[Continuous haemodialysis with citrate anticoagulation in patients with liver failure: three cases]. / Hémodialyse continue avec anticoagulation au citrate chez l'insuffisant hépatique : à propos de trois cas.

Regional citrate anticoagulation for continuous renal replacement therapy provides an efficient alternative to heparin as it reduces the likelihood of haemorrhage in critically ill patients with bleeding risk or coagulopathy and increases the haemofilter survival time. Liver failure is a classic contraindication of regional citrate anticoagulation since it carries the risk of citrate accumulation and its metabolic complications, although it could be attractive for this population of patients with high bleeding risk. We report three cases of continuous haemodialysis with regional citrate anticoagulation performed in patients with severe acute liver failure, without accumulation in two cases and with a suspected beginning of accumulation in the third case. For these patients, close monitoring of the total-to-ionized calcium ratio, pH and anion gap is particularly essential to control the safety of citrate infusion. Increasing effluent flow rate eliminates more calcium-bound citrate and therefore limits citrate accumulation and its consequences.

[Posterior reversible encephalopathy related to tacrolimus in a liver transplanted HIV patient]. / Encéphalopathie postérieure réversible liée au tacrolimus chez un patient transplanté hépatique infecté par le VIH.

Tacrolimus-related posterior reversible leukoencephalopathy (PRLE) is a rare complication which should be recognized by clinicians who regularly use immunosuppressive therapy. We report the case of an HIV-positive, hepatitis C-positive liver transplant patient who presented with this complication. Immunosuppression with tacrolimus was started after postsurgery. On the 20th day, the patient suffered two tonic-clonic convulsive attacks against a background of hypertension. Cerebral magnetic resonance imaging and lumbar puncture led to diagnosis of tacrolimus-related PRLE after eliminating other possible diagnoses. Therapeutic management consisted of withdrawing tacrolimus and initiating treatment with antiepileptogenic and antihypertensive drugs, supplemented with magnesium sulphate. The symptoms regressed in the days following withdrawal of tacrolimus and the majority of lesions on magnetic resonance imaging disappeared within two weeks. The aim of which should be to identify patients at risk of developing this complication. This would enable targeted prevention involving magnesium supplementation, strict control of blood pressure and serial monitoring of tacrolimus blood concentrations.

[Acute liver failure due to a treatment by nimesulide: another case and review]. / Hépatite fulminante liée à un traitement par nimésulide : encore un cas et revue de la littérature.

Nimesulide is a non-steroidal anti-inflammatory drug available in several European countries. A hepatic toxicity due to nimesulide has been reported but fatal cases remain rare. We report the case of a 49-year-old woman treated by nimesulide during three days, admitted to the intensive care unit for an acute liver failure with encephalopathy. A temporary hepatic support by molecular adsorbent recirculating system (MARS) was performed and a hepatic transplantation was performed 12 hours after admission, allowing a rapid improvement and a discharge from intensive care unit four days after transplantation. Nimesulide induced hepatic toxicity is unpredictable and the intensity of symptomatology is variable. Clinical symptoms are often progressive, delayed from the onset of treatment. Our case draws attention to the risk of hepatic failure related to treatment with nimesulide, leading to hepatic transplantation or death. The question of risk/benefit ratio must be asked again for this widely used molecule.

[Use of coupled plasma filtration adsorption for septic shock treatment]. / Utilisation de la coupled plasma filtration adsorption au cours du traitement d'un choc septique.

Coupled plasma filtration adsorption (CPFA) is a new technology proposed for septic shock, removing both pro- and anti-inflammatory mediators. We report the first use of CPFA in France. The patient was 80-years-old and was admitted to the intensive care unit because of septic shock from urinary source. Besides conventional septic shock treatment, four successive CPFA sessions were daily performed and lasted from 6 to 11 hours. At the end of the sessions, a noteworthy hemodynamic and inflammatory improvement was observed. This case confirms the feasibility and the relative simplicity of CPFA. It also illustrates the recent and few scientific data of the medical literature concerning this technology.

Squamous cell carcinoma arising in a giant epidermal cyst: a case report.

Epidermal cysts are commonly encountered in surgical practice. Malignant degeneration of epidermal sebaceous cyst is uncommon. The authors report the case of a 38-year Filipino woman presenting with a voluminous sebaceous cyst of the left buttock. Ultrasonography and computer tomography were made preoperatively without any hint of eventual malignant degeneration. Marginal excision was performed with direct closure of the skin. The histological examination revealed epidermal sebaceous cyst with squamous cell carcinoma in situ, which is a quite rare, but well known complication occurring in sebaceous cysts.

Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group.

The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown. We assessed the direct medical costs induced by hip fractures during and after hospitalization. Hospital costs of 170 consecutive Belgian women with hip fracture were gathered. During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay. A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture. The mean cost of the acute hospital stay was 8,667 Belgian francs and the mean 1-year hip-fracture-related extra costs after hospitalization was 6,636 Belgian francs. During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p<0.001). Although health care costs increased with age, hip-fracture-related extra costs after hospitalization seemed similar in those below or above 81 years old. These extra costs amounted to 7,710 Belgian francs in women not living in nursing homes at the time of fracture, and to 3,479 Belgian francs in women who lived in nursing homes. Health or mental status before hip fracture seemed not to affect extra costs. Taking into account the higher mortality of women with hip fracture, the extra costs during the acute hospital stay and during the 1-year follow-up amounted to a mean 15,151 Belgian francs. In conclusion, both acute hospital stays and subsequent medical care contribute significantly to medical costs induced by hip fractures.

Peroneus quartus muscle: a case report and review of the literature.

The peroneus quartus is a supernumerary muscle of the lateral compartment of the lower leg. There are several variations of this accessory muscle, and its terminology is very confusing. The peroneus quartus is found with a frequency varying from 10 to 21.7% of observed individuals. It is rarely involved in pathologic processes of the foot and ankle. Only a few reports exist in the literature involving peroneus quartus in a "retromalleolar conflict" (lateral ankle stenosis), sometimes in association with longitudinal attrition and tears of the peroneus brevis. We present a novel case, together with a review of the clinical, anatomic, and radiologic references about this muscle, and we try to make order in classification and terminology of its different forms.

[Pathologic fracture of the tibia associated with Charcot-Marie-Tooth disease]. / Fracture pathologique du tibia compliquant une maladie de Charcot-Marie-Tooth.

The authors report a case of pathologic fracture of the distal tibia associated with Charcot-Marie-Tooth disease. Pathologic fracture was visible four weeks after initial pain. Treatment consisted in a short leg walking cast for six weeks. Charcot-Marie-Tooth disease is a slowly progressive neurogenic muscular atrophy affecting the distal parts of the lower limbs. The muscular atrophy is responsible for radiographic bony changes including narrowing of the shaft with thinning of the cortex, rarefaction at the end of the long bones and relative widening of the medullary cavity. Pathologic fractures in neuromuscular disease are rare; a few cases have been reported following application of very small forces. The authors draw attention to the increased risk of pathologic fractures in patients with neuromuscular disease. Ambulatory treatment of fractures should be used whenever possible; prolonged immobilization could result in further loss of function.

Cranio-facial and humeral melorrheostosis.

First described by LERY and JOANNY in 1992, melorrheostosis is an uncommon linear hyperostosis of unknown aetiology, which may be associated with soft tissures changes. Although all bones may be affected, cranio-facial involvement is very rare. Only six such cases have been found in the literature. This report describes a case of cranio-facial and left humeral melorrheostosis with symptomatic radial nerve involvement. Resection of the melorrheostotic bone was performed because of involvement of the radial nerve.

[Tennis elbow: surgical findings in 17 cases and etiopathogenetic hypothesis]. / Les epicondylites: découvertes opératoires dans 17 cas et hypothèses etio-pathogéniques.

Lateral epicondylitis is the most common source of elbow pain. Surgical treatment is easy but precise etiology remains uncertain. We reviewed 17 medical files of surgically treated lateral epicondylitis. Chondral lesions of the radial head were systematically looked for. Out of those 17 elbows, 11 showed extension limitation before surgical treatment. From this sub-group, 9 presented chondral lesions. None of the 6 elbows without extension limitation showed chondral lesions. Increased tension of the extensor carpi radialis brevis associated with the eccentric movement of the radial head, seems to be an important factor in the pathogenesis of those lesions. We believe that chondropathy of the radial head is a consequence of lateral epicondylitis.

Interface peptides as structure-based human immunodeficiency virus reverse transcriptase inhibitors.

Reverse transcriptases from both human immunodeficiency viruses type 1 and 2 are obligatory dimers. A tryptophan-rich repeat motif that is highly conserved between these proteins, as well as in the reverse transcriptase from simian immunodeficiency virus, has been postulated to be involved in hydrophobic subunit interactions. A synthetic 19-mer peptide covering part of this tryptophan repeat motif was recently shown to inhibit human immunodeficiency viruses type 1 reverse transcriptase subunit dimerization (Divita, G., Restle, T., Goody, R. S., Chermann, J.-C., and Baillon, J. G. (1994) J. Biol. Chem. 269, 13080-13083). In the present study, we show that the same peptide can also inhibit human immunodeficiency virus type 2 reverse transcriptase subunit dimerization, suggesting that the same inhibitors might be used as agents against both viruses as well as against variants of human immunodeficiency virus type 1 that differ from the variant against which they were developed. Under appropriate experimental conditions, e.g. at acidic pH, this peptide is also able to induce the dissociation of the enzyme from human immunodeficiency virus type 1.

Restriction of HIV-1 replication in intestinal cells is genetically controlled by the gag-pol region of the HIV-1 genome.

The human colon epithelial line HT29 represents a semipermisive cellular system for human immunodeficiency virus type 1 (HIV-1). It could be productively infected with HIV-1 NDK, a Zairian virus isolate highly cytopathic for CD4 positive lymphocytes, whereas infection with the prototype virus HIV-1 LAV was nonproductive. Recombinant viruses derived from HIV-1 LAV and HIV-1 NDK were used to determine the genetic control, step of virus/cell cycle, and molecular mechanism responsible for productive versus nonproductive infection of intestinal cells. Both parental viruses and all recombinants retrotranscribed their genomes with a similar kinetics and were able to complete HIV-1 DNA synthesis, HIV-1 LAV provirus present in preintegration complexes could be rescued by cocultivation with T-lymphocytes. However, it was aborted during prolonged cultivation of HT29 cells. Our results suggest that (i) gag/pol region of HIV-1 genome (fragment BssHII255-EcoRI4183) genetically controlled productive infection of intestinal cells and that (ii) the difference between productive and abortive infection occurred before synthesis of HIV-1 mRNA, at the integration level.

Lectin-mediated effects on HIV type 1 infection in vitro.

Lectins with specificity for terminal mannose residues and anti-mannan antibodies neutralize HIV-1 infection in vitro. This is assumed to be caused by binding of the agents to the viral glycoproteins. In this study we show that one such agent, the Galanthus nivalis lectin (GNA), also blocks infection at the target cell level. To explore the effect of GNA on HIV infection we used the two HIV-1 isolates LAV and NDK, representing in the first case a prototype virus and in the latter case a highly cytopathic virus, which spreads preferentially via cell-to-cell contact. MT-4 cells were used as target cells and infection was determined from the occurrence of syncytia. Cell-to-cell infection was studied with CEM cells persistently infected with the two virus isolates. GNA, at concentrations in the nanogram per milliliter range, neutralized the HIV-1 isolates LAV, NDK, and MN as well as HIV-2ROD. Pretreatment of cells with the lectin, before addition of virus, or of infected cells, also blocked infection. This effect was more pronounced with HIV-1NDK than with HIV-1LAV. Mannosidase treatment of the target cells abolished the GNA effect on HIV-1NDK infection. It is concluded that GNA inhibits infection of several HIV isolates. It neutralizes infection by binding to the virion but also blocks infection at the target cell level. The latter effect may be different for different virus isolates. Mannosyl residuals at the cell surface are targets for GNA modulation of infection with the cytopathic HIV-1NDK. These do not represent essential virus receptors.

Lectin effects on HIV-1 infectivity.

Lectins with specificity for terminal mannose residues and anti-mannan antibodies are assumed to neutralize HIV-1 by binding to the viral glycoproteins. In this report we demonstrate that one such agents, the lectin from Galanthus nivalis (GNA), blocks infection also at the target cell level.

Inhibition of human immunodeficiency virus type 1 reverse transcriptase dimerization using synthetic peptides derived from the connection domain.

Based on presently available information on the structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, peptides have been synthesized which correspond to the sequence of a particular region of the protein involved in formation of the active heterodimeric form of the enzyme. Several peptides that are 15-19 amino acids long and that are derived from the so-called connection domain of the reverse transcriptase are able to inhibit dimerization of the enzyme and thus inhibit development of its enzymatic activities. In particular, a tryptophan-rich 19-mer corresponding to residues 389-407 was relatively efficient, showing an apparent dissociation constant in the micromolar range for one or both of the subunits. The sequence of this region is identical for both subunits, since one (molecular mass of 51 kDa) is the proteolytic product of the other (molecular mass of 66 kDa). Dissociation of the preformed heterodimer could not be induced by the peptides, but increasing concentrations reduced the rate of dimerization in a concentration-dependent manner until it became immeasurable at high concentrations. The results suggest that inhibition of dimerization of reverse transcriptase is an attractive approach to chemotherapeutic intervention in HIV infection and that further development of peptide-based inhibition strategies is worth pursuing.

Continuous microspectrophotometric measurement of DNA polymerase activity: application to the Klenow fragment of Escherichia coli DNA polymerase I and human immunodeficiency virus type 1 reverse transcriptase.

Progress of DNA- and/or RNA-directed DNA polymerization reactions can be measured continuously using circular dichroism (CD) or ultraviolet (UV) spectroscopy. In the presence of the Klenow fragment of Escherichia coli DNA polymerase I, a CD change of -0.27 +/- 0.06 millidegree at 248 nm and a UV change of -2.7 +/- 0.3 milliabsorbance units at 275 nm occur upon incorporation of 120 pmol of dTMP in a reaction volume of 120 microliters (1 microM dTMP incorporation) into a synthetic template-primer, p(dA)40-60.p(dT)20. The transcription of poly(A).p(dT)12-18 by reverse transcriptases can also be monitored using these methods. Kinetic parameters for the polymerization reaction catalyzed by the Klenow fragment were determined from initial velocity measurements using CD or UV assays and were in close agreement with those measured by the standard single point radiochemical filtration assay. The generality of optical techniques for the measurement of DNA polymerase activity was shown by the use of a partially self-complementary hairpin-shaped oligonucleotide substrate for the Klenow fragment. Addition of a single nucleotide residue under steady-state conditions to this 35-mer at a concentration of 1.5-3 microM gave an easily measurable absorbance decrease at 275 nm, and the absorbance changes upon sequential addition of nucleotide units were additive.

[Standardized evaluation of obsessive phenomena in patients in general medicine. Prevalence and correlations]. / Evaluation standardisée des phénomènes obsessionnels chez les patients de médecine générale. Prévalence et corrélations.

Clinical experience in general hospital psychiatry and literature reviews supported the conjecture that psychopathological disturbances are frequent among medical patients. Wide discrepancies of prevalence data reported by different authors, however, suggested the importance of undertaking screening studies with standardized methods of assessment. Our initial studies in oncological patients confirmed the hypothesis, but also documented obsessive phenomena, assessed with Present State Examination (PSE) criteria, in more than one third of patients diagnosed of depression Consecutive studies in different medical samples have replicated those preliminary findings in the last one, close to one quarter of first day consecutive patients seen in an internal medicine out-patient clinic, and more than three quarters of the ones diagnosed of either anxiety or depression with Research Diagnostic Criteria, had obsessive symptoms as defined by the Clinical Interview Schedule (CIS). Obsessive symptoms, however, have also been observed in individuals considered to be "non-cases" and tend to follow a "continuum" distribution, rather than a categorical one They tend to be more frequent in cases diagnosed as neurotic or reactive, rather than in the endogenous ones and to correlate with neuroticism measured by the EPQ-A. Particularly among out-patients, where the psychopathology seemed to be related to the absence of demonstrable somatic illness and probably to the presence of social distress, the hypothesis could be advanced that obsessive symptoms, among other psychopathological phenomena, are quantitative reactions to environmental situations in predisposed individuals. Nevertheless, in samples such as the endocrine in-patients, correlations have also been demonstrated between obsessive or other psychopathological symptoms and biological deviations such as hormonal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of mammalian spermine synthase by N-alkylated-1,3-diaminopropane derivatives in vitro and in cultured rat hepatoma cells.

A number of N-alkylated-1,3-diaminopropane derivatives [H2N-(CH2)3-NH-(CH2)nH, where n = 1-9] have been tested as potential inhibitors of partially purified rat hepatoma (HTC) cell or pure bovine spleen spermine synthase. Among the compounds described in this paper, the most potent competitive inhibitor of spermine synthase, with respect to spermidine, is N-butyl-1,3-diaminopropane with Ki values of 11.9 nM and 10.4 nM for the HTC cell and bovine spleen enzymes respectively. Inhibition of spermine synthase by this alkylated amine is selective since spermidine synthase activity is not affected up to 100 microM N-butyl-1,3-diaminopropane at a range of 5-200 microM putrescine. Added to the culture medium of growing HTC cells, N-butyl-1,3-diaminopropane causes the expected changes in the polyamine levels with a marked decrease of spermine and an increase of spermidine. Under these conditions cell growth continues unabated. Such N-alkylated-1,3-diaminopropane derivatives may have considerable potential as tools for studying the role of polyamines and in particular the functions of spermine in cell multiplication and differentiation.