C.A. Tony Buffington

Clinical evaluation of multimodal environmental modification (MEMO) in the management of cats with idiopathic cystitis

This prospective observational study evaluated client-reported recurrence of lower urinary tract signs (LUTS) and other signs of abnormalities in cats with idiopathic cystitis after institution of multimodal environmental modification (MEMO). Forty-six client-owned indoor-housed cats with idiopathic cystitis, diagnosed based on a history of recurrent LUTS and evidence of absence of urolithiasis or bacterial urinary tract infection were studied. In addition to their usual care, clients were offered recommendations for MEMO based on a detailed environmental history. Cases were followed for 10 months by client contact to determine the effect of MEMO on LUTS and other signs. Significant (P<0.05) reductions in LUTS, fearfulness, nervousness, signs referable to the respiratory tract, and a trend (P<0.1) toward reduced aggressive behavior and signs referable to the lower intestinal tract were identified. These results suggest that MEMO is a promising adjunctive therapy for indoor-housed cats with LUTS, and should be followed up with prospective controlled clinical trials.

IN VIVO MODELS OF INTERSTITIAL CYSTITIS

PURPOSE We systematically identified and evaluated various animal models that have been studied to help identify the underlying mechanisms of and possible treatment options for interstitial cystitis. MATERIALS AND METHODS Models of interstitial cystitis published between 1983 and 2001 were obtained by searching MEDLINE and other Internet databases using cystitis and model as the primary key words. Models with characteristics of interstitial cystitis similar to those defined by National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases criteria were reviewed. Some articles describing animal models with similar pathological conditions in other organs were also included to enlarge the base of potentially relevant material. RESULTS We identified and evaluated some 16 animal models of interstitial cystitis, which we categorized as bladder inflammation induced by intravesical administration of an irritant or immune stimulant, systemic and environmentally induced inflammation, and a naturally occurring model of interstitial cystitis that occurs in cats. Some abnormalities identified in humans and cats with interstitial cystitis can be reproduced in healthy animals using luminal, systemic or environmental stimuli. At the level of the bladder the source of stimulation cannot be discriminated. Variability in the extent of bladder distention complicated the interpretation of some studies. In addition, the noxious stimuli used can affect many epithelial surfaces as well as the urothelium, suggesting they are nonspecific responses to injury rather than specific to interstitial cystitis. CONCLUSIONS No model in bladder injury in healthy animals currently reproduces as many features of interstitial cystitis as the naturally occurring disease in cats. While induced models of relative injury may help to provide insight into the bladder response to injury, feline interstitial cystitis follows a similar chronic waxing and waning time course as does interstitial cystitis in humans, which may be more suitable for studying the effects of stressors on the severity of clinical signs as well as newly proposed therapies.

Sickness behaviors in response to unusual external events in healthy cats and cats with feline interstitial cystitis

OBJECTIVE To compare sickness behaviors (SB) in response to unusual external events (UEE) in healthy cats with those of cats with feline interstitial cystitis (FIC). DESIGN Prospective observational study. ANIMALS 12 healthy cats and 20 donated cats with FIC. PROCEDURES Cats were housed in a vivarium. Sickness behaviors referable to the gastrointestinal and urinary tracts, the skin, and behavior problems were recorded by a single observer for 77 weeks. Instances of UEE (eg, changes in caretakers, vivarium routine, and lack of interaction with the investigator) were identified during 11 of the 77 weeks. No instances of UEE were identified during the remaining 66 weeks, which were considered control weeks. RESULTS An increase in age and exposure to UEE, but not disease status, significantly increased total number of SB when results were controlled for other factors. Evaluation of individual SB revealed a protective effect of food intake for healthy males. An increase in age conferred a small increase in relative risk (RR) for upper gastrointestinal tract signs (RR, 1.2) and avoidance behavior (1.7). Exposure to UEE significantly increased the RR for decreases in food intake (RR, 9.3) and for no eliminations in 24 hours (6.4). Exposure to UEE significantly increased the RR for defecation (RR, 9.8) and urination (1.6) outside the litter box. CONCLUSIONS AND CLINICAL RELEVANCE SB, including some of the most commonly observed abnormalities in client-owned cats, were observed after exposure to UEE in both groups. Because healthy cats and cats with FIC were comparably affected by UEE, clinicians should consider the possibility of exposure to UEE in cats evaluated for these signs.

AAFP-AAHA Feline Life Stage Guidelines

Background and goals Cats have become the most popular pet in the United States, yet statistics about veterinary care for cats remain troubling. 1 Although most owners consider their cats to be family members, cats are substantially underserved, compared with dogs. In 2006, owners took their dogs to veterinarians more than twice as often as cats, averaging 2.3 times/year, compared with 1.1 times/year for cats, and significantly more dogs (58%) than cats (28%) were seen by a veterinarian one or more times/year. 2 Cat owners often express a belief that cats ‘do not need medical care’. Two reasons for this misconception are that signs of illness are often difficult to detect, and cats are perceived to be self-sufficient. 2 One role of the veterinarian is to develop a partnership with cat owners that will pave the way for a lifelong health care plan. These guidelines aim to outline an evidence-based life stage wellness program to aid the veterinary medical team in delivering the best comprehensive care for cats. Specific goals are to provide: Recommendations for optimal health care for cats throughout the different life stages. Practical suggestions and tools to facilitate improved veterinary visits and to enhance the client-veterinarian clinical encounter. A foundation from which to access sources of additional information. Life stage classification Distinct life stages (age groups) in cats are not well defined, in part because individual animals and body systems age at different rates, a process that is influenced by many factors. These guidelines follow one convenient classification (see box below). These age designations help to focus attention on the physical and behavioral changes that occur at different stages (eg, congenital defects in kittens, obesity prevention in the junior cat). It must be recognized, however, that any age groupings are inevitably arbitrary demarcations along a spectrum, and not absolutes. Evidence-based health care Supporting references for specific recommendations are supplied where possible, and any previously published guidelines on particular topics are referred to where relevant. Readers should note, however, that the guidelines panel was hampered in its efforts by the relative paucity of disease incidence data by age group that is available, and there is an urgent need for research to guide the future of evidence-based feline health care. 3

Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline interstitial cystitis.

Interstitial cystitis (IC) is a painful disorder which affects urinary bladder function in cats and humans. We used patch clamp techniques to measure firing properties and K+ currents of dorsal root ganglion (DRG) neurons (L4-S3) from normal cats and cats with feline interstitial cystitis (FIC) to examine the possibility that the properties of primary afferent neurons are changed in cats with FIC. We found that capsaicin (CAPS)-responsive neurons from FIC cats were increased in size, had increased firing in response to depolarizing current pulses and expressed more rapidly inactivating K+ currents. CAPS-sensitive neurons from FIC cats were 28% larger than those from normal cats but were otherwise similar with respect to membrane potential and action potential (AP) threshold. CAPS-responsive neurons from normal cats fired 1.5 APs in response to a 600 ms depolarizing current pulse, 60-200 pA in intensity. The number of APs was increased 4.5 fold in FIC neurons. Neurons from FIC cats also exhibited after hyperpolarization potentials which were on the average 2x slower than those in normal cat neurons. In addition, there was a lack of K+ currents in the critical voltage range of action potential generation (between -50 to -30 mV). These changes were not detected in CAPS-unresponsive neurons from normal and FIC cats. Our data suggest that FIC afferent neurons exhibit abnormal firing which may be due to changes in the behavior of K+ currents and show that these changes are restricted to a subpopulation of CAPS-responsive neurons.

INCREASED PLASMA NOREPINEPHRINE CONCENTRATION IN CATS WITH INTERSTITIAL CYSTITIS

PURPOSE Interstitial cystitis is a chronic urological syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The symptoms of interstitial cystitis seem to be exacerbated by stress, suggesting involvement of the sympathetic nervous system and/or hypothalamic-pituitary-adrenal axis. Others have described sympathetic nervous system abnormalities in patients with interstitial cystitis but to our knowledge no data on plasma catecholamine concentrations or hypothalamic-pituitary-adrenal axis function in such patients have been reported. To evaluate the role of these systems in cats with feline interstitial cystitis we simultaneously measured baseline plasma concentrations of catecholamines and their metabolites to assess sympathetic activity, and the response of plasma adenocorticotropic hormone and cortisol concentrations to the infusion of corticotropin-releasing factor. MATERIALS AND METHODS Eight healthy cats and 8 with feline interstitial cystitis were anesthetized and a catheter was placed in the external jugular vein. Four hours after recovery samples were obtained for high performance liquid chromatography analysis of plasma norepinephrine, dihydroxyphenylglycol, epinephrine, dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid. In 4 cats per group 1 microg. ovine corticotropin-releasing factor per kg. body weight was infused and blood samples were collected at intervals for 120 minutes for determining adenocorticotropic hormone and cortisol. RESULTS Significant increases in plasma norepinephrine and dihydroxyphenylglycol as well as a trend toward increased epinephrine were found, whereas no effect on dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, adenocorticotropic hormone or cortisol was identified in cats with feline interstitial cystitis. CONCLUSIONS These results support and extend previous studies identifying an increase in sympathetic activity in cats with feline interstitial cystitis.

Decreased Urine Glycosaminoglycan Excretion in Cats with Interstitial Cystitis

PURPOSE The urine protein and glycosaminoglycan (GAG) excretion of normal cats was compared with that of cats suffering from interstitial cystitis (IC), which is reported to decrease urine GAG excretion in humans. MATERIALS AND METHODS Total urine GAG concentration was measured in random and 24-hour urine specimens by spectrophotometry by 1,9-dimethylmethylene blue (DMB) chloride. RESULTS In both random and 24-hour urine samples, GAG and protein concentrations and GAG:creatinine and protein:creatinine ratios all were significantly lower in cats with IC. Total GAG and protein excretion also were significantly lower in 24-hour urine samples from cats with IC. CONCLUSIONS GAG excretion was decreased in cats with IC, as it is in humans. It is unclear whether this is due to changes in synthesis, metabolism, or bladder permeability.

Adrenocortical Hormone Abnormalities in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

OBJECTIVES To identify adrenocortical hormone abnormalities as indicators of endocrine dysfunction in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS We simultaneously measured the serum concentrations of 12 steroids in patients with CP/CPPS and controls, using isotope dilution liquid chromatography, followed by atmospheric pressure photospray ionization and tandem mass spectrometry. RESULTS We evaluated 27 patients with CP/CPPS and 29 age-matched asymptomatic healthy controls. In the mineralocorticoid pathway, progesterone was significantly greater, and the corticosterone and aldosterone concentrations were significantly lower, in the patients with CP/CPPS than in the controls. In the glucocorticoid pathway, 11-deoxycortisol was significantly lower and the cortisol concentrations were not different between the patients and controls. In the sex steroid pathway, the androstenedione and testosterone concentrations were significantly greater in those with CP/CPPS than in the controls. The estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate concentrations were not different between the patients and controls. The National Institutes of Health-Chronic Prostatitis Symptom Index total and pain domain scores correlated positively with the 17-hydroxyprogesterone and aldosterone (P <0.001) and negatively with the cortisol (P <0.001) concentrations. CONCLUSIONS Our results suggest reduced activity of CYP21A2 (P450c21), the enzyme that converts progesterone to corticosterone and 17-hydroxyprogesterone to 11-deoxycortisol. Furthermore, these results provide insights into the biologic basis of CP/CPPS. Follow-up studies should explore the possibility that patients with CP/CPPS meet the diagnostic criteria for nonclassic congenital adrenal hyperplasia and whether the hormonal findings improve or worsen in parallel with symptom severity.

The Effect of Diet on Lower Urinary Tract Diseases in Cats

Because dietary ingredients and feeding patterns influence the volume, pH and solute concentration of urine, diet can contribute to the etiology, management or prevention of recurrence of some causes of lower urinary tract disease. Most research assessing the effect of diet has focused on the latter two aspects, primarily because of interest in struvite urolithiasis. Manipulation of urine pH through dietary means has proven an effective tool for the management and prevention of struvite urolithiasis; acidification of urine, however, may be a risk factor for calcium oxalate urolithiasis, which now appears to occur with approximately equal frequency in cats. Prediction of urine pH from dietary analysis would thus be a valuable tool, but considerable further research is required before this can be achieved with commercial canned foods. With the growing importance of urolith types other than struvite, alternatives to the measurement of urine pH are required to assess critically the likely beneficial (or detrimental) effects of manipulation of nutrient profile. Measurement of urinary saturation may permit the development and fine tuning of nutrient profiles aimed at controlling lower urinary tract diseases in cats that are associated with a range of different mineral types. The majority of cats with signs of lower urinary tract disease do not, however, have urolithiasis; indeed, no specific cause can be established in most of these cats. Recent observations suggest that recurrence rates of signs in cats classified as having idiopathic lower urinary tract disease may be more than halved if affected animals are maintained on high, rather than low moisture content diets. J. Nutr. 2753S-2757S, 1998

HIGH AFFINITY BINDING SITES FOR [(3) H]SUBSTANCE P IN URINARY BLADDERS OF CATS WITH INTERSTITIAL CYSTITIS

PURPOSE Pain is a common feature of interstitial cystitis (IC). Although the effects of IC on sensory neuron density have been investigated, its influence on substance P receptor (SPR) numbers and function are not well known. To evaluate the role of SPR in cats with IC, we measured the affinity (Kd), numbers (Bmax), and substrate specificity of binding sites for [3H]SP in urinary bladders of healthy cats and cats suffering from IC. MATERIALS & METHODS Radioligand binding assays of cat and rat brain, normal cat bladders, and inflamed bladders from cats diagnosed with IC were conducted using [3H]SP to determine SPR affinity and numbers. Binding sites for [125I]SP were identified using autoradiography in slide-mounted frozen tissue sections, and their specificity determined with competition binding studies. RESULTS In bladder homogenate binding studies, low affinity SP binding sites for [3H]SP were found both in normal and inflamed tissue, whereas high affinity binding sites were found in inflamed bladder tissue only. Based on autoradiographic studies, high affinity binding appeared to be to small blood vessels, and to be specific for substance P, a pharmacology consistent with the neurokinin-1 receptor (NK1R). CONCLUSIONS Upregulation of NK1R may be part of the pathophysiology of IC, as it is in some other inflammatory diseases. If so, more specifically targeted therapies for IC may become available.