Severe early-onset manifestations of pseudoxanthoma elasticum resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB: transient improvement in ectopic calcification with sodium thiosulfate.

Pseudoxanthoma elasticum (PXE) is a rare disorder characterized by fragmentation and progressive calcification of elastic fibres in connective tissues. Overlap has been reported between the inherited PXE phenotype associated with ENPP1, ABCC6 or NT5E mutations and acquired PXE clinical manifestations associated with haemoglobinopathies induced by HBB mutations. No treatment is currently available for PXE. A young boy presented with severe early-onset systemic calcifications occurring in the skin as elastosis perforans serpiginosa (EPS) and in the arteries, causing mesenteric and limb ischaemia. Analyses revealed deleterious ABCC6, ENPP1 and HBB mutations. The diagnosis of severe PXE was retained and we have coined the term 'PXE+ syndrome' to describe the cumulative effects of the various mutations in this uncommon phenotype. Given the severity, rapid progression and a potentially fatal prognosis, intravenous sodium thiosulfate (STS) was initiated at 25 g three times weekly for 6 months. Numerous side-effects prompted dosage adjustment to 10 g intravenously daily. Treatment efficacy was evaluated at 6 months. Asthaenia, anorexia and pre-/postprandial pain had subsided, entailing weight gain. Abdominal EPS had diminished. Calcific stenosis of the coeliac and mesenteric arteries was no longer detectable on arterial ultrasonography. Follow-up revealed only transient efficacy of STS. Discontinuation of treatment to evaluate the persistence of effects resulted in relapse of the initial symptomatology after 4 months. STS efficacy is conceivably due to strong antioxidant properties and chelation of calcium to form soluble calcium thiosulfate complexes. This case is suggestive of PXE+ syndrome for which STS may represent potential treatment in severe cases. What's already known about this topic? Generalized arterial calcification of infancy may occur in association with ABCC6 mutations and pseudoxanthoma elasticum (PXE) can be linked to ENPP1 mutations. A PXE-like phenotype has also been reported in a subset of patients with inherited haemoglobinopathies, namely sickle cell disease or ß-thalassaemia, related to HBB mutations. To date, there is still no cure for PXE. What does this study add? We report a severe case of PXE resulting from the cumulative effects of several deleterious mutations in ENPP1, ABCC6 and HBB. We suggest the term 'PXE+ syndrome' to describe such patients. Sodium thiosulfate therapy could represent a potential option in severe cases of PXE+ syndrome.

Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults.

AIM: This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults. METHODS: Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated. RESULTS: Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites. CONCLUSION: Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk.

Disseminated arterial calcification and enhanced myogenic response are associated with abcc6 deficiency in a mouse model of pseudoxanthoma elasticum.

OBJECTIVE: Pseudoxanthoma elasticum is an inherited metabolic disorder resulting from ABCC6 gene mutations. It is characterized by progressive calcification and fragmentation of elastic fibers in the skin, retina, and the arterial wall. Despite calcium accumulation in the arteries of patients with pseudoxanthoma elasticum, functional consequences remain unknown. In the present study, we investigated arterial structure and function in Abcc6(-/-) mice, a model of the human disease. APPROACH AND RESULTS: Arterial calcium accumulation was evaluated using alizarin red stain and atomic absorption spectrometry. Expression of genes involved in osteochondrogenic differentiation was measured by polymerase chain reaction. Elastic arterial properties were evaluated by carotid echotracking. Vascular reactivity was evaluated using wire and pressure myography and remodeling using histomorphometry. Arterial calcium accumulation was 1.5- to 2-fold higher in Abcc6(-/-) than in wild-type mice. Calcium accumulated locally leading to punctuate pattern. Old Abcc6(-/-) arteries expressed markers of both osteogenic (Runx2, osteopontin) and chondrogenic lineage (Sox9, type II collagen). Abcc6(-/-) arteries displayed slight increase in arterial stiffness and vasoconstrictor tone in vitro tended to be higher in response to phenylephrine and thromboxane A2. Pressure-induced (myogenic) tone was significantly higher in Abcc6(-/-) arteries than in wild type. Arterial blood pressure was not significantly changed in Abcc6(-/-), despite higher variability. CONCLUSIONS: Scattered arterial calcium depositions are probably a result of osteochondrogenic transdifferentiation of vascular cells. Lower elasticity and increased myogenic tone without major changes in agonist-dependent contraction evidenced in aged Abcc6(-/-) mice suggest a reduced control of local blood flow, which in turn may alter vascular homeostasis in the long term.

External validation of the "walking estimated limitation calculated by history" (WELCH) questionnaire in patients with claudication.

OBJECTIVE: To externally validate the recently proposed "Walking Estimated Limitation Calculated by History" (WELCH) questionnaire. METHODS: A prospective study was performed on 450 new patients referred to our laboratory for treadmill testing (constant load 3.2 km/h and 10% slope for 15 minutes and then incremental increases). Results are presented as mean ± SD or median [25th-75th percentiles] or number (percentage). An ankle brachial index <0.90 defined the presence of peripheral artery disease (PAD). Typical "vascular-type claudication" is a lower-limb pain or discomfort that is absent at rest, appears at exercise, forces stopping, and disappears within 10 minutes of exercise stopping. The Spearman r coefficient of correlation between maximal walking time (MWT) on treadmill and WELCH scores was calculated for patients with (PAD+) or without (PAD-) PAD, and reporting typical vascular-type claudication (VTC+) or not (VTC-). RESULTS: The WELCH score was obtained in all included patients. The number (%) of patients with a WELCH score <25 was 37 (54%), 198 (65%), 14 (44%), and 18 (38%), and the Spearman correlation coefficient between WELCH score and treadmill MWT was 0.588, 0.609, 0.581, and 0.591 in the VTC-/PAD+, VTC+/PAD+, VTC-/PAD-, and VTC+/PAD- groups respectively (all p < .001). In PAD+/VTC+ patients, the WELCH positive predictive value for the inability to walk for 5 minutes on the treadmill was 79%. CONCLUSION: The WELCH score correlates moderately with treadmill-walking capacity in patients with or without PAD, and with or without typical VTC. It appears to be a simple to complete and easily scored instrument to help clinicians standardise the subjective estimation of walking capacity in their patients.

High-frequency (20-50 MHz) ultrasonography of pseudoxanthoma elasticum skin lesions.

BACKGROUND: In most patients pseudoxanthoma elasticum (PXE) manifests with yellowish cutaneous papules and dermal elastorrhexis on skin biopsy. In a small number of cases there are no skin manifestations on clinical examination, and establishing a diagnosis of PXE in such patients is challenging. High-frequency ultrasonography (HFUS) may be of use in predicting skin areas that would yield a biopsy specimen positive for elastorrhexis. OBJECTIVES: To describe characteristics of clinically visible PXE skin using HFUS, and to evaluate its relevance for diagnosis. METHODS: HFUS was performed in a cohort of patients with PXE and in controls at a referral centre. HFUS images of PXE skin were compared with those of other conditions. Five operators blind-scored multiple HFUS images of photoprotected or photoexposed skin from patients with PXE and controls. The diagnostic indices (sensitivity, specificity, likelihood ratios, interobserver agreement) were calculated. RESULTS: The HFUS changes considered as diagnostic for PXE were primarily oval homogeneous hypoechogenic areas in the mid-dermis. The size of these areas closely matched the extent of the histological changes. The sensitivity and specificity of the diagnostic items and interobserver agreement were high, particularly in photoprotected skin. Dermal hypoechogenicity in PXE could be related to high hydration of connective tissue due to the presence of glycosaminoglycans despite elastic fibre mineralization. CONCLUSIONS: HFUS provides suggestive images of PXE skin lesions. HFUS should now be studied to determine whether it is a potentially valuable technique for the noninvasive identification of elastorrhexis in patients with PXE in whom skin involvement is clinically minimal or absent.

MRI measurement of liver fat content predicts the metabolic syndrome.

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk.

Estimation of running capacity can likely be removed from questionnaires estimating walking impairment in patients with claudication.

OBJECTIVE: The Estimating Ambulation Capacity by History-Questionnaire (EACH-Q) and the Walking Impairment Questionnaire (WIQ) are used to estimate maximal walking distance (MWD). The EACH-Q and WIQ included 4 and 14 items respectively, among which one item dealing with running capacity. We hypothesised that this item was of little interest in patients with claudication. DESIGN: The WIQ and EACH-Q were self-completed and corrected before a constant load (3.2 km h(-1); 10% slope) treadmill tests, maximised to 15 min. PATIENTS: 371 patients (298 males/73 females, 62.9 ± 11.2 years). METHODS: The number of errors (duplicate, absent or paradoxical answers to one item) and correlation of questionnaire scores with MWD on treadmill were calculated, before and after skipping the answer to the running item. RESULTS: The proportion of questionnaires with errors was 27% with the EACH-Q and 48% with the WIQ. Two-hundred and twenty-one (59.6%) and 245 (66%) out of 371 patients reported to be unable to run, for the EACH-Q and WIQ, respectively. The rate of errors was reduced by 15% for the EACH-Q (p < 0.05) when skipping the running item for scoring. The correlation coefficients between the MWD and the questionnaire scores were 0.449 and 0.485 for the EACH-Q and were 0.571 and 0.572 for the WIQ, before and after skipping the running item, respectively. CONCLUSION: Most of our patients reported to be unable to run and skipping the running item reduce the rate of errors in self-completing the questionnaires without impairing the correlation of questionnaire scores with treadmill results. It is likely that the running item could be removed from the WIQ and EACH-Q questionnaires.

Carotid rete mirabile and pseudoxanthoma elasticum: an accidental association?

We report the case of a young female patient with a transient amaurosis due to a carotid rete mirabile (CRM), a rare congenital carotid malformation, and pseudoxanthoma elasticum (PXE), an inherited autosomal recessive systemic metabolic disorder characterised by fragmentation and mineralisation of elastic fibres in connective tissues (skin, eyes) and the vascular system. CRM is a rare form of intracranial carotid malformation whose association with PXE (6 cases at present) would appear not to be accidental. This observation suggests a new link between congenital arterial remodelling and the PXE.

Limitations of self-reported estimates of functional capacity using the Walking Impairment Questionnaire.

OBJECTIVE: A potential issue with the Walking Impairment Questionnaire (WIQ) is that it is relatively complex. We estimated the number of errors made by patients when self-completing the WIQ, and assessed the benefit of correcting missing, duplicate or paradoxical (i.e., reported lower difficulty for a higher-intensity task) answers. DESIGN: Prospective non-interventional study. MATERIALS: All consecutive new patients with claudication over a 3-month period. METHODS: The WIQ was self-completed before patients performed a constant-load treadmill walking test (maximised to 750 m). MAIN OUTCOME MEASURE: We analysed the coefficient of determination of the linear relationship between overall WIQ score (mean of the available subscales when at least two subscales are available) and treadmill maximal walking distance (MWD), before and after correction of errors. RESULTS: We studied 73 patients. Thirty-seven questionnaires had to be corrected for one or more errors. The coefficient of determination between the overall WIQ score and MWD was R(2) = 0.391 (n = 56) and R(2) = 0.426 (n = 73) before and after correction, respectively. CONCLUSION: Supervision of self-completed WIQs detects errors in almost half of the questionnaires, resulting in a missing overall WIQ score in 23% of cases among uncorrected questionnaires. The overall WIQ score correlates only moderately with MWD, even after correction. CLINICAL TRIAL REGISTRATION: NIH database: NCT01114178.

Functional outcome of hypogastric revascularisation for prevention of buttock claudication in patients with peripheral artery occlusive disease.

We have defined proximal lower limb ischaemia as a decrease in Exercise-transcutaneous oxygen pressure (TcPO(2)) lower than minus 15mmHg at the buttock level in patients with peripheral artery occlusive disease. The purpose of this study was to objectively evaluate the benefits of direct versus indirect revascularisation of internal iliac arteries (IIAs) for prevention of buttock claudication in this population. We retrospectively reviewed the charts of proximal ischaemia patients who underwent revascularisation and both preoperative and postoperative stress TcPO(2) testing. Revascularisation procedures were classified as either direct revascularisation, including percutaneous transluminal angioplasty and internal iliac artery bypass, resulting in a direct inflow in a patent IIA (group 1) or indirect revascularisation, including aortobifemoral bypass and recanalisation of the femoral junction on the ischaemic side, resulting in indirect inflow from collateral arteries in the hypogastric territory (group 2). Patency was checked 3 months after revascularisation in all cases. Treadmill exercise stress tests were performed before and after revascularisation using the same protocol designed to assess pain, determine maximum walking distance (MWD) and measure TcPO(2) during exercise. In addition, ankle-brachial indices (ABIs) were calculated. Between May 2001 and March 2008, a total of 93 patients with objectively documented proximal ischaemia underwent 145 proximal revascularisation procedures using conventional open techniques in 109 cases and endovascular techniques in 36. Direct revascularisation was performed on 50 limbs (35%) (group 1) and indirect revascularisation on 95 limbs (65%) (group 2). The mean interval between revascularisation and stress testing was 60+/-74 days preoperatively and 149+/-142 days postoperatively. No postoperative thrombosis was observed. Buttock claudication following revascularisation was more common in group 2 (p<0.001). No difference was observed between the two groups with regard to improvement in MWD (365 / 294 m) and ABI (0.20/0.22). Disappearance of proximal ischaemia was more common after direct revascularisation (p<0.01). The extent of lesions graded according to the TASC II classification appeared not to be predictive of improvement in assessment criteria following revascularisation. Conversely, patency of the superficial femoral artery was correlated with improvement (p<0.01). This study indicates that direct revascularisation, if feasible, provides the best functional outcome for prevention of buttock claudication.

Cerebral hemodynamics in carotid sinus syndrome and atrioventricular block.

Carotid sinus syndrome (CSS) is a cause of syncope due to exaggerated baroreceptor-mediated cardioinhibitory/vasodepressive reflexes. We sought to determine if cerebral hemodynamics and regulation were specifically altered in these patients by comparison with pure asystole without vasodepression in patients with atrioventricular block (AVB). Mean blood flow velocity (transcranial Doppler sonography) and mean arterial blood pressure (Finapres) were recorded during cardioinhibition induced by carotid massage in patients with CSS (n = 14, 75 +/- SD 8 years) and asystole induced by temporary pacemaker inhibition in patients with complete AVB (n = 10, 69 +/- 11 years). Cerebrovascular resistance was estimated by the arterial pressure/cerebral flow velocity ratio, and dynamic cerebral autoregulatory responses were determined by the rate of regulation and autoregulatory index. Asystole and cardioinhibition each induced a decrease in arterial pressure (CSS 55 +/- 9% vs AVB 40 +/- 14%, p <0.05) and cerebral flow velocity (CSS 66 +/- 19% vs AVB 69 +/- 14%, p = NS), with an initial transient increase in cerebrovascular resistance (CSS 102 +/- 136% vs AVB 128 +/- 92%, p = NS) followed by a decrease (CSS 38 +/- 12%, AVB 29 +/- 13%, p = NS). The rate of regulation and autoregulatory index were higher with AVB (0.43 +/- 0.20 and 8.5 +/- 1.1 second(-1)) than CSS (0.20 +/- 0.12 and 4.8 +/- 1.3 second(-1), respectively, p <0.01 and p <0.001 vs AVB). During asystole and vasodepression, cerebral hypoperfusion in CSS is normally compensated for by cerebral autoregulation. The lower rate of regulation in CSS compared with AVB likely results from persistent peripheral vasodepression triggered by carotid massage.

Estimation of intraoperative aortocoronary bypass saphenous vein graft circumference from its preoperative compliance.

The aim of this study was to determine if the intraoperative circumference of aortocoronary saphenous vein bypass grafts could be predicted from preoperative measurement with B-mode ultrasound sonography in 50 patients. The circumference of the saphenous vein was measured during stepwise increments of a thigh congestive cuff from 0 to 60 mmHg. The circumference of the corresponding segment of the coronary bypass vein graft was measured intraoperatively with callipers. The intraoperative circumference was higher (11.8+/-2.3 mm) than the preoperative circumference (10.2+/-2.4 mm, P=0.006) matched to its corresponding intraoperative mean arterial pressure (57+/-15 mmHg). The prediction of the intraoperative circumference by estimation from the preoperative pressure-circumference relationship fitted by a linear model (r = 0.412, P = 0.004) did not improve on the preoperative circumference matched by arterial pressure alone (r = 0.429, P = 0.003). The intraoperative circumference of the graft vein exceeded its preoperative circumference by 12%. Prediction of the intraoperative graft vein circumference is underestimated by a linear model of its preoperative compliance.

Autoregulation of human inner ear blood flow during middle ear surgery with propofol or isoflurane anesthesia during controlled hypotension.

UNLABELLED: We used controlled hypotension to obtain a bloodless cavity during middle ear surgery under an optical microscope. No previous study has assessed the effect of controlled hypotension on inner ear blood flow (IEF) autoregulation in humans receiving propofol or isoflurane anesthesia. In the present study, the IEF autoregulation was determined using laser Doppler flowmetry in combination with transient evoked otoacoustic emissions (TEOAEs) during controlled hypotension with sodium nitroprusside in 20 patients randomly anesthetized with propofol or isoflurane. A coefficient of IEF autoregulation (Ga) was determined during controlled hypotension, with a Ga value ranging between 0 (no autoregulation) and 1 (perfect autoregulation). During controlled hypotension with propofol, IEF remained stable (1%+/-6%; P > 0.05) but decreased by 25%+/-8% with isoflurane (P < 0.05). The Ga was higher during propofol anesthesia (0.62+/-0.03) than during isoflurane anesthesia (0.22+/-0.03; P < 0.0001). Under propofol anesthesia, there were individual relationships between TEOAE amplitude and change in IEF in four patients. Such a correlation was not observed under isoflurane anesthesia. These results suggest that human IEF is autoregulated in response to decreased systemic pressure. Furthermore, isoflurane has a greater propensity to decrease cochlear autoregulation and function than propofol. IMPLICATIONS: The present study shows that inner ear blood flow is autoregulated under propofol, but not isoflurane, anesthesia during controlled hypotension in humans during middle ear surgery. Further studies are needed to explore the postoperative auditory functional consequences of the choice of the anesthetic drug used in middle ear surgery.

Calf vein compliance increases following bed rest after aortocoronary bypass surgery.

Early post-operative ambulation (< 3 days) is expected to decrease the risk of venous thrombosis, whereas late ambulation (> 7 days) increases the risk of orthostatic hypotension. The effect of post-operative bed rest on calf vein compliance was studied before (D - 1) and 7 days (D + 7) after aortocoronary bypass surgery in 50 patients (41 men and nine women, 65 +/- SD 10 years). Calf vein compliance was measured by strain gauge plethysmography and stepwise increases in thigh congestive pressure from 20 to 60 mmHg. Calf compliance [median (25 percentile-75 percentile)] increased significantly by 48% from D - 1 to D + 7 [0.044 (0.039-0.051) vs. 0.065 (0.048-0.083) ml (100 ml mmHg)-1, P < 0.001]. This increase was reflected as increased calf volume for the 50 mmHg [D-1 2.10 (1.75-2.65) vs. D + 7 2.60 (1.70-3.00) ml 100 ml-1, P < 0.01] and 60 mmHg [D - 1 2.50 (2.10-2.95) vs. D + 7 3.20 (2.30-4.00) ml 100 ml-1, P < 0.001] occlusion pressure levels. The associated pathologies (diabetes and arterial hypertension) and NYHA grades had no significant influence on the increase in compliance. Among the vasoactive therapeutic regimens, calcium channel blockers contributed significantly to the increased calf compliance, but only on D-1. The increase in venous compliance following aortocoronary bypass surgery is multifactorial but should be considered for prophylactic management of these patients.

Laser Doppler flowmetry in the diagnosis of chronic compartment syndrome.

Chronic compartment syndrome (CCS) is usually considered to be due to ischaemia of muscle. We have attempted to use the direct measurement of muscle blood flow for diagnosis since the assessment of intracompartmental pressure does not provide accurate knowledge of the vascular state. We recorded simultaneously continuous measurements of the laser Doppler flow (LDF) in muscle and the intracompartment pressure (ICP) after exercise in seven patients with CCS, and in seven control subjects. The mean ICP was 74.1 +/- 4.4 mmHg in CCS patients and 24.2 +/- 3.4 mmHg in control subjects one minute after exercise, decreasing to 34.6 +/- 2.3 mmHg and 15.0 +/- 1.6 mmHg at 20 min, respectively. The LDF was 0.80 +/- 0.11 arbitrary units (AU) in control subjects and 1.09 +/- 0.14 AU in CCS patients one minute after exercise, and 0.41 +/- 0.11 AU and 0.27 +/- 0.04 AU, respectively, at the end of the recovery period. The ICP showed a progressive decrease over time in both groups. The LDF decreased sharply during the first minutes of recovery in control subjects, but in patients with CCS there was a delayed hyperaemic peak with blood flow reaching 0.84 +/- 0.10 AU at nine minutes as against 0.33 +/- 0.06 AU for control subjects (p < 0.01). The ICP increased in both control subjects and CCS patients after exercise with no clear cut-off point between the groups. By contrast, changes in muscle blood flow over time were clearly different between control subjects and patients with CCS. For this reason, LDF should be investigated further as a technique for the diagnosis of CCS.

Lower extremity arterial disease in sports.

The recent description of exercise-induced intimal fibrosis affecting mainly the iliac artery (and therefore usually described as external iliac artery endofibrosis) has dramatically changed the diagnostic approach of unexplained recurrent lower limb exercise pain, especially in cyclists. Because arterial disease is often associated with the aftereffect of various concomitant musculotendinous lesions, several months may pass before an arterial origin is suspected. The arterial origin of the pain must not be eliminated on normal ankle-to-arm index or normal Doppler velocity profiles at rest. Ultrasound examinations taken at rest may show the lesions in 80% of endofibrotic patients and allow for the diagnosis of popliteal entrapment syndrome during dorsiflexion of the foot. However, the hemodynamic consequences of a stenosis on the aortoiliofemoral axis can only be proved by measurement of the ankle-to-arm index after exercise. A cutoff of this index <0.5 provides an 85% sensitivity in the detection of endofibrosis. Invasive investigations (arteriography or angioscopy) will confirm the diagnosis before surgery is discussed. Although long-term results in endofibrosis are unknown, most of the surgically treated patients return to competition.

Prolonged asymptomatic micro-embolism after hip or knee arthroplasty.

We studied the time course of micro-embolism by recording high intensity transient signals (HITS) on Doppler venous blood flow studies during a 7-day period in 57 of 63 consecutive patients after hip or knee replacement. No HITS were found before surgery, or in the non-operated leg after surgery. In the operated leg, the median number of HITS per minute showed an exponential decrease with time; a 50% reduction in the number of HITS took 72 minutes. Regardless of the duration and severity of HITS, we found no clinically apparent embolic event. Colour Doppler imaging at days 8 to 10 after operation showed a deep venous thrombosis in 17% of our patients with one thrombosis of the long saphenous vein. The presence or severity of HITS did not predict the venous thrombi. Although we found no pulmonary complications, we detected micro-emboli over a longer period after surgery than is usually reported. Spectral analysis of the Doppler venous signal is a repeatable and non-invasive monitoring technique in the post-surgical period. We failed to prove a correlation between deep venous thrombi and micro-emboli detected by this method.

[Isolated plantar venous thrombosis. Report of a case]. / Thrombose veineuse plantaire isolée. A propos d'un cas.

We report the case of a patient with isolated plantar thrombophlebitis as a post operative complication of saphenectomy. Risk factors such as prolonged bed rest, perioperative inflammation and surgery of the greater saphenous vein itself should be considered. Moreover multiple episodes of superficial venous thrombosis had already occurred as complication of the superficial venous insufficiency. Literature on this unusual outcome is lacking. Ultrasound imaging revealed this superficial thrombosis. Usual echographic signs (non compressible vein, hypoechogenicity of the vessel lumen) can be found. The main problem is to differentiate veins from adjacent tendinous structures. Slow mobilisation of the toes and comparative analysis on contralateral foot are helpful. Thrombosis of the plantar veins must be considered as a possible diagnosis of unexplained plantar unilateral pains. Development of ultrasonic investigations and knowledge of its occurrence could further improve its diagnosis.

Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.

Cutaneous and subcutaneous blood flow during general anaesthesia.

The vasodilator effect of anaesthetic agents on cutaneous vessels has often been investigated. In contrast, although subcutaneous tissue is concerned with metabolism and thermoregulation, the effects of anaesthesia on subcutaneous blood flow have not been well documented. The purpose of this study was to determine the magnitude of changes in cutaneous and subcutaneous blood flow during general anaesthesia in Man. Anaesthesia was induced with flunitrazepam in 15 patients before facial plastic surgery. Blood flow was estimated using heat thermal clearance (HC). Two HC sensors in different areas allowed the measurement of superficial and deep HC. Systolic (SABP), diastolic (DABP) and mean arterial blood pressure (MABP), heart rate (HR), and rectal and mean skin temperature were also recorded. After induction of anaesthesia, HR increased significantly (p less than 0.05) whereas SABP, DABP and MABP remained unchanged. The rectal-toe temperature gradient fell from 6.3 +/- 4.1 degrees C to 3.4 +/- 1.1 degrees C (p less than 0.01) suggesting a reduction in vasomotor tone. Superficial HC increased from 0.37 +/- 0.06 to 0.42 +/- 0.08 W.m-1.degrees C-1 (p less than 0.05) whereas deep HC decreased from 0.33 +/- 0.07 to 0.31 +/- 0.09 W.m-1.degrees C-1 (NS) and returned to the control value thereafter. Rectal temperature and mean skin temperature were unchanged. The changes in deep HC are similar to those previously observed in muscle during induction of anaesthesia. Our results show that anaesthesia mainly affects cutaneous blood flow, without any significant change in subcutaneous blood flow during the early phase of anaesthesia in human beings.