Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules shown to have a role in migraine pathophysiology. Our objective was to test the hypothesis that migraine subjects are particularly sensitive to these signal molecules. The cutaneous microvascular responses to endothelial and non-endothelial dependent dilators were tested using laser Doppler flowmetry in combination with iontophoresis. The blood flow responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and to local warming (44 degrees C) were compared in this controlled trial. The design was that of two arms: patients diagnosed with migraine without aura (n = 9) for >10 years were compared with nine healthy subjects matched for age and gender (seven female and two male, age range 30-60 years). Iontophoretic administration resulted in local vasodilation. ACh induced a relaxation of 1225 +/- 245% (relative to baseline) in controls and 1468 +/- 368% (P > 0.05) in migraine. The responses to SNP were 873 +/- 193% in controls and 1080 +/- 102% (P > 0.05) in migraine subjects. The responses to CGRP were 565 +/- 89% in controls and 746 +/- 675% (P > 0.05) in migraine patients. The responses to local heating which induced maximum dilation did not differ between the groups (1976 +/- 314% for controls and 1432 +/- 226% in migraine; P > 0.05. We conclude that there is no change in the microvascular responsiveness of the subcutaneous microvasculature in migraine.

Chlamydophila pneumoniae in chronic rhinosinusitis.

CONCLUSIONS: The intracellular bacterium Chlamydophila pneumoniae (Cp) was infrequently found in nasopharynx and lacking in biopsies from the middle turbinate in chronic rhinosinusitis (CRS) patients. Compared with healthy controls, patients suffering from CRS had significantly higher and more prevalent antibody titers to Cp. However, an association between CRS and Cp could not be established. OBJECTIVES: To study the prevalence of Cp in CRS patients and in healthy controls to determine if an association exists between Cp and CRS. MATERIALS AND METHODS: PCR against Cp was run on middle turbinate biopsies and on throat and nasopharyngeal swabs from 25 CRS patients and from 10 healthy controls. Serum samples were tested for Cp-specific antibodies by the microimmunofluorescence method. Patients that tested positive for Cp or had high antibody titers were treated with antibiotics. RESULTS: Cp was found in nasopharyngeal samples from two patients but from none of the controls. Neither patients nor controls had Cp in biopsies from the middle turbinate. Antibody titers against Cp were significantly higher and more prevalent in patients than in controls. Seventeen patients were treated with antibiotics but only four of them recovered from sinusitis symptoms during the 2-year follow-up.

Cutaneous vascular reactivity is reduced in aging and in heart failure: association with inflammation.

In the present study, we have investigated whether changes in vascular reactivity in congestive heart failure (CHF) patients can be detected in the cutaneous microvessels and whether these changes are due to endothelial dysfunction, are affected by increasing age and related to an ongoing inflammation. The responses to local warming and iontophoretically administered endothelium-dependent and -independent vasodilators were investigated in healthy young adults, healthy elderly adults and elderly adults with CHF. The results were correlated with plasma concentrations of vascular risk factors and markers for endothelial dysfunction and inflammation. The vasorelaxant responses were reduced in the elderly groups and were attenuated further in the CHF group. This group also had increases in levels of several markers associated with inflammation, higher blood glucose and homocysteine levels, a lower low-density lipoprotein-cholesterol and a rise in the concentration of von Willebrand factor, indicating a prothrombotic endothelial function. The severity of the heart failure, measured as the plasma level of brain natriuretic peptide, correlated with the intensity of inflammation and to the changes in vascular risk factors and endothelial function. It is concluded that the reactivity of the cutaneous microvessels is reduced with age, and the presence of CHF causes a further impairment. There is endothelial dysfunction in CHF, but it is uncertain to what extent this contributes to the reduced vasodilatory capacity. The inflammatory response appears central for many of the manifestations of the CHF syndrome.

Vasogen's immune modulation therapy (IMT) improves postischemic foot skin blood flow and transcutaneous pO(2) recovery rates in patients with advanced peripheral arterial occlusive disease.

AIM: Vasogen's immune modulation therapy (IMT)* involves the ex vivo exposure of a sample of autologous blood to 3 oxidative stress factors (heat, an oxidative environment, and ultraviolet light), followed by intramuscular re-injection. The primary objective of this study was to assess the effect of Vasogen's IMT on skin blood flow in patients with symptomatic peripheral arterial occlusive disease (PAOD). METHODS: In a double-blind, placebo-controlled pilot study, 18 patients with moderately advanced PAOD were randomized to receive 2 courses each of 6 intramuscular injections of either saline or Vasogen's IMT over a 9-week period. Dorsal foot skin blood flow was assessed directly using laser Doppler fluxmetry (LDF) and indirectly using measurement of transcutaneous pO(2) (tcpO(2)). Key outcome measures of skin blood flow were, for LDF: resting values, peak postischemic values, and the total time to reach peak values following release from 4 min of total foot ischemia and, for tcpO(2): resting values and the time for tcpO(2) to reach 50% of the pre-ischemia value. Measurements were carried out at baseline, at weeks 3, 6, and 9, and at 2 months post-therapy. RESULTS: No significant differences were detected between groups for resting or peak postischemic LDF values for dorsal foot skin blood flow. Patients randomised to IMT experienced a progressive decrease in the time to peak postischemic skin blood flow, reaching statistical significance at 2 months. Treated patients experienced a 26.1 s decrease in time to peak blood flow (p=0.026) vs a 7.9 s decrease in the placebo group (p=ns). Similar but less striking results were achieved for tcpO(2) recovery time to 50% of pre-ischemia values (treated group, p=0.035; placebo group, p=ns). CONCLUSION: Vasogen's IMT improved recovery rates of postischemic dorsal foot skin blood flow in a group of patients with moderately advanced PAOD, probably due to improved endothelial function.

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis.

BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.