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Biomedical subjects

F Parent

Publications and source records attributed to F Parent.

51 records · Page 3Linked to original sources

Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism.

This study reports on the biological data of ten patients with acute venous thrombo-embolism. They were treated for 5 days with continuous intravenous infusion of a fixed dose (0.05 mg/kg/hr) of a recombinant hirudin (r-H HBW 023 Behringwerke, Germany). The plasma level of r-H (HBW 023), assessed by an anti-factor IIa amidolytic activity, was stable after Day 2 and showed considerable individual variations. It correlated with APTT ratio, suggesting that this test is a reliable tool to monitor therapy. In contrast, thrombin time was constantly over 120 sec (control 15 sec) and consequently was not a useful parameter. Prothrombin time showed a slight, but significant, prolongation, which was correlated with the increase of APTT ratio. There was no bleeding time prolongation, platelet count, or ATIII level decrease. Levels of thrombin-antithrombin III complexes, and D-dimers, which were high in all patients on admission, decreased during the course of the treatment but remained abnormal on Day 5, showing an ongoing hemostasis and fibrinolysis activation: this is consistent with the delayed, but only slightly decreased thrombin generation evidenced by thrombin generation test performed on Day 3. These results suggest that thrombin inhibition by rH-hirudin at this dosage is only partial, which allows the generation of traces of thrombin needed for the feed-back thrombin production generated by factor V and VIII activation.

Adult↗

Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin.

To investigate the capacity of the pulmonary vascular bed to acutely vasodilate, we examined in 35 consecutive patients with primary pulmonary hypertension (PPH), the hemodynamic effects of incremental inhalation periods of an air-NO mixture at different concentrations (10, 20, and 40 ppm), and compared them with those of an acute infusion of prostacyclin (PGI2). An individual pulmonary vasodilator response was defined by a fall in total pulmonary resistance (TPR) > or = 30% relative to mean TPR baseline value. Thirteen patients were responders and 22 were nonresponders to both drugs, and they did not significantly differ in overall baseline characteristics except for mean right atrial pressure (p < 0.03). In responders, both drugs produced similar individual vasodilator response. Changes in mean pulmonary arterial pressure and TPR observed during NO and PGI2 were closely correlated (r2 = 0.9, p < 0.001, and r2 = 0.7, p < 0.01, respectively). The vasodilator response to NO was not concentration-related with a maximal effect obtained at 10 ppm. Combination of both drugs did not lead to any additive vasodilator response. Unlike PGI2, NO did not induce any systemic effect, no adverse reaction, but a moderate increase in methemoglobin. Inhaled NO at low dose (10 ppm) appears to be an effective, safe, and reliable substitute for PGI2 in screening for acute pulmonary vasodilator responsiveness during therapeutic assessment of patients with PPH.

Adult↗

[Chronic pulmonary heart disease: therapeutic indications].

Chronic thromboembolic cor pulmonale is a serious condition and its frequency seems to be on the increase. The authors report their personal experience of 100 cases and review the literature to describe the natural history, diagnostic strategy and therapeutic indications of this condition. The mechanisms of this aberrant evolution of acute pulmonary embolism are unknown. They key symptom is effort dyspnea without a ventilatory deficit. The most useful diagnostic investigations are Doppler echocardiography and perfusion pulmonary scintigraphy. The diagnosis is confirmed by pulmonary angiography which, with the aid of a thoracic CT scan or endovascular techniques (ultrasonography or angioscopy), allow assessment of the feasibility of thromboendarteriectomy. Medical treatment is based on long-term anticoagulation, in some cases of lower limb thrombosis associated with interruption of the inferior vena cava. Two possible curative surgical techniques are available in selected patients; thromboendarteriectomy and pulmonary transplantation, the relative indications of which are listed. Of all the causes of pulmonary hypertension, chronic thromboembolic cor pulmonary should be systematically looked for because curative surgical treatment is possible in some cases.

Anticoagulants↗

Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension.

BACKGROUND: Previously reported cases of patients with pulmonary hypertension (PH) and human immunodeficiency virus (HIV) infection are poorly documented regarding baseline hemodynamics and potential for pulmonary vasodilatation. The purpose of this report was to compare HIV-infected patients who had PH with non-HIV-infected patients who had primary pulmonary hypertension (PPH) in terms of (1) clinical characteristics, (2) hemodynamics in baseline conditions and during a short-term vasodilator trial with epoprostenol, and (3) survival. METHODS AND RESULTS: Between April 1987 and August 1992, 20 HIV-infected patients with PH and 93 non-HIV-infected patients with PPH were referred to our department. At the time of referral, baseline right-side heart hemodynamics were obtained in addition to demographic variables and medical history. A short-term vasodilator trial with epoprostenol was performed in 19 of 20 HIV-infected and 86 of 93 non-HIV-infected patients. Outcome and survival were analyzed and compared for both groups (22 transplant recipients were excluded from the group of patients with PPH). At the time of diagnosis of PH, HIV-infected patients significantly differed from non-HIV-infected patients in age (32 +/- 5 versus 42 +/- 13 years; P < .05) and degree of disability (New York Heart Association functional class III or IV, 50% versus 75%; P < .01). The proportion of disease states known to be associated with PPH (Raynaud's phenomenon, migraine, collagen disease without overt symptoms and signs, or a positive family history of PPH) was similar in the two groups. HIV-infected patients had a severe but significantly lower level of PH than patients with PPH. The percentage of responders to epoprostenol and the level achieved in pulmonary vasodilatation were similar in the two groups. PH was the cause of death in 8 of the 10 HIV-infected patients who died within 1 year after the diagnosis of PH. Overall survival was poor and not significantly different between the two groups. Pathological findings in lung tissue obtained from 3 HIV-infected patients were close to those seen in most of the lung specimens available from 27 patients with PPH and resembled plexogenic pulmonary arteriopathy. CONCLUSIONS: These results support the view that HIV infection may now be regarded as another common disease state that can be associated with PPH development. The lower initial severity in HIV-infected patients may be due to the close medical attention usually devoted to such patients, who may account for an earlier diagnosis. However, the overall survival rate of HIV-infected patients with PH appeared to be as poor as in non-HIV-infected patients with PPH.

Adult↗

[Pulmonary arterial hypertension of chronic thromboembolic origin; therapeutic indications].

Chronic thromboembolic pulmonary hypertension is a rare complication of acute pulmonary embolism. The therapeutic approach to the disease is addressed, based on a series of 81 patients referred to our department between 1984 and 1993. Medical treatment associates long-term anticoagulant therapy and, in some cases, inferior vena cava interruption. Two surgical procedures are available in selected patients: lung transplantation and pulmonary thrombo-endareterectomy. Lung transplantation has been performed in 8 patients since 1988 with 6 survivors with a maximal follow-up of 5 years. Twelve patients underwent pulmonary thromboendareterectomy with in 9 patients a dramatic functional and haemodynamic improvement. Chronic thromboembolism should be systematically investigated as the cause of pulmonary hypertension considering that in selected cases, curative surgery is possible.

Adult↗

Treatment of severe venous thrombo-embolism with intravenous Hirudin (HBW 023): an open pilot study.

Recombinant Hirudin (rH) is an anticoagulant agent with a specific antithrombin activity independent of antithrombin III. We report the results of the first open pilot study on the curative treatment of acute venous thrombo-embolism (VTE) with rH (HBW 023) in ten patients. The dose of rH tested was 0.07 mg/kg (i.v. bolus) followed by 0.05 mg kg-1 h-1 (i.v. infusion) for 5 days, without activated partial thromboplastin time (APTT) adjustment. Within the trial, no death, VTE recurrence or major bleeding was observed; lung scan pulmonary vascular obstruction improved from 44 to 37%, whereas the venographic Marder score was unchanged; APTT ratio ranged between 1.2 and 2.8. The dose of rH assessed in this study seems to be safe and efficient in the treatment of acute VTE.

Aged↗

Primary pulmonary hypertension and fenfluramine use.

Not all the risk factors for primary pulmonary hypertension (PPH) are known. Appetite suppressants, including fenfluramine derivatives, are strongly suspected aetiological agents. In a 5 year retrospective study fenfluramine use was evaluated among patients referred to a medical centre specialising in the management of PPH. Fifteen (20%) of 73 patients with PPH had used fenfluramine: all of them were women and in 10 (67%) there was a close temporal relation between fenfluramine use and the development of exertional dyspnoea. Initial right heart catheterisation in the 15 women showed severe resting pulmonary hypertension (mean (SD)) with pulmonary artery pressure (PAP) 57 (9) mm Hg, cardiac index 2.1 (0.5) l/min/m2, and pulmonary vascular resistance (PVR) 29 (10) U/m2. Short-term epoprostenol infusion produced a significant vasodilator response in 10 patients (mean fall in PVR 24 (15%) compared with control values). Three fenfluramine users with PPH showed spontaneous clinical and haemodynamic improvement 3, 6 and 12 months after drug withdrawal but there was no significant difference in overall survival (transplant recipients excluded) between fenfluramine users and controls. Histological examination of lung tissue from five women who had used fenfluramine and 22 controls, with PPH showed features typical of advanced plexogenic pulmonary arteriopathy in all. These results do not accord with earlier reports that PPH associated with fenfluramine is less severe and has a better outcome. Fenfluramine may be one aetiological agent that can precipitate or hasten the development of PPH. The results of a European case-control study should give new insights into risk factors for PPH and the cause and effect relation with fenfluramine.

Adult↗

Early versus delayed introduction of oral vitamin K antagonists in combination with low-molecular-weight heparin in the treatment of deep vein thrombosis. a randomized clinical trial. The ANTENOX Study Group.

OBJECTIVE: To compare oral anticoagulant treatment (fluindione) started on either the 1st or the 10th day of a low-molecular-weight heparin (enoxaparin) treatment for deep vein thrombosis confirmed by venography. DESIGN: An open, multicenter, randomized study in two parallel treatment groups. INTERVENTIONS: All patients received enoxaparin, 1 mg/kg s.c. twice daily, and oral fluindione, 20 mg once daily, either beginning on day 1 or on day 10 of the enoxaparin treatment. Enoxaparin was discontinued once the international normalized ratio under fluindione was stable between 2.0 and 3.0 over 2 days. Fluindione treatment was maintained during a 3-month follow-up period. OUTCOME MEASUREMENTS: Specific examinations (venography and/or V/Q lung scanning and/or angiography) were performed only in the event of a clinically suspected recurrence of venous thromboembolism during the 3-month follow-up period. All cases were blindly assessed by an independent Reading Committee. RESULTS: A clinically suspected venous thromboembolism was confirmed by objective tests in 1 of 223 patients (group of delayed introduction of fluindione; n = 111). Equivalence was demonstrated between the two treatment schedules (p < 0.0001) for a maximal difference of 10% (90% confidence interval: -2.42 to 0.58). The mean duration of hospitalization was significantly reduced (p = 0.0001) in the group with early introduction of fluindione. The incidence of hemorrhage was comparable between the two treatment groups. CONCLUSION: Early and delayed introduction of oral anticoagulant treatment in association with subcutaneous enoxaparin in patients with deep vein thrombosis was shown to be equivalent in preventing the recurrence of venous thromboembolism. In patients with early introduction of oral anticoagulant, hospitalization was significantly reduced.

Administration, Oral↗

Vitamin K metabolism in a patient resistant to vitamin K antagonists.

We investigated various pharmacokinetic and pharmacodynamic parameters in a 63-year-old man, resistant to warfarin, fluindione, acenocoumarol and phenprocoumon. Daily doses of up to 30 mg of the long-acting phenprocoumon yielded a drug concentration of 85 mg/l (usual range 1-5 mg/l) but the international normalized ratio remained around 1. The plasma half-life of phenprocoumon was approximately 350 h (normal 120-150 h). Thus, the resistance was not due to malabsorption or to an accelerated metabolism of the drug. The level of vitamin K1 (1,202 ng/l) was insufficient to induce resistance. Decarboxyprothrombin concentrations were low, demonstrating that the gamma-carboxylation of the precursors of the vitamin K-dependent coagulation factors was not effectively reduced. The concentration of vitamin K epoxide, normally increased under oral anticoagulation, correlated to the vitamin K concentration (r2 = 0.77) but the quotient epoxide/vitamin K remained 4-fold lower than that of 22 warfarin-sensitive patients, suggesting an absence of blockade of the vitamin K reductase by phenprocoumon. This resistance to all the molecular forms of the vitamin K antagonists is most likely due to a reduced affinity of the drugs to a mutant vitamin K reductase.

Drug Resistance↗

Information technologies, health, and "globalization": anyone excluded?

Modern information technologies and worldwide communication through the Internet promise both universal access to information and the globalization of the medico-social network s modes of communication between doctors, laboratories, patients, and other players. The authors, specialists in public health and members of an association that aims to create opportunities for access to training in public health in developing countries, warn that the use of the term "globalization" ignores the reality of the "digital divide," that is, the fact that social inequalities may preclude the realization of this promise on a truly global scale.

CD-ROM↗

Evaluation of the new flexible contour backrest for wheelchairs.

A new flexible contour backrest for wheelchairs was designed with the objectives of offering adequate posture, uniform pressure distribution, and comfort to the users while keeping the advantages of conventional sling backrests, such as easy to fold, light weight, unobtrusive, and airy. The purpose of this study is to compare the new backrest with two commercially available wheelchair backrests, an adjustable-tension (AT) backrest and a back cushion on a rigid support (RS), in terms of pressure distribution, back profile accommodation, and short-term comfort. Evaluations were done with 15 nonimpaired subjects in a static position. It was shown that the new backrest distributes pressure in a more uniform way than the AT and in a way similar to the RS, while giving a better fit to subjects' trunks than other backrests because of its multiple adjustments. Finally, subjects felt that the new backrest is as comfortable as the RS and more comfortable than the AT.

Adult↗

[Complete reconstruction of the nose using a prefabricated free forearm graft].

The aim of prefabricated free transplants is to create a composite graft including a vascular pedicle with artery and vein, a muscle and its nerve, cellular tissue, bony tissue, cartilage, periosteum, and skin with its sensory nerve. This composite transplant is entirely constructed and modelled around the chosen vascular pedicle beforehand. Once the various materials of the future graft are removed and put in contact with the vascular pedicle, the subsequent neovascularisation should nourish the different elements. The vasculonervous pedicle, with the graft, are transplanted five weeks after preconstruction, revascularized and reinnervated. With these free prefabricated transplants, graft tissue which does not exist in the organism can be created. Cosmetic sequellae can be avoided since the vascular pedicle is chosen beforehand. Ear-nose-throat and plastic surgeons have used local structural preconstruction for many years, especially for ear reconstruction. The work presented here has the original feature of revascularized free transplant. From 1988, we have performed two complete reconstructions of the nose using a free forearm transplant modelled into a nasal pyramid. The classical techniques could not be used. In the first case a radius strut was used to form the nasal crest. In the second a chondrocostal cartilage was used. Transplantation was performed five weeks after preconstruction. In both cases, transplant viability was excellent but the cosmetic and functional results were less than satisfactory and required reoperation.

Adult↗

[Multiple free transplants in microsurgery for cervicofacial reconstruction].

Microsurgical techniques open the way for much creativity and originality for cervicofacial reconstruction and tumoral repair. Between 1976 and 1994, we performed 481 free transplants for cervico-facial reconstruction. A recently developed strategy has been the use of multiple free transplants, either simultaneously or successively. Between 1990 and 1994, we operated and reconstructed 9 patients using multiple free cervico-cephalic transplants after multitissular and agressive exeresis for tumoral or traumatic lesions. In 3 cases, the transplants were made simultaneously and in the 6 others successively. Three patients received 3 free transplants and 6 patients had 2. In 8 cases, each of the transplants was micro-anastomosed on different vessels. In one case, the two transplants were anastomosed in series, the most distal portion being connected to the most proximal portion (in comparison with the cervical vessels). One death occurred at 6 weeks due to infectious complications. The final result for the 8 other patients was good both morphologically and functionally. Indications for multiple free transplants include: complex tissue loss, multiple and massive tissue loss of the cervicocephalic region. This situation occurs particularly in case of voluminous tumours invading several structures, in multiple tumours and in firearm wounds. These series of patients allowed a definition of recommended techniques in case of difficulties in these very elaborate surgical procedures and confirmed that if the strategy is correctly planned, it is possible to greatly improve the quality of survival in these patients in terms of aesthetics, morphology and function.

Adolescent↗