaging 200 beats in 18 normal subjects, pairs of high-frequency QRS and low-amplitude signal durations correlated at immediate, short-term, and long-term intervals. The percent high-frequency (60 Hz to 120 Hz) voltages in the late potential region had modest correlations. However, 95% confidence intervals of differences in paired measurements were as much as 7% for high-frequency QRS, 20% for a low-amplitude signal, and 53% for percent high-frequency, similar at all time intervals. With electrocardiograms averaged to 0.3 microV noise, high-frequency QRS and low-amplitude signals prolonged, but variation was similar to that of 200 beat pairs. In contrast, low noise reduced percent high-frequency and lessened variation to 29%. Therefore variation in signal-averaged electrocardiographic measurements was considerable (high-frequency voltage greater than durations). Noise did not appreciably influence variation in durations but was critical to consistent voltage measurements in the frequency domain.

Misonidazole conjugates of the colorectal tumor associated monoclonal antibody 17-1A.

The radiation sensitizer misonidazole has been linked to the monoclonal antibody 17-1A which recognizes a nonshed antigen of a human gastrointestinal tumor. Linkage was accomplished through a hemisuccinate of misonidazole attached by a mixed anhydride coupling and gave a conjugate whose plasma half-life (for drug cleavage) was ca. 70 h. The degree of substitution on the antibody could be precisely regulated by varying the reactant ratios. The binding avidities of the resulting conjugates to the SW1116 colorectal tumor cells decrease logarithmically with increasing drug load. Four to six misonidazoles per antibody represented the optimum drug loading on this system. Enzymatic cleavage of the conjugate-drug union took place at both the ester and the amide linkages with the former scission predominating.

In vitro fertilization in nonhuman primates.

Ovulation induction, sperm capacitation, and fertilization have been studied for over 50 years in nonhuman primates but it has only been in the past 20 years that extensive studies on sizeable numbers of embryos have been carried out. Of over 200 species of nonhuman primates only a few have been studied and the majority of the findings come from studies of the squirrel monkey, baboon, rhesus, and cynomolgus macaque. Nevertheless, the fertilization process appears to be similar to that identified in other mammals and in man.

Fast Fourier transformation of the entire low amplitude late QRS potential to predict ventricular tachycardia.

Signal-averaged electrocardiograms (X, Y and Z leads) were acquired from 24 patients with coronary artery disease and recurrent ventricular tachycardia, 24 control patients with coronary artery disease and 23 normal subjects to assess the discriminant value of fast Fourier transformation of the entire late potential period of the QRS complex. Analysis of the vector magnitude in the temporal domain (25 to 250 Hz bandpass filters) measured high frequency QRS duration, the duration of terminal signals less than 40 microV and the root mean square voltage of the last 40 ms. Late potentials were defined as terminal signals greater than 25 Hz that were less than 40 microV. Analysis in the frequency domain used a 120 ms window that encompassed (had onset with) all of the late potential, but the mean value was first subtracted to eliminate a direct current component. High frequency spectral areas (60 to 120 Hz) and the percent high frequency (100 x [60 to 120 Hz/0 to 120 Hz]) were calculated. Results in both temporal and frequency domains were similar in control patients with coronary artery disease and normal subjects. Patients with ventricular tachycardia had a longer high frequency QRS complex (p less than 0.0001) and longer high frequency terminal signals less than 40 microV (p less than 0.0004), but not significantly lower voltage in the last 40 ms. The most useful temporal domain measurement was high frequency QRS duration (if greater than or equal to 120 ms, odds ratio = 8.2). Patients with ventricular tachycardia had increased high frequency spectral areas (p less than 0.0002) in the late potential, and the percent high frequency was especially increased (p = 0.0000; if percent high frequency greater than 3.1%, odds ratio = 18.4). The odds ratio and the area under the receiver operating characteristic curve were both greater for percent high frequency than for high frequency QRS duration (p less than 0.03). All patients with ventricular tachycardia had a high frequency QRS complex greater than or equal to 107 ms or percent high frequency greater than or equal to 3.1% (sensitivity 100%). For a high frequency QRS complex greater than or equal to 107 ms and percent high frequency greater than or equal to 3.1%, specificity was 96%. Therefore, high frequencies in late potentials, not their duration or reduced voltage, most usefully identify patients with coronary artery disease who are prone to ventricular tachycardia.

Two-muscle coordination versus natural treadmill locomotion.

When a single-muscle learned behavior was superimposed upon natural human treadmill locomotion, in previous work, it operated as a self-contained behavioral unit. The new behavior altered some features, however, of ongoing stepping patterns. These findings prompted broader consideration of how individual muscle actions combine to form large, patterned ensembles. Accordingly, the present experiment constructed a larger, double-muscle learned behavior to see if it would compete with natural treadmill locomotion or combine with it harmoniously. A demanding requirement was made for in-phase bilateral EMG and contraction by rectus femoris (RF), in opposition to its natural out-of-phase interlimb pattern. EMG bursts were controlled, through computer-assisted operant conditioning, by a flash shortly after left heel strike. The new, double ensemble was conditioned rapidly, within 1-6 days, for all four adults. Harmonious stepping continued, for the most part, with little alteration in step cycle timings. Leg positioning was modified appreciably, however, pointing to complex neural mechanisms. The evidence argued that operant conditioning can construct fine-grained behaviors and also participate powerfully across the full range of single- and interlimb coordination.

Ovaries remain functional in squirrel monkeys (Saimiri sciureus) immunized with porcine zona pellucida 55,000 macromolecule.

Fifty female squirrel monkeys were each immunized with 200 micrograms of a purified preparation of the 55,000 macromolecule (ZP3) from porcine zona pellucida. The fertility status of these immunized monkeys, as well as the effect of ZP3 antibodies on ovarian function, was monitored. High anti-ZP3 titers were achieved (greater than 75% binding levels as determined by radioimmunoassay) and remained high (approximately 67% binding level) for the duration of this study. Hormonal evaluations indicated initial disturbances in normal ovarian steroid secretion and function that were confirmed by laparoscopic observation and oocyte production data. Histological examination of ovaries at 6-7 mo post-injection suggested an interference in folliculogenesis. No pregnancies were observed in the immunized monkeys during this period. By 10-15 mo post-immunization, hormonal and laparoscopic data indicated that ovarian function was recovering in injected monkeys despite the continued presence of high titers to ZP3. Collectively, these results demonstrate that although immunization with ZP3 initially produces disturbances in normal ovarian function that inhibit fertility, these effects are reversible. Such findings encourage the continued intensive investigation of purified porcine zona macromolecules for immunocontraceptive purposes.

Alpha-2 adrenergic regulation of norepinephrine release in the rat submandibular gland as measured by HPLC-EC.

In many tissues, norepinephrine appears to inhibit its own release through an interaction at alpha adrenergic receptors. We have developed an assay for measuring the release of endogenous norepinephrine based on HPLC and have studied the regulation of release in the rat submandibular gland by alpha adrenergic antagonists. The method uses electrochemical detection to quantitate norepinephrine released from tissue slices and does not require preloading of the tissue with [3H]norepinephrine. Yohimbine, an alpha-2 adrenergic antagonist, potentiates by 50% the release caused by potassium induced depolarization with an EC50 of 0.14 microM. Prazosin, an alpha-1 antagonist, has a similar effect, but is less potent with an EC50 of 0.77 microM. Thus, the alpha adrenergic receptor mediating the regulation of norepinephrine release is of the alpha-2 subtype. The observed equal efficacies and lack of additivity of release potentiation by yohimbine and prazosin at maximal doses suggest that both drugs act at the same receptor. The five-fold difference in potency between prazosin and yohimbine is consistent with the recent observations indicating species differences between rodent and non-rodent alpha-2 adrenergic receptors.

Regulation of autonomic receptors in rat submandibular gland.

The binding of receptor specific radioligands to autonomic receptors in the rat submandibular gland was characterized after chronic drug administration and surgical sympathetic denervation. Reserpine administration resulted in an up-regulation of both alpha 2-adrenergic receptors labeled by [3H]clonidine and beta 1-adrenergic receptors labeled by [3H]dihydroalprenolol. The increase in alpha 2-receptors was half-maximal 24 hr after a single injection of reserpine, and was about 10-fold greater than control after seven daily injections. By contrast, the beta-adrenergic receptor density was the same as control after 3 days of reserpine administration, but within 7 days was about 2-fold greater than control. Guanethidine or yohimbine administration also resulted in an up-regulation of alpha 2-adrenergic receptors. Reserpine administration or unilateral superior cervical ganglionectomy increased the density of alpha 1-adrenergic receptor binding sites 24-80%. Norepinephrine and methoxamine, but not clonidine, caused potassium to be released from submandibular gland slices. Prazosin, but not yohimbine, blocked this response to norepinephrine, indicating that the response was mediated by alpha 1-adrenergic receptors. Potassium release elicited by alpha 1-agonists was augmented in slices from animals that received reserpine. Neither drug treatment nor sympathetic denervation altered muscarinic cholinergic receptor binding. The densities of muscarinic and beta-adrenergic receptors were found to be 23-51% higher in glands from female rats than in glands from male rats.