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OBJECTIVE: To investigate the possible role of peripheral sympathetic activity in gastric bypass-induced body weight loss. SUBJECTS AND METHODS: In 42 morbidly obese patients (sex: 36 f/6 m; BMI: 46.0+/-0.7 kg/m(2)) undergoing a gastric bypass, the skin vasoconstrictor reflex in answer to a deep inspiration was measured by laser Doppler fluximetry. The extent of vasoconstriction, measured at the second finger of the left hand, was expressed as percent reduction of the basal blood flux (% vasoconstriction). Insulin sensitivity was assessed before surgery in a subset of patients (n=11), by the method of euglycemic, hyperinsulinemic clamp. Body weight and composition were evaluated before, and 3, 6 and 12 months after surgery. At the same time points, energy intake (kJ/day) was evaluated by means of both food record diary and alimentary anamnesis. RESULTS: The % vasoconstriction, which was significantly (P=0.01) greater in normoglycemic subjects than in diabetic ones, was also significantly (P=0.03) related to the extent of insulin sensitivity measured during the euglycemic clamp. The % vasoconstriction showed a significant (P>0.0001), positive correlation with weight reduction obtained between the 6th and 12th months following surgery; as a consequence, % vasoconstriction was significantly (P=0.0004) related to the overall body weight loss achieved during the year following the operation. These correlations remained significant in multiple regression analysis with adjustment for age, initial body weight, plasma glucose and insulin (P=0.0007 and 0.006, respectively). The % vasoconstriction was also significantly (P=0.0006), negatively related to energy intake measured 12 months after surgery. CONCLUSIONS: In conditions of stable body weight, the sympathetic nervous system (SNS) reactivity is influenced by the degree of insulin resistance. A high capacity to activate the SNS, measured before surgery, is associated with both a larger gastric bypass-induced weight loss and a lower energy intake, at the phase of weight stabilization.

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BACKGROUND: Cyclosporine represented a major advance in the medical management of patients with organ transplantation, but its use is limited by the frequent occurrence of hypertension and renal toxicity diagnosed by invasive renal biopsy. Renal histology shows a specific arteriolopathy. It was hypothesized that cyclosporine may also induce subclinical microvascular changes in the skin that might be detected noninvasively by a combination of dynamic capillaroscopy [capillary blood cell velocity (CBV)] with and without intravenous Na-fluorescein (NaF) injection and laser Doppler fluxmetry (LDF). METHODS: The nailfold skin microcirculation was evaluated in 112 consecutive renal transplant recipients (54 +/- 11 years old; 70 males and 42 females) receiving cyclosporine. The investigation was made the same day as a routine renal biopsy performed in all patients more than two years after transplantation. Renal biopsies were blindly classified as positive (N = 33) when significant specific signs of cyclosporine toxicity were clearly observed (AH2-AH3) and were otherwise negative (AH0-AH1, N = 79) according to the Banff classification. RESULTS: Time to fluorescence peak after NaF injection (tpNaF) was significantly longer in patients with positive biopsies than in patients with negative biopsies (13.9 +/- 8.1 vs. 17.5 +/- 9.4 sec, P = 0.009). All patients but three with negative biopsies (93%) had a tpNaF less than 10 seconds (sensitivity 91%, negative predictive value 93%). On the other hand, CBV, LDF, plasma levels of cyclosporine, and endothelin were similar in the two groups. CONCLUSION: Nailfold fluorescence capillaroscopy is an accurate and simple mean to rule out cyclosporine toxicity in renal transplant recipients. A normal test could avoid invasive renal biopsy in about 40% of the patients. Renal biopsy would, however, still be indicated when the test is abnormal.

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We evaluated the effectiveness of a smoking-cessation programme in all patients included between February 1991 and December 1995. After 4 one-hour consultations once a week, 56.2% of patients had quit. Six months later, this rate was between 20 and 25% and few relapses occurred between the 6th and the 12th month. However, the relapse rate was about 50% between the 1st and the 6th month after the consultations and patients certainly need more support during this critical period. In the present study, the 12-month abstinence rate was unrelated to gender, age, and presence of a smoking-related disease. Patients who participated in at least 3 of the 4 sessions of the course had a significantly higher smoking-cessation rate.

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Although microvasculitis is one of the more common manifestations of systemic lupus erythematosus, there is no data on the hemodynamics of the skin microcirculation in such patients. The combination of dynamic capillaroscopy measuring capillary blood cell velocity (CBV) and laser Doppler fluxmetry (LDF) was used to simultaneously evaluate the nutritional and the total skin microcirculation in the fingers of 24 consecutive patients with SLE, using normal matched subjects as controls. The nutritional skin flow, as assessed by the CBV, was significantly impaired in patients, as compared with controls, both at rest (p = 0.001) and during postocclusive reactive hyperemia (p = 0.006). By contrast, no differences were observed in total skin microcirculation, as assessed by LDF (n.s.). There was no significant correlation between hemodynamic parameters and the presence of Raynaud's phenomenon, morphological capillary changes or anticardiolipine antibodies. There was no correlation between the magnitude of the alteration of the capillary blood flow and capillary morphological abnormalities, suggesting that the microvascular damage might be caused by different pathophysiological mechanisms.

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Anticardiolipin antibodies (aCL) are found in about 40-50% of patients suffering from systemic lupus erythematosus (SLE) and their presence carries an increased risk of thromboembolism. Since there is a high prevalence of nailfold capillary abnormalities in patients with SLE, we studied the relationship between aCL and skin microcirculatory changes or vascular symptoms in 51 consecutive patients with SLE (49 women, 2 men, 34.8 +/- 13.7 years). Twenty-two patients (43.1%) had positive aCL (IgG 22 (5-60) GPL; IgM 5 (3-16.5) MPL; median titre and range) and 12 (54.5%) of them had abnormal capilloscopic findings. By contrast, among the 29 patients without aCL, only six (20.7%) had an abnormal capillaroscopy (P = 0.027). There was no correlation between either aCL or capillaroscopy and Raynaud's phenomenon. These results show a relationship between aCL and nailfold capillary changes in patients with SLE, suggesting a direct damage of the vascular endothelium by aCL.

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Percutaneous transluminal angioplasty (PTA) provokes a huge trauma to the arterial wall and potentially liberates fragments of atherosclerotic material that may impair the microcirculation downstream. Incidence and clinical relevance of such embolisms are not known. This study was aimed at investigating the changes of the skin microcirculation in patients with peripheral arterial occlusive disease undergoing PTA of the lower limbs. Pedal transcutaneous oxygen tension (tcpO2) and nailfold skin microcirculation were measured in 21 patients with disabling peripheral arterial occlusive disease before and after PTA. Sixteen matched patients undergoing arteriography alone were used as controls. The skin microcirculation was investigated at the nailfold of the great toe by the combination of laser Doppler fluxmetry and dynamic capillaroscopy. PTA was successful in all patients. The tcpO2 decreased immediately after PTA (delta tcpO2 = -5 mm Hg; p < 0.004), whereas it tended to increase (delta tcpO2 = 1 mm Hg; NS) following arteriography as compared with baseline values. By contrast, blood flow increased in both groups, predominantly for the total circulation in the PTA group and for nutritional circulation (p < 0.0017) in the arteriography group, respectively. Consequently, the 'nutritional index', i.e., the index of nutritional versus total microcirculation, was decreased following PTA, particularly following mechanical recanalization (p < 0.02), but did not change in the controls. The changes of this 'nutritional index' and those of the tcpO2 were positively correlated (r = 0.4, p = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)

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Plasma D-Dimer (DD), a highly sensitive marker of venous thromboembolism, was measured with an ELISA assay preoperatively and on the 12th postoperative day in 173 patients undergoing major hip surgery (78 elective arthroplasties and 95 operations for fractures). Proximal deep venous thrombosis (DVT) was detected by systematic compression venous ultrasonography on the 12th postoperative day in 12 (7%) patients. In one additional case, proximal DVT was diagnosed by venography. Preoperative DD level was significantly higher in patients with fracture than in patients undergoing elective arthroplasty. At a cutoff of 500 micrograms/L as determined by ROC curve analysis, the sensitivity, specificity, positive and negative predictive values of the pre-operative DD concentration for the development of subsequent proximal DVT were 93%, 23%, 36% and 96%, respectively. The diagnostic exclusion value of the DD measurement on the 12th postoperative day was similar but for a cutoff of 2000 micrograms/L. These data suggest that plasma DD measurement might be useful to predict and diagnose proximal DVT following major hip surgery.

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Right atrial thrombosis (RAT) is infrequently diagnosed in children with cancer. Once RAT is documented, medical fibrinolysis or surgical thrombectomy is recommended. A RAT was documented in a child with lymphoma and was successfully lysed with recombinant tissue-type plasminogen activator. The case is presented and therapeutic options reviewed.

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Despite antithrombotic prophylaxis, deep vein thrombosis (DVT) remains a frequent complication following major hip surgery. Most of the postoperative DVTs are asymptomatic but may result in fatal pulmonary embolism. Thus, detection of these events remains a clinical challenge. The present study evaluated prospectively the clinical usefulness of a systematic screening for proximal DVT in 173 consecutive patients undergoing major hip surgery and given systematic antithrombotic prophylaxis. On the 12th postoperative day, real-time B-mode ultrasonography of lower limbs veins detected 12 patients (7%) with proximal DVT. None of the individual or surgical characteristics of the patients could help to predict postoperative DVT. Because the sensitivity of ultrasonography for diagnosing DVT in asymptomatic patients may be low and because we did not screen for distal DVT, it was speculated that up to half proximal DVT and up to 75% of all DVT might have been missed by the screening. Therefore, low-dose oral anticoagulation with an INR 1.5-2.0 might be the most cost-effective modality in the postoperative period after the initial perioperative prophylaxis with low-dose heparin, low-molecular-weight heparins or intermittent pneumatic compression boots. Oral anticoagulant treatment might be continued for a total duration of 6 weeks, thereby also providing efficient therapy of undiagnosed distal DVT and prolonged for 3 months in patients with proximal DVT proven by systematic ultrasonographic screening at the time of discharge. The benefit-to-risk ratio of this management strategy deserves further evaluation in a specially designed, prospective trial.

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Skin microcirculation is rather complex. The skin viability depends upon the nutritional circulation, which cannot be assessed by conventional macrocirculatory methods that evaluate total blood supply. The indisputable advantage of the microcirculatory methods is to provide information directly in diseased skin areas and assess the effectiveness of vasoactive drugs where they are supposed to act. Several techniques are available today to evaluate the skin microcirculation. Among them, capillaroscopy and transcutaneous measurement of the partial oxygen pressure are of special interest because they provide information which is directly useful in clinical practice. Other techniques remain experimental. In this paper, the main microcirculatory techniques are reviewed and their clinical implications discussed.

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Plasma measurement of D-Dimer (DD) represents a definite aid in the diagnostic approach of outpatients with suspected venous thromboembolism (VTE). However, the high sensitivity (about 95%) of the test which allows to rule out VTE when concentrations are below a given cutoff (500 micrograms/L as measured by the ELISA technique) is counterbalanced by a poor specificity (about 40%). Because the specificity might even be lower in patients who are hospitalized we determined the DD plasma concentration in 255 patients who were consecutively admitted in general internal medicine wards with various pathological conditions. The proportion of patients who had DD levels below the cutoff of 500 micrograms/L was 6% (1/18) in patients with VTE and 22% (52/237) in hospitalized patients without VTE: the figure was 21% in patients with pulmonary infections, 14% in patients with other infections, 11% in patients with neoplastic diseases, 34% in patients with coronary or cerebrovascular disease, 19% in patients with cardiac failure, 69% in patients with rheumatologic disease and in 16% in subjects with miscellaneous clinical conditions. The high rate of elevated plasma DD in hospitalized patients questions the usefulness of this test in the diagnostic approach of VTE in aged patients who present with concomitant disease like infections, neoplasia, cardiac failure and many other pathological conditions, except rheumatologic affections and coronary or cerebrovascular diseases.

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Venous thromboembolism (deep venous thrombosis (DVT) and pulmonary embolism (PE)) is a serious and quite frequent disease. In this review, we summarize the present state of knowledge regarding clinical epidemiology and risk factors. These features should allow the general practitioner to assign each individual patient to a particular risk group and to order an personalized prophylaxis.

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BACKGROUND: Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation. CONCLUSIONS: Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD.

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Two patients with Takayasu arteritis presented with either severe renovascular hypertension or profound weight loss due to intestinal angina. The leading clinical signs were cured by successful percutaneous transluminal angioplasty (PTA) of the abdominal aorta and renal arteries in one patient and of the superior mesenteric artery and coeliac trunk in the second. These results and a literature review of the topic suggest that PTA should be the first therapeutic approach in symptomatic arterial stenoses due to TA in the inactive stage of the disease.

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It has been suggested that unstable angina at rest, like acute myocardial infarction, might be associated with a thrombotic process. In order to study the hypothesis that myocardial ischemia during exercise could also be associated with an activation of blood coagulation and/or fibrinolysis, we investigated the presence of plasma markers of a prethrombotic or thrombotic state (thrombin-antithrombin III complexes TAT, prothrombin fragment F1 + 2, and D-dimers DD) in 100 consecutive patients with confirmed or suspected coronary artery disease during ergometric test with myocardial thallium-201 scintigraphy. Symptoms and scintigrams allowed to define three groups of patients: those showing no ischemia (n = 79) and those with symptomatic (n = 8) or silent myocardial ischemia (n = 13). Before exercise, DD and TAT levels were not significantly different among the three groups. On the other hand, the F1 + 2 levels were slightly albeit significantly higher in the patients without ischemia than in the patients with symptomatic or silent ischemia. After exercise, no significant difference was found between the three groups. Exercise induced a significant and parallel increase in both the TAT and the F1 + 2 levels (but not of the DD levels) in the three groups. Thus, our study does not support the hypothesis that myocardial ischemia, silent or symptomatic, is associated with an activation of plasma coagulation and fibrinolysis that can be distinguished from the exercise-induced thrombin generation.

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Ergot's derivatives are widely used to treat and prevent migraine and, associated with heparin, for the prevention of deep vein thrombosis. During a five-year period, 7 patients have been admitted in our hospital for severe vasospasm of one or several extremities due to ergot's derivatives. All patients presented with acute severe ischemia of the lower limb requiring iv infusion of vasodilator drugs. Ergotamine tartrate was the responsible drug in four patients and dihydroergotamine(DHE)-heparin in three patients. Intravenous administration of sodium nitroprusside (n = 6) relieved vasospasm in all but one of the patients within hours to days and no amputation was required. Ankle or great toe to arm systolic pressure index was normalized in the majority of the patients after treatment. A sympathectomy was performed in two patients which did not improve the clinical course. Distal necrosis developed in two patients (DHE-heparin). It is concluded that incidence of severe ergotism is less than 0.5/100,000/year in Geneva. This contrasts with the high prevalence (15%) of subclinical ergotism reported by others. No amputation was required in this series in spite of severe and prolonged vasospasms. Subclinical ergotism most probably precedes for weeks the onset of severe vasospasm, which calls for close monitoring of patients taking ergot's derivatives.

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Twelve patients with port wine stains (both untreated and treated with argon laser) had their microcirculation monitored by laser Doppler flux at rest and after arterial occlusion lasting one minute. The blood cell flux was measured in normal, untreated and treated skin areas. The resting flux was significantly higher in untreated port wine stains than in the normal skin. The reactive hyperemia response was significantly impaired in the untreated skin, although a 60% increase in blood cell flux was achieved by the short arterial occlusion. In most of the recorded parameters the treated areas showed a less pathological reaction than the untreated ones. We conclude that peroperative vasodilation can be induced in port wine stains, and this may be used to improve the outcome of argon laser treatment.

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