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Biomedical subjects

T D O'Brien

Publications and source records attributed to T D O'Brien.

At least 73 records · Page 4Linked to original sources

Crystalluria. Observations, interpretations, and misinterpretations.

Crystalluria results from oversaturation of urine with crystallogenic substance. However, oversaturation may occur as a result of in vitro as well as in vivo events. The microscopic appearance of crystals only represents a tentative identification of their composition because variable conditions associated with their formation, growth, and dissolution may alter their appearance. Definitive identification is dependent on physical methods such as optical crystallography, x-ray diffraction, and electron microscopic analysis.

Animals

Bullous emphysema and recurrent pneumothorax in the dog.

Six cases of recurrent pneumothorax requiring surgical intervention in the dog were reviewed. Radiography was not useful in identifying the source of air leakage. A median sternotomy approach was useful for identifying and removing involved lung tissue. All 6 dogs had microscopic evidence of bullous emphysema. Bronchiolitis, thickened pleura, and bronchiolar smooth muscle hypertrophy also were noticed. Underlying mild obstructive lung disease alone or in combination with a defect in pulmonary collagen probably predisposed these dogs to bullous emphysema and recurrent pneumothorax. Of the 6 dogs, 3 survived for at least 2 years after surgery.

Animals

High dose intravenous glucose tolerance test and serum insulin and glucagon levels in diabetic and non-diabetic cats: relationships to insular amyloidosis.

The high dose intravenous glucose tolerance test and concurrent immunoreactive serum insulin and glucagon levels were measured and the results related to the presence or absence of pancreatic insular amyloid in 16 cats, seven of which were known to be diabetic. Control values for all parameters were established using seven additional clinicopathologically normal cats. Nine of the 16 cats had normal fasting blood glucose levels (less than 120 mg/dl) and impaired glucose tolerance. These cats had attenuated (3/9) or normal (6/9) 0 to 5 minute glucose-stimulated insulin secretion, rising 45 to 60 minute insulin secretion (7/9), low mean insulin/glucose ratio, and normal mean serum glucagon. Three of the nine cats with impaired glucose tolerance had insular amyloidosis. These three cats had significantly higher mean blood glucose levels during the glucose tolerance test than did cats with impaired glucose tolerance and no insular amyloid deposits. Also, these three cats accounted for three of the four longest glucose disappearance one-half times (T1/2S), three of the four lowest glucose disappearance coefficients, and three of the four lowest 0 to 5 minute insulin responses. The seven diabetic cats (fasting blood glucose levels greater than 120 mg/dl) had either low to low normal (6/7) or above normal (1/7) fasting insulin levels, no insulin response to intravenous glucose stimulation (6/7), and elevated mean serum glucagon levels. Insular amyloid was present in six of the seven diabetic cats. Three diabetic cats with marked insular amyloid deposits had glucose disappearance T1/2 and K (coefficient) values, serum insulin levels, serum glucagon levels, and insulin/glucose ratios which were not significantly different from the other three diabetic cats with slight to moderate insular amyloidosis. These results confirm a strong association between the occurrence, but not the extent of insular amyloidosis and diabetes mellitus in adult diabetic cats, although amyloid replacement of pancreatic islets does not appear to be the primary diabetogenic event. Rather, these results appear to be consistent with our hypothesis that insular amyloid deposition is a morphologic marker of primary B-cell dysfunction that is basic to the pathogenesis of the diabetic condition, and is reflected clinically by impaired glucose tolerance.

Amyloidosis

Feline insular amyloid: immunohistochemical and immunochemical evidence that the amyloid is insulin-related.

Utilizing islet amyloid-laden pancreatic tissues from six diabetic cats, we demonstrated substantial immunoreactivity (peroxidase-antiperoxidase technique) of the islet amyloid with antiserum to a B chain-rich insulin fraction, but no reactivity with antisera to insulin, glucagon, or somatostatin. Islet amyloid was purified from two cats and a protein unique to the diabetic and islet amyloid-laden cats was separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Immunoreactivity of this protein with antiserum to the B chain-rich insulin fraction was also shown by immunoblotting. Attempts to obtain the amino acid composition of the purified unique protein (represented by a single 25,000 dalton band on gel electrophoresis) were not successful because the amount of protein was too small. These results provide important additional evidence that an insulin-related protein is involved in the formation of islet amyloid. Our study also shows that the diabetic cat provides several advantages for the continued study of the etiopathogenic relationship of islet amyloid and diabetes mellitus.

Amino Acids

Pancreatic ganglioneuronal amyloid. Occurrence in diabetic cats with islet amyloidosis.

Amyloid in pancreatic ganglia and nerves (ganglioneuronal amyloid) was demonstrated in 4 of 8 diabetic cats with islet amyloid deposits. Eighteen nondiabetic cats (including 4 with islet amyloid) did not have detectable amyloid in pancreatic nerves or ganglia. Ganglioneuronal amyloid had staining characteristics identical to those previously reported for islet amyloid, including 1) congophilia, 2) resistance to oxidation by KMnO4, 3) immunoreactivity (PAP technique) with antiserum to a B-chain-rich insulin fraction, and 4) no reactivity with antisera to insulin, glucagon, or somatostatin. Nonneuronal cells with insulin, glucagon, and somatostatin immunoreactivity were seen in many pancreatic ganglia and nerves; and in a few instances, B cells were found near ganglioneuronal amyloid deposits. The premise that these ganglioneuronal amyloid deposits (like islet amyloid) are insulin-related is supported by their immunoreactivity with antiserum to B-chain-rich insulin and the demonstration of B cells in pancreatic ganglia and nerves.

Amyloid

Effects of plasma treatment with purified protein A and Staphylococcus aureus Cowan I on spontaneous animal neoplasms.

Eleven dogs with spontaneous neoplasms were intensively treated with an immunoadsorption system consisting of a continuous flow centrifuge, Protein A-Sepharose columns, and a semi-automatic elution system. Despite consistent and substantial lowering of immunoglobulin G levels, tumor regression was noted in only one of 11 dogs. In contrast, infusion of small volumes of plasma after incubation with heat and formalin-treated Staphylococcus aureus Cowan I resulted in a tumoricidal response in five of six animals. These results suggest that tumor necrosis is probably not induced by Protein A-mediated removal of humoral "blocking" factors.

Animals

No apology for geriatrics.

A geriatric department is described where turnover has more than kept pace with demand over a period of 17 years. The department provides two basic services-a hospital service to the pensionable population in the community, and support to other hospital departments that care for the elderly.Community emphasis is on a high turnover of patients, enabling early contract and treatment. Over the years a fall in the proportion of "chronic" to "acute" beds has occurred and this has been achieved by having the majority of beds in the general hospital, where it is possible to provide a comprehensive medical service. The hospital role has been to prevent overloading acute resources with potential long-stay cases, and this has been possible without compromising our community obligations.

Aged

Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP.

Two distinct binding sites for [125I]human calcitonin gene-related peptide (hCGRP) were found in rat brain, skeletal muscle, and liver. Each tissue had a high affinity site with an average Kd of 46 pM and a low affinity site with an average Kd of 22 nM. Islet amyloid polypeptide (IAPP), which has N- and C-terminal sequence homology to CGRP and is produced by islet beta-cells, bound to both sites but had a potency closer to that of CGRP at the low affinity binding site. A C-terminal fragment of IAPP competed for [125I]hCGRP binding at the low affinity site with potency comparable to that of hIAPP. No specific binding to membrane preparations was found in experiments using [125I]rIAPP, which was iodinated at the C-terminal tyrosyl residue. These results suggest that some of the previously reported biological effects occurring at nM or microM concentrations of IAPP may be mediated by IAPP binding to low affinity CGRP receptors. This study further indicates that the C-terminal region of IAPP is important for binding to low affinity CGRP receptors, and suggests that C-terminal fragments of IAPP may be of biological importance.

Amino Acid Sequence

A beta-associated cerebral angiopathy and senile plaques with neurofibrillary tangles and cerebral hemorrhage in an aged wolverine (Gulo gulo).

In this study of an aged wolverine (Gulo gulo), we document neuropathologic lesions (cerebral amyloid angiopathy (CAA), neuritic plaques (NPs), neurofibrillary tangles (NFTs), and granulovacuolar degeneration strikingly similar to those present in aging and Alzheimer's disease (AD), with the additional finding of concurrent cerebral hemorrhage. A beta immunoreactive cerebral amyloid angiopathy and senile plaques (neuritic and diffuse) were present throughout the cerebral cortex and hippocampus. Ubiquitin immunoreactivity was noted in peripheral portions of some of the plaques. Argyrophilic intracellular neurofibrillary tangles containing abnormally phosphorylated (Ser 202) tau protein were present within cortical and hippocampal neurons. The wolverine should be added to the list of nonhuman species (dogs, nonhuman primates, polar bears) with amyloid deposits similar to those in aged humans and in humans with AD. The aged wolverine appears to be distinct from other nonhuman species in possessing plaques and NFTs, as well as other histologic cerebral lesions frequently associated with AD.

Aging

Continent jejunal reservoir (Kock pouch) for urinary diversion in dogs.

Urinary diversion by transplantation of both ureters into a reservoir constructed from 60 cm of jejunum was performed in six clinically normal dogs. The reservoir was connected to a stoma on the abdominal wall through a valve constructed from a short segment of intussuscepted bowel to provide continence. The reservoir was emptied three times daily by catheterization. One dog did not survive the surgical procedure and two dogs died within 1 week of surgical complications. The postoperative capacity of the reservoir in surviving dogs was 100 to 200 mL; it increased during the first month to 600 to 750 mL. Continence was excellent in two dogs. One dog was continent until month 2, when partial slippage of the intussusception occurred. A reversible hyponatremic, hypochloremic, hypokalemic metabolic acidosis developed. Bacteriuria was not responsive to systemic or local instillation of antibiotics. Ascending pyelonephritis, hydroureter, and hydronephrosis occurred in two dogs. Struvite urinary calculi formed in one dog. The procedure as described would be unsuitable for clinical use in dogs.

Acidosis

Correlation of urine protein/creatinine ratio and twenty-four-hour urinary protein excretion in normal cats and cats with surgically induced chronic renal failure.

Urine protein/creatinine (UP/C) ratios and 24-hour urinary protein excretion were compared in clinically normal cats and cats with surgically induced chronic renal failure (CRF). Mean 24-hour urinary protein excretion in 30 clinically normal cats fed a 28% protein diet (dry weight basis) was 4.93 mg/kg/24-hour (SD = 1.34) with a range of 2.99 to 8.88. Mean UP/C ratio in these cats was 0.134 (SD = 0.037) with a range of 0.073 to 0.239. Mean 24-hour urinary protein excretion in CRF cats was 10.49 mg/kg/24-hour (SD = 11.28) with a range of 2.16 to 62.93. Mean UP/C ratio in the CRF cats was 0.359 (SD = 0.374) with a range of 0.061 to 1.916. Linear regression showed high correlation (R2 = 0.973, P less than 0.001) between 24-hour urinary protein excretion and UP/C ratio in clinically normal cats and cats with surgically induced chronic renal failure. The regression equation for 24-hour urinary protein excretion versus UP/C ratio was: 24-hour urinary protein excretion = 29.39 (UP/C) + 0.18. Results of this study indicate that UP/C ratios are a valid estimate of 24-hour urinary protein excretion in clinically normal and CRF cats. Dietary protein intake significantly affected UP/C ratios in clinically normal cats and cats with surgically induced CRF. Therefore, the influence of dietary protein should be considered when interpreting UP/C ratios.

Animals

Duplex Doppler estimation of Pourcelot resistive index in arcuate arteries of sedated normal cats.

Renal failure is an important cause of morbidity and mortality in feline patients. In human patients, intrarenal blood flow values obtained with duplex Doppler ultrasonography have been used to aid in the diagnosis and prognosis of renal failure. The purpose of this report is to present values for resistance to intrarenal blood flow in normal cats, derived by duplex Doppler ultrasonography. Ten mature clinically healthy conditioned domestic shorthaired cats were screened for normal renal anatomy and function by CBC, serum biochemical profile, urinalysis, urine protein/creatinine ratio, endogenous creatinine clearance, and renal B-mode ultrasonography; and for normal systemic blood pressure with Doppler pressure cuff measurement. Subsequently, the cats were sedated with ketamine hydrochloride, and values for mean intrarenal (arcuate artery) resistance to blood flow were determined by duplex Doppler ultrasonography, and expressed as the Pourcelot resistive index, a ratio of systolic to diastolic flow commonly used in duplex Doppler sonography in human patients. After duplex Doppler sonographic examination, histological normalcy of the kidneys was verified by evaluation of ultrasound-guided percutaneous renal biopsy. Based on the obtained resistive indices, 95% confidence intervals for normal values were calculated as follows: left kidney, 0.52 to 0.60; right kidney, 0.55 to 0.63. No statistically significant difference was noted between the values obtained for the right versus the left kidney.

Animals

Evaluation of urine gamma-glutamyl transpeptidase-to-creatinine ratio as a diagnostic tool in an experimental model of aminoglycoside-induced acute renal failure in the dog.

The potential diagnostic utility of the urine gamma-glutamyl transpeptidase (GGT)-to-creatinine ratio was evaluated in an experimental canine model of aminoglycoside-induced nephrotoxicity. A therapeutic dosage of gentamicin resulted in a twofold increase in the mean urine GGT-to-creatinine ratio that was not associated with clinically significant nephrotoxicity. In dogs each given a nephrotoxic dosage of gentamicin, an increase in mean urine GGT-to-creatinine ratios approximately three times baseline values preceded clinically significant abnormalities in serum creatinine, urine specific gravity, and urine protein-to-creatinine ratio. The urine GGT-to-creatinine ratio appears superior as an early indicator of aminoglycoside-induced nephrotoxicity. Further studies in canine clinical cases are warranted.

Acute Kidney Injury