A 42-year-old woman with idiopathic Raynaud's phenomenon developed localized necrosis of her fingertip after using an aerosol can of spray hair color. Laboratory measurements indicated that while such products did not achieve freezing temperatures, they did become cold enough to potentially produce vasospasm. Patients with Raynaud's phenomenon should be cautioned that use of some aerosol products may result in a cold induced injury.

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La microcirculation cutanée a été proposée comme modèle d’étude de la dysfonction microvasculaire globale dans les maladies cardiovasculaires. Par ailleurs, elle est spécifiquement atteinte dans le syndrome de Raynaud, qui est une ischémie paroxystique des extrémités déclenchée notamment par le froid. L’exploration de la fonction microvasculaire cutanée suscite donc un réel intérêt, mais les méthodes d’étude souffrent d’une hétérogénéité importante, et leur variabilité intra-individuelle est mal connue. La première partie de ce travail fait la synthèse des différentes méthodes d’étude la fonction microvasculaire cutanée, et rapporte les résultats de deux études consacrées à leur reproductibilité. Nous avons dans une seconde partie étudié grâce à ces tests la réactivité microvasculaire cutanée dans le syndrome de Raynaud, et mis en évidence des anomalies chez ces patients, notamment du contrôle neuro-vasculaire. La dernière partie de cette thèse est consacrée à l’étude d’approches pharmacologiques ciblées sur les anomalies de la microcirculation cutanée identifiées chez les patients. Nous avons évalué l’effet du sildenafil, un inhibiteur de la phosphodiesterase-5, sur le flux sanguin digital et montré son effet vasodilatateur lors d’un refroidissement local dans le syndrome de Raynaud. Enfin, nous avons étudiés chez l’animal et chez l’homme l’iontophorèse de vasodilatateurs, une approche innovante d’administration locale de médicaments pour augmenter le flux sanguin cutané. / The cutaneous microcirculation has been proposed as a model to study generalized microvascular function in various diseases. Moreover, it is specifically affected in Raynaud’s phenomenon, characterized by transient ischemia in the digits in response to cold. Despite recent advances in methods exploring the cutaneous microcirculation, they still suffer from a lack of standardization. In the first part of this dissertation, we have reviewed the different techniques used to assess skin microvascular reactivity, and studied the reproducibility of reactivity tests. We then used these tests to assess cutaneous microvascular reactivity in Raynaud’s phenomenon, and showed abnormal neurovascular control of the microvasculature in these patients. The third part of this dissertation is dedicated to pharmacological studies targeting the cutaneous microcirculation in Raynaud’s phenomenon. We tested the effect of sildenafil, a phosphodiesterase-5 inhibitor, on digital skin blood flow while cooling locally, and showed increase in cutaneous vascular conductance in patients with Raynaud’s phenomenon. Finally, we assessed in animals and in humans the effect of locally administered vasodilating drugs on the cutaneous microcirculation, by using iontophoresis. This innovative approach may be an interesting treatment in Raynaud’s phenomenon.

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Hearing loss from noise exposure is one of the most common occupational injuries, and exposure to vibrations may increase the risk of noise-induced hearing loss. Earlier cross-sectional and longitudinal studies found an increased risk of noise-induced hearing loss among workers with vibration-induced white fingers (VWF) symptoms compared to workers without such symptoms. It has been suggested that vibrations to the hand stimulate the sympathetic nervous system and cause vasoconstriction in both the exposed hand and the ears and that this contributes to noise-induced hearing loss. The overall aim of this thesis was to examine how hand-arm vibrations (HAV) interact with noise in the development of noise-induced hearing loss. The experimental study in this thesis examined the effects of HAV and noise, both separately and combined, on the temporary threshold shift (TTS) in hearing in 22 healthy male and female subjects. The two longitudinal studies in this thesis were based on a cohort of 189 male workers at a heavy engineering workshop. The first cohort study examined the risk of noise-induced hearing loss from long-term exposure to HAV and noise. The second cohort study examined if workers with VWF had an increased risk of noise-induced hearing loss compared to workers without such symptoms. Finally, the questionnaire study in this thesis examined the occurrence of Raynaud’s phenomenon among 133 men and women with noise-induced hearing loss in relation to exposure to vibrations. In the experimental study, no differences in TTS in hearing were observed after combined exposure to HAV and noise compared to exposure to only noise. In the first cohort study, there was an increased risk of noise-induced hearing loss with increased exposure to HAV in a noisy environment. In the second cohort study, it was found that workers with VWF had an increased risk of noise-induced hearing loss compared to workers without VWF. In the questionnaire study, many men and women with noise-induced hearing loss had used hand-held vibrating machines suggesting that vibrations might contribute to noise-induced hearing loss. A high prevalence of Raynaud’s phenomenon was found among men. This thesis demonstrated that there was a long-term effect on noise-induced hearing loss from combined exposure to noise and HAV, but no short-term effect, and that having Raynaud’s phenomenon may also increase the risk of noise-induced hearing loss. / Många arbetare använder sig av handhållna vibrerande verktyg. Det utsätter dem för höga nivåer av både buller och vibrationer. Människor som utsätts för höga bullernivåer under lång tid kan skada sin hörsel. Risken för hörselnedsättning orsakad av buller kan eventuellt öka om personen samtidigt är utsatt för vibrationer från handhållna vibrerande verktyg. Syftet med avhandlingen var att studera om vibrationer i kombination med buller ökar risken för hörselnedsättning. Avhandlingen består av fyra studier. Den första studien är en experimentell studie med 22 friska deltagare med god hörsel. Denna studie undersökte hur hörseln tillfälligt påverkas av buller och vibrationer, separat och i kombination. Den andra och tredje studien bygger på en population bestående av 189 verkstadsarbetare i Sundsvall som följts regelbundet sedan 1987. Den andra studien undersökte om det finns en ökad risk för hörselnedsättning för arbetare som utsätts för buller och vibrationer under lång tid. Den tredje studien undersökte om arbetare med vita fingrar har en ökad risk för hörselnedsättning än arbetare utan vita fingrar. Vita fingrar är en kärlskada orsakad av vibrationer som gör att fingrarna reagerar onormalt snabbt på kyla. Fingrarna blir vita när blodtillförseln till dem stryps. Den fjärde studien är en enkätstudie med 342 kvinnor och män som har en bekräftad hörselnedsättning orsakad av buller. Studien undersökte hur många ur denna grupp som utsätts för vibrationer samt har vita fingrar. Resultaten från studierna visar att det inte finns någon skillnad i hörselpåverkan från buller och vibrationer i kombination jämfört med enbart buller under kort tid. De som utsätts för vibrationer från handhållna vibrerande verktyg i en bullrig miljö under lång tid har en ökad risk för hörselnedsättning. Arbetare med vita fingrar har en högre risk för hörselnedsättning än de utan. En hög andel av de med hörselnedsättning orsakad av buller använder sig av handhållna vibrerande verktyg. I studien fanns även en hög andel med vita fingrar. Sammanfattningsvis visar resultaten att det finns en långtidseffekt av buller och vibrationer på hörselnedsättning men inte någon korttidseffekt, och att vita fingrar kan påverka risken för hörselnedsättning.

Smelter workers who were exposed to air-borne arsenic for a mean of 23 years, and age-matched referents, were examined with clinical, physiological, and neurophysiological methods. Exposure to arsenic in workroom air was estimated to have been around the Swedish occupational limits, which were 500 yg/m before 1975 and 50 yg/ra thereafter. An increased preval ence of Raynaud's phenomenon and a reduced finger systolic blood pressure (FSP) during local and general cooling were found in the smelter workers. Slight, but significant sub-clinical neuropathy, in the form of slightly reduced nerve conduction velocity (NCV) in two or more peripheral nerves, was more common among the arsenic workers than among the referents. There were positive correlations between cumulative exposure to arsenic, reduced NCV in three peripheral motor nerves, and decrease in FSP during cooling. Arsenic levels in urine were 1 ymole/1 (75 yg/1) in the arsenic workers and 0.1 ymole/1 in the referents. In 21 arsenic workers with no or very low exposure to vibra ting hand tools, the FSP during cooling had increased significantly after 3 years wit h the lower arsenic exposure. There was no change in FSP during the summer vacation, whereas urinary levels of arsenic decreased to normal values. Thus there seems to be a slow improvement of finger blood circ ulation which is independent of short-term fluctuations in the exposure to arsenic. No seasonal variation was found in FSP during cooling with the standardized method used. When the NCV-measurements were repeated five years later the difference between arsenic workers and referents had increased, despite the fact that 14 of the 47 arsenic workers had had no exposure to arsenic during the last 1-5 years. These observations indicate, that in subjects with long term exposure to arsenic, sub-clinical neuropathy is not reversible. Ten milligrams of Ketanserin, a serotonin receptor antagonist, was given intravenously to five arsenic workers with cold-induced vasospasm. Skin temperature and FSP during cooling increased significantly with Ketanserin as compared wit h saline solution. After oral treatment, 2 x 40 mg /day for four weeks, no significant increase of FSP during cooling or rise in skin temperature was found in six arsenic workers and eleven patients with Raynaud's phenomenon. The decrease of vasospastic tendency after intravenous injection of Ketanserin indicated that similar mechanisms might operate in arsenic-induced and other types of Raynaud's phenomenon. A general co nclusion from the five studies in this dissertation is that long-term occupational exposure to arsenic has had adverse effects on the peripheral circulation and nerve conduction. The tendency to vasospasm, but not the sub-clinical neuropathy, seemed to be reversible with decreasing exposure. / <p>S. 1-54: sammanfattning, s. 55-112: 5 uppsatser</p> / digitalisering@umu

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