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Biomedical subjects

D R Krawiec

Publications and source records attributed to D R Krawiec.

At least 19 recordsLinked to original sources

Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs.

OBJECTIVE: To evaluate efficacy and nephrotoxicity of amphotericin B lipid complex used for treatment of dogs with naturally developing blastomycosis. DESIGN: Prospective clinical trial. ANIMALS: 11 dogs with blastomycosis. PROCEDURE: All dogs were treated with an amphotericin B lipid complex. Two dogs received a cumulative dose of 8 mg/kg of body weight, 1 received a cumulative dose of 10 mg/kg, and 8 received a cumulative dose of 12 mg/kg. RESULTS: The 2 dogs that received a cumulative dose of 8 mg/kg and 1 of the dogs that received a cumulative dose of 12 mg/kg had a relapse of blastomycosis within 30 days after treatment. Seven of the remaining 8 dogs were clinically free of blastomycosis 6 months after treatment. One dog died of an unrelated cause 5.5 months after treatment, but did not have clinical signs of blastomycosis at the time of death. There were not any adverse clinical effects attributable to drug administration in any of the dogs in this study, and none of the dogs developed clinical signs of renal disease or failure. CLINICAL IMPLICATIONS: Amphotericin B lipid complex was a safe and effective treatment for blastomycosis in these dogs.

Amphotericin B↗

Managing gastrointestinal complications of uremia.

Dogs and cats with uremia may display abnormalities of essentially all parts of the gastrointestinal (GI) tract. Abnormalities may be mild or severe. They may result from inflammation, edema, erosions, ulceration, and/or necrosis. Clinical signs of GI complications or uremia may include anorexia, nausea, vomiting, abdominal pain, diarrhea, and GI bleeding. This article discusses the GI manifestations of uremia according to anatomic sites and also describes the management of common clinical problems as they relate to uremic GI abnormalities.

Animals↗

Evaluation of the single-injection plasma disappearance of technetium-99m mercaptoacetyltriglycine method for determination of effective renal plasma flow in dogs with normal or abnormal renal function.

Effective renal plasma flow (ERPF) was evaluated, using continuous-infusion p-aminohippurate clearance (CLPAH) and single-injection plasma clearance of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3; CLMAG3) methods. Simultaneous clearance determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after renal failure was induced by administration of amphotericin B. Linear regression analysis was used to derive an equation to estimate ERPF from CLMAG3 after the single IV injection. A Student's t-test was used to compare pharmacokinetics between the dogs when they were healthy and when they were in renal failure. An F-test was used to determine the appropriate Student's t-test. Results indicated that CLMAG3 correlated reasonably well (r = 0.83, P < 0.0001) with ERPF obtained from the CLPAH value. The volume of distribution and elimination of 99mTc-MAG3 decreased during renal failure. Although there was minimal binding of 99mTc-MAG3 to erythrocytes, it was significantly (P = 0.0008) lower during renal failure. Protein binding was not significantly different during renal failure. All dogs had signs of nausea and emesis at variable times after injection of 99mTc-MAG3. Determination of CLMAG3 after a single injection provides an adequate means to rapidly assess ERPF in dogs. The technique could easily be performed in dogs with renal disease, thus providing valuable information regarding progression of naturally acquired renal failure.

Animals↗

Quantitative renal scintigraphic determination of effective renal plasma flow in dogs with normal and abnormal renal function, using 99mTc-mercaptoacetyltriglycine.

Effective renal plasma flow (ERPF) was evaluated, using the measurement of p-aminohippurate clearance (CLPAH) and quantitative renal scintigraphy (QRS) with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3). The CLPAH and QRS determinations were made in 6 dogs: 2 determinations for each dog before, and 1 determination after induction of renal failure by administration of amphotericin B. Least-squares regression analysis was used to derive an equation to estimate ERPF from QRS data. The results indicated that QRS, using 99mTc-MAG3, correlated reasonably well (r = 0.82, P < 0.001) with ERPF determined from the CLPAH value. The right kidney contributed 53.3% of global ERPF (P = 0.002). Hepatobiliary excretion of 99mTc-MAG3 was variable within each dog. There was not a consistent pattern with respect to time or renal function. All dogs had nausea or emesis, or both, after IV administration of 99mTc-MAG3. The QRS method with 99mTc-MAG3 provides an adequate means to estimate ERPF in healthy dogs and dogs with renal failure.

Animals↗

Canine IgA glomerulonephropathy.

Three young intact male dogs housed together in a canine blood donor facility developed immune complex glomerulonephropathy within 2 years of each other. All three had membranoproliferative glomerulonephritis with varying clinical presentation and progression. Two dogs had subendothelial, and one dog subepithelial, electron microscopic dense deposits. Immunoperoxidase staining indicated that the primary antibody involved in the glomerular disease of these three dogs was IgA. The nature of the electron dense deposits was further studied by eluting and identifying immunoglobulin from affected kidneys of one dog. The primary antibody identified had a molecular weight greater than 300,000 Da and was determined to be IgA. Although IgA glomerulonephropathy is a common cause of glomerular disease in humans, this study represents the first documentation of the clinical syndrome of IgA glomerulonephropathy in the dog.

Animals↗

Study of prostatic disease in dogs: 177 cases (1981-1986).

Historical and physical signs associated with prostatic disease diagnosed in dogs over a 5.5-year period were defined. One hundred seventy-seven male dogs were determined to have prostatic abnormality. Of the 177 dogs, 87 were determined to have specific prostatic disease. The most common prostatic disease identified in this study was bacterial prostatitis, followed by prostatic cyst, prostatic adenocarcinoma, and benign hyperplasia. The most common prostatic disease identified in neutered dogs was prostatic adenocarcinoma. Mean age at onset of prostatic disease was 8.9 years; statistically significant difference was not observed between age at onset of the various types of prostatic disease identified. Doberman Pinscher was the most common breed with prostate disease. Twenty-nine percent of dogs with a specifically identifiable prostatic disease had signs of systemic illness, 41% had signs of lower urinary tract disease, 28% had signs of gastrointestinal tract abnormalities, and 13% had signs of locomotor difficulty.

Abscess↗

Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid.

The nuclear imaging technique known as quantitative renal scintigraphy was validated as a means to assess the kidney function of cats. Renal function tests were performed in 6 healthy cats and 3 cats with clinical manifestations of kidney failure. In addition, the nephrotoxic drugs, gentamicin sulfate, or amphotericin B were used in an attempt to induce renal failure in 4 cats. Using linear regression analysis, equations were derived to estimate the glomerular filtration rate (GFR) on the basis of the renal percent uptake of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). One-way ANOVA and Student's t test were used to evaluate treatment effects on clearances of inulin and creatinine, percent uptake of 99mTc-DTPA, and serum creatinine concentrations. The results show that the percent uptake of 99mTc-DTPA by the kidneys correlated well with the GFR obtained through the clearance of inulin. Thus, it was concluded that quantitative renal scintigraphy, using 99mTc-DTPA as a marker of kidney function, is an adequate technique to estimate the kidney function of healthy cats and cats with functional renal impairment. The best estimate of the GFR of cats, using the percentage dose of 99mTc-DTPA, was obtained on the 1- to 3-minute postinjection interval of the marker, using data that was background-subtracted, but not corrected for tissue absorption of gamma rays or binding of 99mTc-DTPA to plasma proteins. There was no significant difference in the mean inulin clearance, creatinine clearance, or percent uptake of 99mTc-DTPA between the 3 treatment groups of this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Development of monoclonal antibodies against canine glomerular antigens.

Monoclonal antibody producing hybridomas were developed by fusing spleen cells from BALB/c mice immunized against canine glomeruli with SP2 myeloma cells. Monoclonal antibody reactivity was tested using an indirect immunofluorescence assay on various normal canine tissues and canine kidney affected with glomerulonephritis. Two of the hybridomas developed (3H2 and 3A5) reacted with glomeruli and not with renal tubules. Antibody produced by hybridoma 3A5 also reacted with smooth muscle of all other tissues tested and 3H2 with lung tissue. Antigens recognized by monoclonal antibodies were studied by assessing their heat stability and susceptibility to proteolysis and neuraminidase digestion. Antigen and antibody molecular weights were determined by using a western blotting technique. Glomerular proteins that reacted with antibody produced by hybridoma 3H2 had molecular weights ranging from approximately 92,500 daltons to 200,000 daltons. Antigens reacting with both monoclonal antibodies were likely protein antigens. It was concluded that monoclonal antibodies would be useful in the study of glomerular antigens in normal dogs and dogs with glomerulonephritis.

Animals↗

Urologic disorders of the geriatric dog.

Disorders of the urinary system are common in geriatric dogs. Common urinary disorders that are seen in older dogs include chronic renal failure, urinary incontinence, bladder tumors, and prostate problems. Therapy for chronic renal failure is aimed at both slowing the progression of the disease and ameliorating the signs of uremia. Therapeutic recommendations for the conservative medical management of chronic renal failure include reducing dietary protein, moderately reducing salt intake, maintaining normal serum phosphorus levels, providing free access to water, avoiding stress, supplementing water soluble vitamins, using anabolic steroids to treat the anemia of chronic renal failure, treating acidosis, and controlling hypocalcemia. Urinary incontinence can often be controlled or eliminated. The appropriate approach to management of this disorder is to identify and remove specific causes. Common causes of urinary incontinence are urethral incompetence, urinary tract infection, and polyuria and polydypsia. Bladder tumors are, fortunately, not a common tumor of dogs, but are more common in geriatric dogs than in the young. The most common bladder tumor is the transitional cell carcinoma. Therapy for this tumor is usually palliative because of its malignant nature and because it is usually located in the neck of the bladder. Its location in the bladder often makes it impossible to resect the tumor completely without removing the entire bladder and diverting the ureters. New chemotherapeutic modalities are being evaluated that may increase life expectancy after diagnosis and, therefore, improve prognosis. Prostate disease is also seen in older dogs. Types of prostate abnormalities seen in dogs include prostatic hyperplasia, cysts, abscesses, acute and chronic infection, and neoplasia. The institution of proper therapy requires an accurate diagnosis; neutering is often recommended as a part of therapy regardless of the type of prostatic disease present.

Aging↗

Nephrotoxicity of amphotericin B in dogs: a comparison of two methods of administration.

Two methods of administration of amphotericin B were compared for their ability to produce nephrotoxicity in 12 dogs. Six dogs received six alternate day doses of amphotericin B: 1 mg/kg administered as a rapid bolus in 25 mL 5% dextrose in water. Another six dogs received alternate day treatments of the same dose of amphotericin B in 1 L 5% dextrose in water over 5 h. Both treatment groups experienced significant reductions in glomerular filtration rate, as measured by inulin clearance, 24 h endogenous creatinine clearance, serum creatinine and serum urea. This reduction in glomerular filtration rate was most marked in the group receiving the drug as a rapid bolus. The inulin clearances decreased from 3.54 +/- 0.30 mL/min/kg (means +/- SEM) on day 0 to 1.15 +/- 0.25 mL/min/kg on day 12 in the slow infusion group and from 3.24 +/- 0.25 mL/min/kg on day 0 to 0.46 +/- 0.11 mL/min/kg on day 12 in the rapid bolus group. Renal lesions characteristic of amphotericin B administration were observed in all dogs tested. The dogs which received amphotericin B as a rapid bolus had a significantly greater number of tubular lesions than the slow infusion group. Systemic side effects, such as vomiting, diarrhea and weight loss, were observed in both treatment groups but were most severe in the rapid bolus group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗

Use of 99mTc diethylenetriaminepentaacetic acid for assessment of renal function in dogs with suspected renal disease.

The effectiveness of technetium 99m-labeled diethylenetriaminepentaacetic acid (99mTc DTPA) to assess renal function in 13 dogs with suspected renal disease was evaluated. Glomerular filtration rates (actual GFR) were determined on the basis of endogenous creatinine clearance. Predicted GFR were determined by using 99mTc DTPA within 72 hours after the determination of creatinine clearance. The percentage of an IV administered dose of 99mTc DTPA in the kidneys (percentage dose) was determined. Two equations were used to calculate predicted GFR, which were derived from previously reported linear regression analysis of inulin (In) and creatinine (Cr) GFR vs percentage dose 99mTc DTPA in dog kidneys. The correlations of actual GFR vs predicted GFR (In) and actual GFR vs predicted GFR (Cr) were both r = 0.92. The dogs' mean actual GFR was 1.73 +/- 1.35 ml/min/kg. Their mean predicted GFR (In) and predicted GFR (Cr) were 1.92 +/- 1.42 ml/min/kg and 1.85 +/- 1.27 ml/min/kg, respectively. Therefore, 99mTc DTPA can be used with high accuracy as an agent to predict GFR in dogs with suspected renal disease. The procedure for determining GFR by use of nuclear medicine was rapid and noninvasive and appeared to induce little stress in the animals evaluated.

Animals↗

Evaluation of a short-term saline diuresis protocol for the administration of cisplatin.

A study was undertaken to determine the toxic effects of cisplatin, an antineoplastic agent, on canine kidneys and bone marrow when administered during a 6-hour saline diuresis. Cisplatin (70 mg/m2 of body surface) was administered IV to 6 healthy dogs over a 20-minute period after 0.9% NaCl solution (saline) was administered IV for 4 hours at a rate of 18.3 ml/kg/hr. After cisplatin injection, saline diuresis was continued at the same rate for 2 hours. Each dog vomited within 8 hours after the drug was administered. Clinical status, weight gain, and food consumption were normal throughout the 27-day study. All measures of renal function remained unchanged and were within normal limits for 27 days after the drug was administered. Nadirs in the daily neutrophil count were observed on days 6 (3,240 +/- 404/microliters) and 15 (1,196 +/- 275/microliters). There were no important gross or histologic abnormalities referable to cisplatin administration when the dogs were necropsied at the conclusion of the study (day 27). We concluded that cisplatin can be administered safely at a dosage of 70 mg/m2 of body surface, using a short-term diuresis protocol, and that the drug induces a nadir in the neutrophil count on days 6 and 15.

Animals↗

The effect of general anesthesia on canine lymphocyte function.

The in vitro response of canine peripheral blood lymphocytes to mitogenic stimulation was evaluated following general anesthesia for a relatively minor diagnostic procedure. A marked suppression in the blastogenic response to phytohemagglutinin and concanavalin A was observed 4 hours postinduction which persisted through the first 24 hours and was normal by 4 days. A mild suppression to stimulation with pokeweed mitogen was observed at 4 hours postinduction but the response was back to normal by 24 hours. These results suggest general anesthesia has a transient immunosuppressive effect on canine lymphocytes and T cells are more susceptible to the immunosuppressive effect than B cells.

Anesthesia, General↗

Evaluation of 99mTc-diethylenetriaminepentaacetic acid nuclear imaging for quantitative determination of the glomerular filtration rate of dogs.

The suitability of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) as an agent to assess glomerular filtration rate (GFR) in dogs was evaluated. Glomerular filtration rates of 12 healthy dogs were determined on the basis of creatinine and/or inulin clearance. Glomerular filtration rates also were determined in 7 dogs after induction of acute renal failure by administration of amphotericin B. The healthy dogs and the amphotericin B-treated dogs were given 99mTc-DTPA (1 to 2 mCi) IV. The percentage of the 99mTc-DTPA dose in the kidneys (percentage dose) was determined, with background activity subtracted from total activity at 15-s intervals 0 to 6 minutes after 99mTc-DTPA infusion. Linear regression analyses (LRA) were performed to determine whether the percentage dose at various time intervals after injection correlated with GFR calculated on the basis of creatinine and inulin clearance data. One to 3 minutes after 99mTc-DTPA administration appeared to be the best period for analysis of the data. The percentage dose of 99mTc-DTPA (corrected for kidney depth differences) was determined and LRA against GFR were performed. The percentage dose correlated better with inulin clearance (r = 0.94) than with endogenous creatinine clearance (r = 0.83). Only inulin clearance correlations improved with kidney depth correction. The LRA was used to derive an equation that could be used to calculate GFR on the basis of the percentage dose. The equation derived from inulin regression was: GFR (milliliter/minute/kilogram of body weight) = 0.194 (depth-corrected percentage dose)--0.37; the equation derived from the creatinine regression was: GFR (milliliter/minute/kilogram) = 0.171 (depth-corrected percentage dose)-0.15.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Development and characterization of a hybridoma-derived antibody (Aby 1A1) with specificity to canine thymocytes and peripheral T lymphocytes.

A hybridoma (1A1)-producing antibody with reactivity to canine T-lymphocyte surface antigens was produced, using standard fusion techniques. Antibody secreted from this hybridoma was tested for specific anti-canine lymphocyte activity, using an enzyme-linked immunosorbent assay, an indirect-fluorescent antibody assay, and cytotoxicity assay. Antibody 1A1 reacted with canine T lymphocytes, but not with B lymphocytes, and with brain tissue and connective tissue. The antibody was also characterized. Its heavy chain had a molecular weight (mol wt) of 80,000 and its light chain was 28,000 mol wt. The Aby 1A1 is a monoclonal immunoglobulin M with a kappa light chain, and it binds poorly to Staphylococcus A.

Animals↗

Development and characterization of a monoclonal antibody (Aby 6C6) that distinguishes medullary from cortical thymocytes.

A hybridoma (6C6) producing antibodies with specificities to canine thymocyte surface antigens was produced using standard fusion techniques. The Aby 6C6 has affinity for medullary thymocytes, bone marrow cells, T- and B-peripheral lymphocytes, and monocytes. The Aby 6C6 appears to have 2 heavy chains with different molecular weights, an isoelectric focusing pattern consistent with monoclonality, and is an immunoglobulin G2b antibody with a kappa light chain.

Animals↗