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Biomedical subjects

G V Ling

Publications and source records attributed to G V Ling.

At least 19 recordsLinked to original sources

Exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross.

Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are known to be caused by the silencing of the urate oxidase (uox) gene in humans and higher primates, the molecular basis for the Dalmatian defect is unknown. Transplantation studies show that the organ responsible for the Dalmatian phenotype is the liver, which is where urate oxidase is exclusively expressed and uric acid is converted into allantoin. We cloned and sequenced the canine uox cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No change in cDNA sequence was identified. A Dalmatian x pointer backcross family was used to track the segregation of microsatellite markers surrounding the urate oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on the cDNA sequence identity and negative LOD scores.

Animals↗

Ultrastructure of selected calcium oxalate-containing urinary calculi from dogs.

OBJECTIVE: To elucidate the ultrastructural details of calcium oxalate-containing urinary calculi from dogs. Sample Population-38 specimens selected from a collection of 8,297 oxalate-containing urinary calculi from dogs: 22 specimens composed of calcium oxalate (calcium oxalate monohydrate [COM], calcium oxalate dihydrate [COD], or COM and COD) and 16 specimens composed of calcium oxalate with amorphous calcium phosphate. PROCEDURE: Analyses of specimens included use of plain, reflected, and polarized light microscopy, X-ray diffractometry, scanning electron microscopy (SEM) with backscattered electron (BSE) imagery, and electron microprobe analysis. RESULTS: Four texture types were observed in calcium oxalate calculi; 4 texture types of calcium oxalate-calcium phosphate-mixed calculi were recognized. Texture types were delineated through differences in calcium oxalate crystal sizes, which were affected by urine supersaturation and abundance of crystal nucleation sites. Segregation of calcium oxalate from calcium phosphate indicated they do not precipitate under the same conditions. Deposition of calcium phosphate between calcium oxalate crystals decreased the volume of pore spaces within calculi. Porosity was observed along boundaries between COM and COD. Minute pores increased the surface area of calculi exposed to urine, and this increase in liquid-solid interface promotes interaction of crystals with the surrounding urine. CONCLUSIONS AND CLINICAL RELEVANCE: Calcium oxalate urolithiasis is of major concern, because it is often a recurrent disease among dogs, principally treated by surgical removal of calculi, with few effective dissolution strategies. Understanding the ultrastructure and mineralogic content of calcium oxalate and its association with amorphous calcium phosphate is a step toward the solution of this increasingly important medical problem.

Animals↗

Urolithiasis in dogs V: regional comparisons of breed, age, sex, anatomic location, and mineral type of calculus.

OBJECTIVE: To determine extent and nature of regional differences in distribution of canine urinary calculi. SAMPLE POPULATION: 13,552 calculus specimens: 7,056 (52.1%) from females, 6,492 (47.9%) from males, and 4 from dogs of unrecorded sex. Procedure Records were used to compile information from all specimens submitted between July 1981 and December 1995. Results from mixed-breed and various breeds of stone-forming dogs were analyzed. Interrelations of breed, sex, and age of dogs, and anatomic location and mineral composition of specimens were analyzed and compared for 6 US geographic regions. RESULTS: Struvite-, apatite-, and urate-containing calculi were reported significantly most often from female dogs of the Mountain/Pacific region. Oxalate-, silica-, and brushite-containing calculi were reported significantly most often from male dogs in the New England/mid-Atlantic (NEMA) region. Cystine-containing calculi were reported most frequently from the NEMA and South Central (SC) regions. Dogs from the NEMA region were oldest in average age at diagnosis. Significant regional differences in distribution were found for several breeds. Sex distribution of renal calculi in 11 breeds of dogs (Lhasa Apso, Yorkshire Terrier, Shih Tzu, Basset Hound, Pug, Mastiff, Bichon Frise, Doberman Pinscher, Dalmatian, English Bulldog, and Pekingese) reported to be at high risk of renal lithiasis differed among the 6 geographic regions. Renal and ureteral calculi were reported significantly most often from dogs in the South Atlantic region, and bladder and urethral calculi were reported most often from dogs in the SC region. CONCLUSIONS: Wide regional differences exist in distribution of stone-forming dogs by sex, average age at diagnosis, breed, and minerals contained within and anatomic location of calculi.

Age Factors↗

Urolithiasis in dogs. I: Mineral prevalence and interrelations of mineral composition, age, and sex.

OBJECTIVE: To compile and statistically analyze selected data from a large number of canine urinary calculi. SAMPLE POPULATION: 11,000 specimens: 5,781 from female dogs, 5,215 from male dogs, and 4 from dogs of unrecorded sex. PROCEDURE: Records were used to compile information from all canine calculi analyzed between July 1981 and January 1994. Interrelations of mineral composition, location of specimens within the urinary tract, age and sex of affected dogs, and number of previous episodes of urolithiasis were determined. RESULTS: Approximately 70% of the specimens were from a first episode of urolithiasis. Calculi were located in the urinary bladder of 93.1% of females and 79.0% of males, and in the upper urinary tract of 4% of females and 2% of males. Calculi were found in multiple sites in 23.1% of males and 5.2% of females. Significantly higher proportions of struvite, apatite, and urate were found in uroliths from females; oxalate, cystine, silica, and brushite were significantly more prevalent in males. Sixty-one percent of specimens from males and 29% from females were composed of a single mineral substance. The most common mineral combination of 2 or more minerals included struvite and apatite. An additional 67 specimens from male dogs and 49 from female dogs contained other mineral combinations. In 48% of specimens from males and nearly 62% of specimens from females, the minerals formed several distinct layers of differing composition. CONCLUSIONS: Male and female dogs from urinary calculi composed of 1 or more of several distinct minerals. Prevalence of canine uroliths differs between ages and between the sexes. Many specimens contain complex layering of minerals; most specimens were found in the urinary bladder. CLINICAL RELEVANCE: Sex and age of dogs, mineral types of likely calculi in males versus females, and their anatomic location are important considerations for clinicians when evaluating risk in dogs with urolithiasis.

Age Distribution↗

Urolithiasis in dogs. II: Breed prevalence, and interrelations of breed, sex, age, and mineral composition.

OBJECTIVE: To analyze selected breed-related data for canine urinary calculi. SAMPLE POPULATION: 11,000 specimens: 5,781 from female dogs, 5,215 from males, and 4 from dogs of unrecorded sex. PROCEDURE: Information was compiled for all canine urinary calculi submitted between July 1981 and January 1994. Results for a mixed-breed group and 26 of the most common breeds of stone-forming dogs were analyzed. Interrelations of breed, sex, and age of affected dogs and mineral composition of the specimens were determined. RESULTS: Prevalence of 5 specific mineral types was significantly correlated between the sexes of 27 common breed groups: struvite, calcium phosphate (apatite), calcium oxalate, brushite, and urate. Struvite-containing calculi were seen in high proportions in both sexes of 7 breeds, and in low proportions in both sexes of 7 other breeds. Male and female Lhasa Apsos, Cairn Terriers, and 5 other breeds had high proportions of oxalate-containing calculi; values in males were substantially higher. Low numbers of oxalate-containing calculi were seen in both sexes of 7 breeds; Dalmatians had the lowest numbers. Males and females of 6 breeds had high numbers of urate-containing calculi, Dalmatians and English Bulldogs had the highest numbers. Low amounts of urate were found in calculi from males and females of 6 breeds, Samoyeds had the lowest numbers. Highest proportions of cystine-containing calculi were seen in male Dachshunds, English Bulldogs, and Chihuahuas. Males of 8 breeds had no specimens that contained cystine; only 2 such specimens were obtained from females. CONCLUSIONS: Prevalence of uroliths differs among breed, age, and sex of affected dogs. CLINICAL RELEVANCE: Breed, sex, and age of dogs; mineral types of calculi in males versus females; and their anatomic location within the tract are important considerations for clinicians when evaluating risk in dogs with urolithiasis and in identifying areas that need further in-depth applied or clinical investigation, or both.

Age Distribution↗

Urolithiasis in dogs. III: Prevalence of urinary tract infection and interrelations of infection, age, sex, and mineral composition.

OBJECTIVE: To compile and statistically analyze selected data from a large number of canine urinary calculus specimens that were subjected to quantitative, layer-by-layer mineral analysis. SAMPLE POPULATION: 11,000 canine urinary calculus specimens. 5,781 from female dogs, 5,215 from male dogs, and 4 from dogs of unrecorded sex. PROCEDURE: Records of the Urinary Stone Analysis Laboratory, School of Veterinary Medicine, University of California were used to compile information regarding all canine urinary calculus specimens submitted for analysis between July 1981 and January 1994. Interrelations of sex and age of the affected dogs, mineral composition of the specimens, and associated urinary tract infections were analyzed statistically. RESULTS: Urolithiasis was associated with growth of bacteria isolated from urine or calculi, or both, in 65% of females and nearly 44% of males. Staphylococcus intermedius was isolated most often from either sex (54% for females, 30% for males). In addition to staphylococci, 22 other bacterial species were isolated from specimens from females, and 17 other bacterial species and 1 species of yeast were isolated from males. A single bacterial species was isolated from 87.6% of cultures from females and from nearly 90% of cultures from males. Among females, nearly 98% of pure cultures of staphylococci were associated with calculi that contained struvite; this was true for 80% of pure cultures of staphylococci from males. CONCLUSIONS AND CLINICAL RELEVANCE: There are wide sex differences in prevalence of urolithiasis- and specific mineral-associated bacterial infections. In several instances, bacterial infections were significantly related to urinary calculus location. These variables should be considered in any evaluation of canine patients that have uroliths.

Age Distribution↗

Urolithiasis in dogs. IV: Survey of interrelations among breed, mineral composition, and anatomic location of calculi, and presence of urinary tract infection.

OBJECTIVE: To compile and analyze selected data from a large number of canine urinary calculus specimens that were subjected to quantitative, layer-by-layer mineral analysis. SAMPLE POPULATION: 11,000 canine urinary calculus specimens: 5,781 from female dogs, 5,215 from male dogs, and 4 from dogs of unrecorded sex. PROCEDURE: Records of the Urinary Stone Analysis Laboratory, School of Veterinary Medicine, University of California were used to compile information regarding urinary calculus specimens from dogs. Records surveyed were of all canine calculi submitted for analysis between July 1981 and January 1994. Results analyzed included those of a mixed-breed group and 26 common breeds of stone-forming dogs. Interrelations of breed, sex, and age of the affected dogs, mineral composition of the specimens, and associated urinary tract infections were analyzed statistically. RESULTS: Proportions of culture-positive specimens were significantly correlated between the sexes (r = 0.494, P = 0.008). Staphylococcus intermedius was isolated most often from either sex, ranging from 36.1% (Basset Hounds) to 67.9% (Pekingese) of cultured specimens from females and 8.7% (Chihuahuas) to 71.4% (Scottish Terriers) of specimens from males. The second most frequently isolated bacterial species, Escherichia coli, ranged from 0% in males of 2 breeds and females of 4 breeds to 25% in Cairn Terrier males and 19.4% in Basset Hound females. Streptococcus spp were the third most frequently isolated bacterial species. Significant correlations between the sexes were found for percentages of calculi located in the urinary bladder (r = 0.490, P = 0.008), and for calculi voided in the urine (r = 0.503, P = 0.006). CONCLUSIONS: Breed and sex differences in prevalence of urolithiasis- and mineral-associated bacterial infections are numerous. Staphylococcus intermedius was the most common isolate from specimens from all but 3 of 54 breed/sex groupings. For either sex, streptococcal infections were significantly related to proportions of calculi passed in the urine.

Age Distribution↗

Pharmacokinetics of allopurinol in Dalmatian dogs.

The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Eight dogs were given allopurinol orally at a dose of 10 mg/kg for seven doses prior to sample collection. After a period of at least two weeks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sample collection. Allopurinol was found to follow first-order absorption and elimination kinetics. In the i.v. kinetic study, the elimination constant (Kel) = 0.31 +/- 0.03 per h, the half-life (t1/2) = 2.22 +/- 0.20 h, the initial concentration (C0) = 5.26 +/- 0.34 micrograms/mL and the specific volume (Vd) = 1.14 +/- 0.07 L/kg. Clearance of allopurinol was estimated to be 0.36 +/- 0.03 L/kg.h. In the oral kinetic study, the absorption rate constant (Kab) = 1.06 +/- 0.13 per h, the elimination rate constant (Kel) = 0.26 +/- 0.01 per h, the absorption half-life (t1/2ab) = 0.66 +/- 0.06 h, and the elimination half-life (t1/2el) = 2.69 +/- 0.14 h. Peak plasma concentrations (Cmax) = 6.43 +/- 0.18 micrograms/mL were obtained within 1 to 3 h (mean time of maximum concentration (Tmax) = 1.9 +/- 0.1 h). The volume of distribution corrected by the fraction of dose absorbed (Vd/F) was estimated to be 1.17 +/- 0.07 L/kg. Good agreement was obtained between mean kinetic parameters in the oral and i.v. studies. There was little variation between individual dogs in the i.v. study, whereas the rate of absorption and elimination of orally administered allopurinol was more varied among individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specify an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with hyperuricosuria; rather, the dose must be titrated to the needs of each dog.

Administration, Oral↗

Ultrastructure of selected struvite-containing urinary calculi from cats.

OBJECTIVE: To elucidate the ultrastructural details of struvite-containing urinary calculi from cats. DESIGN: Specimens studied were inclusive of the range of textures visible during preliminary analysis by use of a stereoscopic dissecting microscope. Textural types, which were used to infer crystal growth conditions, were differentiated with regard to crystal habit, crystal size, growth orientation, and primary porosity. SAMPLE POPULATION: Thirty specimens were selected from a collection of approximately 1,600 feline urinary calculi: 20 of these were composed entirely of struvite, and 10 consisted of struvite and calcium phosphate (apatite). PROCEDURE: Qualitative and quantitative analyses of specimens included use of plain and polarized light microscopy, x-ray diffractometry, scanning electron microscopy with backscattered electron imagery, x-ray fluorescence scans, and electron probe microanalysis. RESULTS: Four textural types were recognized among struvite calculi, whereas 2 textural types of struvite-apatite calculi were described. CONCLUSIONS: The presence of minute, well interconnected primary pores in struvite-containing urinary calculi from cats is an important feature, which may promote possible interaction of calculi with changes in urine composition. CLINICAL RELEVANCE: Primary porosity, which can facilitate interaction between the calculus and changing urine composition, may explain the efficacy of dietary or medicinal manipulations to promote the dissolution of struvite-containing uroliths from this species.

Animals↗

Ultrastructure of selected struvite-containing urinary calculi from dogs.

OBJECTIVE: To elucidate the ultrastructural details of struvite-containing urinary calculi from dogs. SAMPLE POPULATION: 38 specimens were selected from a collection of approximately 13,000 canine urinary calculi: 18 of these were composed entirely of struvite, and 20 consisted of struvite and calcium phosphate (apatite). PROCEDURE: Qualitative and quantitative analyses of specimens included use of plain and polarized light microscopy, x-ray diffractometry, scanning electron microscopy with backscattered electron imagery, x-ray fluorescence scans, and electron microprobe analysis. RESULTS: 4 textural types were recognized among struvite calculi, and 4 textural types of struvite-apatite calculi were described. Evidences of calculus dissolution were described from 4 calculi studied. CONCLUSIONS: The presence of small, well interconnected primary pores in struvite-containing urinary calculi from dogs appears to be a significant factor in determining the possible interaction of calculi with changes in the urine composition. The progress of dissolution from the calculus surface to the calculus interior appears to be largely affected by the primary porosity originally present between crystals forming the calculus framework. Apatite was observed to be more resistant to dissolution than struvite. CLINICAL RELEVANCE: The prevalence of fine concentric laminations having low porosity, and the common occurrence of apatite among struvite-containing urinary calculi from dogs may be 2 reasons why the efficacy of dietary and medicinal manipulations in dissolving urinary calculi is greater among cats than it is among dogs.

Animals↗

Evaluation of factors associated with development of calcium oxalate urolithiasis in cats.

OBJECTIVE: To evaluate dietary and environmental factors as potential risk factors for calcium oxalate urolithiasis in cats. DESIGN: Case-control study. ANIMALS: 84 cats with uroliths composed of at least 90% calcium oxalate and 258 age- and gender-matched control cats. PROCEDURE: Owners of cats with calcium oxalate urolithiasis and control cats were surveyed between November 1990 and August 1992. Owners completed a standard questionnaire administered during a single telephone interview. Data collected included information regarding signalment, environment, urination and defecation, diet, and medical history. RESULTS: Calcium oxalate uroliths tended to develop in middle- to older-aged, domestic shorthair cats of typical weight. A gender predilection was not detected. Factors associated with an increase in the risk of calcium oxalate urolithiasis in cats were feeding urine-acidifying diets, feeding a single brand of cat food without providing additional foods or table scraps, maintaining cats in an indoor-only environment, and being of the Persian breed. CLINICAL IMPLICATIONS: Control of diet and environment may help prevent calcium oxalate urolithiasis.

Age Distribution↗

Ultrastructure and mineral composition of urinary calculi from horses.

Urinary calculi from 17 horses with urolithiasis were examined to study their mineral content and ultrastructure. Among the analytic methods used were X-ray diffractometry, scanning electron microscopy, and electron microprobe analysis. The calculi initially were observed by use of a stereoscopic dissecting microscope and generally were found to have nodular surfaces surrounding a banded or granular-to-chalky interior. Observation by scanning electron microscopy revealed an intricate pattern of irregularly concentric, fine bands and spherules. These had a round, finely banded, globular texture formed by precipitation of ultrafine-grained radiating crystals. The original pore spaces (ie, between spherules, between bands and spherules, or between crystal generations) could be observed as primary porosity. Precipitation and dissolution of these urinary calculi were observed to be spontaneous processes, which can occur simultaneously within an individual calculus. Another prominent feature of the ultrastructure was secondary porosity (spontaneous dissolution) which, in its incipient stages, appeared to be site-selective (ie, some bands appeared to be more susceptible to development of pinpoint porosity). Textures indicative of dissolution were observed not only on the calculus surface, but within the calculus interior as well. Areas that had more advanced stages of dissolution, resulting in increased secondary porosity, also were observed. All 17 samples of the study were found to be composed of calcium carbonate in the form of the mineral calcite, although minor quantities of 2 other polymorphs of calcium carbonate, minerals vaterite and aragonite, also were encountered. Vaterite was observed in 5 of the samples, whereas aragonite was found in 1 sample. Strontium and sulfur were observed as trace elements in 3 of the calculi, whereas magnesium was present in all calculi. Magnesium was observed to substitute for calcium within the calcite crystal lattice in larger quantities than those of strontium or sulfur. Magnesium K alpha X-ray dot maps generated by use of an electron microprobe analyzer indicated that the distribution pattern of magnesium appeared to closely follow layer-by-layer growth of the calculus. Magnesium distribution also appeared to be related to porosity development. In samples where preferential dissolution was observed, the more porous areas had higher magnesium content. Quantitative chemical analyses, using the electron microprobe analyzer, confirmed these observations. Association of the magnesium distribution pattern to the primary growth texture of the calculus indicated that magnesium content of the calculus varied during the formation process. This also indicated that changes in urine chemical analytes may be reflected in composition of the calculi formed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Urolithiasis in Dalmations: 275 cases (1981-1990).

From July 1, 1981 to December 31, 1990 the Urinary Stone Analysis Laboratory, School of Veterinary Medicine, University of California received 292 urinary calculi from 275 Dalmations (14 females, 14 episodes; 261 males, 278 episodes). The mean age of dogs at the time of the first episode of calculus formation was 4.5 years for males and 5.5 years for females. Bacteria were isolated from 22 of 49 calculi (45%). The bacteria were gram-positive with 2 exceptions; coagulase-positive staphylococci accounted for 62.5% of the isolates. Polarized light microscopy was used to determine the mineral content of the calculi. One hundred ninety three calculi were 100% urate; 78 calculi contained > or = 50% urate in 1 or more layers and were classified as mixed urate calculi; 7 calculi contained < 50% urate in all layers; and 14 calculi contained no urate. The secondary minerals most commonly encountered in mixed urate calculi were struvite (77%, 60 of 78 calculi), and oxalate (17%, 13 of 78 calculi). There were 65 struvite-containing calculi, 16 oxalate-containing calculi, 7 apatite-containing calculi, 5 silica-containing calculi, and 1 calculus specimen was composed of 100% cystine. The risk of forming urate-containing calculi was high in Dalmations, whereas the risk of forming calculi containing other minerals was consistently lower in Dalmations than in other breeds. X-ray diffraction and high pressure liquid chromatography were performed on all calculi from dogs known to have been given allopurinol (n = 19).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Cystine-containing urinary calculi in dogs: 102 cases (1981-1989).

One hundred and seven cystine-containing urinary calculi from 1 female and 101 male dogs were analyzed. Cystine-containing calculi accounted for 2% (107 of 5,375) of all canine urinary calculi submitted to the urinary stone analysis laboratory from July 1981 through December 1989. Male dogs that formed cystine calculi were compared with 3 other canine populations to determine whether certain breeds were apparently at increased or decreased risk for cystine calculus formation. In one or more of 3 population comparisons, significantly increased risk of cystine calculus formation was found in Mastiffs, Australian Cattle Dogs, English Bulldogs, Chihuahuas, Bullmastiffs, Newfoundlands, Dachshunds, Basenjis, Australian Shepherd Dogs, Scottish Deerhounds, Staffordshire Terriers, Miniature Pinschers, pitbull terriers, Welsh Corgis, Silky Terriers, and Bichon Frises. Significantly low risk of cystine calculus formation was found in German Shepherd Dogs, Poodles, Schnauzers, and mixed-breed dogs.

Animals↗

Xanthine-containing urinary calculi in dogs given allopurinol.

Clinical features and laboratory findings were evaluated in 10 dogs that formed xanthine-containing urinary calculi during the period that they were given allopurinol (9 to 38 mg/kg of body weight/d). Duration of allopurinol treatment was 5 weeks to 6 years. Of the 10 dogs, 9 (all Dalmatians) had formed uric acid-containing calculi at least once before allopurinol treatment was initiated. It was not possible to recognize xanthine as a crystalline component of the calculi by use of a chemical colorimetric method or by polarized light microscopy. We concluded that the best diagnostic method for recognition of xanthine-containing calculi was high-pressure liquid chromatography because it is quantitative, sensitive, and accurate, and can be conducted on a small amount (1 to 2 mg) of crystalline material.

Allopurinol↗

Comparison of two sample collection methods for quantitative bacteriologic culture of canine prostatic fluid.

Ejaculate, urine, urethral swab specimens, and ultrasonography-guided small-needle prostatic cyst aspiration and/or tissue core biopsy specimens were collected for bacteriologic culture from 25 dogs in which prostatic disease was suspected on the basis of history, clinical signs of disease, or results of physical examination. The prostate gland in each dog was examined ultrasonographically, and the tissue core biopsy specimens were examined histologically and bacteriologically. Two methods were used to assess bacterial prostatitis. In 5 dogs (20%), bacteriologic culture results of paired urethral swab and ejaculate specimens differed from culture results of specimens obtained by needle aspiration of prostatic cyst fluid or tissue core biopsy. The prostate gland in 17 dogs had 1 or more cystic, fluid-filled structures (0.5 to 4.0 cm in diameter). Ultrasonographic appearance of the prostate gland did not have obvious correlation with culture results from dogs of the study. Histologic results of prostatic tissue core biopsy specimens correlated well with culture results.

Animals↗