[What is the evidence to support screening for abdominal aortic aneurysm and what is the role of the primary care physicians ?]. / Quel est l'intérêt de dépister et de suivre un anévrisme de 1'aorte abdominale ?

Abdominal aortic aneurysm is a serious and potentially fatal vascular disease. Surgical intervention is typically reserved for aneurysms 55 mm in diameter or greater. Randomized trials addressing the efficacy of ultrasound screening for abdominal aortic aneurysm have shown that screening reduced aneurysm-related mortality in men but not in women who have a lower prevalence of abdominal aortic aneurysm. Screening with ultrasonography is recommended in men 65 to 75 years of age with a history of smoking and is suggested in women in this age group if they have risk factors such as smoking and hypertension. Men and women with a family history of abdominal aortic aneurysm should undergo screening as well. Persons who have a stable aneurysm should undergo regular surveillance or operative intervention depending on aneurysm size. Primary care physicians have to play a key role before prescribing screening in assessing risks and benefits of repair in each patient. For persons with an aneurysm of less than 55 mm in diameter, the primary care physicians should provide information and interventions for the prevention of cardiovascular disease such as screening for and treating hypertension and interventions for tobacco cessation for smokers. The family physicians should also ensure that radiological monitoring of aneurysms is complete.

Accuracy of X-ray with perfusion scan in young patients with suspected pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients aged ≤50years with suspected PE. METHODS: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (κ=0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively. CONCLUSION: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm.

[New oral anticoagulants: emerging clinical data and role of the primary care physician]. / Les nouveaux anticoagulants oraux: actualisation de l'intérêt clinique et rôle du médecin généraliste.

New oral anticoagulants offer several potential advantages including oral administration, fixed doses, no regular coagulation monitoring and dose adjustment and wide therapeutic index. The results from clinical studies for prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation show that these agents are at least as effective as or superior to currently available therapies depending on the molecules and dose regimen. Physicians will have to make choices among available new agents taking into account their pharmacokinetic properties, half-life, route of elimination and patient comorbidities. But the use of these new agents in daily practice raises some issues such as temporary discontinuation in patients undergoing invasive procedures and management of patients with bleeding in the absence of specific antidote. New oral anticoagulants should be used with caution in daily practice in special populations such as elderly patients, patients with renal impairment and patients with cancer. Primary care physicians will have to play a role in monitoring and evaluating the long-term efficacy and safety of these agents in daily practice.

Current primary care practice in the diagnosis and management of patients with suspected venous thromboembolism and prescription of initiation dose of enoxaparin.

AIM: Ambulatory care of patients with deep vein thrombosis (DVT) has been well validated but limited data exist on the diagnostic and therapeutic management of venous thromboembolism (VTE) in primary care. METHODS: A cross-sectional survey on the clinical conditions for the initiation of once daily (OD) enoxaparin and on the diagnostic and therapeutic strategy of VTE in ambulatory patients using a single-visit questionnaire to be filled out by the general practitioner (GP). RESULTS: Of the 4522 included patients, 2164 (48%) were started on therapeutic OD enoxaparin for confirmed or suspected proximal DVT, 464 (10%) for distal DVT, 493 (11%) for pulmonary embolism (PE), and 742 (16%) for superficial venous thrombosis (SVT). Further indications included bridging of oral anticoagulation in 173 patients (4%), atrial fibrillation in 77 patients (2%) and prevention of VTE in 78 patients (2%). Enoxaparin was initiated on the basis of clinical probability before objective confirmation in 17%, 33%, 53% and 69% of patients with a diagnosis of PE, proximal DVT, distal DVT and SVT, respectively. No objective testing was planned for 3%, 9%, 18% and 41% of patients in these respective categories. Patients were referred to specialist care in 88%, 49%, 42% and 21% of patients with PE, proximal DVT, distal DVT and SVT, respectively. CONCLUSION: Therapeutic OD enoxaparin is prescribed in primary care for the whole clinical spectrum of VTE. However, the diagnostic work-up is unsatisfactory to suboptimal in a substantial proportion of these patients.

Early increase in pulmonary vascular reactivity with overexpression of endothelin-1 and vascular endothelial growth factor in canine experimental heart failure.

Heart failure is a cause of pulmonary vasoconstriction and remodelling, leading to pulmonary hypertension (PH) and decreased survival. The pathobiology of PH in heart failure remains incompletely understood. We investigated pulmonary vascular function and signalling molecules in early stage PH secondary to experimental heart failure. Eight beagle dogs with overpacing-induced heart failure underwent haemodynamic assessment and postmortem pulmonary arterial reactivity, morphometry and quantification of genes encoding for factors involved in vascular reactivity and remodelling: endothelin-1 (ET-1), ETA and ETB receptors, vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), endothelial nitric oxide synthase, angiopoietin-1, bone morphogenetic protein receptors (BMPR1A and BMPR2), serotonin transporter (5-HTT) and the 5-HT(2B) receptor. Overpacing was associated with a decrease in cardiac output and an increase in pulmonary vascular pressures. However, there were no changes in pulmonary vascular resistance or in arteriolar medial thickness. There were increased expressions of genes encoding for ET-1, ETB, VEGF and VEGFR2, while expression of the other genes analysed remained unchanged. In vitro, pulmonary arteries showed decreased relaxation and increased reactivity, while systemic mammary arteries were unaffected. Early PH in heart failure is characterized by altered vasoreactivity and increased ET-1/ETB and VEGF/VEGFR2 signalling.

[Diagnosis and treatment of pulmonary embolism]. / Prise en charge diagnostique et thérapeutique de l'embolie pulmonaire.

Pulmonary embolism (PE) is a common disease that poses a major diagnostic challenge because symptoms and signs are neither sensitive nor specific. However, patients with suspected PE can be classified into low, moderate and high clinical probability groups on the basis of symptoms and signs of PE, the presence of risk factors and the presence or absence of a likely alternative diagnosis. Stratification of patients into groups according to the clinical or pretest probability is imperative for proper selection of further diagnostic tests. The role of D-dimer testing is limited to the ruling out of PE in patients with low or moderate clinical probability. Conversely D-dimer testing is useless in patients, with high clinical probability. Chest CT has become an attractive means for an accurate diagnosis of PE and may replace lung scanning as first-line imaging test in particular in patients with underlying pulmonary disease or abnormal chest radiograph. Initial treatment for patients with non massive PE consists of therapeutic anti-coagulation with low molecular weight heparin (LMWH) and early overlapping with oral anticoagulants. In patients with active cancer, long-term treatment with LMWH is recommended. Duration of anticoagulant treatment is based on the balance between the risk of recurrent venous thromboembolism (depending mainly on the reversibility of risk factor, the presence of cancer, thrombophilia or previous venous thromboembolic episodes) and the risk of bleeding.

Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects.

OBJECTIVE: To characterize the pharmacokinetics of R-roscovitine, a novel cyclin-dependent kinase inhibitor, and its carboxylate metabolite in man. METHOD: Twelve healthy male subjects received single oral doses of 50, 100, 200, 400 or 800 mg in a hierarchical 3-period, 6-sequence crossover design. One dose was given after breakfast, the others under fasting conditions. R-roscovitine and the carboxylate metabolite were measured in plasma and urine. A 2-compartment model for R-roscovitine with 1 compartment for the metabolite and a component for first-pass extraction was adequate. Protein binding was calculated from plasma and urine data. RESULTS: R-roscovitine undergoes nonsaturatable first-pass extraction, rapid metabolism, exhibits high nonsaturated protein binding, is slowly absorbed from the GI tract and is rapidly and extensively distributed into tissues. The slow release of the molecule from tissue determines the apparent terminal half-life. Food delays the absorption and slows down the absorption rate but does not influence bioavailability. The formation rate of the carboxylate is a determinant of the plasma concentrations of this metabolite. It has low protein binding, limited tissue distribution and a renal clearance reflecting with good water solubility. CONCLUSION: The compartmental analysis clarified important pharmacokinetic aspects relevant for the clinical development of the compound.

Expression of the serotonin 1b receptor in experimental pulmonary hypertension.

The pathogenesis of pulmonary arterial hypertension (PAH) remains uncertain. Both the serotonin and endothelin (ET) systems are believed to be involved. Recent studies pointed to the importance of the serotonin 2B receptor as a limiting step. The current authors investigated the lung tissue expression of serotonin receptors and of the serotonin transporter (5-HTT) by real-time-quantitative polymerase chain reaction in chronic overcirculation-induced PAH in growing piglets, with and without treatment with the dual ET receptor blocker bosentan. Pulmonary haemodynamic changes were described by pulmonary arterial impedance spectra. Three months after the surgical anastomosis of the left subclavian artery to the pulmonary arterial trunk, there was a shift of the impedance spectra to higher ratios of pressure and flow moduli, with increases in both 0 Hz impedance and characteristic impedance, and these changes were completely prevented by bosentan therapy. There was an increase in the expression of the serotonin 1B receptor. There was no change in the expression of the 5-HTT, and of the serotonin 2B, 1D, and 4 receptors. The overexpression of the serotonin 1B receptor was partially prevented by bosentan therapy. The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor.

One-compartment model for amino acids and other biological molecules in peritoneal dialysis.

OBJECTIVES: Investigation of the main factors determining the concentration-time course of amino acids and biological molecules in serum and dialysates. METHODS: In a randomized, 3-period crossover study, 11 patients were treated once with each of 3 peritoneal dialysis solutions, 1 containing amino acids and bicarbonate, 1 containing glucose and bicarbonate and 1 containing glucose and lactate. Nineteen amino acids, 3 proteins, 2 metabolites and 2 ions were measured in serum and dialysate. A standard compartment model was fitted to the data. RESULTS: The amino acids differed significantly in their kinetic characteristics (p < 0.001), mainly volume of distribution and elimination rate. Differences in absorption were small compared to the interpatient variation. The average transport rate from serum to dialysate was 0.50-1.14 h(-1), from dialysate to serum 0.33-0.41 h(-1), for elimination from the central compartment 0.35 to 2.27 h(-1), for volume of distribution 0.29 to 0.83 l/kg, for serum protein binding 19-47%, for amount in tissue 82 - 95%, for endogenous metabolic rate 16-151 micromol x kg(-1) x h(-1). The volume of distribution correlated with the R group (polar positive < aliphatic < polar uncharged). For the various proteins, the 2 bicarbonate solutions had higher serum-to-dialysate transport rates than the lactate solution (p = 0.018-0.601). CONCLUSION: The compartment model demonstrated its usefulness. Accordance with literature data for healthy volunteers indicated the validity of the estimates.

[The medico-surgical department of vascular disease]. / Le Service Médico-Chirurgical de Pathologie Vasculaire.

The Department of Vascular Diseases can be defined as a multidisciplinary integrated clinical entity involving internists and surgeons interested in patient care, education and research in the field of arterial, venous and lymphatic diseases. Because of the increasing medical complexity with the proliferation of treatment options available, the combined expertise of specialists from different training background is required to provide the optimal patient management. The truly integrated entity with interactions on daily basis between internists and surgeons also provides opportunities for improvement in the training of fellows in vascular medicine. Basic and clinical research is focused on thrombosis and atherosclerosis. The main topics that have been developed include: the pathophysiology of thrombosis, atherogenesis and the diagnosis and treatment of venous thromboembolic disease. The successful development of our Department demonstrates that the combined expertise of internists and surgeons has resulted in marked improvement in the efficiency of patient management.

Pharmacokinetics of human growth hormone administered subcutaneously with two different injection systems.

The bioavailability of recombinant human growth hormone (somatropin, CAS 12629-01-5) was compared between a transcutaneous jet injection device and subcutaneous cannula injection. Thirteen healthy male subjects received 8.64 IU somatropin once with jet and once with cannula injection in a randomized cross-over study. Baseline-corrected somatropin serum concentrations were evaluated with non-compartmental and compartmental methods. The 90% confidence intervals with two one-sided t-tests around the ratios of injection devices were 91-120% for maximum concentration, 94-110% for area-under-curve until 14 h, and 92-103% for area-under-curve to infinity. Somatropin has a known metabolic half-life of ca. 20-30 min while the observed terminal half-lives were 2-4 h. Absorption and elimination rate constants were similar. Times of maximum concentrations, terminal half-lives and lag times to start of absorption appeared to be shorter and the absorption rate constant appeared to be larger for jet than for cannula injection. In conclusion, the kinetics of somatropin from subcutaneous tissue had a "flip-flop" characteristic. Bioavailability of somatropin after jet injection was equivalent to cannula injection.

Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular outcome in CVVH patients.

BACKGROUND: Bicarbonate-buffered replacement fluid (RF-bic) in continuous venovenous hemofiltration (CVVH) may be superior to lactate-buffered replacement fluid (RF-lac) in acute renal failure. In an open, randomized, multicenter study, we investigated the effects of RF-bic and RF-lac on cardiovascular outcome in patients requiring CVVH following acute renal failure. METHODS: One hundred seventeen patients between the age of 18 and 80 years were randomized to CVVH either with RF-bic (N = 61) or RF-lac (N = 56). Patients were treated with CVVH for five days or until either renal function was restored or the patient was removed from the study. Data were analyzed on day 5 or according to the "last observation carried forward" (LOCF) option. Adverse events were classified according to the WHO-Adverse Reaction Terminology system. RESULTS: Blood lactate levels were significantly lower and blood bicarbonate levels were significantly higher in patients treated with RF-bic than in those treated with RF-lac (lactate, 17.4 +/- 8.5 vs. 28.7 +/- 10.4 mg/dL, P < 0.05; bicarbonate, 23.7 +/- 0.4 vs. 21.8 +/- 0.5 mmol/L, P < 0. 01). The number of hypotensive crises was lower in RF-bic-treated patients than in RF-lac-treated patients (RF-bic 14 out of 61 patients, RF-lac in 29 out of 56 patients; 0.26 +/- 0.09 vs. 0.60 +/- 0.31 episodes per 24 h, P < 0.05). Nine out of 61 patients (15%) treated with RF-bic and 21 out of 56 patients (38%) treated with RF-lac developed cardiovascular events during CVVH therapy (P < 0. 01). A multiple regression analysis showed that the occurrence of cardiovascular events was dependent on replacement fluid and previous cardiovascular disease and not on age or blood pressure. Patients with cardiac failure died less frequently in the group treated with RF-bic (7 out of 24, 29%) than in the group treated with RF-lac (12 out of 21, 57%, P = 0.058). In patients with septic shock, lethality was comparable in both groups (RF-bic, 10 out of 27, 37%; RF-lac, 7 out of 20, 35%, P = NS). CONCLUSIONS: The results show that the administration of RF-bic solution was superior in normalizing acidosis of patients without the risk of alkalosis. The data also suggest that the use of RF-bic during CVVH reduces cardiovascular events in critically ill patients with acute renal failure, particularly those with previous cardiovascular disease or heart failure.

Early inflammatory response after elective abdominal aortic aneurysm repair: a comparison between endovascular procedure and conventional surgery.

OBJECTIVE: To determine the nature of and to compare the inflammatory responses induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA) repair. MATERIAL AND METHODS: Twelve consecutive patients undergoing elective infrarenal AAA repair were prospectively studied. Seven patients were selected for endovascular procedures (the EAAA group); five patients underwent open surgery (the OAAA group). Three control patients undergoing carotid thromboendarterectomy were also included. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or placement of the endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response expression of peripheral T lymphocyte and monocyte activation markers and adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay), and liberation of complement products (nephelometry) were measured. RESULTS: Regarding acute phase response, the EAAA and OAAA groups showed significant increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035 and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course patterns were observed with respect to body temperature (P =.372). Statistically significant different patterns were demonstrated for C-reactive protein (P =.032) and leukocyte count (P =.002). Regarding leukocyte activation, a significant upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54 revealed no perioperative fluctuations in any group. Regarding circulating cell adhesion molecules, the EAAA and OAAA groups displayed significant increases in soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no intergroup difference (P =.193). All groups demonstrated high soluble von Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in any group. Regarding cytokine release, although a tendency toward high tumor necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group, global time course effects failed to reach statistical significance (P =.543 and P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P <.001, and P =.004). Time course patterns did not differ between the EAAA and OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio disclosed significant postoperative elevations in the EAAA and OAAA groups (P =.013 and P =.009). This complement product release was reduced in the EAAA group (P <.001). CONCLUSIONS: The current study indicated that both endovascular and coventional AAA repair induced significant inflammatory responses. Our findings showed that there were no large differences between the procedures with respect to circulating cell adhesion molecule and cytokine release. Moreover, the endoluminal approach produced a limited response in terms of acute phase reaction, T lymphocyte activation, and complement product liberation. This might support the concept that endovascular AAA repair represents an attractive alternative to open surgery. Given the relatively small sample size, further larger studies are required for confirmation of our observations.

Abdominal aortic coarctation with splanchnic arterial occlusion.

Abdominal aortic coarctation is found in only 2% of aortic coarctation and is usually manifested by renovascular hypertension. Splanchnic arterial occlusive lesions occur in 22% of these patients and are exceptionally symptomatic. We present a case report of a young patient with abdominal aortic coarctation causing hypertension and visceral angina. The aetiopathogeny and treatment are discussed.

Non-linear pharmacokinetic modelling of intravenous elgodipine.

UNLABELLED: OBJECTIVE, SUBJECTS AND METHODS: The 1,4-dihydropyridine elgodipine was given as continuous infusion at various rates (5, 10, 15, 20, 40 microg/kg/h for 48, 48, 48, 24, or 6 h, respectively) to five groups of 6-12 healthy male subjects (total 42). Elgodipine plasma concentrations were measured with HPLC in 20-24 samples from each subject. Concentrations increased overproportionally with dose. Non-compartmental and compartmental evaluations were made. A two-compartment model with lag time and Michaelis-Menten term for elimination was found to be appropriate. RESULTS: Based on Michaelis-Menten parameters and concentration time courses during infusions, the elimination appeared to be saturated already at low dosages. There appeared to be two distinct subpopulations with two-fold differences in the maximal elimination velocity. In 9/42 subjects, more frequently in the groups with lower infusion rates, the model failed and the Michaelis-Menten term had to be replaced with a constant rate to fit. A dose-dependent increase in the volume of distribution and differences in and difficulties with estimations of the Michaelis-Menten constant KM might indicate a non-linear plasma protein binding. The transfer rate constants to or from the peripheral compartment correlated with blood hemoglobin or creatinine and bilirubin concentrations, respectively. CONCLUSION: The results indicated that tissue distribution and protein binding had marked influence on the plasma concentrations and, thus, attenuated the impact of saturation in the elimination.

Occluding aortic endoluminal stent graft combined with extra-anatomic axillofemoral bypass as alternative management of abdominal aortic aneurysms for patients at high risk with complex anatomic features: a preliminary report.

PURPOSE: To describe an exclusion endoluminal technique for management of abdominal aortic aneurysms among high-risk patients with complex anatomic features. METHODS: From January 1995 to December 1996, among 143 patients with infrarenal abdominal aortic aneurysm treated by means of endograft placement, 9 (6.3%) had complex aortic or aortoiliac morphologic features. For these patients, the endograft was delivered through a femoral cutdown in an occluding aortoiliac configuration. The contralateral iliac artery was occluded with an iliac endograft. Axillofemoral bypass grafting was performed. Computed tomographic scans were obtained regularly. RESULTS: There was 1 postoperative death of severe arrhythmia. All aneurysms were found to be affected by thrombosis on immediately postoperative computed tomographic scans, except in 1 patient with a proximal leak, which was managed successfully with angiographic embolization. The mean follow-up time was 12 months. Aortic aneurysm diameter decreased from 2 mm at 6 months (2 patients) to 6 mm at 12 months (6 patients). All axillofemoral bypass grafts are patent. CONCLUSIONS: Placement of an occluding endograft associated with axillofemoral bypass grafting is a good alternative for patients at high risk with complex anatomic features. Longer-term follow-up study is needed to evaluate this endoluminal technique.

Adventitial cystic disease of the popliteal artery communicating with the knee joint. A case report.

We describe the case of a patient with adventitial cystic disease of the popliteal artery in which a direct anatomic communication between the cysts and the nearby knee joint was demonstrated by magnetic resonance imaging and confirmed by surgery. This unusual observation could shed some light on the much debated question of the cause, the pathogenesis, and the management of the affection. Moreover, it emphasizes the importance and the role of magnetic resonance imaging in the diagnosis of adventitial cystic disease of the popliteal artery.

[Actions of pentaerithritol tetranitrate, isosorbide mononitrate and placebo on headache and ability to work of healthy subjects]. / Wirkungen von Pentaerithrityltetranitrat, Isosorbidmononitrat und Plazebo auf den Kopfschmerz und auf die Beeinträchtigung der Arbeitsfähigkeit gesunder Probanden.

In a randomised, double-blind, four-way crossover study, 24 healthy volunteers received 240 mg/d pentaerithritol tetranitrate (PETN, CAS 78-11-5), 150 mg/d PETN, 60 mg/d isosorbide mononitrate slow release (ISMN, CAS 16051-77-7) or placebo in each study period for two days. Headache and disability to work were self-rated six times per day; individual measurements were combined to total scores. ISMN caused headaches more frequently (in approx. 90% of volunteers) and more severe (average total score 15.2) and a greater disability (average total score 6.0) than the high or low PETN-dosage (both in approx. 50%, headache score 4.9 or 6.4, disability score 1.1 or 2.1, resp.) and placebo (in approx. 10%, headache 0.8, disability 0), all these differences were statistically significant (p < 0.01, Wilcoxon). The high PETN-dosage showed a non-significant trend to produce fewer systemic side effects than the low PETN-dosage (not vice versa). With ISMN six volunteers prematurely terminated the study period and one volunteer who was replaced withdrew from the entire study due to side effects; all volunteers completed the study periods with the other medications.

[The role of season in the incidence of deep venous thrombosis]. / Rôle de la saison dans l'incidence de la thrombose veineuse profonde.

INTRODUCTION: The question of the role of season as a predisposing factor for development of venous thromboembolic disease still remains a matter of debate. Actually, most reports described a higher incidence of thrombotic disorders in winter, while a recent study showed no seasonal variation in the incidence of deep vein thrombosis (DVT). These data led us to study the seasonal distribution of all outpatients with DVT admitted to our Department over a period of 14 years. METHODS: Retrospective review of the files of all outpatients with confirmed (venography or ultrasound) DVT of the legs admitted from Jan. 1st 1982 to Dec. 31st 1995 (n = 512; mean age 59.4 years; 49.4% women). RESULTS: DVT occurred in spring in 135 (26.4%), in summer in 104 (20.3%), in autumn in 142 (27.7%) and in winter in 131 (25.6%) patients. This distribution appears to be similar to an expected uniform distribution [chi 2(3) df = 6.48; p = 0.090 (NS)]. CONCLUSIONS: In our study, by investigating retrospectively 512 outpatients with confirmed DVT, no correlation was found between season and development of thrombosis, suggesting that cold seasons do not represent a predisposing factor for DVT. Further large prospective studies are needed in order to validate our data and to investigate the clinical implications and the precise role of the season in the risk of occurrence of venous thrombosis.