Association of smoking with dsDNA autoantibody production in systemic lupus erythematosus.

OBJECTIVE: To determine whether exposure to tobacco smoke is associated with double stranded DNA (dsDNA) seropositivity in patients with systemic lupus erythematosus (SLE). METHODS: Medical record review was used to confirm the diagnosis of SLE and evaluate dsDNA antibody status. Smoking status at the time of autoantibody testing was assessed by patients' questionnaire responses. Multivariate regression analysis was used to determine whether exposure to tobacco smoke is associated with dsDNA seropositivity, while controlling for sex and age at SLE diagnosis. RESULTS: A significantly higher risk of dsDNA seropositivity in current smokers than never smokers (odds ratio (OR) = 4.0, 95% confidence interval (CI) 1.6 to 10.4) was shown by multivariate analysis. Current smokers were found to be at higher risk for dsDNA seropositivity than former smokers (OR = 3.0, 95% CI 1.3 to 7.1). The association between current smoking and dsDNA seropositivity remained significant after adjustment for sex, age at SLE diagnosis, amount smoked, age when smoking began, and the duration of smoking cessation (for former smokers). CONCLUSION: The association of smoking with dsDNA seropositivity provides insight into the potential mechanisms underlying autoantibody formation. This information may also serve as a possible point of intervention to prevent disease or target treatment.

Recovery of C-starts, equilibrium and targeted feeding after whole spinal cord crush in the adult goldfish Carassius auratus.

Central nervous system neurons of many adult teleost fish are capable of regrowth across spinal cord lesions, which may result in behavioral recovery of swimming. Since there have been few, if any, studies that examine the return of behaviors other than swimming, we provide a quantitative analysis of the recovery of C-starts that occur in adult goldfish after spinal cord injury. In addition, we include a qualitative analysis of the return of targeted feeding and equilibrium. Whole spinal cord crushes near the junction of the brain and spinal cord [spinomedullary level (SML)] were made in 45 experimental fish. Eight sham-operated goldfish served as controls for the effects of the surgery procedures alone. After spinal cord crush and recovery from the anesthetic, experimental fish lay on their sides with no movement caudal to the wound. The fish were monitored for the return of behaviors for up to 190 days postoperatively. Twenty-five fish survived the course of this study. Of these fish, 12 regained equilibrium and C-starts, two regained equilibrium but not C-starts, and 11 did not regain equilibrium (one of these did display a C-start). Twenty-two of the 25 experimental fish that survived the 190 days were able to target food from the water surface. Quantitative analysis of recovered C-starts in this study revealed that the probability of eliciting the response is reduced, that latencies from stimulus to response are longer and that movement parameters (i.e. angles, distance and velocity) are reduced compared with those of sham-operated control animals for up to 190 days postoperatively. The recovery of C-starts, equilibrium and targeted feeding was due to re-growth across the wound site, since re-crushing the spinal cord at the SML resulted in the loss of these behaviors. Mauthner cells are known to initiate C-starts in goldfish. Since the majority of M-axons that regrow across a crush wound associate with an inappropriate pathway (i.e. the first ventral root), it is unlikely that these cells play a major role in the return of C-starts. We propose that regeneration of Mauthner cell homologues across the wound site is responsible for the recovery of most C-starts. The identifiability of the M-cell and its homologues provides a unique opportunity to analyze the mechanisms underlying behavioral recovery at the cellular level.

Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatic mechanisms.

BACKGROUND: Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine. METHODS AND RESULTS: Eight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6 micrograms.kg-1.min-1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P < .05 using repeated-measures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P < .05 for % delta of forearm versus % delta of finger readings during the 0.4 microgram.kg-1.min-1 infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 microgram.kg-1.min-1 infusion. CONCLUSIONS: As expected, laser Doppler readings at the finger decreased during infusion of an alpha 1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4 microgram.kg-1.min-1 infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.