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Objective: To identify demographic or signalment factors associated with calcium carbonate urolith formation in goats., Design: Retrospective case series and case-control study., Animals: 354 goats with calcium carbonate uroliths (case animals) and 16,366 goats without urinary tract disease (control animals)., Procedures: Medical records of the Minnesota Urolith Center were reviewed to identify case goats for which samples were submitted between January 1, 1984, and December 31, 2012. Control goats evaluated at US veterinary teaching hospitals in the same time period were identified by searching Veterinary Medical Database records. Age, breed, sex, reproductive status, geographic location, season, and anatomic location of collected uroliths were analyzed to identify risk or protective factors associated with calcium carbonate urolithiasis., Results: Nigerian dwarf goats had higher odds of developing calcium carbonate uroliths than did Pygmy goats (reference group). Several breeds had lower odds of this finding, compared with Pygmy goats; odds were lowest for mixed, Anglo-Nubian, and Toggenburg breeds. Breeds of African origin (Pygmy, Nigerian Dwarf, and Boer) comprised 146 of 275 (53%) case goats with data available. Goats of African descent had a higher risk of developing calcium carbonate uroliths than did goats of non-African descent (reference group). Males and neutered goats had higher odds of calcium carbonate urolithiasis, compared with females and sexually intact goats, respectively. Age category, geographic location, and season were associated with detection of calcium carbonate uroliths., Conclusions and Clinical Relevance: Goats with calcium carbonate uroliths were typically neutered males, > 1 year of age, and of African descent. This study identified factors associated with calcium carbonate urolithiasis in goats; however, these associations do not allow conclusions regarding cause-and-effect relationships.

Objective: To determine relative concentrations of selected major brain tissue metabolites and their ratios and lobar variations by use of 3-T proton (hydrogen 1 [(1)H]) magnetic resonance spectroscopy (MRS) of the brain of healthy dogs., Animals: 10 healthy Beagles., Procedures: 3-T (1)H MRS at echo times of 144 and 35 milliseconds was performed on 5 transverse slices and 1 sagittal slice of representative brain lobe regions. Intravoxel parenchyma was classified as white matter, gray matter, or mixed (gray and white) and analyzed for relative concentrations (in arbitrary units) of N-acetylaspartate (NAA), choline, and creatine (ie, height at position of peak on MRS graph) as well as their ratios (NAA-to-choline, NAA-to-creatine, and choline-to-creatine ratios). Peak heights for metabolites were compared between echo times. Peak heights for metabolites and their ratios were correlated and evaluated among matter types. Yield was calculated as interpretable voxels divided by available lobar voxels., Results: Reference ranges of the metabolite concentration ratios were determined at an echo time of 35 milliseconds (NAA-to-choline ratio, 1.055 to 2.224; NAA-to-creatine ratio, 1.103 to 2.161; choline-to-creatine ratio, 0.759 to 1.332) and 144 milliseconds (NAA-to-choline ratio, 0.687 to 1.788; NAA-to-creatine ratio, 0.984 to 2.044; choline-to-creatine ratio, 0.828 to 1.853). Metabolite concentration ratios were greater in white matter than in gray matter. Voxel yields ranged from 43% for the temporal lobe to 100% for the thalamus., Conclusions and Clinical Relevance: Metabolite concentrations and concentration ratios determined with 3-T (1)H MRS were not identical to those in humans and were determined for clinical and research investigations of canine brain disease.

Objectives: To compare serum concentrations of total thyroxine (TT4), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), as well as measures of thyroid follicular colloid and epithelium, between groups of healthy dogs and severely sick dogs., Design: Cross-sectional study., Animals: 61 healthy dogs and 66 severely sick dogs., Procedure: Serum samples were obtained before euthanasia, and both thyroid lobes were removed immediately after euthanasia. Morphometric analyses were performed on each lobe, and serum TT4, fT4, and TSH concentrations were measured., Results: In the sick group, serum TT4 and fT4 concentrations were less than reference range values in 39 (59%) and 21 (32%) dogs, respectively; only 5 (8%) dogs had high TSH concentrations. Mean serum TT4 and fT4 concentrations were significantly lower in the sick group, compared with the healthy group. In the healthy group, a significant negative correlation was found between volume percentage of colloid and TT4 or fT4 concentrations, and a significant positive correlation was found between volume percentage of follicular epithelium and TT4 or fT4 concentrations. A significant negative correlation was observed between volume percentages of colloid and follicular epithelium in both groups., Conclusions and Clinical Relevance: TT4 and fT4 concentrations are frequently less than reference range values in severely sick dogs. Therefore, thyroid status should not be evaluated during severe illness. The absence of any significant differences in mean volume percentages of follicular epithelium between healthy and severely sick dogs suggests that these 2 groups had similar potential for synthesizing and secreting thyroid hormones.

Under controlled, but varied dietary conditions 35 geriatric, uninephrectomized, spayed Beagle bitches (dogs) observed for 4 years, renal cortical and renal medullary echogenicity was measured relative to hepatic and splenic echogenicity. Regardless of the diet fed, 60-75% of these aged dogs had renal cortical echogenicity less than that of either the liver or spleen across time; 25-35% of these dogs had renal cortical echogenicity equal to that of the liver, but less than that of the spleen across time. Less than 3% of these dogs had renal cortical echogenicity greater than that of the liver, but less than that of the spleen. Only 1 (one) of these dogs had renal cortical echogenicity equal to that of the spleen and that occurred at only one of the 14 chronologic assessments. Therefore, in either mature or aged dogs imaged with 4.0 to 5.0 MHz equipment, the renal cortical echogenicity should be considered normal if it is less than or equal to that of the liver and less than that of the spleen. In 29 dogs imaged with the 4.0/5.0 MHz equipment and 6 dogs imaged with 7.5 MHz equipment, there was no significant diet or individual dog effect. The 7.5 MHz (6 dog) group had significantly higher average cortical echogenicity scores than the 4.0/5.0 MHz (29 dog) group. However, the occurrence of renal cortical echogenicity greater than liver echogenicity was seen in only 5 of 83 samples (approximately 6.0%) made on 6 dogs imaged with 7.5 MHz equipment and only 1 of 375 samples (approximately 0.27%) made on 29 dogs with 4.0/5.0 MHz equipment. With the exception of one occurrence, all dogs had renal medullary echogenicity less than that of the liver or spleen regardless of imaging equipment frequency. The renal medulla was always hypoechoic compared to the cortex.

Under controlled, but varied dietary conditions among geriatric, uninephrectomized Beagle bitches (dogs) observed for 4 years, renal size increase as assessed radiographically and ultrasonographically occurred at variable rates, but on a seemingly continuous basis. The maximum observed mean renal linear parameter increase found was approximately 15%. However, a 10 and 15% increase is a more representative expectation among the 4 parameters (sonographic length, radiographic length, sonographic width, radiographic width) under consideration. The rate of renal size increase was rapid during the first 2 to 3 months following uninephrectomy. Thereafter, the rate of increase was slow, but occurred to varying degrees in both the length and width as assessed radiographically or ultrasonographically. The mechanism creating the size change was hypertrophy, not hyperplasia. Within limits of the 3 diets used in the study, no significant diet effect was found on the rate or degree of long term compensatory hypertrophy. Radiographically and ultrasonographically measured renal length had the greatest correlation with each other as well as with post mortem measurements and are, therefore, the recommended parameter for imaging assessment of compensatory hypertrophy. When the prenephrectomy, radiographic renal lengths and widths were normalized as a ratio of the second lumbar vertebral body length (L2) measured from ventrodorsal radiographs, the diet group means across dogs (approximately three L2 lengths for renal length; two L2 lengths for renal width) were in the middle of the respective previously published normal radiographic ranges for mature dogs (e.g. 2.5 L2 < or = length < or = 3.5 L2; 1.58 L2 < or = width < or = 2.38 L2 lengths). Even after the hypertrophic changes occurred, the radiographic group mean lengths and widths across dogs were still within the specified normal ranges, although toward the upper end of the respective range. This information provides background for clinical interpretation of potential compensatory hypertrophy that may be encountered following uninephrectomy for spontaneous disease in aged dogs. In addition, it appears that available radiographic renal linear ranges for normal mature dogs are applicable to geriatric dogs as well.

Objective: To evaluate the effects of dilution and alkalinization, separately and together, on the stability of uric acid in canine urine stored at -20 C., Design: Prospective-controlled study., Animals: 5 dogs with confirmed ammonium urate uroliths, 6 Beagles, and 6 mixed-breed dogs., Procedure: Dogs were fed a 31.4% protein (dry weight), meat-based diet for 21 days, and urine samples were collected on day 22. Urine samples were preserved, using combinations of dilution and alkalinization, and divided into 1-ml aliquots for storage at -20 C for 1 to 12 weeks. Urine uric acid concentrations were measured, using high-performance liquid chromatography, on day of collection (baseline), and after 1, 2, 4, 8, and 12 weeks., Results: Alkalinization did not have a significant effect on reproducibility of measurements of uric acid concentrations in urine; however, dilution did have a significant effect. Compared with baseline, uric acid concentrations in urine samples collected from dogs with ammonium urate uroliths and Beagles and diluted 1:10 or 1:20 with deionized water were not different after storage for 1 to 12 weeks. Uric acid concentrations in urine samples collected from mixed-breed dogs did not differ from baseline values during the 12-week storage period whether samples were undiluted or were diluted 1:10 or 1:20 with deionized water., Conclusions: Measurements of uric acid concentration are most reproducible in canine urine samples stored at -20 C for 1 to 12 weeks when samples are diluted 1:20 with deionized water., Clinical Relevance: To ensure reproducibility of measurements of uric acid concentration in urine samples collected from dogs affected with urate uroliths, urine should be diluted 1:20 with deionized water. Alkalinization is not necessary, and is not recommended because of the additional step in processing and its potential to interfere with measurement of other urinary analytes.

Paired ureters, urinary bladder, and urethra constitute the lower urinary tract. Oblique passage of ureters through the bladder wall results in compression of the distal ureter to preclude urine reflux. Ureters are anchored by longitudinal ureteral musculature that outlines the bladder trigone and extends into dorsal submucosa of the urethra as urethral crest. The urinary bladder can be divided into apex, body, and neck. The male urethra has penile and pelvic components, the latter is divisible into preprostatic, prostatic, and postprostatic regions. The muscle coat of the bladder-urethra forms three functional entities in craniocaudal series. These are the detrusor muscle (to effect voiding), internal urethral sphincter (smooth muscle for generating tonic resistance), and external urethral sphincter (striated urethralis m. for phasic and voluntary continence). The vesical neck is a transition region. It is part of the internal urethral sphincter by virtue of its histology and innervation, but it contains detrusor fascicles that pull it open during micturition. Viscous accommodation plus sympathetic reflex inhibition of the vesical wall allows the urinary bladder to greatly expand in volume with minimal increase of intravesical pressure, within limits. At low volumes continence can be maintained by passive resistive elements of the urethral outlet. As volume increases, sympathetic reflex activity is necessary for continence. The striated external urethral sphincter is reflexly contracted to counter abrupt elevations of intravesical pressure and to maintain continence voluntarily. The pelvic plexus conveys sympathetic and parasympathetic innervation to the urinary tract. The pudendal nerve supplies the urethra and urethralis muscle. Ureters are largely independent of innervation. Internal and external urethral sphincters are activated by spinal reflexes, sympathetic and somatic reflexes, respectively. Normal micturition (sustained detrusor contraction and sphincter inhibition) is a brainstem-driven reflex, involving a spino-bulbo-spinal pathway and a pontine micturition center that switches from urine storage to micturition. All of the reflexes depend on neural activity in tension mechanoreceptors of the bladder wall and sacral afferent fibers.

Both ovaries from 88 bovine fetuses in the fifth month or later of gestation were studied histologically to determine the prevalence, origin, and time of appearance of atretic corpora lutea (ACL). Ovaries from 36 (41%) fetuses had ACL; fetuses < 6 months of gestation did not have ACL. Six fetuses had more than 25 ACL, but there was no apparent relationship between fetal age and number of ACL. Formation of ACL involved disintegration of the stratum granulosum of secondary follicles, concomitant with proliferation and invasion by vascularized elements of the theca. Fully developed ACL consisted of a large primary oocyte surrounded by a prominent zona pellucida and encased in a well-vascularized, largely thecal, fibrocellular wall. They measured approximately 0.5 to 1.0 mm in diameter. Empty, collapsed zona pellucidas were seen in many of the degenerating ACL.

The action of perchlorate (ClO4-), an agonist of the voltage sensor in excitation-contraction (EC) coupling, has been examined using bundles of intact muscle cells, isolated membrane vesicles [sarcoplasmic reticulum (SR) and transverse tubule (TT)], and cultured myotubes. The effect of ClO4- on mechanical parameters was investigated in isolated murine limb muscles. The presence of ClO4- (5 or 10 mM) greatly increased twitch tension ( > 250%), slightly enhanced tetanic tension, and increased K contracture tension. K contracture thresholds of extensor digitorum longus (EDL, 40 mM K+) and soleus (30 mM K+) muscles were not altered by ClO4-. However, in whole cell patch clamp studies of mouse myotubes, contractile activation was shifted by approximately -10 mV by 10 mM ClO4-. To further define the site of alteration of EC coupling by ClO4-, studies were conducted with isolated porcine SR and TT vesicles and with cultured mouse myotubes. The rate constant of Ca-induced 45Ca release from SR vesicles was significantly increased by ClO4-. However, neither the affinity nor level of [3H]PN200-110 binding to TT vesicles was significantly affected by ClO4- concentrations that increased twitch tension. Furthermore, slow plasmalemmal Ca currents of myotubes recorded in the whole cell patch-clamp mode were enhanced by 10 mM ClO4-, and the current-voltage relationship was shifted approximately -7mV. Thus, in enhancing EC coupling in mammalian muscle, ClO4- may act at multiple sites including the SR Ca release channel and the TT Ca channel-voltage sensor.

In a prospective study, 141 cats with hematuria, dysuria, urethral obstruction, or combinations of these signs were evaluated by contemporary diagnostic methods and compared with 26 clinically normal cats (controls). Specific diagnosis was established in 45% (64/141) of cats affected with lower urinary tract disease (LUTD). Crystalline matrix plug-induced urethral obstruction was diagnosed in 21% (30/141) of affected cats, uroliths were identified in 21% (30/141) of affected cats, uroliths with concomitant bacterial urinary tract infection (UTI) were identified in less than 2% (2/141) of affected cats, and bacterial UTI alone was identified in less than 2% (2/141) of cats with LUTD. Viruses, mycoplasmas, and ureaplasmas were not isolated from urine samples collected from affected or control cats. Bovine herpesvirus 4 (BHV-4)-neutralizing antibodies were not detected in any serum sample obtained from cats with LUTD or from control cats. In contrast, BHV-4 antibodies were detected by an indirect immunofluorescent antibody (IFA) test in sera obtained from 31% (44/141) of cats with LUTD and 23% (6/26) of control cats. The prevalence of positive BHV-4 IFA test results in affected cats was not significantly different from that observed in control cats. Significant association was not apparent between positive BHV-4 IFA test results and clinical diagnosis, abnormal laboratory findings, or cat age. However, the number of male cats with BHV-4 IFA titer was significantly (P less than 0.02, chi 2 test) greater than that of female cats. Detection of BHV-4 antibodies in approximately 30% of affected and control cats indicates prior virus exposure. Further investigations are warranted to clarify the specific role of BHV-4 in cats with naturally acquired LUTD.

The ultrastructural changes of typical lesions in canine globoid cell leukodystrophy (GLD) have been studied. The globoid cells were located in the cerebral parenchyma as well as in the perivascular Virchow--Robin space. Features suggestive of a passage of the globoid cells from the cerebral parenchyma to the Virchow--Robin space were also observed through the interruptions in the basal lamina. The globoid cells had numerous thin pseudopods and contained various cytoplasmic inclusions which have been described previously. Detailed studies of these inclusions suggest that they represented aggregates of filamentous or linear sub-unit structures. Typical oligodendroglial cells were found on only a few occasions. Both globoid cells and oligodendroglia contained myelin debris, dense bodies and honey-comb like inclusions composed of numerous small myelin figures. In a few instances, crystalline polygonal inclusions identical to those found in the globoid cells, were found in the cytoplasm of the cells which were, with reasonable certainty, identifiable as oligodendroglia. In less affected areas where myelin was still present, degenerating oligodendroglia, with or without recognizable inclusions, were frequently encountered. Astrocytes and endothelial cells contained concentric lamellar inclusions and dense bodies but did not contain the tubular inclusions as seen in globoid cells. The possible significance of the ultrastructural features in regard to the pathogenesis of the GLD have been discussed.

Urinary bladders and urethrae were collected from six adult and two juvenile female dogs. Five urethral regions and the neck and body of the bladder were sampled. Volume fractions for connective tissue including elastic fibers, smooth and striated muscle, and epithelium were obtained by projecting section images onto an array of points and computing the number of points overlying a tissue constituent per total points overlying the tissue section. Smooth muscle occupied approximately half the volume of the bladder wall, one-third the volume of the vesical neck, and one-fourth the volume of the proximal urethra. Striated muscle was present in the distal half of the urethra, where the total muscle coat occupied about one-third of the urethral wall volume. Smooth muscle was practically absent in the terminal urethra, where the striated urethralis muscle encircles urethra and vagina in common. Epithelial area and lumen perimeter were not significantly different along the length of the urethra except that urethral epithelium was significantly thicker adjacent to the vesical neck. In terms of histological proportions, the vesical neck was intermediate between the body of the bladder and the proximal urethra.

Lesion distribution in the spinal cord was investigated by sampling an average of 26 spinal cord segments in each of ten dogs severely affected by canine globoid leukodystrophy (GLD). GLD lesions were quantified by subdividing spinal white matter into small unit areas and judging the quartile extent of lesion involvement for each unit area. Along the length of the spinal cord, lesions declined from cranial to caudal, decreasing precipitously in the midlumbar region. The lumbosacral region had the least amount of lesion, and, based on lesion per unit area, the thoracic region was most severely involved. The dorsal funiculus had the greatest concentration and the least dispersion of lesion generally amoung the three funiculi. White matter at the periphery of the spinal cord was involved earlier and more severely than white matter adjacent to gray matter. Amount of lesion per spinal cord could be estimated adequately by sampling one segment from each of five regions. Dogs could be divided into two groups based on rate of lesion development. Clinical signs did not correlate closely with total amount of lesion per spinal cord. Of the total amount of variability among dogs in amount of spinal pathologic involvement, 78% could be accounted for by a mathematical model expressing spinal cord pathologic involvement as a quadratic function of age at onset and duration of the clinical syndrome.

In an investigation of canine globoid leukodystrophy, cerebroside beta-galactosidase activities were assayed in 24 brains from neonatal and older dogs and in 90 canine leukocyte pellets from nine samplings. The neonatal brains had significantly less enzyme activity than the brains of older dogs, which indicates a potential complication in making neonatal and fetal enzymatic diagnoses. For leukocytes, heterozygous activities averaged 51 percent and globoid leukodystrophy activities 18 percent of mean enzyme activity of normal leukocytes. Variability of leukocyte enzyme activities among the nine samplings was large, but within each sample, variability per genotypic category was moderate. A statistical model was developed to facilitate enzyme diagnosis in the dog and, by implication, in human globoid leukodystrophy and other sphingolipidoses.

Lumbar and sacral afferent axons in the submucosa of the urinary bladder were recognized by degeneration in seven cats subjected to spinal ganglionectomies. Of 2,935 observed terminating axon profiles, 145 were found degenerating. Lumber afferent axons were 3.7 times more numerous than sacral afferent axons in the submucosa, a reversal of the ratio reported for the muscle coat of the bladder. Sacral afferent axons were evenly distributed to different regions of the bladder, but lumbar afferents were concentrated in the bladder neck. Apparent afferent endings in the submucosa of the urinary bladder were principally free nerve endings. Synaptic vesicles were found in 57% of observed terminating axon profiles. The bladder neck had more terminating axon profiles of all kinds than other regions of the urinary bladder.

The anatomical distribution and volume fractions of pancreatic A cells (glucagon), B cells (insulin) and D cells (somatostatin) were evaluated by an immunoperoxidase technique in 6 diabetic cats, 6 normoglycaemic glucose-intolerant cats and 6 normal control cats. Islets lacking A cells were observed in some sections from the right lobe of the pancreas which correlated with a significantly lower A cell volume fraction in the right pancreatic lobe. Endocrine cell volume fractions in normoglycaemic glucose-intolerant cats were not significantly different from controls. Thus, a reduction in B cell volume fraction was not necessary for the occurrence of impaired glucose tolerance in these cats. However, the reduction of B cell volume fraction in the 2 normoglycaemic glucose-intolerant cats with insular amyloidosis may in part explain the more severely impaired glucose tolerance previously observed in these cats. Insular amyloidosis in our feline diabetics, as in human type II diabetics, was associated with a significant decrease in A and B cell volume fractions. In both human type II and feline diabetes mellitus, however, the reduction in B cell mass does not appear sufficient alone to lead to diabetes mellitus. Therefore, amyloid replacement of functional endocrine cells does not appear to be the primary diabetogenic event in feline diabetes mellitus, but may contribute to progression of the condition due to loss of functional B cell reserves. We thus postulate that a B cell defect precedes deposition of islet amyloid and that these amyloid deposits may thus provide an important biochemical clue to specific B cell derangements occurring in adult-onset diabetics.

The distribution of serotonin-like immunoreactivity in five regions of the rodent midbrain periaqueductal gray (PAG) was studied by using light and electron microscopic immunohistochemistry in combination with quantitative analysis. Light microscopic analysis revealed the presence of serotonin-like immunoreactive cell bodies located in the ventrolateral and ventromedial regions of the caudal PAG and serotonin-like immunoreactive processes throughout the PAG. Ultrastructural analysis showed dendritic profiles that stained positively for serotonin primarily in ventral regions, although an occasional profile was seen dorsally. Numerous synaptic contacts between unstained axon terminals and ventral dendritic profiles were seen. Axonal profiles that contained reaction product were identified throughout the PAG, but were rarely observed to make any type of specialized contact. Ultrastructural quantification of serotonin-like immunoreactive processes indicated that the highest volume fraction of serotonin immunoreactivity occurred caudoventrally where stained processes constituted 2.6% of the neuropil volume. Rostroventrally stained processes constituted only 0.14% of the neuropil volume at the level of the posterior commissure. By contrast the amount of serotonin-like immunoreactivity found dorsally remained relatively constant at all rostrocaudal levels. Analysis of serotonin staining among PAG regions demonstrated the lowest overall volume fraction in the dorsal region and the highest overall volume fraction in the ventromedial region. No significant differences were observed between medial and lateral regions. A comparison of the results of light microscopic quantitative analysis of serotoninergic processes with electron microscopic quantitative analysis indicated that both techniques produce comparable results.

Two control dogs and 2 dogs that had globoid cell leukodystrophy (GLD) were studied to document vascular alterations associated with the leukodystrophic lesion. Spinal white matter was sampled by transverse and frontal planes of section from dorsal and ventral halves of the lateral funiculus of five spinal segments. Vessel profiles were classified as capillaries or larger vessels. GLD lesion was associated with an increase in capillary mean diameter. Vascular density, estimated by profiles per area, was compared in affected and control tissues. Capillary density was not significantly different, but the density of larger vessels was increased in proportion to the extent of GLD lesion. The increased density is presumed to be the result of lengthening or proliferation of vessels which had normal density prior to lesion formation.

Maximal kidney dimensions from serial ultrasonograms were measured in 10 healthy cats. Because clinical ultrasonographic examination is often performed in conjunction with excretory urography, the effect of radiographic contrast medium-induced diuresis on dimensional change also was evaluated. Although a slight, statistically significant increase in size was observed (compared with kidneys scanned without contrast medium), this increase could not be detected on the basis of visual image evaluation alone.

Furazolidone (FZ) at a dose of 700 ppm was fed to turkey poults 2-5 weeks posthatch. At 3, 4, and 5 weeks of age, seven poults each were sacrificed from control and FZ-fed groups. A section of ventricular tissue 1 mm thick was excised from the heart distal to the base at a level one-fourth of the distance between the base and apex. Parameters estimated from tracings of each section were area and circumference of both right and left ventricular lumen profile, area and circumference of entire heart profile, area of right ventricular free wall profile, area of left ventricular and septal wall profile, and area of entire heart muscle profile. A major finding was a sequential increase in the area of the ventricular lumina in the FZ-fed poults. Differences between the control and FZ-fed poults were statistically significant for the right lumen profile at 3 and 5 weeks of age and for the left lumen profile at 4 and 5 weeks of age. The area of the heart muscle profile was decreased in FZ-fed poults, but this difference was statistically significant only at 4 weeks of age. Data suggest that the pathogenesis of FZ-induced cardiomyopathy involves a dilation of ventricular lumina resulting in increased intraventricular blood volume and altered ECG patterns. Relationships between gross morphology and ECGs may be seen only in terminal cases of several weeks duration. This explains the inability to correlate ECGs with gross morphologic changes in all poults observed at necropsy.

Urinary bladders and pelvic urethrae were collected from six adult and two juvenile male dogs. Within two vesical and six urethral sampling regions, volume densities were estimated for smooth and striated muscle, connective tissue and elastic fibers, stratum cavernosum, luminal epithelium, and prostate. The neck had significantly less smooth muscle and more connective tissue than the body of the bladder. In the prostatic urethra, smooth muscle was associated principally with trabeculae surrounding prostate lobules. Smooth muscle was sparse superficially in the prostatic capsule and practically absent in relation to the mid-prostatic urethra. Thus there was no mechanism for active closure of the middle prostatic urethra, and elastic fiber density was correspondingly high in this region. The smooth muscle sphincter needed to maintain urinary continuence and prevent semen reflux was primarily the vesical neck. Caudal to the body of the prostate, striated muscle comprised more than 40% of the urethral wall. Juvenile and adult postprostatic urethrae were similar except for a decreased quantity of stratum cavernosum in the pups.

In 29 rats, responses evoked by pelvic and hypogastric nerve stimulation were recorded from postganglionic nerves to bladder and penis (clitoris). Responses to pelvic nerve stimulation had nonsynapsing and synapsing components. The nonsynapsing component was relatively large in main nerve to penis and small in lateral nerve to penis and nerves to bladder. Pelvic nerve fiber synapsing on pelvic ganglion neurons to bladder had a large subliminal fringe, while fibers synapsing on neurons supplying penis (clitoris) had a small subliminal fringe. Recruitment was greater in nerves to bladder and lateral nerve to penis (clitoris) compared to main nerve to penis (clitoris), indicating more synapsing fibers in the former nerves. Almost all hypogastric fibers to bladder were direct. A small subliminal fringe was demonstrated for hypogastric fibers synapsing on neurons supplying penis. No subliminal fringe was evident for the bladder. Pelvic and hypogastric nerve interaction on pelvic ganglion neurons could not be demonstrated with either single shock or tetanic trains of conditioning stimuli. With antidromic stimulation, conduction velocities of afferent fibers in pelvic nerve ranged from 0.15 m per sec to 2.9 m per sec. In hypogastric nerve they ranged from 0.35 m per sec to 2.8 m per sec.

Sub-plasmalemmal linear densities of variable length (0.1 approximately 1.0 mu) were found to be a constant feature of globoid cells in human as well as in canine globoid cell leukodystrophy (GLD). Similar densities were also observed in experimental globoid cells and epithelioid cells in chronic granuloma but not in glial cells. The linear densities always appeared without any relation to basal laminae. These observations together with the other reports of similar structures in lymphoma, fibroma and sarcoidosis suggest that the sub-plasmalemmal density is a structure frequently observed in mesenchymal cells, and may be another supporting feature for possible mesenchymal origin of globoid cells.

The defect causing malignant hyperthermia has been proposed to involve cardiac as well as skeletal muscle. We tested the hypothesis that histomorphometric parameters for ventricular wall from malignant hyperthermia-susceptible swine and dogs were abnormal. Hearts were obtained from: mature dogs, age- and weight-matched young swine (89 +/- 15 days, 30 +/- 3 kg); and market-weight swine (102 +/- 10 kg). Using light microscopy, estimates were made for muscle nuclear dimensions and the volume-fraction of nuclei, sarcoplasm, blood vessels, and interstitial space. Cardiac maturation in both MH and normal swine was accompanied by decreased myocyte volume-fraction due to decreased nuclear volume-fraction and increased interstitial space volume-fraction. Sarcoplasm and vasculature volume-fraction were unchanged after maturation. Nuclear volume-fraction was slightly greater (p less than 0.05) in the right ventricle than the left for malignant hyperthermia and normal swine. Myocyte nuclear dimensions were generally similar among animals. Dogs and the oldest group of swine were not significantly different. Myocytes of all swine contained multiple nuclei, closely spaced in rows of 2 to 12. In contrast, most myocytes of mature dogs apparently contained one or two nuclei. Histomorphometric values were not significantly different between normal and malignant hyperthermia young swine and dogs. However, within the market-weight swine, volume-fraction for malignant hyperthermia myocytes and myocyte nuclei was decreased and interstitial space was increased compared to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Cilia in neonatal canine articular chondrocytes were studied using morphometric techniques and transmission electron microscopy. The cilia in chondrocytes were morphologically similar to cilia in a variety of other cell types. A chondrocytic cilium consisted of a basal body and a ciliary shaft. The cylindrical basal body was 0.21 micron (S.D. = 0.01 micron) in diameter, 0.50 micron (S.D. = 0.03 micron) in length and contained nine microtubular triplets. The ciliary shaft was 0.196 micron (S.D. = 0.02 micron) in diameter and 1.76 micron (S.D. = 0.80 micron) in length. The number of microbtubular doublets in the ciliary shaft varied depending on where along the length of the shaft the section was taken. This study demonstrates that on the average the frequency of cilia in neonatal articular chondrocytes, as estimated sterologically, was about one cilium per cell.

The pelvic urethra and bladder of the male cat were examined for comparison with those of the male dog which have been previously studied. Morphometric data were generated and analyzed statistically to provide an objective basis for comparing regions and species. Tissue quantities in the body of the bladder were significantly different from the vesical neck. The vesical neck of the cat was significantly different from the canine vesical neck. The smooth muscle sphincter in the cat was better developed than in the dog, and the cat had longitudinal smooth muscle arranged to actively open the sphincter. The feline urethra had relatively more elastic fibers and less stratum cavernosum than the canine urethra. Since canine and feline urethrae are structurally different, physiological interpretations based on one of the species should not be applied indiscriminantly to the other.

The distribution of muscarinic cholinergic receptors within the rat deep cerebellar nuclei was analyzed using in vitro receptor binding of [3H]quinuclidinylbenzilate (QNB) in conjunction with autoradiography. The highest density of QNB binding sites occurred in the lateral cerebellar (dentate) nucleus. Interpositus nuclei displayed an intermediate density of muscarinic cholinergic binding sites with the posterior interpositus nucleus demonstrating higher binding than the anterior nucleus. The fastigial (medial) cerebellar nucleus exhibited the lowest levels of QNB binding among the four cerebellar nuclei. These results indicate that muscarinic cholinergic receptors are present in the deep cerebellar nuclei and that differences in receptor density occur among the four nuclear groups.

Tissues composing the lower urinary tract of the female cat were discribed and analyzed morphometrically. Statistical comparisons were made with the female dog using previously obtained canine morphometric data. Despite a superficial similarity, the cat differs from the dog in having a significant component of longitudinally oriented urethral smooth muscle and appreciably less striated urethral sphincter. It is suggested that the cat requires an active mechanism for overcoming continence due to an inherently smaller urethral lumen, compared to the dog. The implication of our morphometric findings is that urethral mechanics are different for the female cat and dog.

Capillary density and capillary orientation in canine spinal cords were estimated by calculating actual lengths, surfaces, and volumes of capillary segments in tissue sections. Transverse, sagittal, and frontal section planes were samples from dorsal, ventral, and lateral funiculi and from dorsal and ventral gray horns of spinal segments C3, T6, and L3 from three dogs. Capillaries were defined as vessels less than 10 micrometer in diameter. Electron microscopy of 104 such vessels revealed no muscle coat but collagen fibrils between endothelium and astrocyte process in 68% of the white matter capillaries and 16% of those in gray matter. Capillary diameter was significantly different among regions in some cases, but consistent patterns of variation were not found. Capillary density was four to five times greater in gray matter than in white matter. Capillary density differed significantly among the same-size dogs, but within dogs, density was similar among segments and within gray matter and white matter regions. In 62% of the transverse sections, capillary orientation was always along the craniocaudal axis of the spinal cord. The craniocaudal orientation was significant in 96% of the white matter sections and 78% of the gray sections, and in 97% of the cervical and thoracic sections but only 73% of the lumbar sagittal and frontal sections. Because capillary orientation is neither isotropic nor regular, unbiased, low-variance estimates of capillary density cannot be expected without resorting to excessive sampling. An efficient method of quantifying spinal capillaries for comparative purposes by counting number of profiles per unit area is recommended.

A possible relationship between muscle cell injury or deterioration and enhanced halothane sensitivity was studied by monitoring mechanical responses of skeletal muscles from normal pigs and pigs susceptible to malignant hyperthermia (MH). Increased time postbiopsy and decreased maximum control tetanic tension both correlated significantly with enhanced sensitivity to halothane. In both normal and MH-susceptible (MHS) muscles, greater halothane sensitivity was observed in cut cell than in intact cell bundles and in low tetanic tension as compared to high tension preparations. Subsequent to halothane exposure, twitches of high tension (greater than or equal 1.75 kg . cm-2) intact bundles of both normal and MHS muscles were potentiated. Tetani of normal intact bundles were not altered, whereas those of MHS bundles were depressed after halothane exposure. Control twitch-to-tetanus ratios (twitch ratios) were higher in MHS (0.23) than in normal (0.12) intact bundles. According to discriminant analysis, the best distinction between normal and MHS muscles, either cut or intact, was obtained by comparing halothane-induced changes in tetanic tension and control twitch ratios.

Acetohydroxamic acid (AHA), a potent urease inhibitor used for treatment of infection-induced struvite urolithiasis, was teratogenic after administration of 25 mg of AHA/kg of body weight/day orally to 5 clinically normal Beagles from the onset of proestrus until parturition. Thirty pups exposed to AHA in utero developed anomalies of the skeletal system, heart, and ventral midline. Cardiac anomalies included atrial septal defects (20%), ventricular septal defects (3%), and atrial and ventricular septal defects (3%). Skeletal anomalies included coccygeal hemivertebrae and fused coccygeal vertebrae (50%), supernumerary vertebrae (67%), supernumerary ribs (50%), duplicated sternebrae (3%), and lumbar hemivertebrae (3%). Defects of the ventral midline of the abdominal wall occurred in 20% of AHA-exposed pups. Other abnormalities included retarded growth, high neonatal mortality, and a decreased number of circulating RBC, compared with those in 30 control pups born to 5 Beagles given a placebo. Adverse effects of AHA in pregnant Beagles were limited to morphologic alterations (Howell-Jolly bodies, spherocytes, and target cells) in a small number of circulating RBC. Slight neutrophilic leukocytosis and monocytosis occurred between 0 and 30 days of pregnancy in dogs given AHA, compared with those in controls. Seemingly, AHA did not influence fertility, conception rate, or length of gestation.

Gal et al. ((1977) Clin. Chim. Acta 77, 53-59) reported the use of a new synthetic substrate, 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside for the diagnosis of human globoid cell leukodystrophy. Assay of beta-galactosidase in brain homogenates from normal, carrier, and globoid cell leukodystrophy-affected dogs utilizing this new substrate demonstrated overlapping activities. Instead of reflecting specific D-galactosyl-N-acylsphingosine galactohydrolase (EC 3.2.1.46), the 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside beta-galactosidase activity in canine brain is highly correlated with nonspecific 4-methylumbelliferyl beta-galactosidase. Optimization of the 2-hexadecanoyl-amino-4-nitrophenyl-beta-D-galactopyranoside assay system for canine brain and the use of varying concentrations of taurocholate or taurodeoxycholate in the assay mixture did not alter the lack of specificity. These results indicate a significant difference in the nature of the underlying defect in galactosylceramide beta-galactosidase in canine globoid cell leukodystrophy compared to human globoid cell leukodystrophy.

The role of chondroclasts in the pathogenesis of Fusarium roseum-induced tibial dyschondroplasia (TD) was examined in a histomorphometric study. TD developed rapidly in broiler chickens placed at 1 day of age on rations containing either 3% (Experiment 1) or 2% (Experiment 2) F roseum cultures. In Experiment 1 the frequency of TD in birds killed at 4 weeks of age was 90%. In Experiment 2, birds were killed at intervals from 4 days until 4 weeks of age. By 1 week of age, 70% of birds examined had characteristic accumulations of prehypertrophic cartilage at the proximal tibial physis, and the frequency of TD in 4-week-old birds was 80%. Sections of hypertrophic cartilage from F roseum-fed and control birds from both experiments were examined for determination of the volume density of chondroclasts along the vascular channel boundary. Chondroclast density was consistently lower in F roseum-fed than in control birds, but the difference was significant only at 4 weeks of age. The fact that gross lesions were evident before a significant decrease in chondroclast density occurred indicates that a decrease in the density of chondroclasts was not an essential factor in the accumulation of cartilage characteristic of TD.

The calculolytic effect of a diet designed to reduce the urine concentration of urea, P, and Mg was evaluated in female Beagles with induced urease-positive urinary tract infections and struvite urolithiasis and in female Beagles with induced sterile struvite urolithiasis. The reduced-protein calculolytic diet induced urolith dissolution in 5 of 6 infected dogs with struvite urolithiasis in 2 to 5 months (means = 14.4 weeks). At the end of 6 months, uroliths in comparable control dogs fed a maintenance diet were 5 times larger and 14 times heavier than at the beginning of the study. The calculolytic diet induced urolith dissolution in 6 of 6 noninfected dogs with struvite uroliths in 2 to 4 weeks (means = 3.3 weeks). Four uroliths in noninfected dogs fed the maintenance diet dissolved over a period of 2 to 5 months (means = 14 weeks). Urolith dissolution in dogs fed the calculolytic diet was associated with diet-induced diuresis, reduction in urine pH, reduction in urine concentration of urea ammonia, P, and Mg, and increase in urine titratable acidity. Consumption of the calculolytic diet was also associated with significant (P = less than 0.01) reduction in the serum concentration of urea and albumin and a significant (P = less than 0.01) increase in serum hepatic alkaline phosphatase activity. Concomitant occurrence of hydropic degeneration of hepatocytes indicated that these biochemical and morphologic changes were associated with dietary protein restriction.