Differences in taurine synthesis rate among dogs relate to differences in their maintenance energy requirement

Diet-induced (taurine deficiency) dilated cardiomyopathy is reported more in large than small dogs possibly because taurine biosynthesis rate (TBR) is lower in large than small dogs. The TBR in 6 mongrels (37.9 +/- 2.1 kg) and 6 beagles (12.8 +/- 0.4 kg) was determined from the fractional dilution rate of urinary [1,2-(2)H(2)]-taurine, (d4-tau). All dogs were given a 15.6% protein, 0.60% sulfur amino acid (SAA) diet in amounts to maintain an ideal body condition score. After 3 mo, 14.6 mg/kg body weight of d4-tau was given orally and TBR determined from d4-tau to taurine ratio in urine collected each d for 6 d. Enrichments of d4-tau were determined by GC-MS. Thereafter, mongrels and beagles were paired by ranking of SAA intake per metabolic body weight per kg(0.75). Each pair received the same amount of diet/kg(0.75) for 2 wk, then TBR was again determined. Concentrations of taurine in plasma, blood, and urine and concentrations of plasma thiols were measured during each TBR determination. In Expt. 1, TBR and taurine concentrations in plasma and urine of mongrels were lower (P < 0.05) than those of beagles. In Expt. 2, TBR and taurine concentrations in blood and plasma of mongrels were lower (P < 0.05) than beagles. Together, the results support the hypothesis that large compared with small dogs have lower TBR when fed diets near-limiting in dietary SAA, but adequate to maintain ideal body condition.     

Pathergy test in Behcet's disease: change in incidence over the time

Introduction: Pathergy phenomenon (PP) is used as a criterion in many diagnostic criteria for Behcet's disease (BD): Curth, Japan, Hubault and Hamza, Cheng and Zhang, Dilsen, International Study Group, Iran criteria (traditional format and the Classification Tree), Korea criteria, and the new International Criteria. PP is rather specific to BD. It has been reported with high frequency from most countries along the Silk Road, but with much lower frequency from other countries (UK, US). The incidence of PP has been reported from some countries (Japan, Turkey) to decrease gradually. The aim of this study was to test the above hypothesis in a large cohort of patients in Iran. Materials: Patients (6057) were divided into several groups by two methods. Method 1: patients were divided into six groups according to the time of their first visit. Method 2: patients were divided into four groups according to the date of the beginning of their first manifestation. Results: In method 1, the percentage of PP was 71.8% from patients 1–1000. The percentage became 55.9% from patients 1001–2000, 57.6% from patients 2001–3000, 58.8% from patients 3001–4000, 45.3% from patients 4001–5000, and 33.9% from patients 5001–6000. In method 2, the percentage of PP was 61.5% for patients with their disease onset before 1977. The percentage was 59.9% for patients with their disease starting between 1978 and 1987. The percentage dropped to 52.1% for patients with disease onset between 1988 and 1997. The percentage finally dropped to 41% for patients having their disease onset between 1998 and 2007. Conclusion: The incidence of PP is decreasing gradually. It is now 34%, which is rather low for a criterion used in many diagnosis criteria. It is important to find a surrogate for it because with the decrease in the incidence of PP the sensitivity of the diagnosis criteria will drop significantly.     

The antihypertensive effect and safety of lisinopril in patients with mild to moderate essential hypertension. A Belgian multicenter study

The safety and efficacy of lisinopril in the treatment of mild to moderate essential hypertension was evaluated by Belgian general practitioners in patients whose hypertensive condition remained uncontrolled by previous treatment and/or in whom the prior drug regimen was not tolerated. In this 8-week study, 3060 eligible patients were initially treated with 20 mg lisinopril once daily; this dose was increased to 40 mg if diastolic blood pressure (DBP) was greater than 90 mm Hg after 4 weeks. Lisinopril monotherapy in the 1902 patients completing the trial resulted in marked reductions of systolic (SBP) and DBP from 172.5/102.4 mm Hg at baseline to 147.4/86.6 mm Hg by week 8. More than 90% of patients achieved a DBP less than 95 mm Hg. The decrease in blood pressure was similar in patients older and younger than 65 year of age. Only about 20% of patients required an increase in their daily intake of lisinopril to 40 mg. Treatment was well tolerated and the profile of adverse events was similar to the pattern found with other nonsulfydryl angiotensin converting enzyme inhibitors. Tolerance in the elderly was similar to that experience by hypertensives under 65 years of age. Thus, lisinopril at 20 or 40 mg once daily proved both well tolerated and effective in reducing blood pressure in patients with mild to moderate essential hypertension.     

Management of ocular manifestations of Behcet's disease: outcome with cytotoxic drugs

Background and aim: Cytotoxic drugs, combined with steroids, are the first line of treatment for serious ocular manifestations in Behcet's disease (BD) such as uveitis and retinal vasculitis. If used judiciously, they are effective and safe, even in the long‐term. In our unit, the following cytotoxic drugs have been used for this purpose – oral or pulse cyclophosphamide, weekly methotrexate, chlorambucil, cyclosporin, azathioprine, or a combination of these. In our experience, these cytotoxic drugs had a similar range of efficacy regarding improvement in visual acuity. Having obtained the same treatment response, we pooled all our data together to evaluate the overall outcome of the eye complications in our cohort of BD patients. Methods: The treatment protocol was the same regardless of which cytotoxic drug was used. Prednisolone was given to all patients at an initial dose of 0.5 mg per kilogram of body weight per day. The dose was later tapered as necessary. If a patient was resistant to a given cytotoxic drug, the drug was changed to another. In pooled data, the results before the first treatment were compared with those after the last treatment. Visual acuity (VA) was measured using a Snellen chart (on a scale of 10). The Disease Activity Index (DAI) for anterior uveitis (AU), posterior uveitis (PU), and retinal vasculitis (RV) was measured according to the criteria of Ben Ezra. The Total Inflammatory Activity Index (TIAI) and the Total Adjusted Disease Activity Index (TADAI) were also calculated. Statistical analysis was performed using a Student's t‐test for paired samples comparing the data obtained before and after treatment. Results: At the last evaluation of our database (March 2004) on patients who had an active posterior uveitis and/or retinal vasculitis, 1104 were treated with cytotoxic drugs, of whom 290 patients received more than one treatment protocol. The mean duration of eye lesions was 32.8 months (SD 37.6). The mean treatment time was 20.1 months (SD 20.3). Overall, the VA of 70% of patients improved or maintained after treatment. The mean VA improved from 3.8 to 4.7 (t = 10.099, P < 0.000001). The mean DAI of AU improved from 2.5 to 0.8 (t = 19.575, P < 0.000001). The mean DAI of posterior uveitis improved from 2.1 to 0.9 (t = 28.616, P < 0.000001). The mean DAI of retinal vasculitis improved from 2.5 to 1.5 (t = 12.070, P < 0.000001). The mean TIAI improved from 16.5 to 7.9 (t = 20.13, P < 0.000001). The mean TADAI improved from 37.1 to 25.6 (t = 20.24, P < 0.000001). Further analysis showed methotrexate at a dose of 15 mg/week, and azathioprine at 2 mg/kg/day were preferred for posterior uveitis, while low dose pulsed cyclophosphamide (0.5 g/m²/month) – azathioprine combination therapy for retinal vasculitis. Conclusion: Cytotoxic drugs are efficacious in the treatment of serious ocular manifestations of BD.     

Prevalence of Behcet's disease in Iran: a WHO‐ILAR COPCORD stage I study

Aim: To elucidate the prevalence of Behcet's disease (BD) during the World Health Organization‐International League of Associations for Rheumatology Community Oriented Program for Control of Rheumatic Disease study in Iran. The old estimate was 16 per 100,000 inhabitants, but this was just an estimation and a more precise figure was required. Materials and methods: Tehran, the capital of Iran with 1/10th of Iran's population, was selected as the field for the COPCORD study. The population of Iran is of mixed ethnicity (Caucasians 75.4%, Turks 22%, and Semites 2.6%). The same distribution was found in Tehran's general population. Tehran has 22 districts; 50 clusters were randomly selected from them. Interviewers passed an exam by interviewing 20 subjects. The observed agreement was 0.96. The chance expected agreement was 0.531325. The kappa coefficient was 0.919 (standard error: 0.112). The z‐score was 8.19. The one tailed P‐value was < 0.0001. Rheumatologists were selected from the ‘Rheumatology Subspecialty’, that is, those who were scheduled to become a rheumatology professor in one of Iran's medical schools. Results: The response rate was 75%. From 10,291 subjects interviewed all subjects with positive questionnaires were examined; seven had definitive BD and five probable BD. The prevalence was calculated on the seven definitive cases. It was 68 for 100,000 inhabitants. The confidence interval was 33.5–137. Four patients were female and three were male. All had oral and genital aphthosis, four had ocular lesions, three had pseudo‐folliculitis, and one had joint manifestations. Conclusions: The prevalence of BD in Iran is 68 per 100,000 inhabitants, which is the second highest prevalence after Turkey (80–370) in the world, and far behind comes Saudi Arabia with 20, China 14, and Japan 13.4 per 100,000 inhabitants.     

Enhanced efficacy of single-dose versus multi-dose azithromycin regimens in preclinical infection models

OBJECTIVES: As a result of the prolonged half-life and unique pharmacokinetic and pharmacodynamic (PK-PD) characteristics of azithromycin, shorter dosing regimens are being evaluated for the treatment of community-acquired infections. To provide further support for a shorter dosing regimen, the efficacy of azithromycin was determined in preclinical infection models comparing single- versus multi-dose regimens. METHODS: The efficacy of single versus multi-dose regimens of azithromycin was compared in mouse pneumonia, acute peritonitis, and neutropenic thigh infection models and in a gerbil model of Haemophilus influenzae acute otitis media. Azithromycin was administered as a single oral dose on the first treatment day, or as two divided doses over 2 treatment days, or as three divided doses over 3 treatment days. The pharmacokinetics of azithromycin was profiled following single and multi-dose regimens with the single dose data fit to an Emax model to characterize the PK-PD of azithromycin. RESULTS: In the mouse efficacy models, administration of single-dose azithromycin produced superior rates of survival and bacterial clearance compared with the same total dose divided over 2 or 3 days. In the gerbil model, a single dose sterilized the middle ear and more rapidly cleared H. influenzae. The pharmacokinetic evaluation confirmed similar total exposure (AUC) in serum and pulmonary tissue for the three regimens. Correlation of PK-PD parameters and antimicrobial efficacy confirmed a concentration-dependent and dosing-independent relationship for azithromycin. CONCLUSIONS: These data are consistent with data reported from clinical studies and indicate that a single-dose regimen would be at least as effective as the same dose administered over several days.     

Enhanced external counterpulsation improves exercise tolerance in patients with chronic heart failure.

OBJECTIVES: The PEECH (Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure) study assessed the benefits of enhanced external counterpulsation (EECP) in the treatment of patients with mild-to-moderate heart failure (HF). BACKGROUND: Enhanced external counterpulsation reduced angina symptoms and extended time to exercise-induced ischemia in patients with coronary artery disease, angina, and normal left ventricular function. A small pilot study and registry analysis suggested benefits in patients with HF. METHODS: We randomized 187 subjects with mild-to-moderate symptoms of HF to either EECP and protocol-defined pharmacologic therapy (PT) or PT alone. Two co-primary end points were pre-defined: the percentage of subjects with a 60 s or more increase in exercise duration and the percentage of subjects with at least 1.25 ml/min/kg increase in peak volume of oxygen uptake (VO2) at 6 months. RESULTS: By the primary intent-to-treat analysis, 35% of subjects in the EECP group and 25% of control subjects increased exercise time by at least 60 s (p = 0.016) at 6 months. However, there was no between-group difference in peak VO2 changes. New York Heart Association (NYHA) functional class improved in the active treatment group at 1 week (p < 0.01), 3months (p < 0.02), and 6 months (p < 0.01). The Minnesota Living with Heart Failure score improved significantly 1 week (p < 0.02) and 3 months after treatment (p = 0.01). CONCLUSIONS: In this randomized, single-blinded study, EECP improved exercise tolerance, quality of life, and NYHA functional classification without an accompanying increase in peak VO2.