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Biomedical subjects

G E Lees

Publications and source records attributed to G E Lees.

At least 19 recordsLinked to original sources
PubMed2000

Expression of the alpha6 chain of type IV collagen in glomerular basement membranes of healthy adult dogs.

OBJECTIVE: To evaluate expression of the alpha6 chain of type IV collagen in the glomerular basement membranes (GBM) of healthy dogs. SAMPLE POPULATION: Kidney specimens from 12 healthy dogs. For comparison, kidney specimens from 8 human subjects between 25 and 83 years old also were evaluated. PROCEDURE: Sections were immunolabeled with a monospecific antibody that cross-reacts with human and canine alpha6(IV) chains and examined by means of fluorescence microscopy. RESULTS: Immunolabeling of the alpha6(IV) chain was not observed in GBM of 6 dogs < or = 30 months old but was observed in GBM of the remaining 6 dogs, all of which were > or = 45 months old. Expression of the alpha6(IV) chain was not observed in GBM of the human subjects, regardless of the age of the subject. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that the alpha6(IV) chain is expressed in GBM of healthy dogs, but the expression is age-dependent. Composition and structural organization of type IV collagen in the GBM of healthy adult dogs is different from that described for other species.

Adult↗
PubMed1999

New form of X-linked dominant hereditary nephritis in dogs.

OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.

Animals↗
PubMed1998

A model of autosomal recessive Alport syndrome in English cocker spaniel dogs.

BACKGROUND: Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal models of Alport syndrome. METHODS: An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expression of basement membrane (BM) proteins was examined with an immunohistochemical technique using monospecific antibodies. RESULTS: Affected dogs had proteinuria and juvenile-onset chronic renal failure. Glomerular basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dogs, and severity of GBM ultrastructural abnormalities varied with the clinical stage of disease. Expression of alpha3(IV) and alpha4(IV) chains was totally absent in the kidney of affected dogs. Expression of alpha5(IV) and a6(IV) chains was normal in Bowman's capsule, collecting tubular BM and epidermal BM of affected dogs. The alpha5(IV) chain was not expressed in distal tubular BM of affected dogs. Expression of alpha5(IV) chains was markedly reduced but not absent, and expression of alpha6(IV) chains was present in GBM of affected dogs. Expression of alpha1-alpha2(IV) chains in GBM of affected dogs was increased. Features of obligate carriers were similar to those of unaffected dogs. CONCLUSIONS: We conclude that HN in ECS dogs is a naturally occurring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha5(IV) chains in GBM and in the appearance of a6(IV) chains in GBM.

Animals↗
PubMed1996

Congenital renal diseases.

Congenital renal diseases of assorted pathologic types occur in dogs and cats. Many of the conditions are known or suspected to be inherited in specific breeds. However, for most of these disorders the causative defect, pathogenesis, and mode of inheritance remain unknown. Congenital renal diseases usually are progressive and they often cause chronic renal failure in affected animals. Presumptive diagnosis usually is based on clinical findings after exclusion of other conditions, but definitive diagnosis generally requires appropriate pathologic studies.

Animals↗
PubMed1996

Bacterial urinary tract infections.

Bacterial urinary tract infection rarely is the initial cause of lower urinary tract disease in cats; however, a substantial number of cats with various lower urinary tract disorders develop urinary infections as a complication of the underlying disease or its treatment. Examination of urine sediment for pyuria is a good screening test for urinary tract infection, but results of urine cultures are needed to diagnose such infections reliably, as well as to guide therapeutic decisions. Appropriate antimicrobial drug therapy is the cornerstone of treatment for urinary tract infection. Treatment of the underlying urinary disorder also is important, and follow-up urine cultures should be performed to determine therapeutic outcome.

Animals↗
PubMed1994

Comparison of species and numbers of bacteria in concurrently cultured samples of proximal small intestinal fluid and endoscopically obtained duodenal mucosa in dogs with intestinal bacterial overgrowth.

Concurrent bacterial culturing of duodenal/proximal jejunal fluid and duodenal mucosa was performed on 2 occasions in each of 16 IgA-deficient German Shepherd Dogs with small intestinal bacterial overgrowth. The interval between sample collections in each dog was 74 to 78 days. Species of bacteria and numbers of bacterial colony-forming units (CFU) per milliliter of fluid were compared with species and numbers found in the concurrent duodenal mucosa sample. There was inconsistent correlation for number of CFU and minimal correlation for species of bacteria isolated from the 2 sites. Fewer bacterial CFU usually were isolated from the mucosa than from the concurrent fluid sample. When the same numeric criteria used for diagnosing small intestinal bacterial overgrowth in samples of intestinal fluid (ie, > or = 10(5) bacterial or > or = 10(4) anaerobic CFU/ml) were used to interpret results of culturing duodenal mucosa, quantitations of bacterial CFU in duodenal mucosa was found to be a specific, but insensitive test.

Animals↗
PubMed1994

Effect of dietary sodium intake on glomerular filtration rate in partially nephrectomized dogs.

Exogenous creatinine clearance rate was determined in 8 partially (approx 75%) nephrectomized dogs fed 2 concentrations of dietary sodium, beginning 9 weeks after partial nephrectomy was performed. In a double crossover design, dogs were then fed low-sodium diet (0.18% sodium on a dry-weight basis) or high-sodium diet (1.3% sodium on a dry-weight basis) in 2 sequences (L/H/L or H/L/H) for 3 consecutive 4-week observation periods. Glomerular filtration rate (GFR) was measured by exogenous creatinine clearance before and after partial nephrectomy, and every 2 weeks during the experimental diet periods. Initial mean +/- SD GFR (3.76 +/- 0.78 ml/min/kg of body weight) decreased precipitously after nephrectomy (1.25 +/- 0.45 ml/min/kg); however, during the postnephrectomy and experimental diet periods, GFR gradually increased in all dogs to nearly half the prenephrectomy values (1.87 +/- 0.22 ml/min/kg). Significant differences in GFR were not observed when dogs were fed the L/H/L or the H/L/H sequence. Therefore, it was concluded that abrupt changes from high dietary sodium (1.3%) to restricted dietary sodium (0.18%), or vice versa, does not cause deterioration of renal function in dogs with moderate renal impairment. However, caution should be used in extrapolating these findings to dogs with clinically evident (azotemia, isosthenuria) renal failure.

Animals↗
PubMed1994

Effects of dietary sodium intake on blood pressure measurements in partially nephrectomized dogs.

Systolic, diastolic, and mean arterial blood pressure were measured by femoral artery puncture every other day in 2 groups (n = 4) of partially nephrectomized (approx 75%) dogs fed 2 concentrations of dietary sodium beginning 9 weeks after partial nephrectomy was completed. In a double crossover design, dogs were fed a low-sodium (0.18% sodium on a dry-weight basis) or high-sodium (1.3% sodium on a dry-weight basis) diet in 2 sequences (L/H/L or H/L/H) for 3 consecutive 4-week observation periods. Significant effect of sequence was found in dogs fed the L/H/L sequence, compared with those fed the H/L/H sequence. Systolic blood pressure was significantly (P < 0.05) increased in dogs fed the L/H/L sequence (175 +/- 16 mm of Hg), compared with dogs fed the H/L/H sequence (156 +/- 14 mm of Hg). Mean arterial blood pressure was higher, but not significantly different, for the L/H/L sequence (116 +/- 8 mm of Hg) vs the H/L/H sequence (109 +/- 6 mm of Hg). Significant difference in diastolic pressure was not observed between the L/H/L (86 +/- 10 mm of Hg) and H/L/H (86 +/- 10 mm of Hg) sequences. Restricted sodium intake (0.18% sodium on a dry-weight basis) was associated with moderate systolic hypertension in dogs with experimentally induced chronic renal disease. Acute fluctuations in dietary sodium intake had no apparent immediate effect on blood pressure in dogs with this mild to moderate degree of renal dysfunction.

Animals↗
PubMed1992

Effects of lithium carbonate administration to healthy cats.

Lithium carbonate administration to healthy cats was evaluated in 2 controlled studies (a dose-response study and a bone marrow evaluation study) to determine the effectiveness of lithium as a bone marrow stimulant. Lithium carbonate was administrated at dosage ranging from 300 to 1,050 mg/m2 of body surface/d. Complete blood count, serum lithium concentration determination, serum biochemical analysis, urinalysis, and bone marrow aspiration and biopsy were periodically performed. Serum lithium concentration greater than 2 mEq/L was associated with significant decrease in numbers of circulating segmented neutrophils (less than 1,200 cells/microliter; P less than 0.01) and lymphocytes (less than 1,300 cells/microliter; P less than 0.0001), as well as significant (P less than 0.05) decrease in urine specific gravity. Bone marrow evaluation revealed apparent maturation arrest of the neutrophil cell line. Coincident with the changes in laboratory values, the lithium-treated cats became ill. Changes in behavior and vocalization were seen, followed by anorexia, vomiting, and diarrhea. In later stages of intoxication, cats became hyperexcitable and manifested coarse muscular tremors. It was concluded that lithium carbonate does not have potential value as a bone marrow stimulant and is toxic to cats at serum concentration greater than 2 mEq/L.

Animals↗
PubMed1991

Toxoplasmosis in two cats with inflammatory intestinal disease.

Lymphocytic-plasmacytic enteritis, a chronic inflammatory intestinal disease, was diagnosed in 2 cats. In 1 cat, recurrence of clinical signs after initiating treatment was attributed to relapse of the inflammatory intestinal disease, but was found to be attributable to relapsing toxoplasmosis secondary to immunosuppressive drug therapy. Treatment with clindamycin resolved the recurrent toxoplasmosis. In the second cat, clinical signs of toxoplasmosis did not develop, but serologic testing yielded evidence of active toxoplasmosis. Treatment with clindamycin caused the titers to decrease. Relapsing toxoplasmosis may be responsible for apparent resistance to treatment in cats for inflammatory intestinal disease being treated with immunosuppressive drugs.

Animals↗
PubMed1991

Comparison of four methods of estimating glomerular filtration rate in cats.

Four methods of evaluating renal function were performed in 6 cats anesthetized with halothane in oxygen. Glomerular filtration rate (GFR) was measured simultaneously in each cat by exogenous creatinine clearance (ECC), bolus inulin clearance, and 99mTc(Sn)-diethylene-triaminepentaacetic acid (DTPA) clearance determined by 2 different methods. In the first DTPA clearance method (DTPA-1), we measured radioactivity in serial blood specimens to construct plasma disappearance curves for calculation of GFR. In the second DTPA clearance method (DTPA-2), we used serial external head counts of radioactivity and a single blood specimen to construct plasma disappearance curves for calculation of GFR. Bolus inulin clearance was calculated from plasma disappearance curves using a 1-compartment open pharmacokinetic model (IN-1) and a 2-compartment open pharmacokinetic model (IN-2). Glomerular filtration rates were measured over 3 hours, for creatinine and DTPA methods, and over 4 hours for the inulin methods. The GFR obtained with the reference method (ECC) was 2.56 +/- 0.61 ml/min/kg of body weight (mean +/- SD). Values for GFR determined by ECC and DTPA-1 were significantly correlated (r = 0.852; P less than or equal to 0.05). Correlation between ECC and DTPA 2 was not as good (r = 0.783; P less than or equal to 0.10), but the 2 DTPA methods significantly correlated with one another (r = 0.897; P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Disposition of clorazepate in dogs after single- and multiple-dose oral administration.

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate. Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 +/- 334 ng/ml), at 59 to 180 minutes (97.9 +/- 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 +/- 187.6 ng/ml), at 120 to 239 minutes (153 +/- 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 +/- 214 minutes) was longer (P less than 0.05) than after a single dose (527 +/- 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 +/- 0.647 L/kg) was smaller (P less than 0.02) than after a single dose (3.18 +/- 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 +/- 0.726 ml/min/kg) was less (P less than 0.001) than after a single dose (6.54 +/- 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P less than 0.01) than after a single dose (33 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Effects of single-dose and three-day trimethoprim-sulfadiazine and amikacin treatment of induced Escherichia coli urinary tract infections in dogs.

Efficacy of single-dose and 3-day trimethoprim-sulfadiazine (TMS) and amikacin treatment regimens for induced Escherichia coli urinary tract infections (UTI) in dogs was evaluated. Using each regimen, effects of giving TMS combination or amikacin were compared in males and females, and the response of treated dogs was compared with that of nontreated controls. Response to treatment was evaluated, using results of quantitative urine cultures and urinalyses obtained on 4 occasions. Abacteriuria was identified by finding a lack of bacterial organisms in specimens collected for the initial and final posttherapy evaluations. Before treatments, magnitudes of bacteriuria were similar in all experimental groups, and UTI persisted in all nontreated dogs. Single-dose treatment regimens did not reliably eradicate UTI in males or females, whether amikacin or TMS was administered. Magnitude of bacteriuria often diminished immediately after single-dose treatment, and such reductions of bacteriuria persisted in 2 of 8 dogs. However, no male dogs and only 1 of 4 females became abacteriuric after a single-dose treatment regimen. The single female in which UTI was eradicated was treated with a single dose of amikacin. The 3-day TMS treatment regimen eradicated UTI in each of 4 females, but the 3-day amikacin treatment regimen resulted in abacteriuria in only 1 of 4 females. Three-day treatment regimens were not effective in male dogs, regardless of the antimicrobial drug used. Of the short-course treatments for canine UTI evaluated by this model, only 3-day TMS treatment of females was consistently effective.

Amikacin↗
PubMed1986

Evaluation of renal function in cats, using quantitative urinalysis.

Two consecutive 24-hour quantitative urinalyses were performed on each of 12 healthy adult cats to evaluate the technique and obtain reference values for measurements of urinary excretion of several substances. Endogenous creatinine clearance (2.31 +/- 0.47 ml/min/kg) and urinary protein excretion (17.43 +/- 9.05 mg/kg/day) were determined. Additionally, clearances and ratios to creatinine clearances were calculated for phosphate, sodium, potassium, and chloride. The endogenous creatinine clearance value was compared with another estimate of glomerular filtration rate that was based on 99mTc(Sn) diethylene-triaminepentaacetic acid clearance (2.52 +/- 0.58 ml/min/kg). Evaluation of feline renal function, using 24-hour quantitative urinalysis techniques, has potential for clinical application, but has several important limitations as well.

Animals↗
PubMed1984

Results of analyses and bacterial cultures of urine specimens obtained from clinically normal cats by three methods.

Six urine specimens were obtained from each of 6 male and 6 female cats in a 3-week period. The first and last specimens from each cat were obtained by cystocentesis, 2 were obtained by urethral catheterization, and 2 were caught during voiding stimulated by manual bladder compression. Quantitative urine cultures did not reveal bacteriuria in specimens obtained by cystocentesis, and urinary tract infection did not develop during the study. Bacteria were found in 3 (25%) of 12 urine specimens obtained by catheterization of males and in 1 (8%) of 12 specimens obtained by catheterization of females. Magnitude of bacteriuria in specimens obtained by catheterization was 10 to 1,000 organisms/ml. Bacteria also were found in specimens obtained during voiding. Each of 11 (100%) cleanly caught specimens obtained from males and 7 (58%) of 12 voided specimens from females contained bacteria. Magnitude of bacteriuria in voided specimens was usually 100 to 10,000 organisms/ml, but 3 voided specimens contained greater than 10,000 organisms/ml. Many bacteriuric specimens contained more than 1 type of organism; however, bacteria that might be suspected of causing urinary tract infections in cats were found frequently. Urinalyses were performed on 66 specimens. Completeness of urinalyses depended on the volume of specimens available, but results were normal except for evidence of hematuria in a few specimens obtained by cystocentesis or catheterization. Hematuria was usually mild and was attributed to hemorrhage caused by minor urinary tract trauma during urine collection.

Animals↗