Meryl Littman - Academia.edu (original) (raw)

Papers by Meryl Littman

Advances in genomics and genetics, Apr 1, 2015

Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spo... more Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man.

PubMed, Aug 15, 1988

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that w... more Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.

PubMed, Aug 15, 1988

Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included ... more Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included CBC; serum biochemical evaluation; urinalysis; urine and uterine bacteriologic culture; uterine morphologic features; and light, electron, and immunofluorescent microscopic evaluation of renal tissues. Measurements of 24-hour creatinine clearance, protein excretion, Na excretion, and urine volume were made in 12 dogs without azotemia. Of 27 dogs, 26% were azotemic and 89% had a urine sp gr less than 1.035. Glomerular filtration rate was reduced in 75% of 12 dogs without azotemia. None of these 12 dogs was proteinuric. Examination of renal biopsy specimens revealed a high prevalence of mild tubulointerstitial nephritis, but few specific glomerular lesions. Minimal immunofluorescence was detected within the mesangium in 18% of the dogs. Immunofluorescence was not associated with the interstitium or tubules. Urinary tract infection was detected in 22% of the dogs. Escherichia coli and Klebsiella were recovered from the uterus in 59 and 15% of the dogs, respectively. Low urine specific gravity values were obtained from dogs without azotemia and from dogs with uterine cultures considered negative for E coli and other gram-negative bacteria. The reduction in glomerular filtration rate was a functional abnormality not correlated with structural damage in the glomerulus.

Journal of Small Animal Practice, Oct 1, 1983

Squamous cell carcinoma of the middle ear and tympanic bulla was diagnosed in a 13-year-old cat. ... more Squamous cell carcinoma of the middle ear and tympanic bulla was diagnosed in a 13-year-old cat. This is the first report of squamous cell carcinoma in this location in a cat.

PubMed, Aug 15, 1987

Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive di... more Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive disease. During the 3-month illness (before euthanasia), the dog had ulcerative granulomatous inguinal lymphadenitis, fever, anorexia, dyspnea, generalized lymphadenopathy, retinochoroiditis, and seizures. Fungal organisms isolated from inguinal and prescapular lymph nodes before the dog was euthanatized were identified histologically. Paecilomyces variotii was isolated from the prescapular lymph node specimen. Paecilomyces variotii may be more pathogenic (once it has gained bodily entry) than previously thought.

PubMed, Jul 1, 1989

Severe hypertension was diagnosed in a dog that initially was referred for evaluation of visual d... more Severe hypertension was diagnosed in a dog that initially was referred for evaluation of visual deficits and retinal hemorrhage and eventually was donated for medical treatment of hypertension. Initial blood pressure measured by direct methods was markedly high (systolic, 275 mm of Hg; diastolic, 170 mm of Hg). Measures of renal function were within normal limits, with the exception of hypotonic urine. A test protocol was designed to exclude possible secondary causes of hypertension; negative results of such tests allowed the diagnosis of essential hypertension. The consistency of the hypertension and its response to medical control were studied for 5 years. Blood pressure while the dog was untreated during those years was 240 +/- 24 mm of Hg (systolic) and 146 +/- 14 mm of Hg (diastolic). Plasma renin activity was within normal limits, and the response of the renin-angiotensin system to varied salt intake was normal. The most effective medications used to lower blood pressure were propranolol and captopril, both of which were more effective than salt restriction alone. Five years after the diagnosis of hypertension, the dog was euthanatized because of chronic renal failure secondary to pyelonephritis. Hypertension was less severe as the condition progressed into chronic renal failure. Complete necropsy did not reveal an obvious cause of the hypertension, and histopathologic changes were limited to the cardiovascular system, eyes, and kidneys.

Mammalian Genome, Jan 17, 2013

Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically ... more Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically complex, protein-losing nephropathy (average onset age = 6.3 ± 2.0 years). A genome-wide association study using 62 dogs revealed a chromosomal region containing three statistically significant SNPs (p raw B 4.13 9 10-8 ; p genome B 0.005) when comparing DNA samples from affected and geriatric (C14 years) unaffected SCWTs. Sequencing of candidate genes in the region revealed single nucleotide changes in each of two closely linked genes, NPHS1 and KIRREL2, which encode the slit diaphragm proteins nephrin and Neph3/filtrin, respectively. In humans, mutations in nephrin and decreased expression of Neph3 are associated with podocytopathy and proteinlosing nephropathy. The base substitutions change a glycine to arginine in the fibronectin type 3 domain of nephrin and a proline to arginine in a conserved proline-rich region in Neph3. These novel mutations are not described in other species, nor were they found in 550 dogs of 105 other breeds, except in 3 dogs, including an affected Airedale terrier, homozygous for both substitutions. Risk for nephropathy is highest in dogs homozygous for the mutations (OR = 9.06; 95 % CI = 4.24-19.35). This is the first molecular characterization of an inherited podocytopathy in dogs and may serve as a model for continued studies of complex genetic and environmental interactions in glomerular disease.

Journal of the American Veterinary Medical Association, Jan 15, 1987

Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive di... more Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive disease. During the 3-month illness (before euthanasia), the dog had ulcerative granulomatous inguinal lymphadenitis, fever, anorexia, dyspnea, generalized lymphadenopathy, retinochoroiditis, and seizures. Fungal organisms isolated from inguinal and prescapular lymph nodes before the dog was euthanatized were identified histologically. Paecilomyces variotii was isolated from the prescapular lymph node specimen. Paecilomyces variotii may be more pathogenic (once it has gained bodily entry) than previously thought.

Journal of the American Veterinary Medical Association, Jan 15, 1988

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that w... more Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.

BSAVA Manual of Canine and Feline Nephrology and Urology, 2017

An inherited illness, based on genotype, is suspected when multiple family members are affected o... more An inherited illness, based on genotype, is suspected when multiple family members are affected or a breed predisposition is noted beyond its popularity or what is seen in the general population. This chapter examines inherited glomerulopathies, inherited nephropathies, inherited tubular disorders, lower urinary tract disorders, DNA testing and genetic counselling.

Textbook of Small Animal Emergency Medicine, 2018

Veterinary Pathology, 2017

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of prote... more Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binuclea...

Journal of Veterinary Internal Medicine, 2020

Abstract Background Recently, urine protein:creatinine ratios (UPC) were shown to be lower in uri... more Abstract Background Recently, urine protein:creatinine ratios (UPC) were shown to be lower in urine samples from dogs collected at home (AH) as compared to those collected in hospital (IH). Stress‐inducing procedures and travel to the hospital have been hypothesized to cause prerenal proteinuria. Objectives Evaluate patient stress using urine cortisol:creatinine ratios (UCCr) and correlate UCCr to UPC in urine samples obtained AH and IH. Animals Thirty‐six healthy, client‐owned dogs. Methods Prospective, non‐masked study. Two voided urine samples were obtained (AH and IH). Complete urinalysis as well as UPC and UCCr were performed. Clients graded their dogs' stress level AH, in transport, and IH. Results The UCCr was significantly higher in IH samples than in AH samples (P < .0001), but UPC was not significantly different between AH and IH urine samples (P = .14). In all samples and in both collection settings, UCCr was not significantly correlated with UPC. Travel time and time IH were not correlated with change in UCCr or UPC. In 8 dogs with borderline or overt proteinuria, no significant difference was found in UPC between settings, but UCCr was significantly higher in IH samples. Conclusions and Clinical Importance The UPC was not higher when measured in urine samples collected IH compared to AH. Dogs had higher UCCr IH, but UCCr was not associated with UPC. Stress, as estimated by UCCr, did not affect proteinuria. Further evidence is needed to support the claim that stress may result in proteinuria in healthy dogs.

The Canadian veterinary journal = La revue veterinaire canadienne, 2016

The objective of this retrospective case series, which included 82 client-owned soft-coated wheat... more The objective of this retrospective case series, which included 82 client-owned soft-coated wheaten terriers, was to characterize clinical features of hypoadrenocorticism in this breed. Median age at diagnosis was 3.5 years. There was no gender predilection. Clinicopathologic findings included sodium/potassium ratio < 27 (85%), hyperkalemia (76%), hyponatremia (63%), elevated blood urea nitrogen (83%) or creatinine (71%), and hypercalcemia (36%). Nine dogs with normal sodium and potassium (11%) were older and less often azotemic, hyperphosphatemic, or hypercalcemic. Twenty-one dogs (26%) developed protein-losing nephropathy (n = 18) and/or end-stage renal disease (n = 3). Overall median survival time was 5.4 years, but was shorter in dogs with normal sodium and potassium at diagnosis (4.2 years), or those with subsequent protein-losing nephropathy (4.2 years). This population showed no gender predilection, unlike that reported in the general canine population with hypoadrenocorti...

Bartges/Nephrology and Urology of Small Animals, 2014

Advances in Genomics and Genetics, 2015

Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spo... more Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man.

Journal of the American Veterinary Medical Association, 2013

To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers ag... more To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers against Leptospira serogroups, and importance of convalescent titers in dogs with leptospirosis. Retrospective case series. 51 dogs with leptospirosis. Criteria for inclusion were at least 1 positive microscopic agglutination test (MAT) result (titer ≥ 1:1,600 in vaccinated dogs, titer ≥ 1:800 in nonvaccinated dogs, or ≥ 4-fold increase in convalescent titer), a complete medical record (including leptospirosis vaccination date, reason for initial evaluation, and CBC, serum biochemical analysis, and urinalysis results), and clinical signs or laboratory findings consistent with leptospirosis. Initial clinical signs, temporal distribution, and signalment were similar to previous reports. Convalescent MAT titers were necessary for diagnosis in 45% of cases. Atypical abnormalities included radiographic evidence of pulmonary disease in 10 of 23 dogs and hepatic involvement alone in 7 of 51 dogs. Other abnormalities included proteinuria in 34 of 51 dogs, thrombocytopenia in 26 of 51, coagulopathy in 7 of 24 dogs, hypoalbuminemia in 14 of 51 dogs, and glucosuria in 9 of 51 dogs. Significant associations were found between antibodies against serogroup Grippotyphosa and renal involvement and serogroup Icterohaemorrhagiae and hepatic involvement. Increased awareness of atypical abnormalities may decrease misdiagnosis of leptospirosis in dogs. Results of concurrent infectious disease testing should be interpreted with caution; misdiagnosis of leptospirosis could pose a public health risk. Convalescent titers were necessary to identify infection when acute testing results were negative. Further research is needed to determine the true associations between antibodies against identified serogroups and clinical features.

Veterinary Clinics of North America: Small Animal Practice, 2011

The prevalence of protein-losing nephropathy (PLN) in the general population is much greater in d... more The prevalence of protein-losing nephropathy (PLN) in the general population is much greater in dogs than cats but is largely unknown and probably higher than currently recognized. 1-3 Renal failure is arguably the most common organ failure in dogs and cats. The prevalence of glomerular lesions, mostly immune-mediated glomerulonephritis (IMGN), was found in 43% to 90% of random dogs. 1,3 Increased urine protein/creatinine ratio (UPC), as an indicator of glomerular disease, is a negative predictor of outcome. 4-7 Microalbuminuria (MA) is detected in about 25% of all dogs and cats, increasing with age (36% in dogs 9-11 years, 49% in dogs !12 years, 39% in cats !12 years, and 65% of cats !16 years), 8 but its clinical significance is not known. When the first insult to the nephron is at the glomerulus, proteinuria occurs, which ultimately damages the rest of the nephron. By the time end-stage renal disease (ESRD) is discovered, the initiating glomerular cause may go undetected. Because proteinuria decreases with nephron dropout and decreased glomerular filtration, hypoalbuminemia may no longer exist or it may be masked by dehydration. Therefore, glomerular disease as the initiating cause of ESRD may go unrecognized. Renal biopsy results may not settle the question of chicken-or-egg regarding whether glomerular versus tubular damage (chronic interstitial nephritis) was the primary cause, because both are often seen in end-stage kidney samples. Even when renal biopsies are taken earlier in the disease process, pathologists' interpretations using routine histopathology techniques do not necessarily agree. 9 There is inherent subjectivity with visual analysis of membrane thickening or mesangial cell numbers present. Tissue sections traditionally cut at 5 to 6 mm for light microscopy are too thick for careful examination of renal lesions. Therefore, the incidence of subtypes of glomerulonephritis reported may not be accurate, and treatment protocols that might work for a particular subset (for instance, steroids or cyclosporine) may not seem beneficial because these cases were not properly identified.

Advances in genomics and genetics, Apr 1, 2015

Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spo... more Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man.

PubMed, Aug 15, 1988

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that w... more Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.

PubMed, Aug 15, 1988

Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included ... more Renal function and pathologic changes in 27 dogs with pyometra were studied. Evaluation included CBC; serum biochemical evaluation; urinalysis; urine and uterine bacteriologic culture; uterine morphologic features; and light, electron, and immunofluorescent microscopic evaluation of renal tissues. Measurements of 24-hour creatinine clearance, protein excretion, Na excretion, and urine volume were made in 12 dogs without azotemia. Of 27 dogs, 26% were azotemic and 89% had a urine sp gr less than 1.035. Glomerular filtration rate was reduced in 75% of 12 dogs without azotemia. None of these 12 dogs was proteinuric. Examination of renal biopsy specimens revealed a high prevalence of mild tubulointerstitial nephritis, but few specific glomerular lesions. Minimal immunofluorescence was detected within the mesangium in 18% of the dogs. Immunofluorescence was not associated with the interstitium or tubules. Urinary tract infection was detected in 22% of the dogs. Escherichia coli and Klebsiella were recovered from the uterus in 59 and 15% of the dogs, respectively. Low urine specific gravity values were obtained from dogs without azotemia and from dogs with uterine cultures considered negative for E coli and other gram-negative bacteria. The reduction in glomerular filtration rate was a functional abnormality not correlated with structural damage in the glomerulus.

Journal of Small Animal Practice, Oct 1, 1983

Squamous cell carcinoma of the middle ear and tympanic bulla was diagnosed in a 13-year-old cat. ... more Squamous cell carcinoma of the middle ear and tympanic bulla was diagnosed in a 13-year-old cat. This is the first report of squamous cell carcinoma in this location in a cat.

PubMed, Aug 15, 1987

Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive di... more Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive disease. During the 3-month illness (before euthanasia), the dog had ulcerative granulomatous inguinal lymphadenitis, fever, anorexia, dyspnea, generalized lymphadenopathy, retinochoroiditis, and seizures. Fungal organisms isolated from inguinal and prescapular lymph nodes before the dog was euthanatized were identified histologically. Paecilomyces variotii was isolated from the prescapular lymph node specimen. Paecilomyces variotii may be more pathogenic (once it has gained bodily entry) than previously thought.

PubMed, Jul 1, 1989

Severe hypertension was diagnosed in a dog that initially was referred for evaluation of visual d... more Severe hypertension was diagnosed in a dog that initially was referred for evaluation of visual deficits and retinal hemorrhage and eventually was donated for medical treatment of hypertension. Initial blood pressure measured by direct methods was markedly high (systolic, 275 mm of Hg; diastolic, 170 mm of Hg). Measures of renal function were within normal limits, with the exception of hypotonic urine. A test protocol was designed to exclude possible secondary causes of hypertension; negative results of such tests allowed the diagnosis of essential hypertension. The consistency of the hypertension and its response to medical control were studied for 5 years. Blood pressure while the dog was untreated during those years was 240 +/- 24 mm of Hg (systolic) and 146 +/- 14 mm of Hg (diastolic). Plasma renin activity was within normal limits, and the response of the renin-angiotensin system to varied salt intake was normal. The most effective medications used to lower blood pressure were propranolol and captopril, both of which were more effective than salt restriction alone. Five years after the diagnosis of hypertension, the dog was euthanatized because of chronic renal failure secondary to pyelonephritis. Hypertension was less severe as the condition progressed into chronic renal failure. Complete necropsy did not reveal an obvious cause of the hypertension, and histopathologic changes were limited to the cardiovascular system, eyes, and kidneys.

Mammalian Genome, Jan 17, 2013

Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically ... more Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically complex, protein-losing nephropathy (average onset age = 6.3 ± 2.0 years). A genome-wide association study using 62 dogs revealed a chromosomal region containing three statistically significant SNPs (p raw B 4.13 9 10-8 ; p genome B 0.005) when comparing DNA samples from affected and geriatric (C14 years) unaffected SCWTs. Sequencing of candidate genes in the region revealed single nucleotide changes in each of two closely linked genes, NPHS1 and KIRREL2, which encode the slit diaphragm proteins nephrin and Neph3/filtrin, respectively. In humans, mutations in nephrin and decreased expression of Neph3 are associated with podocytopathy and proteinlosing nephropathy. The base substitutions change a glycine to arginine in the fibronectin type 3 domain of nephrin and a proline to arginine in a conserved proline-rich region in Neph3. These novel mutations are not described in other species, nor were they found in 550 dogs of 105 other breeds, except in 3 dogs, including an affected Airedale terrier, homozygous for both substitutions. Risk for nephropathy is highest in dogs homozygous for the mutations (OR = 9.06; 95 % CI = 4.24-19.35). This is the first molecular characterization of an inherited podocytopathy in dogs and may serve as a model for continued studies of complex genetic and environmental interactions in glomerular disease.

Journal of the American Veterinary Medical Association, Jan 15, 1987

Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive di... more Disseminated paecilomycosis was diagnosed in an adult dog without underlying immunosuppressive disease. During the 3-month illness (before euthanasia), the dog had ulcerative granulomatous inguinal lymphadenitis, fever, anorexia, dyspnea, generalized lymphadenopathy, retinochoroiditis, and seizures. Fungal organisms isolated from inguinal and prescapular lymph nodes before the dog was euthanatized were identified histologically. Paecilomyces variotii was isolated from the prescapular lymph node specimen. Paecilomyces variotii may be more pathogenic (once it has gained bodily entry) than previously thought.

Journal of the American Veterinary Medical Association, Jan 15, 1988

Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that w... more Spontaneous (not experimentally induced) systemic hypertension was detected in 5 male dogs that were examined because of apparent blindness caused by intraocular hemorrhage and/or retinal detachment. Secondary causes of hypertension, including renal, adrenal, and thyroid disease, were investigated. Four of the dogs had glomerulonephropathy, renal insufficiency, and proteinuria. Four dogs had compensatory cardiac hypertrophy. Hypertension in 4 of 5 dogs was associated with glomerulosclerosis with chronic renal insufficiency, bilateral adrenocortical hyperplasia, adrenocortical adenoma with renal amyloidosis, and immune-mediated glomerulonephritis with chronic renal insufficiency, respectively. The fifth dog was determined to have essential hypertension. The dogs were treated for their primary diseases. Sodium restriction alone was inadequate to reduce blood pressure; 4 of the dogs also required antihypertensive medications.

BSAVA Manual of Canine and Feline Nephrology and Urology, 2017

An inherited illness, based on genotype, is suspected when multiple family members are affected o... more An inherited illness, based on genotype, is suspected when multiple family members are affected or a breed predisposition is noted beyond its popularity or what is seen in the general population. This chapter examines inherited glomerulopathies, inherited nephropathies, inherited tubular disorders, lower urinary tract disorders, DNA testing and genetic counselling.

Textbook of Small Animal Emergency Medicine, 2018

Veterinary Pathology, 2017

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of prote... more Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binuclea...

Journal of Veterinary Internal Medicine, 2020

Abstract Background Recently, urine protein:creatinine ratios (UPC) were shown to be lower in uri... more Abstract Background Recently, urine protein:creatinine ratios (UPC) were shown to be lower in urine samples from dogs collected at home (AH) as compared to those collected in hospital (IH). Stress‐inducing procedures and travel to the hospital have been hypothesized to cause prerenal proteinuria. Objectives Evaluate patient stress using urine cortisol:creatinine ratios (UCCr) and correlate UCCr to UPC in urine samples obtained AH and IH. Animals Thirty‐six healthy, client‐owned dogs. Methods Prospective, non‐masked study. Two voided urine samples were obtained (AH and IH). Complete urinalysis as well as UPC and UCCr were performed. Clients graded their dogs' stress level AH, in transport, and IH. Results The UCCr was significantly higher in IH samples than in AH samples (P < .0001), but UPC was not significantly different between AH and IH urine samples (P = .14). In all samples and in both collection settings, UCCr was not significantly correlated with UPC. Travel time and time IH were not correlated with change in UCCr or UPC. In 8 dogs with borderline or overt proteinuria, no significant difference was found in UPC between settings, but UCCr was significantly higher in IH samples. Conclusions and Clinical Importance The UPC was not higher when measured in urine samples collected IH compared to AH. Dogs had higher UCCr IH, but UCCr was not associated with UPC. Stress, as estimated by UCCr, did not affect proteinuria. Further evidence is needed to support the claim that stress may result in proteinuria in healthy dogs.

The Canadian veterinary journal = La revue veterinaire canadienne, 2016

The objective of this retrospective case series, which included 82 client-owned soft-coated wheat... more The objective of this retrospective case series, which included 82 client-owned soft-coated wheaten terriers, was to characterize clinical features of hypoadrenocorticism in this breed. Median age at diagnosis was 3.5 years. There was no gender predilection. Clinicopathologic findings included sodium/potassium ratio < 27 (85%), hyperkalemia (76%), hyponatremia (63%), elevated blood urea nitrogen (83%) or creatinine (71%), and hypercalcemia (36%). Nine dogs with normal sodium and potassium (11%) were older and less often azotemic, hyperphosphatemic, or hypercalcemic. Twenty-one dogs (26%) developed protein-losing nephropathy (n = 18) and/or end-stage renal disease (n = 3). Overall median survival time was 5.4 years, but was shorter in dogs with normal sodium and potassium at diagnosis (4.2 years), or those with subsequent protein-losing nephropathy (4.2 years). This population showed no gender predilection, unlike that reported in the general canine population with hypoadrenocorti...

Bartges/Nephrology and Urology of Small Animals, 2014

Advances in Genomics and Genetics, 2015

Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spo... more Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man.

Journal of the American Veterinary Medical Association, 2013

To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers ag... more To determine clinicopathologic features, percentage of atypical abnormalities, antibody titers against Leptospira serogroups, and importance of convalescent titers in dogs with leptospirosis. Retrospective case series. 51 dogs with leptospirosis. Criteria for inclusion were at least 1 positive microscopic agglutination test (MAT) result (titer ≥ 1:1,600 in vaccinated dogs, titer ≥ 1:800 in nonvaccinated dogs, or ≥ 4-fold increase in convalescent titer), a complete medical record (including leptospirosis vaccination date, reason for initial evaluation, and CBC, serum biochemical analysis, and urinalysis results), and clinical signs or laboratory findings consistent with leptospirosis. Initial clinical signs, temporal distribution, and signalment were similar to previous reports. Convalescent MAT titers were necessary for diagnosis in 45% of cases. Atypical abnormalities included radiographic evidence of pulmonary disease in 10 of 23 dogs and hepatic involvement alone in 7 of 51 dogs. Other abnormalities included proteinuria in 34 of 51 dogs, thrombocytopenia in 26 of 51, coagulopathy in 7 of 24 dogs, hypoalbuminemia in 14 of 51 dogs, and glucosuria in 9 of 51 dogs. Significant associations were found between antibodies against serogroup Grippotyphosa and renal involvement and serogroup Icterohaemorrhagiae and hepatic involvement. Increased awareness of atypical abnormalities may decrease misdiagnosis of leptospirosis in dogs. Results of concurrent infectious disease testing should be interpreted with caution; misdiagnosis of leptospirosis could pose a public health risk. Convalescent titers were necessary to identify infection when acute testing results were negative. Further research is needed to determine the true associations between antibodies against identified serogroups and clinical features.

Veterinary Clinics of North America: Small Animal Practice, 2011

The prevalence of protein-losing nephropathy (PLN) in the general population is much greater in d... more The prevalence of protein-losing nephropathy (PLN) in the general population is much greater in dogs than cats but is largely unknown and probably higher than currently recognized. 1-3 Renal failure is arguably the most common organ failure in dogs and cats. The prevalence of glomerular lesions, mostly immune-mediated glomerulonephritis (IMGN), was found in 43% to 90% of random dogs. 1,3 Increased urine protein/creatinine ratio (UPC), as an indicator of glomerular disease, is a negative predictor of outcome. 4-7 Microalbuminuria (MA) is detected in about 25% of all dogs and cats, increasing with age (36% in dogs 9-11 years, 49% in dogs !12 years, 39% in cats !12 years, and 65% of cats !16 years), 8 but its clinical significance is not known. When the first insult to the nephron is at the glomerulus, proteinuria occurs, which ultimately damages the rest of the nephron. By the time end-stage renal disease (ESRD) is discovered, the initiating glomerular cause may go undetected. Because proteinuria decreases with nephron dropout and decreased glomerular filtration, hypoalbuminemia may no longer exist or it may be masked by dehydration. Therefore, glomerular disease as the initiating cause of ESRD may go unrecognized. Renal biopsy results may not settle the question of chicken-or-egg regarding whether glomerular versus tubular damage (chronic interstitial nephritis) was the primary cause, because both are often seen in end-stage kidney samples. Even when renal biopsies are taken earlier in the disease process, pathologists' interpretations using routine histopathology techniques do not necessarily agree. 9 There is inherent subjectivity with visual analysis of membrane thickening or mesangial cell numbers present. Tissue sections traditionally cut at 5 to 6 mm for light microscopy are too thick for careful examination of renal lesions. Therefore, the incidence of subtypes of glomerulonephritis reported may not be accurate, and treatment protocols that might work for a particular subset (for instance, steroids or cyclosporine) may not seem beneficial because these cases were not properly identified.