Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism.

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

Effect of Dentoxol® in the treatment of recurrent mild aphthous ulcers. A prospective observational pilot study

ABSTRACT: Background: Recurrent aphthous stomatitis (RAS) is the most common oral ulceration. Its prevalence in the general population varies between 5% and 60%, and during the acute period, it causes pain and interferes with basic activities, such as eating, swallowing and talking. Dentoxol® is a medical mouthrinse that cleans, moisturizes and lubricates the mouth, mechanically stimulating local epithelial regeneration. The aim of this study was to evaluate the efficacy of Dentoxol® in improving the general state of patient with minor RAS using two different treatment schemes. Material and methods: Thirty-nine patients with RAS were recruited in a prospective observational pilot study. Two dosing regimens, 5 ml of Dentoxol® twice daily and 5 ml of Dentoxol® three times daily were evaluated. Results: Efficacy to improve the general state was significant superior in "Three time daily" group compared with "twice daily" at 72 h (66% vs 33% respectively). No pain was reported in approximately 90% of cases at 96 h of use in both group without significant differences between the groups in any evaluation time-point. Conclusion: Despite the limitations of these preliminary data, Dentoxol® shows promising beneficial properties for the management of minor RAS.

Denosumab is not associated with risk of malignancy: systematic review and meta-analysis of randomized controlled trials.

The immunomodulatory effects of denosumab have raised concerns for risk of malignancy. This meta-analysis of 25 randomized controlled trials (21,523 patients) shows similar risk of malignancy between denosumab (60 mg every 6 months, up to 48 months) and any comparator. Post-marketing surveillance may detect rare or late-occurring drug effects. Possible increased risk of malignancy in patients treated with denosumab has been concerned due to inhibition of the immune modulator receptor activator of nuclear factor κ-Β ligand (RANKL). We aimed to assess the risk of malignancy associated with denosumab treatment. PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019 to include all randomized controlled trials of denosumab (60 mg every 6 months) versus any comparator. Trials using higher drug doses for prevention of skeletal-related events were excluded. Data were independently extracted by two reviewers and analyzed using a fixed-effect model to pool risk ratios (RRs) with 95% confidence intervals (CI). Twenty-five trials (21,523 patients) were included. The risk of malignancy was similar between denosumab and other comparators (absolute risk difference 0%, RR 1.08 [95% CI, 0.93-1.24], I2 = 0%). Sensitivity analysis based on adequate allocation concealment showed similar results. The risk of malignancy did not differ between groups in any of the subgroup analyses, including stratification by race, individual comparators, indications for treatment, and longer drug exposure (≥ 24 months, 9 studies). The risk ratio of malignancy-related death was similar between groups. Early concerns about a potential increased risk of malignancy resulting from an immunomodulatory effect of denosumab are not supported by evidence from this meta-analysis of 25 RCTs with drug exposure of up to 48 months. Since RCTs with longer observation for safety outcomes are not expected, post-marketing surveillance will be the main means for detection of rare or late-occurring events.

The Moving to Health (M2H) approach to natural experiment research: A paradigm shift for studies on built environment and health.

Improving the built environment (BE) is viewed as one strategy to improve community diets and health. The present goal is to review the literature on the effects of BE on health, highlight its limitations, and explore the growing use of natural experiments in BE research, such as the advent of new supermarkets, revitalized parks, or new transportation systems. Based on recent studies on movers, a paradigm shift in built-environment health research may be imminent. Following the classic Moving to Opportunity study in the US, the present Moving to Health (M2H) strategy takes advantage of the fact that changing residential location can entail overnight changes in multiple BE variables. The necessary conditions for applying the M2H strategy to Geographic Information Systems (GIS) databases and to large longitudinal cohorts are outlined below. Also outlined are significant limitations of this approach, including the use of electronic medical records in lieu of survey data. The key research question is whether documented changes in BE exposure can be linked to changes in health outcomes in a causal manner. The use of geo-localized clinical information from regional health care systems should permit new insights into the social and environmental determinants of health.

Filaroidosis Infection in an Immunocompetent Adult Dog from France.

A dog from Paris (France) was referred with a 2-week history of dry cough, intermittent acute onset of dyspnoea, and acute abdominal pain. A generalised bronchoalveolar infiltrate with a patchy distribution was observed at chest x-rays and computed tomography (CT) scans. Negative results were obtained through several faecal examinations for cardiorespiratory nematodes by using the Baermann technique and at two blood analysis with a commercially available test for the detection of A. vasorum antigen (the first one at the first visit and second one at the control visit, one month later). PCR methods for the identification of A. vasorum and C. vulpis were also accomplished. At the control visit, nematode L1s were found during direct microscopic examination of bronchoalveolar lavage fluid (BALF). Thus, a different antigen-based assay for the detection of A. vasorum was performed with a positive result. Moreover, based on morphology, isolated larvae were identified as Filaroides hirthi. The dog was treated with fenbendazole (50 mg/kg per os once daily) for two consecutive weeks. After five months, the dog was referred again for the intermittent acute onset of dyspnoea and was found to be still positive for F. hirthi larvae at BALF examination. A 15-day treatment regimen with fenbendazole in combination with three subcutaneous injections of ivermectin (0.4 mg/kg, once every two weeks), was then performed. No larvae were detected at two BALF microscopical examinations performed one month apart. Results from this case report underline the importance of including F. hirthi infections in the differential diagnosis of dog bronchopneumonia.

Proopiomelanocortin processing and prohormone convertase 1 level in dogs with pituitary corticotroph tumors.

Preliminary data suggest that prohormone convertase 1 (PC1/3) protein expression and proopiomelanocortin (POMC) processing are altered in large corticotroph tumors. The aim of this study was to characterize the levels of ACTH precursors and PC1/3 protein in small and large corticotroph tumors of dogs with Cushing's disease. Pituitary tumors of dogs with Cushing's disease were collected postmortem 30 min to 12h after natural death or euthanasia, and classified as small or large. POMC, pro-ACTH, and PC1/3 were detected by Western blotting. Five small and 6 large corticotroph tumors were collected. POMC and pro-ACTH signals were visualized in 5/6 large tumors and in 4/5 small tumors. The strongest signal intensity was observed in 2 large tumors. The PC1/3 signal was weak to undetectable in 6/6 large tumors but strong in 5/5 small tumors. These results suggest differences in PC1/3 protein levels and patterns of POMC processing between large and small corticotroph tumors. If confirmed in larger groups of tumors, further studies will be required to characterize the mechanism involved in these differences.

Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma.

This study aimed to compare the real-life results of TECAM, a thiotepa-based conditioning regimen consisting of thiotepa (40 mg/m2 days -5 to -2), etoposide (200 mg/m2 days -6 to -3), cytarabine (200 mg/m2 days -4 to -1), cyclophosphamide (60 mg/kg day -3), and melphalan (60 mg/m2 days -2 to -1) with that of the conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a large tertiary transplantation center between 1999 and 2014. TECAM (n=65) and BEAM (n=60) had comparable results (3yPFS 49 vs 62%, P=0.16; 3yOS 64 vs 71%, P=0.44; TRM 1.6 vs 5%, P=0.35) without a difference in toxicity or time to engraftment. Notably, comparable outcomes were observed even though patients treated with TECAM were older (55 vs 44) and had a trend towards more prior lines of therapy (>2 prior lines: 43 vs 27%, P=0.08). In this regard, 23% of TECAM patients were over the age of 65 yet could withstand therapy with similar results to younger patients. We conclude that, replacing carmustine by thiotepa and cyclophosphamide for ASCT conditioning, has comparable efficacy and safety profiles with a possible advantage in older patients.

Correction to: Variations of characteristic time scales in rotating stratified turbulence using a large parametric numerical study.

After publication of the paper, an error in computing the ratio γ of kinetic to potential energy transfer times has been detected, which has led the authors to amend two figures, as explained in the main text.

Genome-wide DNA methylation profiling reveals cancer-associated changes within early colonic neoplasia.

Colorectal cancer (CRC) is characterized by genome-wide alterations to DNA methylation that influence gene expression and genomic stability. Less is known about the extent to which methylation is disrupted in the earliest stages of CRC development. In this study, we have combined laser-capture microdissection with reduced representation bisulfite sequencing to identify cancer-associated DNA methylation changes in human aberrant crypt foci (ACF), the earliest putative precursor to CRC. Using this approach, methylation profiles have been generated for 10 KRAS-mutant ACF and 10 CRCs harboring a KRAS mutation, as well as matched samples of normal mucosa. Of 811 differentially methylated regions (DMRs) identified in ACF, 537 (66%) were hypermethylated and 274 (34%) were hypomethylated. DMRs located within intergenic regions were heavily enriched for AP-1 transcription factor binding sites and were frequently hypomethylated. Furthermore, gene ontology analysis demonstrated that DMRs associated with promoters were enriched for genes involved in intestinal development, including homeobox genes and targets of the Polycomb repressive complex 2. Consistent with their role in the earliest stages of colonic neoplasia, 75% of the loci harboring methylation changes in ACF were also altered in CRC samples, though the magnitude of change at these sites was lesser in ACF. Although aberrant promoter methylation was associated with altered gene expression in CRC, this was not the case in ACF, suggesting the insufficiency of methylation changes to modulate gene expression in early colonic neoplasia. Altogether, these data demonstrate that DNA methylation changes, including significant hypermethylation, occur more frequently in early colonic neoplasia than previously believed, and identify epigenomic features of ACF that may provide new targets for cancer chemoprevention or lead to the development of new biomarkers for CRC risk.

A setup for synchrotron-radiation-induced total reflection X-ray fluorescence and X-ray absorption near-edge structure recently commissioned at BESSY II BAMline.

An automatic sample changer chamber for total reflection X-ray fluorescence (TXRF) and X-ray absorption near-edge structure (XANES) analysis in TXRF geometry was successfully set up at the BAMline at BESSY II. TXRF and TXRF-XANES are valuable tools for elemental determination and speciation, especially where sample amounts are limited (<1 mg) and concentrations are low (ng ml(-1) to µg ml(-1)). TXRF requires a well defined geometry regarding the reflecting surface of a sample carrier and the synchrotron beam. The newly installed chamber allows for reliable sample positioning, remote sample changing and evacuation of the fluorescence beam path. The chamber was successfully used showing accurate determination of elemental amounts in the certified reference material NIST water 1640. Low limits of detection of less than 100 fg absolute (10 pg ml(-1)) for Ni were found. TXRF-XANES on different Re species was applied. An unknown species of Re was found to be Re in the +7 oxidation state.

Impact of electrical stimulation of the stomach on gastric distension-induced emesis in the musk shrew.

BACKGROUND: Gastric electrical stimulation (GES) is implicated as a potential therapy for difficult-to-treat nausea and vomiting; however, there is a lack of insight into the mechanisms responsible for these effects. This study tested the relationship between acute GES and emesis in musk shrews, an established emetic model system. METHODS: Urethane-anesthetized shrews were used to record emetic responses (monitoring intra-tracheal pressure and esophageal contractions), respiration rate, heart rate variability, blood pressure, and gastrointestinal electromyograms. We investigated the effects of acute GES pulse duration (0.3, 1, 5, and 10 ms), current amplitude (0.5, 1, and 2 mA), pulse frequency (8, 15, 30, and 60 Hz), and electrode placement (antrum, body, and fundus) on emesis induced by gastric stretch, using a balloon. KEY RESULTS: There were four outcomes: (i) GES did not modify the effects of gastric stretch-induced emesis; (ii) GES produced emesis, depending on the stimulation parameters, but was less effective than gastric stretch; (iii) other physiological changes were closely associated with emesis and could be related to a sub-threshold activation of the emetic system, including suppression of breathing and rise in blood pressure; and (iv) a control experiment showed that 8-OH-DPAT, a reported 5-HT1A receptor agonist that acts centrally as an antiemetic, blocked gastric stretch-induced emesis. CONCLUSIONS AND INFERENCES: These results do not support an antiemetic effect of acute GES on gastric distension-induced emesis within the range of conditions tested, but further evaluation should focus on a broader range of emetic stimuli and GES stimulation parameters.

Variations of characteristic time scales in rotating stratified turbulence using a large parametric numerical study.

We study rotating stratified turbulence (RST) making use of numerical data stemming from a large parametric study varying the Reynolds, Froude and Rossby numbers, Re, Fr and Ro in a broad range of values. The computations are performed using periodic boundary conditions on grids of 1024(3) points, with no modeling of the small scales, no forcing and with large-scale random initial conditions for the velocity field only, and there are altogether 65 runs analyzed in this paper. The buoyancy Reynolds number defined as R(B) = ReFr2 varies from negligible values to ≈ 10(5), approaching atmospheric or oceanic regimes. This preliminary analysis deals with the variation of characteristic time scales of RST with dimensionless parameters, focusing on the role played by the partition of energy between the kinetic and potential modes, as a key ingredient for modeling the dynamics of such flows. We find that neither rotation nor the ratio of the Brunt-Väisälä frequency to the inertial frequency seem to play a major role in the absence of forcing in the global dynamics of the small-scale kinetic and potential modes. Specifically, in these computations, mostly in regimes of wave turbulence, characteristic times based on the ratio of energy to dissipation of the velocity and temperature fluctuations, T(V) and T(P), vary substantially with parameters. Their ratio γ=T(V)/T(P) follows roughly a bell-shaped curve in terms of Richardson number Ri. It reaches a plateau - on which time scales become comparable, γ≈0.6 - when the turbulence has significantly strengthened, leading to numerous destabilization events together with a tendency towards an isotropization of the flow.

Service users' experiences of participation in decision making in mental health services.

ACCESSIBLE SUMMARY: Despite the potential positive impact of shared decision making on service users knowledge and experience of decisional conflict, there is a lack of qualitative research on how participation in decision making is promoted from the perspective of psychiatric service users. This study highlights the desire of users to participate more actively in decision making and demonstrates that persons with SMI struggle to be seen as competent and equal partners in decision-making situations. Those interviewed did not feel that their strengths, abilities and needs were being recognized, which resulted in a feeling of being omitted from involvement in decision-making situations. The service users describe some essential conditions that could work to promote participation in decision making. These included having personal support, having access to knowledge, being involved in a dialogue and clarity about responsibilities. Mental health nurses can play an essential role for developing and implementing shared decision making as a tool to promote recovery-oriented mental health services. ABSTRACT: Service user participation in decision making is considered an essential component of recovery-oriented mental health services. Despite the potential of shared decision making to impact service users knowledge and positively influence their experience of decisional conflict, there is a lack of qualitative research on how participation in decision making is promoted from the perspective of psychiatric service users. In order to develop concrete methods that facilitate shared decision making, there is a need for increased knowledge regarding the users' own perspective. The aim of this study was to explore users' experiences of participation in decisions in mental health services in Sweden, and the kinds of support that may promote participation. Constructivist Grounded Theory (CGT) was utilized to analyse group and individual interviews with 20 users with experience of serious mental illness. The core category that emerged in the analysis described a 'struggle to be perceived as a competent and equal person' while three related categories including being the underdog, being controlled and being omitted described the difficulties of participating in decisions. The data analysis resulted in a model that describes internal and external conditions that influence the promotion of participation in decision making. The findings offer new insights from a user perspective and these can be utilized to develop and investigate concrete methods in order to promote user's participation in decisions.

Neural dysfunction in ADHD with Reading Disability during a word rhyming Continuous Performance Task.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous, neurodevelopmental disorder which co-occurs often with Reading Disability (RD). ADHD with and without RD consistently have higher inattentive ratings compared with typically developing controls, with co-occurring ADHD and RD also demonstrating impaired phonological processing. Accordingly, inattention has been associated with greater phonological impairment, though the neural correlates of the association are poorly understood from a functional neuroimaging perspective. It was postulated that only the co-occurring subgroup would demonstrate hypoactivation of posterior, left hemispheric, reading-related areas and, to a lesser extent, alterations in right hemispheric, attention areas compared with controls. METHODS: A novel word rhyming Continuous Performance Task assesses functional activation differences in phonology- and attention-related areas between three groups: ten boys with ADHD and RD, fourteen boys with ADHD without RD, and fourteen typically developing controls. Subjects respond to words that rhyme with a target word as mono- and disyllabic, English words are visually presented over 90s blocks. RESULTS: Behavioral performance was not different between groups. Some hypoactivation of left hemispheric, reading-related areas was apparent in ADHD and RD, but not ADHD without RD, compared with controls. Right hemispheric, attention areas showed alterations in both ADHD subgroups relative to controls; however, the differences for each subgroup were dissimilar. CONCLUSIONS: The dorsal decoding subnetwork may not be grossly compromised in ADHD with Reading Disability. The role of cognitive impairments, including the level of inattention, on phonology requires clarification from a neuroimaging perspective.

Resolving the paradox of oceanic large-scale balance and small-scale mixing.

A puzzle of oceanic dynamics is the contrast between the observed geostrophic balance, involving gravity, pressure gradient, and Coriolis forces, and the necessary turbulent transport: in the former case, energy flows to large scales, leading to spectral condensation, whereas in the latter, it is transferred to small scales, where dissipation prevails. The known bidirectional constant-flux energy cascade maintaining both geostrophic balance and mixing tends towards flux equilibration as turbulence strengthens, contradicting models and recent observations which find a dominant large-scale flux. Analyzing a large ensemble of high-resolution direct numerical simulations of the Boussinesq equations in the presence of rotation and no salinity, we show that the ratio of the dual energy flux to large and to small scales agrees with observations, and we predict that it scales with the inverse of the Froude and Rossby numbers when stratification is (realistically) stronger than rotation. Furthermore, we show that the kinetic and potential energies separately undergo a bidirectional transfer to larger and smaller scales. Altogether, this allows for small-scale mixing which drives the global oceanic circulation and will thus potentially lead to more accurate modeling of climate dynamics.

Large-scale anisotropy in stably stratified rotating flows.

We present results from direct numerical simulations of the Boussinesq equations in the presence of rotation and/or stratification, both in the vertical direction. The runs are forced isotropically and randomly at small scales and have spatial resolutions of up to 1024(3) grid points and Reynolds numbers of ≈1000. We first show that solutions with negative energy flux and inverse cascades develop in rotating turbulence, whether or not stratification is present. However, the purely stratified case is characterized instead by an early-time, highly anisotropic transfer to large scales with almost zero net isotropic energy flux. This is consistent with previous studies that observed the development of vertically sheared horizontal winds, although only at substantially later times. However, and unlike previous works, when sufficient scale separation is allowed between the forcing scale and the domain size, the kinetic energy displays a perpendicular (horizontal) spectrum with power-law behavior compatible with ∼k(⊥)(-5/3), including in the absence of rotation. In this latter purely stratified case, such a spectrum is the result of a direct cascade of the energy contained in the large-scale horizontal wind, as is evidenced by a strong positive flux of energy in the parallel direction at all scales including the largest resolved scales.

Spontaneous acromegaly: a retrospective case control study in German shepherd dogs.

Acromegaly results from the overproduction of growth hormone in adulthood and is characterised by overgrowth of soft tissue and/or bone as well as insulin resistance. There are few data indicating the risk factors associated with this disease in dogs or its clinicopathological features and sequelae. The objective of this retrospective study was to catalogue and assess these aspects of the disease in German shepherd dogs (GSDs) which were found to be over-represented among acromegalic dogs attending two veterinary referral clinics over a period of 7 years. Each acromegalic dog (AD) was compared with two breed/age/sex matched controls. Clinical signs of acromegaly included panting, polyuria/polydipsia, widened interdental spaces, weakness, inspiratory stridor, macroglossia, weight gain, redundant skin folds, thick coat, exophthalmos and mammary masses. Serum alkaline phosphatase, creatine-kinase, glucose, triglyceride, phosphate ion, and 'calcium per phosphate product' concentrations were significantly higher in acromegalic animals while haemoglobin concentration, blood urea nitrogen, sodium and chloride ion concentrations, and urinary specific gravity, osmolality and fractional excretion of phosphate were significantly lower. Although, in the majority of cases clinicopathological abnormalities resolved following ovariohysterectomy, in one dog, acromegalic signs abated and insulin-like growth factor-1 concentrations normalised only following the surgical excision of mammary tumours carried out 2 months after ovariohysterectomy. The findings of this study indicate that GSDs are predisposed to the development of acromegaly with a suspected inherited susceptibility.

Clinical findings, diagnostic test results, and treatment outcome in cats with spontaneous hyperadrenocorticism: 30 cases.

BACKGROUND: Spontaneous hyperadrenocorticism (HAC) is rare in cats. Clinical findings, diagnostic test results, and response to various treatment options must be better characterized. OBJECTIVES: To report the clinical presentation, clinicopathologic findings, diagnostic imaging results, and response to treatment of cats with HAC. ANIMALS: Cats with spontaneous HAC. METHODS: Retrospective descriptive case series. RESULTS: Thirty cats (15 neutered males, 15 spayed females; age, 4.0-17.6 years [median, 13.0 years]) were identified from 10 veterinary referral institutions. The most common reason for referral was unregulated diabetes mellitus; dermatologic abnormalities were the most frequent physical examination finding. Low-dose dexamethasone suppression test results were consistent with HAC in 27 of 28 cats (96%), whereas ACTH stimulation testing was suggestive of HAC in only 9 of 16 cats (56%). Ultrasonographic appearance of the adrenal glands was consistent with the final clinical diagnosis of PDH or ADH in 28 of 30 cats (93%). Of the 17 cats available for follow-up at least 1 month beyond initial diagnosis of HAC, improved quality of life was reported most commonly in cats with PDH treated with trilostane. CONCLUSIONS AND CLINICAL IMPORTANCE: Dermatologic abnormalities or unregulated diabetes mellitus are the most likely reasons for initial referral of cats with HAC. The dexamethasone suppression test is recommended over ACTH stimulation for initial screening of cats with suspected HAC. Diagnostic imaging of the adrenal glands may allow rapid and accurate differentiation of PDH from ADH in cats with confirmed disease, but additional prospective studies are needed.

Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs.

Pharmacological management of feline hyperthyroidism offers a practical treatment option for many hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its pro-drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of 2·5 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases should be monitored for side-effects, especially during the first months of treatment. Some side-effects may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life should also be evaluated, with special attention to possible development of azotaemia, hypertension and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre-existing azotaemia have shorter survival times. However, development of mild azotaemia during the initial course of treatment, unless associated with hypothyroidism, does not appear to decrease survival time. The long-term effects of chronic medical management require further study.