[Prophylactic prescription of low-molecular-weight heparin in the non-surgical setting: impact of recommendations]. / Prescription préventive des héparines de bas poids moléculaire en milieu non chirurgical: l'impact de recommandations.

OBJECTIVE: Low-molecular-weight heparins (LMWH) had official approval for use for venous thromboembolism prophylaxis only for surgery patients when this survey was conducted, but were nevertheless often used in non-surgery patients. We conducted this "before and after" survey from May 1998 to April 1999 to assess the impact of the recommendations implemented in the beginning of 1999. METHODS: Data on the use of LMWH were collected on three different days within a three week interval in all non-surgery departments at the Tenon hospital before distribution of expert recommendations early in 1999. Published in La Presse Médicale in January 2000, these recommendations issued from an external panel of 43 experts who were contacted to establish a consensus opinion using the Delphi method. Data were again collected on three different days after implementation of the recommendations. Implementation was based on a patient-specific prescription order form requested by the hospital pharmacy for delivery to the department. RESULTS: Data were collected for 121 prescriptions prior to the recommendations and for 158 after. Sex-ratio, mean age and percentage of LMWH prescriptions did not differ significantly between the two periods. There was a lower number of non-appropriate prescriptions after implementation of the recommendations from 54.5% to 35.4% (p = 0.01) with better conformity for recommendation A (high-risk patients) (36% versus 43%, NS) and for recommendation B (= 2 risk situations or = 1 risk situation and = 2 aggravating factors) (10% versus 22%, p = 0.01). Better conformity of LMWH prescriptions in oncology and radiotherapy departments partially explained this general improvement, but the difference remained significant when excluding these two departments (p = 0.04). CONCLUSION: This study shows that physician compliance with recognized expert recommendations can improve their implementation. This procedure is now in general use in the Tenon hospital.

Long-term administration of high-dose deferoxamine 2 days per week in thalassemic patients.

OBJECTIVE: Compliance with parenteral administration of deferoxamine is often poor in thalassemic patients with iron overload. We tested the efficacy and tolerance of the drug at high dosage 2 d per week for 24 months in two adult thalassemic patients with permanently high serum ferritin using a portable pump and an implanted chamber. METHODS: Deferoxamine was administered using a pressure-operated portable pump through an implanted chamber. The patients were infused over 48 h every week with 198 mg/kg/d (patient 1) and 170 mg/kg/d (patient 2). Serum ferritin levels were measured at regular intervals. RESULTS: Serum ferritin decreased progressively from 2967 to 457 microg/L in patient 1 and from 6476 to 1951 microg/L in patient 2. Compliance and tolerance to treatment were excellent in the two patients. CONCLUSION: Intravenous administration of high-dose deferoxamine over 48 h per week using a portable pump and implanted chamber improved compliance in two thalassemic adult patients, resulting in a significant decrease in iron overload. We suggest that high-dose chelation therapy should be assessed in selected groups of iron-overload thalassemic patients receiving regular blood transfusions.

[Spinal cord compression secondary to extramedullary hematopoiesis in a patient with thalassemia]. / Compression médullaire par hématopoïèse ectopique chez un patient atteint de bêta-thalassémie.

A 19-year-old man with homozygous beta thalassemia presented with signs of thoracic spinal cord compression secondary to extramedullary hematopoiesis. The patient was treated with hypertransfusion and hydroxyurea. After two months, clinical signs had resolved and magnetic resonance imaging showed significant regression of the extradural mass. Pathophysiology and therapeutic options in this condition are briefly discussed.

[Renal and metabolic complications of lithium]. / Complications rénales et métaboliques du lithium.

Renal and metabolic adverse effects of lithium therapy are illustrated by the case report of a manic depressive woman aged 78 years, so treated for about 25 years. Long term lithium therapy with plasma lithium level in the therapeutic range impairs renal concentrating ability in 25-50% of the patients (when the total ingested amount reaches 100-200 mol, 700-1400 g). About 10-15% of the patients have overt nephrogenic diabetes insipidus (NDI) with elevated antidiuretic hormone plasma level and unresponsiveness to desmopressin. In rats, lithium treatment down regulates expression of the main water channel, aquaporin 2, in the renal collecting duct. NDI may be complicated by hypernatremic dehydration if the access to water is restricted, whatever the cause. Treatment of NID is best started with nonsteroidal antiinflammatory drugs, being then substituted for amiloride. Prolonged lithium therapy may induce chronic interstitial nephritis. In some patients this may result in mild or moderate non progressive chronic renal insufficiency. Acute lithium intoxication (with supratherapeutic doses) may be complicated by acute renal failure (ARF); even in the absence of ARF hemodialysis is indicated when plasma lithium level reaches 4 mmol/l or more. Other metabolic adverse effects of lithium therapy include: hypercalcemia due to hyperparathyroidism (in 5-10% of the patients); hypothyroidism (often latent); hyperthyroidism. In conclusion, these renal and metabolic adverse effects are generally mild or moderate, allowing the continuation of lithium therapy in most affected patients.

[Prevention of sickle cell crises with multiple phlebotomies]. / Prévention des crises douloureuses drépanocytaires par saignées itératives.

OBJECTIVES: Sickle cell disease patients suffering from frequent painful crises were submitted to phlebotomies in order to reduce hospitalization days due to pain, through hemoglobin (Hb) level reduction and iron deficiency in patients with an hemoglobin level equal to or above 9.5 g/dL. PATIENTS: Seven sickle cell disease patients (four SC, three SS), aged four to 24 years, were submitted to sequential phlebotomies during periods from 18 months to four years. METHODS: The number of hospitalization days for crises was considered. The volumes and frequencies of phlebotomies were adjusted according to the patients ages, the hemoglobin concentrations and the serum ferritin levels. RESULTS: One hundred and forty-four hospitalization days were recorded in the seven patients in the year preceding the treatment. During the study period, the annual numbers of hospitalization days were respectively 20, five, six and one. Mean hemoglobin concentration was 10.7 g/dL before phlebotomies and 8.8 to 9.2 g/dL during the four years of treatment. Mean corpuscular volume, mean corpuscular hemoglobin concentration and serum ferritin were also reduced. The volume of phlebotomies was 116 to 39 mL/kg/year according to the patients. COMMENTS AND CONCLUSION: The striking decrease of the number of hospitalization days for all the patients suggests a closed relationship between therapy and clinical improvement. The mechanism of this effect is probably multifactorial: a) the concentration of Hb level is known to influence the blood viscosity and its decrease always improved rheology in sickle cell disease patients; b) the mean corpuscular hemoglobin concentration is a critical factor concerning the HbS molecule polymerization in sickle cell disease, and its slight reduction may have an important biological effect. We observed these two biological modifications in our patients and suggest that they mediate the clinical effects. The iron deficiency induced by phlebotomies has no evident deleterious consequence either on height and weight in the children or on intellectual performance in any patients.

[Prevention of venous thromboembolism in a non-surgical medical ward. Proposed indications for low molecular weight heparin]. / Prévention de la maladie thromboembolique veineuse en milieu hospitalier non chirurgical. Propositions d'indications des héparines de bas poids moléculaire.

OBJECTIVE: The efficiency of venous thromboembolism prophylaxis with low molecular weight heparins (LMWH) has not been established in non surgical patients, so their official preventive use has been limited in France since 1995 to surgery. However, a survey conducted in 5 university hospitals in non surgical patients showed that 21-29% of patients still received a LMWH prescription. It seemed necessary to define the medical conditions for which the practical use of these heparins would be justified. We contacted external experts to obtain a consensus by using the Delphi method. METHODS: The Delphi method, created by the "Rand Corporation" in the USA and used in medicine since the nineteen seventies, is based on a light logistic, with questionnaires been sent by mail with a feed-back report A total of 48 experts were chosen by local staff teams in the 5 hospitals. For the 3 rounds, from March to October 1998, questions were devised by a multicentred staff team. RESULTS: Among the 48 experts contacted, 32 completed the 3 questionnaires, 7 of them did for 2, and 43 did for at least one questionnaire. The experts first defined a list of 12 risk or high risk situations and 11 aggravating factors. For any high risk situation, prescription is justified. For other cases, 2 risk situations are required, or one risk situation with at least 2 aggravating factors, to justify a prescription. If no risk situation is present, prescription is, according to experts, usually not justified. CONCLUSION: The maximal agreement defines the situations in which one use of low molecular weight heparins is proposed to prevent deep venous thrombosis in non surgical inpatients, in most current hospital situations and for more than 24 hours of hospitalization. Clinical trials are needed, to validate their effectiveness and define the optimal dose in these indications. To date, epidemiological studies should be conducted to evaluate the experts proposals by estimating risk factors for deep venous thrombosis.

Natural history of the TT virus infection through follow-up of TTV DNA-positive multiple-transfused patients.

Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA-positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA-positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)

Impact of guidelines implemented in a paris university hospital: application to the use of antiemetics by cancer patients.

AIMS: To assess the impact with time of guidelines on antiemetic use in an 850-bed Paris university hospital with a high proportion of cancer patients. METHODS: Guidelines on the use of antiemetics available in cancer chemotherapy were drafted according to the Delphi technique. Their implementation was based upon a patient-specific antiemetic prescription form. To assess the impact of guideline implementation over time, discrepancies between current practice and the guidelines were compared before guideline implementation (between March and August 1995) and after implementation (between March and August 1997, and March and August 1998). RESULTS: Before the Delphi panel's guidelines were implemented, 5-HT3 antagonists were inappropriately administered in 70% of cases. After guideline implementation, this proportion dropped significantly (P<0.0001, Fisher's exact test) to 22% between March and August 1997 and 28% between March and August 1998. CONCLUSIONS: Implementation of guidelines seems to have resulted in significant changes with time, although a causal relationship has not been demonstrated. The development of guidelines by our hospital's multidisciplinary working group helped the various consultants to adjust medical practices to take account of these changes.

Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.

Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.

Increased placental antifibrinolytic potential and fibrin deposits in pregnancy-induced hypertension and preeclampsia.

Preeclampsia is characterized by maternal hypercoagulable state and intravascular coagulation, microthromboses in several organs, and impairment of uteroplacental circulation. Excessive fibrin deposition occurs in the placenta, suggesting that disorders of placental coagulation and fibrinolysis physiologic systems may have a role in hemostasis activation. Term placentas were collected from 17 hypertensive/preeclamptic women and from 17 healthy pregnant women, and processed for both histologic and hemostasis studies. Placental fibrinoid deposition was visualized by cresyl-violet staining and quantified by histomorphometric analysis. The content in hemostasis factors was measured on extracts from homogenized placentas treated by a nonionic detergent. The percentage of villi with fibrinoid deposits was higher in the diseased placentas than in controls: 13.2 +/- 11.2 versus 6.75 +/- 2.7% (p < 0.001) for the total amount of deposits; 4.8 +/- 6.7 versus 1.5 +/- 1.0% (p = 0.04) for perivillous fibrinoid deposits, which are considered as histologic markers of intraplacental fibrin. The content in type 2 plasminogen activator inhibitor (PAI-2) antigen was higher in the diseased placentas than in controls: 124 +/- 8 versus 104 +/- 6 ng/mg placental protein (p = 0.046); there was a negative correlation between PAI-2 antigen and thrombomodulin activity (r = -0.57, p = 0.02) in the diseased placentas. No significant differences were found between the two groups for placental procoagulant tissue factor and anticoagulant thrombomodulin activities, and for the content in plasminogen activators and PAI-1 antigens. Placental antifibrinolytic potential is increased in pregnancy-induced hypertension and preeclampsia. This change, and the association of the highest PAI-2 placental concentrations with the lowest concentrations of thrombomodulin, may contribute to the prethrombotic state and to the excessive placental perivillous fibrin deposition observed in these situations.

[Hemolytic-uremic syndrome with renal thrombotic microangiopathy]. / Syndrome hémolytique et urémique avec microangiopathie thrombotique rnale.

Hemolytic-uremic syndrome (HUS) is characterized by intravascular hemolytic anemia with fragmented erythrocytes and thrombocytopenia, acute renal failure, and glomerular/arteriolar fibrin deposition. Most childhood HUS are postdiarrheal (enterocolitic) while adult HUS have various causes, such as shigellosis, pregnancy, malignant hypertension, AIDS, antineoplastic chemotherapy and organ transplantation. Disorders of endothelial hemostatic functions, induced in some cases by bacterial toxins, may have a role in the onset of microthromboses. HUS treatments are both supportive, including antihypertensive drugs and dialysis, and antithrombotic, including plasma infusions or plasma exchanges and antiplatelet agents.

[Etiologic aspects of acute renal insufficiency in the adult]. / Aspects étiologiques des insuffisances rénales aiguës de l'adulte.

Acute renal failure (ARF) is a syndrome with numerous underlying causal conditions--upon which depends vital prognosis, and various pathogenetic mechanisms of either functional or lesional nature--upon which depends renal prognosis. Lesions can affect different parts of the renal parenchyma, and may or may not be reversible. Here are described: a) the basic investigations that allow to diagnose both the underlying conditions and the mechanisms of ARF in adults; b) an etiologic classification of ARF. Elements of the renal syndrome, composed of anamnestic, clinical, laboratory, imaging and, if necessary, histological data, have to be gathered in each individual case. Emphasis is laid on some forms of ARF of increasing frequency: ARF induced by angiotensin-converting enzyme inhibitors, rapidly progressive glomerulonephritides, necrotizing vasculitides with circulating antineutrophil cytoplasmic antibodies and hemolytic-uremic syndrome. Early diagnosis of spontaneously non-reversible parenchymal lesions leads to timely etiopathogenic therapy and increases the likelihood of renal anatomical and functional recovery.

Unraveling the web of personality judgments: the influence of social networks on personality assessment.

Contemporary assessment models have focused on the degree to which self- and other reports of personality description agree in an effort to define consensus and agreement about personality attributes. In general, we believe that analyses of this type of data have been limited in that they tend to focus on both simple models (usually dyad-based) and simple aggregations of data (usually correlations between self- and other ratings). In addition, the behaviors used as stimuli in experimental settings lack the richness of behaviors in natural social settings. Here, we present some ideas from social network models in an effort to influence broader conceptualizations of agreement and consensus in assessment. Social network models provide a more complete description of interpersonal behavior beyond the dyadic level in both laboratory and natural settings. After defining some basic social network concepts, we go on to suggest the applicability of these concepts to personality assessment and, more specifically, to how these models might be used to study self-other agreement and consensus about personality judgments. Empirical data are used to illustrate social network concepts in the domain of personality assessment.

Methylprednisolone and cyclophosphamide pulse therapy in crescentic glomerulonephritis: safety and effectiveness.

In a previous study, we found that aggressive immunosuppressive therapy with continuous high-dose oral steroid and cyclophosphamide combined with plasma exchanges for extracapillary crescentic glomerulonephritis gave controversial results since, although disease activity was controlled, iatrogenic complications had led to death in some aged patients. We then modified our therapeutic regimen, and we analyze here the evolution of 30 consecutive patients who were admitted for biopsy-proven crescentic glomerulonephritis between 1989 and 1991. The mean plasma creatinine level at admission was 393 +/- 59 mumol/L (range 70 to 1100), and 15 patients had crescent formation in more than 50% of glomeruli on initial renal biopsy. Ten patients did not receive any immunosuppressive treatment since they either had a normal renal function or they had terminal renal failure and no severe extrarenal manifestation. The 20 other patients received initial steroid pulses 500 mg x3 (n = 17), low oral steroid treatment (n = 20), cyclophosphamide pulses (n = 13), or oral cyclophosphamide (n = 3). In 4 cases plasma exchanges were also used. As a whole, 10 patients (33%) were discharged with a normal renal function, and 18 patients (60%) had chronic renal failure, 7 of them requiring dialysis or transplantation; only 2 patients died of pulmonary hemorrhage. No severe iatrogenic complication was observed. These results indicate that reduction in oral steroid dosage, cyclophosphamide pulse therapy rather than continuous oral treatment, and plasma exchanges do not induce overimmunosuppression and iatrogenic complication. It can be safe, well tolerated, and as effective as a more intensive immunosuppressive regimen for the treatment of crescentic extracapillary glomerulonephritis.

[Prognosis of rapidly progressive glomerulonephritis: the influence of age]. / Pronostic des glomérulonéphrites rapidement progressives: influence de l'âge.

The evolution and prognosis of extracapillary glomerulonephritis were compared in two cohorts of patients treated between 1981 and 1986 (n = 39) and between 1989 and 1991 (n = 30). In the first group, the classical immunosuppressive treatment (steroids and cyclophosphamide) was given daily and combined with plasma exchanges. In the second group, IV pulses of methylprednisolone and cyclophosphamide were administered, followed by daily low-dose steroid therapy. Plasma exchanges were performed only in cases of extrarenal disease, particularly pulmonary hemorrhage. Although the two groups are not strictly similar, it could be concluded that aggressive immunosuppression including plasma exchanges impairs the vital prognosis by inducing infectious and/or hemorrhagic complications, especially in the elderly. On the other hand, methylprednisolone and cyclophosphamide pulses appear to have effectively treated extracapillary glomerulonephritis and were well tolerated. Thus they could be administered to all patients with rapidly progressive glomerulonephritis, including aged patients.

Species-specific properties of the glomerular mesangium.

Mesangial cells play a central role in the physiology and pathophysiology of the glomerulus. To date, most of the in vitro studies have been performed in cultured rat mesangial cells, with only 10% of them performed in human mesangial cells. In this article, the major differences between results obtained with these two types of cultured cells will be reviewed. In rats and in humans, most of the mesangial cells appear to be of smooth muscle origin. In the rat, some of the cultured cells also express a phenotype suggesting a monocyte/macrophage origin. Phagocytosis and synthesis of cytokines or proinflammatory proteins that have been described in cultured rat cells seem mostly linked to this monocyte/macrophage subtype of resident mesangial cells. In humans, macrophages are only detected in pathologic conditions, suggesting that they are not resident but rather infiltrating cells. Mesangial receptors, most notably angiotensin II receptors, are clearly present on mesangial cell membranes and are linked to prostaglandin E2 synthesis and to cell contraction. In humans, spontaneous prostanoid synthesis is low and is increased by the induction of cyclooxygenase by sodium butyrate in the medium. Even so, the amount of prostaglandin E2 synthesized by human mesangial cells is quantitatively low comparatively with that in rats. In rats, accordingly, mesangial cells play a role in the regulation of single-nephron GFR. In humans, angiotensin II also exerts a control on GFR but it is more difficult to demonstrate its contractile effect on human than on rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of glomerular injury: overview and relation with hemostasis.

The mechanisms of glomerular injury can be separated into nonimmunologically mediated glomerulonephritis (GN) such as diabetes, leading to glomerular hypertension and into immunologically mediated GN. The immunologically mediated GN may induce chronic glomerulopathy such as membranous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In inflammatory GN, most of the mediators could be synthesized either by infiltrating cells or by resident glomerular cells. They include cytokines, lymphokines, complement activation, generation of superoxyde anions, arachidonic acid metabolites, and fibrin deposition. (a) We have investigated the interaction between isolated glomeruli and platelets and have demonstrated that lipidic and proteic extracts of glomeruli enhance thromboxane B2 platelet synthesis. This fact is related to the generation by isolated glomeruli of saturated fatty acids and tissue factor. (b) We investigated the interaction between rat isolated glomeruli and peritoneal macrophages. We have demonstrated that 12-HETE synthesized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis. (c) We have demonstrated, using human glomerular epithelial cells, that alpha-thrombin, the active form of thrombin, generated before fibrin formation, is able to induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are complex, certainly acting by multiple pathways. So far, the mediators leading to proteinuria and renal failure after glomerular injury remain under investigation.