Background: Familial dysautonomia is a genetic disease that affects the sensory and autonomic nervous systems with varying severity. The deep breath test is one of several measures used to assess the severity of autonomic diseases, but its value in familial dysautonomia has not yet been investigated.

Objectives: To determine the diagnostic value of the DBT[1] in patients with familial dysautonomia.

Methods: Eight patients with familial dysautonomia and eight healthy volunteers were examined by electrocardiography for 1 minute at rest and during forced deep breathing. The following values were recorded: maximum expiratory and minimum inspiratory heart rate and the difference between them (ΔE/I), standard deviation of the heart rate values, interbeat intervals, and E/I[2] ratio. Spectral power analysis of heart rate variability was also performed.

Results: The patients with familial dysautonomia showed a lesser change in heart rate in response to the change in breathing pattern than the controls. Mean values in the study group were significantly higher for minimal inspiratory heart rate and significantly lower for ΔE/I, heart rate standard deviation and E/I ratio, indicating a non-flexible heart response and abnormal parasympathetic function. These findings were supported by power spectral analysis.

Conclusions: Patients with familial dysautonomia have a significantly disturbed response to physiological stimuli. The DBT may serve as a reliable means to quantify autonomic dysfunction in this patient population.

Background: Spontaneous coronary reperfusion occurs in 7–27% of patients with ST elevation myocardial infarction, and is an independent predictor of myocardial salvage, percutaneous coronary intervention success, and improved outcome.

Objectives: To determine the optimal PCI[1] time for patients admitted to the hospital due to STEMI[2] with SCR[3].

Methods: We performed a retrospective analysis of all patients admitted to the coronary care unit between July 2002 and November 2004 with a diagnosis of STEMI with SCR.

Results: The study group comprised 86 patients. There was not a single reinfarction episode during an observation period of 6579 patient hours. Cardiac catheterization was executed early (< 24 hours from pain onset) in 26 patients and late (> 24 hours) in 55. Pre-PCI angiographic TIMI flow 2–3 was seen in > 95% in both groups. PCI was performed more frequently in the “early” group (P = 0.024), while multi-vessel coronary artery disease (P = 0.094) requiring coronary bypass surgery (P = 0.056) was observed more frequently in the “late catheterization” group. Myocardial infarction and angina pectoris at 30 days occurred more frequently in the early catheterization group (P = 0.039), however no difference in any major adverse cardiac events was detected during long-term follow-up (491 ± 245 days).

Conclusions: Reinfarction after STEMI with SCR is a rare event. Early PCI in patients with STEMI and SCR, even when executed with aggressive anti-platelet therapy, seems to result in an excess of early MACE, without any long-term advantage. Prospective randomized trials should determine the optimal PCI timing for these patients.

Objectives: To evaluate the safety and efficacy of external counter-pulsation therapy in heart failure patients.

Methods: Fifteen symptomatic heart failure patients (subsequent to optimal medical and device therapy) underwent 35 hourly sessions of ECPT[1] over a 7 week period. Before and after each ECPT session we performed pro-B-type natriuretic peptide and brachial artery function studies, administered a quality of life questionnaire, and assessed exercise tolerance and functional class.

Results: Baseline left ventricular ejection fraction was 28.1 ± 5.8%. ECPT was safe and well tolerated and resulted in a reduction in pro-BNP[2] levels (from 2245 ± 2149 pcg/ml to 1558 ± 1206 pcg/ml, P = 0.022). Exercise duration (Naughton protocol) improved (from 720 ± 389 to 893 ± 436 seconds, P = 0.0001), along with functional class (2.63 ± 0.6 vs. 1.93 ± 0.7, P = 0.023) and quality of life scores (54 ± 22 vs. 67 ± 23, P = 0.001). Nitroglycerine-mediated brachial vasodilatation increased (11.5 ± 7.3% vs. 15.6 ± 5.2%, P =0.049), as did brachial flow-mediated dilation (8.35 ± 6.0% vs. 11.37 ± 4.9%, P = 0.09).

Conclusions: ECPT is safe for symptomatic heart failure patients and is associated with functional and neurohormonal improvement. Larger long-term randomized studies with a control arm are needed to confirm these initial encouraging observations.

Background: The frequent systemic side effects associated with the use of systemic carbonic anhydrase inhibitors have adversely affected the compliance to treatment in glaucoma patients, obviating their long-term use. The introduction of the topical CAI[1], dorzolamide, has further reduced their use. However, the tolerability of dorzolamide in patients who have been intolerant to systemic CAIs has not been evaluated prospectively.

Objectives: To study the tolerability and efficacy of dorzolamide (a topical CAI) in a selected group of glaucoma and ocular hypertensive patients who have been intolerant to systemic CAI.

Methods: A 3 month prospective study was conducted in 39 patients. Following recruitment, patients were evaluated on the day of switching from systemic CAI to dorzolamide and for five more visits. The SF-36 health assessment questionnaire was used to evaluate changes in well-being and quality of life, and the intraocular pressure was measured periodically.

Results: Within 4 weeks of switching from systemic CAI to dorzolamide, the mean health assessment scores improved significantly in seven of the eight categories of the SF-36, and remained generally unchanged for the rest of the study. No significant differences were noted between the mean IOP[2] on day 0 and the following measurements throughout the 84 days of dorzolamide therapy.

Conclusion: In glaucoma patients who were intolerant to systemic CAI, topical CAI dorzolamide offers a similar efficacy and better tolerability.

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

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[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever