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Biomedical subjects

G K Smith

Publications and source records attributed to G K Smith.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effect of purine synthesis inhibition on WiDr spheroids in vitro or on WiDr or colon 38 tumors in vivo. Complete growth inhibition but not regression.

Clinical responses for anticancer agents are based upon tumor regression. We have investigated the potential of glycineamide ribonucleotide transformylase (GAR TFase) inhibitors to produce regressions in multiple preclinical models of colon carcinoma. The growth of multicellular tumor spheroids of WiDr human colon carcinoma was inhibited by the GAR TFase inhibitors 5-deazaacyclotetrahydrofolate (5-DACTHF), its 2'-fluoro, 3'-fluoro, 10-deaza, and 10-thia analogs as well as 5,10-dideazatetrahydrofolate, but none of the compounds caused spheroid regressions. By contrast, complete spheroid disruption was observed with exposure to etoposide, m-AMSA (amsacrine), piritrexim, or 2-desamino-2-methyl-10-propargyl-5,8-dideazafolate (DMPDDF). Light microscopy of the spheroids treated with either 5-DACTHF or DMPDDF suggested that the reason for the difference is extensive cell kill throughout the spheroid in the presence of DMPDDF compared with little or no kill, over that found in controls, with 5-DACTHF. Treatment of spheroids with 5-DACTHF in the presence of 1 microM hypoxanthine resulted in no significant reversal of growth inhibition; 50% reversal required 10 microM hypoxanthine. The spheroid studies were extended to in vivo studies examining the effects of 5-DACTHF on established WiDr and colon 38 tumors. The results showed that, in contrast to melphalan, which produced cures and tumor regressions, 5-DACTHF produced reversible growth inhibition with no significant regression of tumors. The results predict that clinical response, typically measured by tumor regression, may be rare following single agent therapy with inhibitors of de novo purine biosynthesis.

Acyltransferases↗
PubMed1994

Destruction of WiDr multicellular tumor spheroids with the novel thymidylate synthase inhibitor 1843U89 at physiological thymidine concentrations.

The activity of a novel thymidylate synthase inhibitor, 1843U89, against WiDr human colon carcinoma multicellular tumor spheroids was investigated. Continuous exposure of the spheroids to 3 nM 1843U89 for 10 days resulted in spheroid disruption, whereas 100 nM methotrexate (MTX) was required for similar effects. Short-term treatment experiments demonstrated that a 3-day exposure to 100 nM 1843U89 caused spheroid disruption 9 days after drug removal. A 4-day exposure to 10 nM 1843U89 caused spheroid disruption 8 days after drug removal. In contrast, treatment with 10 or 100 nM 1843U89 for 6-48 h or treatment with 1 nM 1843U89 for up to 5 days caused only growth delay. Continuous exposure of spheroids to 30 nM 1843U89 in the presence of 0.05-0.3 microM thymidine was as effective in causing spheroid disruption as treatment in the absence of thymidine, but treatment in the presence of 0.7-3.0 microM thymidine caused partial reversal of spheroid disruption. The results of these experiments suggest that 1843U89 should have potent solid tumor activity in humans but should be less effective in mice due to differences in circulating thymidine levels (0.1 vs 1 microM, respectively).

Antineoplastic Agents↗
PubMed1994

The treatment of intracranial lesions with stereotactic radiosurgery.

Stereotactic radiosurgery is a new method of delivering a high dose of megavoltage, ionizing radiation therapy to a localized area in the brain in a single session. A substantial variety of intracranial lesions can be treated with the use of a stereotactic head frame and set up of tertiary collimators on an existing linear accelerator. This state-of-the-art technique has been used since June 1992 at the Robert C. Byrd Health Sciences Center of West Virginia University in Morgantown. Radiosurgery treatment has been well tolerated by all 24 patients treated thus far.

Brain Neoplasms↗
PubMed1994

Analysis of physeal growth in dogs, using biplanar radiography.

Biplanar radiography was used to study normal growth of the left and right radius in 5 Beagles and growth of the left radius alone in 15 additional Beagles. We explored the applicability of this radiographic method in veterinary medicine by measuring the contribution to total radius length from each growth plate. Spherical tantalum markers (0.5 mm) were embedded in the proximal epiphysis, diaphysis, and distal epiphysis of each dog's radius at 10 weeks of age. Simultaneous biplanar radiographic views were obtained every 4 weeks until skeletal maturity was documented. A three-dimensional coordinate system was constructed allowing for measurement of growth (in millimeters). Resolution of the measuring system was 0.074 mm. Mean +/- SEM length of the skeletally mature Beagle's radius, as measured from proximal epiphyseal bead to distal epiphyseal bead, was 95.33 +/- 1.07 mm. The percentage of contribution to the total radius length from the proximal and distal growth plates was 36.76 and 64.73%, respectively, with 95% confidence interval of 2.29%. The percentage of contribution to radius length from the distal radial growth plate increased for each consecutive time segment, with the distal radial physis contributing 61.75% from 10 to 14 weeks of age and increasing to 70.22% from 22 to 26 weeks of age. Significant growth was not observed after 26 weeks of age. The period of most rapid growth was between 10 and 14 weeks of age. Biplanar radiography was accurate and precise in quantifying the relative contribution of the proximal and distal growth plate to radius length in Beagles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives.

Several folate-like thymidylate synthase inhibitors are described in which the pteridine nucleus of the folic acid molecule is replaced by a benzoquinazoline moiety, which in turn is attached to the benzoylglutamate side chain by a sulfonamide link. The most potent compounds had Ki values as low as 2.5 nM against the human enzyme, were good substrates for the cellular reduced folate transport system and for folylpolyglutamate synthetase, and had IC50 values for growth inhibition of tumor cell lines as low as 70 nM.

Glutamates↗
PubMed1993

Joint laxity and its association with hip dysplasia in Labrador retrievers.

A study was done to determine whether radiographic-distraction measurement of coxofemoral joint (hip) laxity at 4 and 8 months of age can serve as a predictor of hip dysplasia in older Labrador Retrievers. The method of Smith, Biery, and Gregor was used for radiologic examination of hips and for evaluation of radiographs. Mean (+/- SEM) distraction laxity (ie, distraction index) for 10 adult disease-free dogs was 0.29 +/- 0.05, whereas a group of 8 dogs with dysplastic hips had mean distraction index of 0.60 +/- 0.10 (P < 0.05). Mean distraction index at 4 months of age for 11 pups of 4 litters from matings between dogs with normal hips was 0.39 +/- 0.07, and was 0.54 +/- 0.04 for 31 pups of 7 litters from matings between dogs with hip dysplasia. The distraction index and, thus, joint laxity at that age was significantly (P = 0.0351) different for the 2 groups. The distraction index at 4 months correlated positively with the distraction index at a later age at necropsy (r = 0.43; P = 0.0289). Distraction index < 0.4 at 4 months of age predicted normal hips in 88% of cases and distraction index > or = 0.4 predicted hip dysplasia in 57% of the dogs. Logistic regression modeling indicated that the odds of a hip being normal decreased with increasing distraction index, and thus, with increasing joint laxity. The logistic regression models provided a reasonable mathematical description of the data. Based on the logistic model of the data, distraction indexes between 0.4 and 0.7 at either 4 or 8 months of age were not associated strongly enough with evidence of disease to be clinically reliable in predicting, on an individual basis, the outcome for dysplastic hip conformation when dogs were older. Index > 0.7 was associated with high probability for developing dysplastic joints and distraction index < 0.4 predicted normal hips with high probability.

Animals↗
PubMed1993

Coxofemoral joint laxity from distraction radiography and its contemporaneous and prospective correlation with laxity, subjective score, and evidence of degenerative joint disease from conventional hip-extended radiography in dogs.

A 3-year prospective study of large-breed dogs (4 months to 3 years of age) was conducted to evaluate the influence of radiographic positioning and age on coxofemoral joint (hip) laxity, subjective hip score, and development of degenerative joint disease (DJD). The dogs (n = 142) were breeder- or client-owned and represented 14 breeds. With dogs under heavy sedation, hips were radiographed in the standard hip-extended position and in the new compression/distraction position at 4, 6, 12, 24, and 36 months of age. The standard hip-extended radiographic view was evaluated by 3 methods: subjective evaluation by a board-certified veterinary radiologist (WHR), according to the standard 7-point Orthopedic Foundation for Animals (OFA) scoring scheme (OFA/WHR); joint laxity quantitation, using the Norberg angle (NA) method; and subjective scoring by a veterinary orthopedic surgeon for radiographic evidence of DJD. The hips in the distraction radiographic view were evaluated for passive hip laxity, as measured by use of a unitless distraction index (DI). Results of the study indicated that at a specific age (4, 6, 12, 24, or 36 months), all methods of hip evaluation correlated with each other at a moderate level (P < 0.05). The strength of contemporaneous correlation tended to increase with age of evaluation. Longitudinally, the between-method correlations were usually significant (P < 0.05), but not at a sufficiently high level to permit reliable between-method prediction. Prospective intraclass (within-method) statistical analysis of the various hip-scoring methods indicated that DI was superior to NA and OFA/WHR in comparability of score over time. The intraclass correlation coefficient ranged from 0.55 to 0.91 for DI in contrast to 0.40 to 0.78 for NA, and 0.06 to 0.39 for OFA/WHR over the age intervals of the study. For reference, the highest Kappa of 0.39 for the subjective OFA/WHR scoring reflected a maximal level of agreement between time intervals, only slightly better than chance. The associated large error questions the predictive use of the 7-point, subjective hip-scoring scheme, particularly prior to the age of 2 years.

Aging↗
PubMed1993

Biomechanical study of the effect of coxofemoral positioning on passive hip joint laxity in dogs.

Ten coxofemoral joints from 5 dog cadavers were used to study the effect of coxofemoral positioning on passive hip laxity. A material test system was used to measure lateral translation when force was between 20 N of compression and 40 N of distraction. Using the orthogonal coordinate system imposed in this study, neutral position was empirically defined at 15 degrees of extension and 10 degrees of abduction, relative to the plane of the pelvis, and no internal or external rotation of the femur. The hips were mounted in a custom-designed jig that allowed 1 rotational degree of freedom (ie, either flexion/extension, adduction/abduction, or internal/external rotation), while holding the other 2 constant. Lateral translation of the hips was tested at 10 degrees intervals from 30 degrees of flexion to 70 degrees of extension, 40 degrees of adduction to 60 degrees of abduction, and 30 degrees of internal rotation to 40 degrees of external rotation. Lateral displacement was maximal at 10 degrees of extension, 20 degrees of abduction, and 10 degrees of external rotation, approximating the neutral coxofemoral position during stance. As the hips were rotated into extreme positions, the amount of lateral displacement occurring with the same applied load decreased significantly to 32.0 to 65.3% of the maximal displacement. Determining the position of the hip associated with maximal passive laxity in vitro is essential to the design of a precise and accurate clinical stress-radiographic method to quantitate joint laxity in dogs. Our results confirm earlier work that passive hip joint laxity is at a maximum with the hip approximately in a neutral weight-bearing position.

Animals↗
PubMed1993

Effects of dietary electrolyte balance on subluxation of the femoral head in growing dogs.

Effects of increased dietary chloride and reduced sodium and potassium ion concentrations on coxofemoral joint conformation, as assessed by radiography, were examined in growing dogs. Dietary electrolyte balance was quantified by dietary anion gap (DAG), defined as Na+ + K+ - Cl- in milli-equivalents per 100 g of food. Diets had anion gap ranging from 8 to 41 mEq/100 g of food. One hundred sixty-seven pups from 27 litters representing 5 breeds were studied during the period of rapid growth. The extent of subluxation of the femoral head was measured on radiographs, using the method of Norberg. On average, less subluxation of the femoral head (P < 0.05) was observed when diets with lower DAG were fed. Differences in DAG balance did not result in different rates of weight gain; therefore, the reduction in coxofemoral joint subluxation attributable to low DAG was unrelated to weight gain. Norberg angles measured at 30 weeks of age were highly correlated with coxofemoral joint status at 2 years of age, as measured by the Swedish diagnostic system and the scoring system of the Orthopedic Foundation for Animals (lrl > or = 0.70, P < 0.0002, n = 24). This diet-related improvement in coxofemoral joint subluxation would be expected, on average, to delay or mitigate the characteristic clinical and radiographic signs of hip dysplasia in growing dogs.

Animals↗
PubMed1992

Effects of limited food consumption on the incidence of hip dysplasia in growing dogs.

Forty-eight 8-week-old Labrador Retrievers were allotted to 2 groups of 24 dogs each; 1 group was fed ad libitum and the other group was given 25% less of the same feed until the dogs were 2 years old. Radiography of the hip joints was done when the dogs were 30, 42, 54, 78, and 104 weeks old. Subluxation was measured by the Norberg angle on radiographs made with the dog in the standard (extended limb) position. Independent of age at which the radiography was done, there was less subluxation of the femoral heads in the limit-fed dogs. Using the Swedish method of hip joint evaluation on the same radiographs, it was found that fewer dogs on limited food intake had signs of hip dysplasia. Radiographs done when dogs were 2 years old, for all the methods used (Norberg angle in standard and frog-limb position, the Orthopedic Foundation for Animals [OFA] score, and the Swedish score), revealed less hip dysplasia (less joint subluxation and less degenerative joint disease) in the limit-fed dogs. Using the OFA method, 7 of the 24 limit-fed dogs and 16 of the 24 ad libitum-fed dogs were diagnosed as having hip dysplasia. Similarly, using the Swedish method, 5 of the 24 limit-fed dogs and 18 of the 24 ad libitum-fed dogs were diagnosed as having hip dysplasia. The food-intake-related differences were significant both for the OFA score and for the Swedish score.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1992

Metabolic effects and kill of human T-cell leukemia by 5-deazaacyclotetrahydrofolate, a specific inhibitor of glycineamide ribonucleotide transformylase.

Metabolic effects and mode of cytotoxicity of 5-deazaacyclotetrahydrofolate (5-DACTHF, BW543U76), a glycineamide ribonucleotide transformylase inhibitor, were studied in MOLT-4 cells, a human T-cell leukemia line. 5-DACTHF inhibits purine synthesis with 50% inhibitory concentration values of 0.5 microM and 0.08 microM following 6- or 24-h exposure to drug, respectively. At 6 h, adenine nucleotide synthesis is preferentially inhibited over guanine nucleotide synthesis. A similar effect was observed with another glycineamide ribonucleotide transformylase inhibitor, 5,10-dideazatetrahydrofolate. GTP was depleted to 40% of control and ATP to 10% of control by 5 microM 5-DACTHF. After a transitory increase, UTP and CTP were depleted to 30% of control. Deoxynucleotides were also depleted by the drug; dCTP was depleted to the greatest extent, followed by dATP, dTTP, and dGTP, respectively. MOLT-4 cell growth was inhibited by 5-DACTHF with a 50% inhibitory concentration of 0.066 microM. Complete reversal was effected by hypoxanthine, and there was no reversal by thymidine. The drug was cytotoxic to MOLT-4 cells in the range 0.25 to 5.0 microM, but a minimum of 48 h was required for trypan blue-staining dead cells to appear. The rate and extent of kill with the thymidylate synthase inhibitor 2-methyl-10-propargyl-5,8-dideazafolate was greater than with 5-DACTHF, which indicates that kill by inhibition of thymidylate synthase is more effective than that by inhibition of purine synthesis. Electron microscopy of MOLT-4 cells exposed to 5-DACTHF showed electron-dense mitochondria and nuclear changes reminiscent of apoptosis. These morphological changes were accompanied by the appearance of DNA strand breaks at approximately 180-base pair intervals (internucleosomal breaks). Concomitant proteolysis of nuclear proteins poly(ADP-ribose) polymerase and lamin B was observed.

Acyltransferases↗
PubMed1992

Synthesis and biological activity of open-chain analogues of 5,6,7,8-tetrahydrofolic acid--potential antitumor agents.

This study describes the synthesis and in vitro antitumor activity of inhibitors of purine de novo biosynthesis that are analogues of N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl) propyl]amino]benzoyl-L-glutamic acid (5-DACTHF). Benzene ring substituted analogues were synthesized from a protected pyrimidinyl propionaldehyde and a substituted benzoyl glutamate moiety by a key reductive amination step. Pyrimidine and linking chain substituted analogues were built up stepwise from p-aminobenzoic acid or analogues. The compounds were tested as inhibitors of methotrexate uptake as a measure of binding to the reduced folate transport system, as inhibitors of glycinamide ribonucleotide transformylase, as substrates for folylpolyglutamate synthetase, and as inhibitors of tumor cell growth in cell culture. With the exception of 2'-F substituent, the ring-substituted analogues are less active than the parent compound. Replacement of the 10-nitrogen by carbon, sulfur, or oxygen produced less than 2-fold changes to biological activity in vitro. A four-atom linking chain and an amino group at the 2-position on the pyrimidine ring are important for good activity.

Adenocarcinoma↗
PubMed1992

New inhibitors of sepiapterin reductase. Lack of an effect of intracellular tetrahydrobiopterin depletion upon in vitro proliferation of two human cell lines.

N-Acetylserotonin (compound 1) and N-acetyldopamine (compound 7) inhibit bovine adrenal medullary sepiapterin reductase in a manner competitive with the pterin substrate and have Ki values of 0.12 and 0.4 microM, respectively. Molecular modeling suggests that the phenyl rings of the two compounds bind in the pyrimidine pocket of the enzyme with the 3-hydroxyl of dopamine or the 5-hydroxyl of serotonin aligned at the pyrimidine 4-position. Further, the acetyl moieties of the two inhibitors appear to mimic the substrate side chain. Consistent with this analysis, N-acetyl-m-tyramine (compound 13) is also an excellent competitive inhibitor (Ki = 0.13 microM), whereas N-acetyltryptamine (compound 2), N-acetyl-p-tyramine (compound 14) and N-acetylphenylethylamine (compound 15) all bind poorly. Interestingly, restricted-rotation analogs of N-acetyldopamine and N-acetyl-m-tyramine are noncompetitive inhibitors of the enzyme. Modification of N-acetyldopamine to N-chloroacetyldopamine (compound 10) or of N-acetylserotonin to the N-chloroacetyl (5) or N-methoxyacetyl (compound 6) analogs results in greatly increased competitive affinity, with Ki = 0.014 microM for the dopamine analog and 0.006 and 0.008 microM, respectively, for the serotonin analogs. In MOLT-4 T-cell leukemia and MCF-7 breast adenocarcinoma in culture, 0.1 mM N-methoxyacetylserotonin depleted tetrahydrobiopterin by greater than or equal to 97 and greater than 50%, respectively, with no effect upon cell growth. In both cell lines, the GTP cyclohydrolase inhibitor, 2,4-diamino-6-hydroxypyrimidine at 1-5 mM also depleted tetrahydrobiopterin greater than or equal to 97%. In this case, however, modest growth inhibition did occur. Since the growth inhibition could not be reversed upon tetrahydrobiopterin repletion, inhibition was due to other effects of the inhibitor rather than to tetrahydrobiopterin depletion. The results show that there is no effect on cell growth when at least 97% of the tetrahydrobiopterin in these cell lines is depleted. Since the sepiapterin reductase inhibitor depleted tetrahydrobiopterin with fewer nonspecific effects than the cyclohydrolase inhibitor, it will be useful for determining metabolic effects of tetrahydrobiopterin depletion.

Alcohol Oxidoreductases↗
PubMed1991

Studies on the mechanism of antitumor action of 2-desamino-2-methyl-5,8-dideazaisofolic acid.

The new folate analogue, 2-desamino-2-methyl-5,8-dideazaisofolic acid, 2c, was synthesized and evaluated using a variety of biochemical and antitumor assays. For purposes of comparison, its 2-desamino, 2b, and 2-amino, 2a, counterparts, as well as N10-propargly-5,8-dideazafolic acid, 1a, and the corresponding 2-desamino, 1b, and 2-desamino-2-methyl, 1c, modifications were included in these studies. Compound 2c was found to be a potent inhibitor of the growth of L1210 and MCF-7 cells in culture, being only 2-fold and 5-fold less effective than 1c, respectively. However, although analogue 2c was 189-fold less inhibitory toward L1210 thymidylate synthase (TS) than 1c, its cytotoxicity was reversed completely by thymidine alone which suggests that the compound behaves as a TS inhibitor in cells. Enzymatically synthesized polyglutamates of 2c were substantially more inhibitory toward human TS than the parent compound. Compound 2c was the most efficient substrate for mammalian folyl-polyglutamate synthetase of the compounds studied having a Vmax/Km nearly 12-fold larger than 1c. Both 1c and 2c were effective inhibitors of the uptake of [3H]methotrexate into MOLT-4 cells, implying that each is efficiently transported into tumor cells. These results suggest that a weak inhibitor of TS in vitro can be a potent cytotoxic agent if it can readily gain entry into target cells and be converted to polyglutamated metabolites.

Animals↗
PubMed1991

Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues.

Prompted by recent disclosures concerning the potent antitumor activities of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8-tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4- oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9-CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also synthesized. Each of the new analogues was evaluated with a variety of folate-requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of ca. 1 microM against MCF-7 cells and was nearly 100-fold less potent than DDATHF in this regard. The three oxidized isofolate analogues were all poor inhibitors of tumor cell growth.

Animals↗
PubMed1991

Folate analogues. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogues of N10-propargyl-5,8-dideazafolic acid.

Structural modifications at the pyrimidine ring and at the C9,N10-bridge region of the thymidylate synthase (TS) inhibitors N10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

Biological Transport↗
PubMed1990

New concepts of coxofemoral joint stability and the development of a clinical stress-radiographic method for quantitating hip joint laxity in the dog.

From mechanical principles and postmortem observations of coxofemoral joints of dogs, a hydrostatic mechanism influencing hip joint stability was discovered. This discovery led to the development of a stress-radiographic positioning method to quantitate hip joint laxity in dogs. The method incorporated 2 views with the dog in supine position and hips at neutral flexion/extension angle: a compression view, with the femoral heads fully seated in the acetabula; and a distraction view, with the femoral heads at maximal lateral displacement. An index measurement method was formulated to quantitate the relative degree of joint laxity appearing in either the compression or distraction view. Clinical evaluation of 6 dogs was done to compare the compression/distraction method with the standard hip-extended radiographic method. Also, the stress-radiographic method was performed on 16-week-old Borzoi and German Shepherd Dogs to compare the characteristics of inherent hip joint laxity in these breeds. In all dogs tested, hip joint laxity was masked by the standard hip-extended view as indicated by a 2.5-fold improvement in sensitivity to hip joint laxity of the new method (P less than 0.00001). Moreover, the mean hip joint laxity of 16-week-old German Shepherd Dogs exceeded the mean hip joint laxity of Borzois by 79% (P less than 0.00001). Reports in the literature document the incontrovertible association of hip joint laxity to the development of hip dysplasia in dogs. We believe the ability to accurately quantitate hip joint laxity will provide key diagnostic and prognostic criteria for the selection of pet dogs, and more importantly, breeding stock.

Animals↗