Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate: rationale and design of the CENS study.

Purpose: Until recently, it has been believed that donating a kidney not represents any risk for development of cardiovascular disease. However, a recent Norwegian epidemiological study suggests that kidney donors have an increased long-term risk of cardiovascular mortality. The pathophysiological mechanisms linking reduced kidney function to cardiovascular disease are not known. Living kidney donors are screened for cardiovascular morbidity before unilateral nephrectomy, and are left with mildly reduced glomerular filtration rate (GFR) after donation. Therefore, they represent an unique model for investigating the pathogenesis linking reduced GFR to cardiovascular disease and cardiovascular remodelling. We present the study design of Cardiovascular rEmodelling in living kidNey donorS with reduced glomerular filtration rate (CENS), which is an investigator-initiated prospective observational study on living kidney donors. The hypothesis is that living kidney donors develop cardiovascular remodelling due to a reduction of GFR.Materials and methods: 60 living kidney donors and 60 age and sex matched healthy controls will be recruited. The controls will be evaluated to fulfil the Norwegian transplantation protocol for living kidney donors. Investigations will be performed at baseline and after 1, 3, 6 and 10 years in both groups. The investigations include cardiac magnetic resonance imaging, echocardiography, bone density scan, flow mediated dilatation, laser Doppler flowmetry, nailfold capillaroscopy, office blood pressure, 24-h ambulatory blood pressure, heart rate variability and investigation of microbiota and biomarkers for inflammation, cardiovascular risk and the calcium-phosphate metabolism.Conclusions: The present study seeks to provide new insight in the pathophysiological mechanisms linking reduced kidney function to cardiovascular disease. In addition, we aim to enlighten predictors of adverse cardiovascular outcome in living kidney donors. The study is registered at Clinical-Trials.gov (identifier: NCT03729557).

Acral coldness - severely reduced blood flow to fingers and toes.

The term acral coldness is used to describe physiologic or pathologic situations in humans where the fingers and toes are exceptionally cold in spite of normal central body temperature. In the thermoneutral zone, the blood flow to acral skin normally shows large fluctuations between high and low values, with a frequency of about 3 cycles per minute. At an acral skin temperature of about 21°C, finger blood flow is constantly low. At lower temperatures the fingers and toes become painful. This is a normal physiologic reaction, probably because of ischemia. The characteristics of the most frequent acral vascular syndromes, Raynaud phenomenon, acrocyanosis, and chilblains, are discussed. Common to all three is pathologically low blood flow and disappearance of physiologic fluctuations even in the thermoneutral zone. Ischemic vascular diseases in acral skin are usually diagnosed from clinical observations. Measurements of fluctuating blood flow by laser or ultrasound Doppler could be useful, but should be carried out at a room temperature of 24-25°C.

Oscillatory pattern of acral skin blood flow within thermoneutral zone in healthy humans.

The acral skin contains arteriovenous anastomoses, which probably is the main part of skin microcirculation for blood flow adjustments and thermoregulation in the thermoneutral zone. The objective was to investigate if an increase in sympathetic activation during cooling influences the oscillatory pattern of acral skin blood flow. We had measurements of bilateral acral skin blood flow (n = 12) during lowering of ambient temperature from 32 °C to 18 °C. We quantified the oscillatory pattern as the time averaged wavelet spectral powers, coherence and phase angles in three frequency intervals (0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz). The differences were tested by Wilcoxon signed rank sum method between adjacent intervals. The absolute fluctuations in laser Doppler flux at 0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz were similar at 32 °C and 25 °C, and decreased at 18 °C (p < 0.001). The relative fluctuations (amplitude of the fluctuations relative to median flux value) in laser Doppler flux at 0.01-0.02 Hz, 0.02-0.05 Hz and 0.05-0.08 Hz were higher at 25 °C and 18 °C as compared to 32 °C (p < 0.002). The coherence between the oscillations of signals from right and left finger tips was highest (median coherence > 0.89) at 25 °C, and lower at 32 °C and at 18 °C.The median phase angles between the flux signals from right and left finger tips were close to 0 radians. We found that the relative fluctuations in acral skin blood flow increased during vasoconstriction due to cooling. Wavelet analysis of acral skin blood flow oscillations could serve as a future clinical tool.

Cold-induced sympathetic tone modifies the impact of endothelium-dependent vasodilation in the finger pulp.

OBJECTIVE: In thermoneutral and cold subjects, the sympathetic nervous system regulates skin blood flow by adjusting frequency of the tonic vasoconstrictor impulses. However, the way these thermoregulatory impulses influence the vascular endothelium is not well known. We studied how the sympathetic nervous system influences endothelium-dependent vasodilation (EDV) caused by shear stress in skin containing arteriovenous anastomoses (AVAs) and arterioles in healthy subjects. METHODS: Thirteen healthy subjects were exposed to thermoneutral (29°C) and cold (22°C) ambient temperatures on separate days. EDV was induced by releasing suprasystolic pressure cuff applied to the forearm or third finger after 4min. Bilateral laser Doppler flux from the finger pulp, dorsal finger and dorsal wrist was measured together with ultrasound Doppler from the right radial artery. Absolute EDV response (EDV peak minus baseline) and normalized relative EDV response (ratio EDV peak/baseline) were calculated (median, 95% confidence interval). The relative EDV response reflect the size of EDV response independent of the baseline level and is thus used to compare the EDV responses in the finger pulp and wrist skin in the two temperature conditions. RESULTS: In finger pulp (dominated by AVAs), the absolute EDV response (flux, au) in thermoneutral (137.8 (67.5, 168.8)) and cold (130.3 (97.2, 154.9)) was the same (p=0.85), whereas the relative EDV response was significantly higher in cold (3.6 (2.5, 5.9)) than in thermoneutral (1.4 (1.1, 1.6), p=0.002). The same patterns were found in the radial artery. In the dorsal wrist (dominated by arterioles) the absolute EDV response (flux, au) was smaller in cold (30.9 (15.91, 38.0)) than in thermoneutral (52.1 (38.4, 57.8), p=0.04), whereas the relative EDV responses in cold (3.5 (2.3, 4.2)), and thermoneutral (2.3 (1.6, 2.7)) were equal (p=0.16). CONCLUSIONS: The relative EDV responses show that the impact of EDV on skin perfusion in cold conditions is significantly greater in the finger pulp than in wrist skin. However, the absolute EDV responses indicate that vascular smooth muscle relaxation during EDV is probably not affected by higher mild cold-induced sympathetic activity either in AVAs or in arterioles.

Improved Clinical Efficacy with Wound Support Network Between Hospital and Home Care Service.

OBJECTIVE: The aim of this study was to test the efficacy of a wound support network model between the primary home care service and the hospital. The impact on wound healing rate, cost benefit, and transfer of knowledge was investigated. INTERVENTION: The intervention group was exposed to a wound support network (n = 32), and the control group continued standard organization of treatment (n = 21). DESIGN: Nonrandomized controlled study; observations were made before (baseline) and after the implementation of the intervention (12 weeks). PATIENTS: Patients with chronic wounds (lasting >6 weeks and with wound area >1 cm) in Oslo, Norway. MAIN OUTCOME MEASURES: Closure of the observation wound; wound size; total number of wounds; presence of eczema, edema, and pain; number of dressings per week; time spent per dressing; and number of control appointments at the hospital. The economic impact is calculated for the hospital and for the community of Oslo, Norway. MAIN RESULTS: The number of control appointments (t = 3.80, P < .001) was significantly decreased, and the number of completed treatments (P = .02) was significantly increased after 12 weeks in the intervention group compared with the control group. A significant improvement was evident in the intervention group in terms of eczema (P = .02), edema (P = .03), and closing of the observational wound (46.7% cases in the intervention group versus 25.0% in the control group). CONCLUSIONS: A wound support network between the primary home care service and the hospital is cost-effective, improves clinical efficacy of the home care services' work, and reduces the need for consultations at the hospital.

Responses in acral and non-acral skin vasomotion and temperature during lowering of ambient temperature.

Arteriovenous anastomoses (AVA) in acral skin (palms and soles) have a huge capacity to shunt blood directly from the arteries to the superficial venous plexus of the extremities. We hypothesized that acral skin, which supplies blood to the superficial venous plexus, has a stronger influence on blood flow adjustments during cooling in thermoneutral subjects than does non-acral skin. Thirteen healthy subjects were exposed to stepwise cooling from 32 °C to 25 °C and 17 °C in a climate chamber. Laser Doppler flux and skin temperature were measured simultaneously from the left and right third finger pulp and bilateral upper arm skin. Coherence and correlation analyses were performed of short-term fluctuations at each temperature interval. The flux from finger pulps showed the synchronous spontaneous fluctuations characteristic of skin areas containing AVAs. Fluctuation frequency, amplitude and synchronicity were all higher at 25 °C than at 32 °C and 17 °C (p<0.02). Bilateral flux from the upper arm skin showed an irregular, asynchronous vasomotor pattern with small amplitudes which were independent of ambient temperature. At 32 °C, ipsilateral median flux values from the right arm (95% confidence intervals) were 492 arbitrary units (au) (417, 537) in finger pulp and 43 au (35, 60) in upper arm skin. Flux values gradually decreased in finger pulp to 246 au (109, 363) at 25 °C, before an abrupt fall occurred at a median room temperature of 24 °C, resulting in a flux value of 79 au (31, 116) at 17 °C. In the upper arm skin a gradual fall throughout the cooling period to 21 au (13, 27) at 17 °C was observed. The fact that the response of blood flow to ambient cooling is stronger in acral skin than in non-acral skin suggests that AVAs have a greater capacity to adjust blood flow in thermoneutral zone than arterioles in non-acral skin.

[A 62-year-old woman with non-pitting leg oedema]. / En kvinne med leggødem og arrforandringer.

A patient presented with non-pitting lymphoedema of the legs and finger clubbing. A skin biopsy showed epidermal hyperkeratosis and abundant mucinous material (Alcian blue positive) in reticular dermis. Treatment (radioactive iodine) for Grave's disease (with exophthalmus) 20 years ago, raised suspicion of thyroid dermopathy. Together, these three extrathyroidal manifestations of Graves' disease are typical of the EMO syndrome. In addition, the patient had elevated serum concentrations of thyroid-stimulating hormone receptor autoantibodies. Autoimmune mechanisms are involved in the stimulation of fibroblasts and the production of large amounts of mucin. Pretibial myxoedema relates to scars, mechanical factors, and dependent position. Lack of steroid treatment during radioactive iodine therapy and smoking, may have exacerbated the thyroid dermopathy in this case. Awareness of pretibial myxoedema as a late autoimmune manifestation of Graves' disease, may contribute to earlier diagnosis and correct treatment.

Effect of maternal age on uterine flow impedance.

PURPOSE: This study was conducted to determine possible maternal age-related changes in uterine artery impedance in normal late pregnancy. PATIENTS AND METHODS: In a cross-sectional design study, Doppler velocimetry of the uterine vessels was performed in 884 pregnant women with normal, late, singleton pregnancies. We hypothesized that maternal age is associated with changes in uterine blood flow Doppler parameters. We tested for univariate associations and for an adjusted relationship between these factors using a multivariate model to control for confounders. RESULTS: We found a statistically significant, nonlinear relationship between mean uterine artery impedance (pulsatility index) and maternal age, with an increase of the pulsatility index in women above the age of 35. This association continued to be significant even when adjusted for gestational age and parity as confounders. CONCLUSIONS: In normal pregnancy, an increase in uterine artery impedance was noted in women above the age of 35. This finding may be related to the physiologic process of aging and may partly explain why pregnancies in older women are associated with diverse complications more often than those in younger women.