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1.
Can J Vet Res ; 87(4): 260-264, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37790268

ABSTRACT

Interstitial glucose monitoring systems are commonly being used in diabetic dogs. The aim of this study was to document the incidence of complications associated with the use of a flash glucose monitoring system (FGMS) in dogs. Medical records of dogs that had placement of a 14-day FGMS during a 1-year period were reviewed. Data retrieved included the number of days the sensor remained attached and functional, sensor detachment, sensor failure prior to the end of the 14-day monitoring period, and dermatologic changes at the sensor site. Descriptive statistics were used to characterize the data. Thirty-four dogs had FGMSs placed. Most [32/34 (94%)] sensors were placed over the dorsolateral aspect of the thorax caudal to the scapula. Twenty-four sensors (71%) remained attached for the full 14 days. Incidence of complications associated with FGMS use was 13/34 (38%). The most frequent complication was mild dermatologic changes at the sensor site [6/34 (18%)]. Erythema and crusting at the attachment site were common and could be related to contact dermatitis, hypersensitivity, or skin preparation prior to placement. Flash glucose monitoring systems are safe in dogs, although there are some potential complications that should be discussed with dog owners.


Les systèmes de surveillance du glucose interstitiel sont couramment utilisés chez les chiens diabétiques. Le but de cette étude était de documenter l'incidence des complications associées à l'utilisation d'un système de surveillance flash du glucose (FGMS) chez le chien. Les dossiers médicaux des chiens qui ont eu la mise en place pendant 14 jours d'un FGMS au cours d'une période d'un an ont été examinés. Les données récupérées comprenaient le nombre de jours pendant lesquels le capteur est resté attaché et fonctionnel, le détachement du capteur, la défaillance du capteur avant la fin de la période de surveillance de 14 jours et les changements dermatologiques au site du capteur. Des statistiques descriptives ont été utilisées pour caractériser les données. Trente-quatre chiens ont eu des FGMS placés. La plupart [32/34 (94 %)] des capteurs ont été placés sur la face dorsolatérale du thorax caudal à l'omoplate. Vingt-quatre capteurs (71 %) sont restés attachés pendant les 14 jours complets. L'incidence des complications associées à l'utilisation du FGMS était de 13/34 (38 %). La complication la plus fréquente était de légers changements dermatologiques au niveau du site du capteur [6/34 (18 %)]. L'érythème et la formation de croûtes au site de fixation étaient courants et pouvaient être liés à une dermatite de contact, à une hypersensibilité ou à la préparation cutanée avant la mise en place. Les systèmes de surveillance flash de la glycémie sont sans danger pour les chiens, bien qu'il existe certaines complications potentielles qui devraient être discutées avec les propriétaires de chiens.(Traduit par Docteur Serge Messier).


Subject(s)
Diabetes Mellitus , Dog Diseases , Dogs , Animals , Glucose , Blood Glucose Self-Monitoring/veterinary , Blood Glucose , Diabetes Mellitus/veterinary , Monitoring, Physiologic/veterinary , Monitoring, Physiologic/methods
3.
Can J Vet Res ; 86(1): 52-58, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34975223

ABSTRACT

The aim of this study was to investigate the effect of bexagliflozin on glycemic control in poorly regulated diabetic cats and to evaluate for adverse events associated with this medication. Sodium-glucose cotransporter 2 inhibitors are a newer class of drugs used in the management of humans with type 2 diabetes mellitus. The objective of this study was to evaluate the effect of the orally administered drug, bexagliflozin in a group of poorly regulated diabetic cats over a 4-week study period. Five client-owned cats with poorly controlled diabetes mellitus receiving insulin therapy were enrolled. Bexagliflozin was administered once daily. Serum fructosamine, serum biochemistry profile, and 10-hour blood glucose curves were assessed at baseline (Day 0), Day 14, and Day 28. All cats had a significant reduction in insulin dose requirement (P = 0.015) and insulin was discontinued in 2 cats. There was a significant decrease in blood glucose concentration obtained from blood glucose concentration curves during the study period (P = 0.022). Serum fructosamine decreased in 4 of the 5 cats with a median decrease of 152 µmol/L (range: 103 to 241 µmol/L), which was not statistically significant (P = 0.117). No cats had any documented episodes of hypoglycemia. Adverse effects were mild. The addition of bexagliflozin significantly improved diabetic management in this group of cats.


Le but de cette étude était d'étudier l'effet de la bexagliflozine sur la maitrise de la glycémie chez les chats diabétiques mal régulés et d'évaluer les événements indésirables associés à ce médicament. Les inhibiteurs du cotransporteur sodium-glucose 2 sont une nouvelle classe de médicaments utilisés dans la prise en charge des personnes atteintes de diabète de type 2. L'objectif de cette étude était d'évaluer l'effet du médicament administré par voie orale, la bexagliflozine, dans un groupe de chats diabétiques mal régulés sur une période d'étude de 4 semaines. Cinq chats appartenant à des clients atteints de diabète sucré mal maitrisé et recevant une insulinothérapie ont été inclus. La bexagliflozine a été administrée une fois par jour. La fructosamine sérique, le profil biochimique sérique et les courbes de glycémie sur 10 heures ont été évalués au départ (jour 0), au jour 14 et au jour 28. Tous les chats ont présenté une réduction significative de la dose d'insuline requise (P = 0,015) et l'insuline a été interrompue chez deux chats. Il y avait une diminution significative de la concentration de glucose dans le sang obtenue à partir des courbes de concentration de glucose dans le sang au cours de la période d'étude (P = 0,022). La fructosamine sérique a diminué chez 4 des 5 chats avec une diminution médiane de 152 µmol/L (plage : 103 à 241 µmol/L), ce qui n'était pas statistiquement significatif (P = 0,117). Aucun chat n'a eu d'épisodes documentés d'hypoglycémie. Les effets indésirables étaient légers. L'ajout de bexagliflozine a considérablement amélioré la gestion du diabète dans ce groupe de chats.(Traduit par Docteur Serge Messier).


Subject(s)
Cat Diseases , Diabetes Mellitus, Type 2 , Pyrans , Administration, Oral , Animals , Blood Glucose/drug effects , Cat Diseases/blood , Cat Diseases/drug therapy , Cats , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/veterinary , Fructosamine/blood , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacology , Insulin/therapeutic use , Pyrans/administration & dosage , Pyrans/adverse effects , Pyrans/pharmacology , Treatment Outcome
4.
J Feline Med Surg ; 23(6): 557-562, 2021 06.
Article in English | MEDLINE | ID: mdl-33078691

ABSTRACT

OBJECTIVES: Glucose monitoring is an integral part of diabetes management. Interstitial glucose monitoring systems are increasingly commonly being used for this purpose in dogs and cats, including the use of a flash glucose monitoring system (FGMS). The aim of this study was to describe the incidence and nature of complications associated with the use of an FGMS in diabetic cats. METHODS: The medical records of all cats that had placement of a 14-day FGMS during a 1-year period were retrospectively reviewed. Data retrieved included the number of days the sensor remained attached and functional, location of sensor placement and complications associated with the sensor. Complications were defined as early sensor detachment, sensor failure prior to the end of the 14-day monitoring period and dermatologic changes at the sensor site. Descriptive statistics were used to characterize the data. RESULTS: Twenty cats had a total of 33 FGMSs placed. The majority (30/33 [91%]) of sensors were placed over the dorsolateral aspect of the thorax just caudal to the scapula. Twenty (61%) FGMSs remained attached and functional for the full 14 days. The overall incidence of complications associated with FGMS use was 10/33 (30%). The most frequent complication was early sensor detachment (n = 5/33 [15%]). Mild dermatologic changes (erythema, crusts) were noted with 4/33 (12%) FGMSs. More serious complications (skin erosions, abscess formation) were noted with 2/33 (6%) FGMSs. CONCLUSIONS AND RELEVANCE: The use of the FGMS is relatively safe in cats, although there are potential complications that owners should be made aware of.


Subject(s)
Cat Diseases , Diabetes Mellitus , Dog Diseases , Animals , Blood Glucose , Blood Glucose Self-Monitoring/veterinary , Cat Diseases/epidemiology , Cats , Diabetes Mellitus/veterinary , Dogs , Retrospective Studies
5.
J Clin Pathol ; 72(8): 562-565, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31097491

ABSTRACT

AIMS: This case series intends to expand currently limited knowledge regarding the existence and diagnostic significance of intramucosal fat in colorectal polyps. METHODS: Clinicopathological features of nine such polyps were reported following histopathological review, including S100 and EMA immunohistochemistry. RESULTS AND CONCLUSIONS: Such review subdivided seven polyps into three groups: (1) mucosal perineurioma/serrated polyps with fat among the perineurial stroma (three cases); (2) submucosal lipomas with adipose tissue extending into the overlying mucosa (two cases) and (3) polyps with intramucosal adipose tissue only, that is, the newly described but less-recognised entity known as intramucosal lipoma (two cases). The two remaining polyps of this series did not include submucosa but, from assessing their muscularis mucosae, were favoured to represent intramucosal lipomas. The first two phenomena are formally described for the first time by this case series. The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic.


Subject(s)
Adipose Tissue/pathology , Colonic Polyps/pathology , Colorectal Neoplasms/pathology , Intestinal Mucosa/pathology , Intestinal Polyps/pathology , Lipoma/pathology , Rectal Diseases/pathology , Aged , Colonic Polyps/chemistry , Colorectal Neoplasms/chemistry , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Intestinal Mucosa/chemistry , Intestinal Polyps/chemistry , Lipoma/chemistry , Male , Middle Aged , Mucin-1/analysis , Predictive Value of Tests , Rectal Diseases/metabolism , S100 Proteins/analysis
6.
J Vet Diagn Invest ; 29(1): 14-19, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27852811

ABSTRACT

Cats with cholestatic liver disease experience significant morbidity and mortality when they undergo invasive procedures under anesthesia. Although inadequate adrenal response might account for these outcomes, adrenal function in cats with cholestatic liver disease has not been documented, to our knowledge. The goal of our study was to describe adrenal function in these cats. Twenty-seven cats with a serum bilirubin >230 µmol/L (3 mg/dL) and serum alanine aminotransferase >2 times the upper limit of normal had pre- and 60-min post-adrenocorticotropic hormone (ACTH) cortisol analysis after administration of 5 µg/kg cosyntropin intravenously. The change in cortisol concentrations (delta cortisol) was calculated. Pre- and post-ACTH cortisol concentrations were compared to reference values. Pre-ACTH, post-ACTH, and delta cortisol values were compared between cats surviving to discharge or for 30 d postdischarge. Mean pre-ACTH cortisol levels (205 ± 113 nmol/L [7.4 ± 4.2 µg/dL]) and post-ACTH cortisol levels (440 ± 113 nmol/L [15.9 ± 4.1 g/dL]) in cholestatic cats were significantly greater than reference values in clinically normal cats. There was no association of pre- or post-ACTH cortisol with survival. Cats with a delta cortisol <179 nmol/L (6.5 µg/dL) were more likely to be non-survivors at 30 d post-discharge ( p = 0.037) than cats with delta cortisol >179 nmol/L (6.5 µg/dL). Results indicate that cats with cholestasis have high basal and ACTH-stimulated cortisol values. A delta cortisol <179 nmol/L (6.5 µg/dL) defines a population of cats that have decreased 30-d survival.


Subject(s)
Adrenocorticotropic Hormone/blood , Cat Diseases/blood , Cholestasis, Intrahepatic/veterinary , Alanine Transaminase/blood , Animals , Bilirubin/blood , Case-Control Studies , Cats , Cholestasis, Intrahepatic/blood , Female , Hydrocortisone/blood , Hypothalamo-Hypophyseal System , Male , Pituitary-Adrenal System
7.
Can Vet J ; 57(10): 1077-1080, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27708447

ABSTRACT

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.


Développement mammaire, hyperœstrogénémie et hypocortisolémie chez un chat mâle atteint d'un corticosurrénalome malin. Un corticosurrénalome malin, causant l'hyperœstrogénémie et produisant une hyperplasie mammaire et un comportement sexuel, a été diagnostiqué chez un chat domestique à poil court mâle stérilisé âgé de 14 ans. Une surranélectomie droite et une biopsie de la glande mammaire ont été réalisées. Un diagnostic de corticosurrénalome devrait être éliminée chez tout chat stérilisé ayant un développement mammaire et/ou manifestant un comportement sexuel.(Traduit par Isabelle Vallières).


Subject(s)
Adrenal Cortex Neoplasms/veterinary , Carcinoma/veterinary , Cat Diseases/etiology , Estrogens/metabolism , Mammary Glands, Animal/pathology , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/surgery , Adrenalectomy/veterinary , Animals , Carcinoma/complications , Carcinoma/surgery , Cat Diseases/pathology , Cat Diseases/surgery , Cats , Estrogens/blood , Hydrocortisone/blood , Hydrocortisone/metabolism , Male
9.
J Feline Med Surg ; 18(2): 77-84, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25714105

ABSTRACT

OBJECTIVES: The objective of this retrospective study was to describe the clinical signs and diagnostic findings in cats with histopathologically confirmed adrenal neoplasms, and to assess correlations with survival data. METHODS: Study data were acquired by reviewing medical records for all cats diagnosed with adrenal neoplasms at seven referral institutions between 2002 and 2013. Inclusion criteria required a histopathologic diagnosis of an adrenal neoplasm (ante-mortem or on necropsy). RESULTS: Thirty-three cats met the inclusion criteria for the study. The most common presenting complaints included weakness (n = 12), respiratory signs (n = 4), blindness (n = 4) or gastrointestinal signs (n = 3). Laboratory abnormalities included hypokalemia (n = 18), alkalemia (n = 12), elevated creatine kinase (>3000, n = 5) and azotemia (n = 4). In addition, hypertension was noted in 13 cats. Thirty cats were diagnosed with cortical tumors (17 carcinomas, 13 adenomas) and three cats were diagnosed with pheochromocytomas. Twenty-five cats underwent tests to evaluate the function of the adrenal tumors; 19/25 cats had functional tumors (hyperaldosteronism [n = 16], hypercortisolemia [n = 1], high estradiol [n = 1], and hypersecretion of aldosterone, estradiol and progesterone [n = 1]). Twenty-six cats underwent adrenalectomy, one cat was medically managed and six were euthanized without treatment. Long-term survival postoperatively ranged from 4-540 weeks, with 20 (77%) cats surviving the perioperative period of 2 weeks. The only variable that was found to be negatively associated with survival was female sex. The most common complications noted during the perioperative period were hemorrhage and progressive lethargy and anorexia. CONCLUSIONS AND RELEVANCE: Surgical treatment for feline adrenal tumors (regardless of tumor type) resulted in good long-term survival. Given that pre- and postoperative hypocortisolemia was identified in this study, and, in addition, hypersecretion of more than one adrenal hormone occurred in one cat, adrenal panels prior to surgery may be beneficial as part of the preoperative work-up.


Subject(s)
Adrenal Gland Neoplasms/veterinary , Adrenalectomy/veterinary , Cat Diseases/diagnosis , Cat Diseases/surgery , Adenoma/veterinary , Animals , Cats , Female , Hyperaldosteronism/veterinary , Hypertension/veterinary , Hypokalemia/veterinary , Retrospective Studies
10.
Can Vet J ; 56(1): 44-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25565713

ABSTRACT

Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the family history revealed the dogs' maternal grandmother also had hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian dogs.


Hypoadrénocorticisme dans un parentage de chiens Poméraniens. Trois chiens Poméraniens adultes, tous issus de deux portées ayant les mêmes parents, ont été diagnostiqués d'hypoadrénocorticisme primaire après l'apparition d'une crise hypoadrénale. L'examen des antécédents familiaux a révélé que la grand-mère maternelle des chiens souffrait aussi d'hypoadrénocorticisme. Le pédigrée des 4 chiens a été certifié par l'American Kennel Club. Une hérédité d'hypoadrénocorticisme est proposée chez ces Poméraniens.(Traduit par Isabelle Vallières).


Subject(s)
Adrenal Insufficiency/veterinary , Dog Diseases/genetics , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/drug therapy , Adrenal Insufficiency/genetics , Animals , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dogs , Female , Male , Pedigree , Prednisone/administration & dosage , Prednisone/therapeutic use
11.
Article in English | MEDLINE | ID: mdl-25546713

ABSTRACT

OBJECTIVE: The goal of this pilot study was to compare regular insulin administered by continuous rate infusion (CRI) to an approach using insulin glargine and regular insulin administered intermittently. DESIGN: Prospective randomized clinical trial. SETTING: University teaching hospital. ANIMALS: Sixteen cats with diabetic ketoacidosis (DKA). INTERVENTIONS: Cats with DKA were randomized to either low-dose regular insulin CRI (CRI group; n = 8) or intermittent short- and long-acting insulin injections (subcutaneous [SC] glargine plus intramuscular [IM] regular insulin; SC/IM group; n = 8). MEASUREMENTS AND MAIN RESULTS: Time of normalization of pH, bicarbonate, hyperglycemia, ketonemia, and appetite, as well as duration of hospitalization were recorded. Eleven of 16 cats (59%) survived to discharge, with no difference in survival between groups (P = 0.99). Times of resolution of hyperglycemia (P = 0.02) and ketonemia (P = 0.04), and normalization of pH (P = 0.04), and bicarbonate (P = 0.03) were significantly shorter in the SC/IM group. Cats in the SC/IM group also had a significantly shorter duration of hospitalization (SC/IM: median = 54 hr [range, 19-118 hr]; CRI: median = 111 hr [range, 58-271 hr]; P = 0.04). Time of first meal was not significantly different between groups. CONCLUSIONS: Although further research is required, an approach using intermittent short- and long-acting insulin injections appeared to be an effective option for treatment of DKA in cats.


Subject(s)
Cat Diseases/drug therapy , Diabetic Ketoacidosis/drug therapy , Diabetic Ketoacidosis/veterinary , Insulin Glargine/administration & dosage , Insulin/administration & dosage , Animals , Cats , Critical Care , Drug Administration Schedule/veterinary , Drug Therapy, Combination/veterinary , Female , Infusions, Intravenous/veterinary , Injections, Intramuscular/veterinary , Injections, Subcutaneous/veterinary , Male , Pilot Projects , Prospective Studies , Treatment Outcome , Veterinary Medicine
12.
Histopathology ; 61(6): 1209-13, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22882180

ABSTRACT

AIMS: Colonic and rectal biopsies, often taken from an endoscopically normal large bowel, form a significant proportion of the histopathology workload. The aim of this study was to determine diagnostic yield from mucosal biopsies in patients with normal colonoscopy or sigmoidoscopy, and whether or not diarrhoea is predictive of abnormal histology. METHODS AND RESULTS: A retrospective analysis of pathology requests, endoscopy and pathology reports taken during 1 year was undertaken in a tertiary care hospital for all biopsies from endoscopically normal ileal, colonic and rectal mucosa. Of 626 patients fulfilling inclusion criteria, 602 had at least one colonic or rectal biopsy. Colorectal histology was abnormal in 65 (14.5%) of 447 patients with diarrhoea, while of 155 patients without diarrhoea, histology was abnormal in 17 (11%; P=0.41). Patients older than 60 years had a markedly increased likelihood of a specific histological abnormality [odds ratio 2.76 (1.30-5.79); P=0.0045]. Diagnoses included microscopic colitis, distorted mucosal architecture consistent with inflammatory bowel disease, ischaemia, polyps, mucosal prolapse and schistosomiasis. CONCLUSIONS: Biopsy of an endoscopically normal large bowel, and of the normal terminal ileum in isolation, yields little abnormal histology. Diarrhoea per se does not identify patients at higher risk of abnormal histology. Increased age, however, does, and mucosal biopsy in the endoscopically normal colon and rectum may be more cost-effective in patients aged more than 60 years.


Subject(s)
Colitis/pathology , Colon/pathology , Colonic Polyps/pathology , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/pathology , Rectum/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy/economics , Colitis/complications , Colitis/diagnosis , Colonic Polyps/complications , Colonic Polyps/diagnosis , Colonoscopy/economics , Cost-Benefit Analysis , Diarrhea/etiology , Female , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnosis , Male , Middle Aged , Retrospective Studies , Sigmoidoscopy/economics , Young Adult
14.
Cancer Res ; 69(10): 4434-42, 2009 May 15.
Article in English | MEDLINE | ID: mdl-19366804

ABSTRACT

Mutations in the androgen receptor (AR) that enable activation by antiandrogens occur in hormone-refractory prostate cancer, suggesting that mutant ARs are selected by treatment. To validate this hypothesis, we compared AR variants in metastases obtained by rapid autopsy of patients treated with flutamide or bicalutamide, or by excision of lymph node metastases from hormone-naïve patients. AR mutations occurred at low levels in all specimens, reflecting genetic heterogeneity of prostate cancer. Base changes recurring in multiple samples or multiple times per sample were considered putative selected mutations. Of 26 recurring missense mutations, most in the NH(2)-terminal domain (NTD) occurred in multiple tumors, whereas those in the ligand binding domain (LBD) were case specific. Hormone-naïve tumors had few recurring mutations and none in the LBD. Several AR variants were assessed for mechanisms that might underlie treatment resistance. Selection was evident for the promiscuous receptor AR-V716M, which dominated three metastases from one flutamide-treated patient. For the inactive cytoplasmically restricted splice variant AR23, coexpression with AR enhanced ligand response, supporting a decoy function. A novel NTD mutation, W435L, in a motif involved in intramolecular interaction influenced promoter-selective, cell-dependent transactivation. AR-E255K, mutated in a domain that interacts with an E3 ubiquitin ligase, led to increased protein stability and nuclear localization in the absence of ligand. Thus, treatment with antiandrogens selects for gain-of-function AR mutations with altered stability, promoter preference, or ligand specificity. These processes reveal multiple targets for effective therapies regardless of AR mutation.


Subject(s)
Mutation , Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Amino Acid Substitution , Anilides/therapeutic use , Antineoplastic Agents/therapeutic use , Autopsy , Cycloheximide/pharmacology , DNA Primers , Flutamide/therapeutic use , Humans , Lymphatic Metastasis/pathology , Male , Nitriles/therapeutic use , Prostatic Neoplasms/drug therapy , RNA, Neoplasm/drug effects , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tosyl Compounds/therapeutic use
15.
J Feline Med Surg ; 11(2): 125-30, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18835801

ABSTRACT

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.


Subject(s)
Cat Diseases/diet therapy , Cat Diseases/drug therapy , Diabetes Mellitus/veterinary , Diet, Diabetic/veterinary , Hypoglycemic Agents/administration & dosage , Insulin/analogs & derivatives , Animals , Blood Glucose/analysis , Cat Diseases/blood , Cats , Diabetes Mellitus/diet therapy , Diabetes Mellitus/drug therapy , Diet, Carbohydrate-Restricted/veterinary , Diet, Diabetic/methods , Dietary Carbohydrates/administration & dosage , Dietary Proteins/administration & dosage , Female , Fructosamine/blood , Insulin/administration & dosage , Insulin Glargine , Insulin, Long-Acting , Male , Treatment Outcome
16.
Mol Cancer Res ; 6(11): 1691-701, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19010817

ABSTRACT

Gain-of-function mutations in the androgen receptor (AR) are found in prostate cancer and are implicated in the failure of hormone therapy. Most studies have emphasized the ligand-binding domain (LBD) where mutations can create promiscuous receptors, but mutations in the NH(2)-terminal transactivation domain have also been found. To assess AR alteration as a mechanism of treatment resistance, a mouse model (h/mAR-TRAMP) was used in which the murine AR coding region is replaced by human sequence and prostate cancer initiated by a transgenic oncogene. Mice received either no treatment, androgen depletion by castration, or treatment with antiandrogens, and 20 AR transcripts were sequenced per end-stage tumor. All tumors expressed several mutant alleles, although most mutations were low frequency. Some mutations that occurred multiple times within the population were differentially located dependent on treatment. Mutations in castrated or antiandrogen-treated mice were widely dispersed but with a prominent cluster in the LBD (amino acids 736-771), whereas changes in intact mice centered near the NH(2)-terminal polymorphic glutamine tract. Functional characterization of selected LBD mutant alleles showed diverse effects on AR activity, with about half of the mutations reducing transactivation in vitro. One receptor, AR-R753Q, behaved in a cell- and promoter-dependent manner, although as a germ-line mutation it causes androgen insensitivity syndrome. This suggests that alleles that are loss of function during development may still activate a subset of AR targets to become gain of function in tumorigenesis. Mutant ARs may thus use multiple mechanisms to evade cancer treatment.


Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Mutation , Orchiectomy , Prostatic Neoplasms/therapy , Receptors, Androgen/genetics , Animals , DNA Mutational Analysis , Disease Models, Animal , Female , Gene Expression Regulation, Neoplastic , Gene Knock-In Techniques/methods , Humans , Male , Mice , Mice, Transgenic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Protein Interaction Domains and Motifs/genetics , Receptors, Androgen/physiology
17.
J Steroid Biochem Mol Biol ; 108(3-5): 230-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17936615

ABSTRACT

Androgen, acting via the androgen receptor (AR), is central to male development, differentiation and hormone-dependent diseases such as prostate cancer. AR is actively involved in the initiation of prostate cancer, the transition to androgen independence, and many mechanisms of resistance to therapy. To examine genetic variation of AR in cancer, we created mice by germ-line gene targeting in which human AR sequence replaces that of the mouse. Since shorter length of a polymorphic N-terminal glutamine (Q) tract has been linked to prostate cancer risk, we introduced alleles with 12, 21 or 48 Qs to test this association. The three "humanized" AR mouse strains (h/mAR) are normal physiologically, as well as by cellular and molecular criteria, although slight differences are detected in AR target gene expression, correlating inversely with Q tract length. However, distinct allele-dependent differences in tumorigenesis are evident when these mice are crossed to a transgenic prostate cancer model. Remarkably, Q tract variation also differentially impacts disease progression following androgen depletion. This finding emphasizes the importance of AR function in androgen-independent as well as androgen-dependent disease. These mice provide a novel genetic paradigm in which to dissect opposing functions of AR in tumor suppression versus oncogenesis.


Subject(s)
Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Amino Acid Sequence , Animals , Glutamine/genetics , Humans , Male , Mice , Mice, Transgenic , Peptides/chemistry , Peptides/genetics , Prostatic Neoplasms/metabolism
18.
Hum Mol Genet ; 17(1): 98-110, 2008 Jan 01.
Article in English | MEDLINE | ID: mdl-17906287

ABSTRACT

The androgen receptor (AR) is involved in the initiation and progression of prostate cancer and its transition to androgen independence. Genetic variation in AR may contribute to disease risk and has been studied for a polymorphic N-terminal glutamine (Q) tract that shows population heterogeneity. While the length of this tract is known to affect AR in vitro, association with disease is complicated by genetic and environmental factors that have led to discordant epidemiological findings. To clarify the effect of Q tract polymorphism on prostate cancer, we created mice bearing humanized AR genes (h/mAr) varying in Q tract length. ARs with short Q tracts (12Q), which are transcriptionally more active, induce earlier disease in the transgene-induced TRAMP prostate cancer model than alleles with median (21Q) or long (48Q) tracts. Disease length varies within each genotype, with greater differentiation and AR expression in slower growing tumors. Remarkably, following androgen ablation, Q tract length has effects that are also allele-dependent and in directions opposite to those in hormone intact mice. Differences in AR activity conferred by Q tract length thus appear to direct distinct pathways of androgen-independent as well as androgen-dependent progression, and highlight substantial risk that may be associated with alterations in the androgen axis. This AR allelic series in humanized mice provides an experimental paradigm to dissect the role of AR in prostate cancer initiation and progression, to model response to treatment and to test therapies targeted specifically to the human AR.


Subject(s)
Neoplasms, Hormone-Dependent/genetics , Neoplasms, Hormone-Dependent/metabolism , Peptides/chemistry , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Receptors, Androgen/chemistry , Receptors, Androgen/genetics , Animals , Base Sequence , DNA Primers/genetics , Genotype , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neoplasms, Hormone-Dependent/etiology , Orchiectomy , Prostatic Intraepithelial Neoplasia/etiology , Prostatic Intraepithelial Neoplasia/genetics , Prostatic Intraepithelial Neoplasia/metabolism , Prostatic Neoplasms/etiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Receptors, Androgen/metabolism
19.
Vet Radiol Ultrasound ; 47(3): 287-94, 2006.
Article in English | MEDLINE | ID: mdl-16700181

ABSTRACT

Dilation of the pancreatic duct has been described as an ultrasonographic feature of pancreatitis in cats. The purpose of this study was to determine normal pancreatic duct width in healthy older cats and assess the significance of pancreatic duct dilation observed in a clinical population. In a prospective study, pancreatic ultrasound was performed in 15 healthy cats (mean age 13 +/- 3 years). Mean pancreatic width of left lobe, body, and right lobe was 0.65 +/- 0.16 cm (0.46-1.03 cm), 0.64 +/- 0.14 cm (0.46-0.9 cm), and 0.43 +/- 0.09 cm (0.3-0.57 cm), respectively. Mean pancreatic duct width was 0.13 +/- 0.04 cm (0.06-0.24 cm), which was significantly larger than previously reported for younger cats (0.08 +/- 0.025 cm) (P < 0.001). One hundred and four of 1445 clinical patients (7.2%) were diagnosed with a dilated pancreatic duct and were reviewed in a retrospective study. Incidence of pancreatic duct dilation was significantly higher in older than in younger cats (2.7% in cats < 1-5 years vs. 18.1% in cats 15 years or older; P < 0.001). Mean pancreatic duct width was 0.23 +/- 0.07 cm (0.14-0.52 cm), and there was a significant correlation between age and pancreatic duct width (P = 0.01). There was also a significant relationship between the mean ratio of pancreatic duct width and pancreatic thickness (n = 98) (0.29 +/- 0.09; 0.09-0.58; P = 0.041). There was no significant difference in age between cats with and without pancreatic disease. There was no association between pancreatic disease and pancreatic duct width or pancreatic duct width/pancreatic thickness ratio. Pancreatic duct width and pancreatic duct width/pancreatic thickness ratio in cats are significantly associated with age.


Subject(s)
Aging , Cat Diseases/diagnostic imaging , Cats/anatomy & histology , Pancreas/diagnostic imaging , Pancreatic Ducts/diagnostic imaging , Pancreatitis, Chronic/veterinary , Animals , Cat Diseases/epidemiology , Female , Male , Massachusetts/epidemiology , Pancreas/anatomy & histology , Pancreatic Ducts/anatomy & histology , Pancreatitis, Chronic/diagnostic imaging , Prospective Studies , Records , Reference Values , Retrospective Studies , Ultrasonography
20.
J Vet Intern Med ; 20(2): 234-8, 2006.
Article in English | MEDLINE | ID: mdl-16594577

ABSTRACT

The goals of this study were to compare the efficacy of once-daily administered Glargine insulin to twice-daily administered Lente insulin in cats with diabetes mellitus and to describe the use of a high-protein, low-carbohydrate diet designed for the management of diabetes mellitus in cats. All cats with naturally occurring diabetes mellitus were eligible for inclusion. Baseline testing included a physical examination, serum biochemistry, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were fed the high-protein, low-carbohydrate diet exclusively. Cats were randomized to receive either 0.5 U/kg Lente insulin q12h or 0.5 U/kg Glargine insulin q24h. Re-evaluations were performed on all cats at weeks 1, 2, 4, 8, and 12, and included an assessment of clinical signs, physical examination, 16-hour blood glucose curve, and serum fructosamine concentrations. Thirteen cats completed the study (Lente, n = 7, Glargine, n = 6). There was significant improvement in serum fructosamine and glucose concentrations in all cats but there was no significant difference between the 2 insulin groups. Four of the 13 cats were in complete remission by the end of the study period (Lente, n = 3; Glargine, n = 1). The results of the study support the use of once-daily insulin Glargine or twice-daily Lente insulin in combination with a high-protein, low-carbohydrate diet for treatment of feline diabetes mellitus.


Subject(s)
Cat Diseases/drug therapy , Diabetes Mellitus/veterinary , Hypoglycemic Agents/therapeutic use , Insulin, Long-Acting/therapeutic use , Insulin/analogs & derivatives , Animals , Cats , Diabetes Mellitus/drug therapy , Diet , Drug Administration Schedule/veterinary , Female , Insulin/therapeutic use , Insulin Glargine , Male
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