Georg Schulthess

Roxithromycin Treatment Prevents Progression of Peripheral Arterial Occlusive Disease in Chlamydia pneumoniae Seropositive Men A Randomized, Double-Blind, Placebo-Controlled Trial

Background—Evidence has been provided that the atherosclerotic process may be associated with chronic infection with Chlamydia pneumoniae. The effect of antibiotic treatment on peripheral arterial occlusive disease has not been investigated yet. Methods and Results—Forty C pneumoniae seropositive men suffering from peripheral arterial occlusive disease were randomly assigned to receive either roxithromycin (300 mg daily) or placebo for 28 days. During the 2.7-year follow-up, the number of invasive revascularizations per patient, the walking distance before intervention (in patients without intervention at study end), and the change of carotid plaque size were assessed. Five interventions were performed on 4 patients (20%) in the roxithromycin group, and 29 interventions were performed on 9 patients (45%) in the placebo group. Limitation of walking distance to 200 m or less was observed in 4 patients (20%) in the roxithromycin group and in 13 patients (65%) in the placebo group. The effect of macrolide treatment on the number of interventions per patient and on preinterventional walking distance was significant. Possible confounding variables such as classical vascular risk factors were excluded by multiple regression analyses. Carotid plaque areas monitored over 6 months decreased in the roxithromycin group (mean relative value, 94.4%) but remained constant in the placebo group (100.2%). Regression of carotid plaque size observed in roxithromycin-treated patients was significant for soft plaques. Conclusions—This study indicates that macrolide treatment for 1 month is effective in preventing C pneumoniae seropositive men from progression of lower limb atherosclerosis for several years.

Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis.

Background Clinical penetrance of hereditary hemochromatosis is highly variable. We hypothesized that it might be modified by factors involved in the cellular immune response, such as toll-like receptors (TLRs) or nucleotide oligomerization domain proteins (NODs). Methods Clinical expression of hemochromatosis was assessed as a function of TLR4, TLR9, and NOD2 polymorphisms in 99 homozygous carriers of the HFE C282Y mutation with mild-to-severe iron overload. Results Thirteen (13%) of the 99 hemochromatosis patients were heterozygous for a TLR4 Asp299Gly polymorphism and 86 (87%) were TLR4 wild-type-only carriers. Clinical expression of hemochromatosis was observed more frequently in carriers of the TLR4 polymorphism (100%) than in TLR4 wild-type carriers (56%, P = 0.002). This was based on higher prevalences of liver disease (92 vs. 45%, P = 0.002) and arthropathy of metacarpophalangeal joints (69 vs. 35%, P = 0.018) in TLR4 polymorphism carriers. The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011). The TLR4 polymorphism did, however, not correlate with body iron overload. The study results remained significant in multiple regression analyses after excluding possible confounding effects, such as age, sex, alcohol, or meat intake, and in the subgroup of 84 patients presenting as the first members of their families. Conclusion TLR4 Asp299Gly polymorphism modulates clinical expression in patients with hereditary hemochromatosis. The polymorphism does not correlate with iron overload suggesting that TLR4 plays a role in an inflammatory process arising from toxic effects of iron accumulation.

Effect of roxithromycin treatment on the endothelial function of Chlamydia pneumoniae seropositive men suffering from peripheral arterial occlusive disease.

To the Editor: Parchure et al1 have recently reported that azithromycin therapy for 5 weeks significantly improved flow-mediated dilation (FMD) of the brachial artery in Chlamydia pneumoniae seropositive men suffering from coronary heart disease. Our group has recently reported that roxithromycin treatment for 1 month significantly improved the walking distance and reduced the number of revascularization procedures in C pneumoniae seropositive men suffering from peripheral arterial occlusive disease.2 In this prospective, randomized, double-blind, placebo-controlled study, we also investigated the effect of roxithromycin on the endothelial function. Determination of radial artery hemodynamics was performed at study entry, at the end of 1-month treatment with either roxithromycin or placebo, and at the 6-month follow-up. Radial artery diameter was measured using a high-precision A-mode echo-tracking device (NIUS 02, Asulab) to determine FMD and glyceryl trinitrate-induced dilation, which was 10.9±4.2% (mean ±1 SD). At baseline, no FMD of the radial artery could be detected in 6 of 20 patients in the placebo group and in 9 of 20 patients in the roxithromycin group. …