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BACKGROUND: An in-house Histoplasma urine antigen test for cats might be desirable in certain situations. OBJECTIVE: To validate and compare the diagnostic performance of a monoclonal antibody-based IMMY urine Histoplasma antigen enzyme immunoassay (IMMY EIA) to the commercially available urine Histoplasma antigen enzyme immunoassay (MiraVista Diagnostics, MV EIA). ANIMALS: One hundred ninety-three urine samples from 105 client-owned and purpose-bred research cats. METHODS: Cats were classified as Histoplasma positive or negative based on diagnostic investigation. The IMMY EIA and MV EIA were performed on all urine samples. Correlation and agreement between the assays were determined. Diagnostic performance was determined and compared between assays. RESULTS: The IMMY EIA, with a 0.25 ng/mL diagnostic cutoff, provided a diagnostic sensitivity (DSe), diagnostic specificity (DSp), and diagnostic accuracy (DAc) of 89% (95% confidence interval [CI]; 73%-97%), 80% (67%-89%), and 83% (74%-90%), respectively. The IMMY EIA, with a 1.1 ng/mL diagnostic cutoff, provided a DSe, DSp, and DAc of 77% (95% CI 60%-90%), 97% (88%-100%), and 89% (81%-95%), respectively. The MV EIA provided a DSe, DSp, and DAc of 94% (95% CI 81%-99%), 97% (89%-100%), and 96% (90%-99%), respectively. Moderate overall agreement was found between MV EIA and IMMY EIA using the 0.25 ng/mL cut-off (к = 0.44; 95% CI 0.31-0.57) and the 1.1 ng/mL cut-off (к = 0.43, 95% CI, 0.31-0.56). CONCLUSIONS AND CLINICAL IMPORTANCE: The IMMY EIA might be useful as a diagnostic test for histoplasmosis in cats. Further modifications of the IMMY EIA are required to achieve the diagnostic performance of the MV EIA.

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Phaeohyphomycosis is a rare but emerging disease caused by dematiaceous fungi. Here we describe the case of an immunosuppressed dog with disseminated phaeohyphomycosis secondary to Bipolaris spicifera infection. Regionally extensive infiltration of the paw pads, skin, myocardium, liver, renal interstitium and diaphragm was identified on histopathology. Candida glabrata and Fusarium oxysporum were also cultured from multiple sites post-mortem. The dog was treated with fluconazole, itraconazole, terbinafine and liposomal amphotericin B, but was euthanized due to its poor prognosis after 12 days of therapy.

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Conidiobolomycosis is a rare fungal disease of both humans and animals, occurring mainly in tropical and subtropical climates. We describe a disseminated fungal infection in a young, apparently immunocompetent dog who initially presented for antibiotic resistant pneumonia. Histopathology and mycology identified a Conidiobolus sp., further confirmed as Conidiobolus incongruus through DNA sequencing of D1/D2 regions. This is the first report of this species causing disease in dogs and the fifth reported infection in animals.

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BACKGROUND: Studies suggest that inflammation is involved in the neurodegenerative cascade leading to Alzheimer's disease (AD) pathology and symptoms. This study sought to quantitatively summarize the clinical cytokine data. METHODS: Original English language peer-reviewed studies measuring cytokine concentrations in AD and healthy control subjects were included. Mean (± standard deviation) cytokine concentrations for AD and control subjects were extracted. RESULTS: Forty studies measuring peripheral blood cytokine concentrations and 14 measuring cerebrospinal fluid (CSF) cytokine concentrations were included. In peripheral blood, there were significantly higher concentrations (weighted mean difference [95% confidence interval]) of interleukin (IL)-6 (2.86 [1.68, 4.04] pg/mL, p < .00001, N[AD/control subjects] = 985/680, 14 studies), tumor necrosis factor (TNF)-α (3.25 [.76, 5.74] pg/mL, p = .01, N = 680/447, 14 studies), IL-1ß (.55 [.32, .78] pg/mL, p < .00001, N = 574/370, 10 studies), transforming growth factor (TGF)-ß (67.23 [28.62, 105.83] pg/mL, p = .0006, N = 190/158, 5 studies), IL-12 (7.60 [5.58, 9.62] pg/mL, p < .00001, N = 148/106, 5 studies), and IL-18 (15.82 [1.98, 29.66] pg/mL, p = .03, N = 131/94, 4 studies) but not of IL-4, IL-8, IL-10, interferon-γ, or C-reactive protein in AD subjects compared with control subjects. There were significantly higher concentrations of TGF-ß (7.81 [2.27, 13.35] pg/mL, p =.006, N = 113/114, 5 studies) but not IL-6, TNF-α, and IL-1ß in the CSF of AD subjects compared with control subjects. CONCLUSIONS: These results strengthen the clinical evidence that AD is accompanied by an inflammatory response, particularly higher peripheral concentrations of IL-6, TNF-α, IL-1ß, TGF-ß, IL-12 and IL-18 and higher CSF concentrations of TGF-ß.

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OBJECTIVE: To determine whether there is a relationship between inflammatory markers (serum C-reactive protein (CRP) and cytokines) and post stroke cognitive impairment (PSCI). METHODS: This was a cross-sectional observational study. Patients were recruited from 4 sources: (1) the acute stroke unit of a general hospital, (2) an outpatient stroke prevention clinic, (3) a stroke rehabilitation unit in a specialized geriatric hospital, or (4) a stroke rehabilitation unit of a rehabilitation hospital. Patients meeting National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) project criteria for stroke were invited to participate in this study within the first 5 to 31 days post stroke. Patients with subarachnoid or intracranial hemorrhage, decreased level of consciousness, severe aphasia or dysarthria, or a significant acute medical, neurological, or psychiatric illness were excluded. Clinical assessments included the Mini-Mental State Examination (MMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of CRP, interleukin 6 (IL-6), and interferon gamma (IFN-gamma). RESULTS: A total of 48 patients with ischemic stroke (age [mean +/- SD] 71.6 +/- 13.2 years, 54.2% male, MMSE 26.4 +/- 3.8, NIHSS 6.8 +/- 4.0) were recruited within their first month post stroke. Backward stepwise elimination linear regression showed that higher concentrations of serum CRP (beta(CRP) = -0.46, p( CRP) = 0.002) predicted lower post stroke global cognition ([MMSE], F1,44 = 11.31, P = .002), with age (P = .92), level of education (P = .22), infarct side (P = 0.49), IL-6 (P = 0.36), and IFN-gamma (P = .57) removed from the final model. CONCLUSIONS: A post stroke inflammatory response may be important in subacute, PSCI.

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OBJECTIVE: The authors aim to quantify the extent, and to assess student perception, of alcohol and tobacco use among medical students at the University of Calgary, and the relationship of these attitudes to problem drinking (according to the CAGE questionnaire). METHODS: A questionnaire was distributed to first-, second-, and third-year medical students attending the University of Calgary medical school. RESULTS: Of the 327 students enrolled, 175 of students responded to the questionnaire. Six percent of the students currently smoke while 24% of students reported cigarette smoking at some point in their life. Eighty-six percent of students currently drink, with a majority drinking fewer than 11 drinks per week. Fifteen percent of students were at an increased risk for problem drinking according to the CAGE questionnaire. An increased risk for problem drinking was significantly related to believing more strongly that getting drunk is acceptable on occasion and less strongly that increased alcohol has many negative health consequences, as well as feeling less in control of alcohol consumption. CONCLUSION: Medical students at the University of Calgary consume less alcohol and cigarettes than a comparable population. However, a high proportion of students are at risk for alcohol abuse according to the CAGE questionnaire. The results of this study suggest that although the quantity of alcohol consumed is not a substantial concern at this time, students might be at risk for future alcohol abuse.

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OBJECTIVE: To assess the role of the dopaminergic brain reward system (BRS) in apathy associated with Alzheimer disease (AD). DESIGN: BRS function was probed in 20 AD patients using dextroamphetamine (d-amph) challenge. After baseline behavioral testing, patients were given a single 10 mg dose of d-amph. The time course of the subjective response to d-amph was assessed at hourly intervals for 4 hours. SETTING: Three outpatient dementia clinics associated with a university-affiliated hospital. PARTICIPANTS: Twenty AD patients aged 77 +/- 8 years with Neuropsychiatric Inventory (NPI) apathy scores of 3.4 +/- 3.5 and Mini-Mental State Examination scores of 20.4 +/- 5.1. MEASUREMENTS: Patients were classified as apathetic based on an NPI apathy subscore of > or =4. Apathy severity was assessed using the Apathy Evaluation Scale (AES). The subjective and behavioral responses to d-amph were assessed using computerized versions of the Addiction Research Centre Inventory (ARCI), Profile of Mood States and Connor's Continuous Performance Task. RESULTS: Repeated measures ANOVA revealed a significant interaction between the presence of apathy and the peak subjective response to d-amph on the ARCI, such that while nonapathetic AD patients were responsive to the rewarding effects of d-amph, apathetic patients were not (F(1,17) = 4.93, p = 0.04). Continuous AES scores were predicted by peak ARCI positive effects scores and baseline overall behavioral disturbances (NPI total) in a backward linear regression analysis using the entire study sample (F(2,17) = 10.00, p = 0.01, R(2) = 0.49). CONCLUSIONS: Apathy in AD is associated with a blunted subjective response to d-amph, which may be indicative of dysfunction in the BRS.

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Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; chi = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.

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BACKGROUND: Alzheimer's Disease (AD) is frequently associated with changes in appetite. This study investigated the relationship between regional cerebral perfusion and appetite loss in AD. METHODS: 64 patients with possible or probable AD were characterized as being with (n=22) or without (n=44) appetite loss based on the Neuropsychiatric Inventory (NPI) Appetite subscale. 99mTc-ECD SPECT scans were coregistered to a standardized template in Talairach space generating mean ratios of uptake referenced to the cerebellum. Regions of interest (ROIs) included anterior cingulate cortex (ACC), middle mesial temporal cortex (MTC-m), inferior mesial temporal cortex (MTC-i), insula (INS), orbitofrontal cortex (OFC) and thalamus-hypothalamus (THAL). RESULTS: Backward stepwise logistic regression analysis of these ROIs showed hypoperfusion in the L-ACC (p=0.015) and L-OFC (p=0.015), relative sparing of perfusion in the R-ACC (p=0.010), R-OFC (p=0.010) and L-MTC-m (p=0.006), and greater anxiety (p=0.005) independently predicted loss of appetite (chi(2)=22.24, p=0.001, Nagelkerke R(2)=0.41). CONCLUSIONS: Hypoperfusion in the left anterior cingulate and left orbitofrontal cortices, and relative sparing of perfusion in the right anterior cingulate, right orbitofrontal and left middle mesial temporal cortices emerged as predictors of appetite loss in this sample of patients. These findings are consistent with impairments in the extrinsic motivational pathways of eating and impaired reward value of food as components of appetite loss in AD.

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BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.

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BACKGROUND: Losses of gamma-aminobutyric acid (GABA) have been variably demonstrated in Alzheimer's disease (AD) and may be related to the presence of behavioral and psychological symptoms of dementia (BPSD) in AD. Our objective was to assess the relationship between plasma GABA (pGABA) levels and specific BPSD in patients with severe AD. METHODS: pGABA levels and BPSD were measured in 14 institutionalized AD patients (8M/6F, mean age +/- S.D. = 85.6 +/- 4.5 years) with severe cognitive impairment (Mini-mental State Examination score = 4.5 +/- 4.6) and prominent behavioral disturbances (Neuropsychiatric Inventory (NPI) score = 33.4 +/- 23.6). RESULTS: pGABA was positively correlated with depression and apathy scores on the NPI and negatively correlated with age. Apathy and age were independent predictors of pGABA levels. CONCLUSIONS: The final stages of AD are associated with GABAergic changes, which may contribute to depression and apathy in AD.

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BACKGROUND/AIMS: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer's disease (AD). METHODS: This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering. RESULTS: Fourteen patients (8 male/6 female) aged 85.6 +/- 4.5 years with baseline Mini Mental State Examination scores of 4.5 +/- 4.6 and NPI agitation/aggression scores of 6.4 +/- 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = -2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = -2.82, p = 0.005). CONCLUSION: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.

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This study compared patient and caregiver perceptions of natural health products (NHPs) and conventional medications in a memory clinic population. A total of 620 mildly cognitively impaired patients and their caregivers participated in interviews enquiring about their perceptions of NHPs in 4 areas: (1) disclosure of NHP usage information to health care professionals, (2) safety and benefits of NHPs, (3) safety and benefits of conventional medications, and (4) physician knowledge about NHPs. Differences in responses between NHP users and nonusers and between patients and caregivers were examined. A total of 51.8% of subjects were current NHP users, with vitamin E, ginkgo biloba, and glucosamine being the most commonly used products. Multivariate analysis of variance showed that NHP use significantly influenced participant interview responses (Pillai's trace, F[4, 613] = 3.488, P = .008), while interviewee (patient or caregiver; Pillai's trace, F[8, 1228] = 1.499, P = .153) and gender (Pillai's trace, F[4, 615] = 0.528, P = .715) did not. Subsequent univariate tests showed that NHP users were significantly more likely to endorse the effectiveness and safety of NHPs compared with nonusers (F[1, 616] = 7.826, P = .005). Careful questioning during visits with health care providers and better counseling may be necessary to reduce the potential for adverse events and NHP-drug interactions.

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