Biomedical subjects
Publications and source records attributed to J Etienne.
The lipoprotein lipase gene (LPL) was mapped to chromosome band 8p22 by in situ hybridization to human chromosomes. This confirms the status of this assignment, which was still provisional.
A prospective survey of post-operative infections, conducted since 1986 at the Pierre Wertheimer Neurology Hospital, revealed an annual rate of infection varying between 2.9 and 7.3%. Definition criteria for each infection were given, including episodes of aseptic meningitis. The most frequently encountered infections were suppurations at the surgical site and meningitis. Staphylococci and enterobacteriacae, the most frequently isolated germs, were generally sensitive to antibiotics with the exception of coagulase negative staphylococci, causative agents in foreign body infections. Based on the epidemiological data and the pharmacokinetic and economic characteristics of the different antibiotics, a second generation cephalosporin was proposed for antibiotic prophylaxis. Vancomycin is an alternative choice in cases of allergy and when there is a risk of coagulase negative staphylococci infection.
In order to update our information about the incidence and demographic, microbiological and clinical characteristics of infective endocarditis (IE) in France, a 12 month long study was carried out in three regions: Ile de France, Rhône-Alpes and Lorraine. Four hundred and fifteen cases of IE were recensed: certain (32%), probable (53%) or possible (15%). The annual incidence was 24.3 per million. The average age was 56 +/- 19 years. There was no past history of cardiac disease in 34% of cases; 33% had native valvular heart disease and 22% had one or more valvular prostheses. The site of IE was mitral in 39%, aortic in 36%, tricuspid in 6% and other or multivalvular in 19% of cases. The causal microorganism was isolated in 92% of cases. It was a streptococcus in 58% of cases (S. viridans in 27%; group D streptococcus + enterococcus in 23%); a staphylococcus was isolated in 23% of cases (Staphylococcus Aureus in 18%) and another microorganism in 11% of cases. The presumed portal of entry was dental in 24%, gastro-intestinal in 13%, cutaneous in 6% and urinary in 4% of cases. Twenty patients were intravenous drug addicts. Forty-five patients had medical or surgical procedure. Twenty-four per cent of patients were operated during the first two months, 17% died during this period (15% of operated and 18% of non-operated patients). Despite the advances in antibiotic therapy and in cardiac surgical techniques, IE seems to be as common and as severe as ten years ago.(ABSTRACT TRUNCATED AT 250 WORDS)
The bacteria causing infective endocarditis have not changed significantly despite the diversity of potential portals of entry. Streptococci (viridans) cause 35 to 45% of cases of endocarditis. Group D streptococci of gastrointestinal origin cause about 20% of cases of endocarditis: Streptococcus bovis is the most commonly isolated species followed by the enterococcus. The beta-haemolytic streptococci of Groups A, B, C and G are rarely isolated. Seventeen to thirty per cent of endocarditis is caused by staphylococci, above all Staphylococcus aureus. These infections are mainly observed in patients with prosthetic valves or intravenous catheters and in intravenous drug addicts. With respect to gram-negative bacilli, enterobacteria are rarely responsible for endocarditis and those of the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, etc.) were isolated in 3% of cases. Q fever and Chlamydia endocarditis are rare, as are fungal infections usually due to Candida. Endocarditis with negative blood cultures is still observed in about 10% of cases.
The authors undertook a retrospective study of 69 cases of infective endocarditis (IE) in 68 children treated from 1971 to 1992. The comparison between two groups (Group I comprising 34 patients treated between 1971 and 1981; Group II comprising 34 patients treated between 1982 and 1992) based on a review of the literature showed that the natural history of paediatric IE has changed during these two decades: a slight increase in the incidence in young children. The sequellae of rheumatic heart disease play no role in determining IE in France. Congenital heart disease plays a major role (72% of cases) with increasing numbers having undergone surgical treatment for more complex lesions. Mitral valve prolapse has become a more common cause with multiple portals of entry, predominantly buccal and oto-rhino-laryngeal. Blood cultures are positive in 75% of cases, the commonest organisms being Streptococci and Staphylococci, but the frequency of uncommon pathogens is increasing. Echocardiography plays a major role in the diagnosis and inventory of IE (vegetations demonstrated in 64% of cases in Group II). Although mortality is progressively decreasing (3% in Group II) because of more frequent surgical indications (32% in Group II) and more severe sequellae: only 27% of children in Group II were cured without sequellae or aggravation of their previous cardiac lesion.
In order to recognize particular characteristics of pathogenic strains, epidemiologic markers of 27 Staphylococcus epidermidis strains (9 pathological and 18 commensal) were studied. Nine strains were responsible of infective endocarditis (8 on native valves, and 1 on prosthetic valve). No case occurred after admission to hospital or surgery. Eighteen commensal strains were isolated from control subjects who had had no contact with the hospital environment and who had not received a recent antibiotic treatment. The microbiological characteristics were so diverse that no differentiation between the pathogenic strains and commensal strains could be done and no particular pathogenic clone was recognized.
Lipoprotein lipase (LPL) is important for the delivery of triglyceride fatty acids (TGFA) to a variety of tissues. We have used measurements of heparin-releasable LPL activity, immunohistochemistry, in situ hybridization, and Northern analysis to more fully characterize the location of LPL within the entire central nervous system (CNS) of the rat. Surprisingly, the levels of LPL activity and mRNA in the caudal spinal cord were 5- to 10-times higher than those found in any other area of the brain, levels similar to those found in adipose tissue or skeletal muscle. A number of cell types including neurons in the hippocampus, Purkinje cells of the cerebellum, and cells deep within the cortex were identified as sources of LPL mRNA. LPL protein was found within many vascular structures throughout the CNS, and within Purkinje cells. The strongest immunostaining was around nerve rootlets associated with the caudal spinal cord. Feeding studies were carried out with [14C]oleic acid to see whether CNS LPL functioned in the uptake of TGFA. These studies demonstrated uptake of chylomicron triglyceride fatty acids throughout the CNS. The localization of LPL within these structures suggests that the uptake of triglyceride fatty acids is an integral part of normal lipid metabolism of the central nervous system and may be important in regulating feeding behavior and/or maintaining normal neuronal function.
Previous studies have demonstrated that endotoxin/lipopolysaccharide treatment causes a decrease in adipose tissue and heart lipoprotein lipase (LPL) activities in rats, producing hypertriglyceridemia in these animals. To examine the mechanisms for this effect of endotoxin, we studied the effects of endotoxin administration on LPL mRNA, and LPL synthetic rates and activity in rat adipose tissue and heart. Endotoxin treatment (i.p., 3 mg/100 g body weight or higher doses) produced a pronounced increase in serum triglycerides associated with a 65% decrease in adipose tissue and heart LPL activities within 7 h. Fast protein liquid chromatography (FPLC), used to separate lipoproteins in rat serum, showed that the increase in triglyceride was all in the very low density lipoprotein fraction which was accompanied by a concomitant decrease in high density lipoprotein. In contrast, there was no change in adipose tissue or heart LPL mRNA up to 24 h after treatment and no change in adipose tissue LPL synthetic rate, as measured by L-[35S]methionine incorporation and immunoprecipitation. Plasma insulin levels remained unchanged. The results indicate that endotoxin-induced hypertriglyceridemia in rats can be attributed to an impaired triglyceride clearance associated with a decrease of LPL activity mediated at a post-transcriptional level.
A rat lipoprotein lipase (LPL)-encoding cDNA (LPL) has been entirely sequenced and compared to the sequences of all the LPL cDNAs reported in other species. As expected, high homology was found between the coding exons. The putative catalytic triad, Ser132, Asp156, His241, according to human numbering, is conserved in rat. As is the case in mouse, an Asn444 present in human LPL is also missing. The major divergences between human, mouse and rat LPLs were observed in the untranslated exon 10, where (i) the rat cDNA exhibits a 157-bp insertion and an 81-bp deletion relative to human; (ii) neither the B1 repeat nor the homopurine stretch reported in mouse can be recognized, and (iii) the rat cDNA displays several A+T-rich stretches.
Plasmids that confer resistance to cadmium (MIC > or = 125 microM), were found in 18 out of 30 independent Staphylococcus lugdunensis strains from clinical specimens. Variants that were cured of their plasmid were cadmium sensitive. Restriction endonuclease sites of a 3.2-kb cadmium-resistance plasmid of S. lugdunensis, designated pLUG10, were similar to those of pOX6, a S. aureus cadmium-resistance plasmid containing the cadB gene. Southern-blot hybridisation was performed with a probe intragenic to cadB. Hybridisation was found with the cadB probe in the cadmium-resistant S. lugdunensis isolates to the 2.9-, 3.2- and 3.7-kb plasmids. These findings suggest that cadmium-resistance in some S. lugdunensis strains is due to a gene sharing homology with the cadB gene of S. aureus.
Five pathogenic strains each of Staphylococcus epidermidis, S. haemolyticus, S. lugdunensis and S. schleiferi were analysed by conventional electrophoresis and field inversion gel electrophoresis. For these coagulase-negative staphylococci, the restriction endonuclease SmaI emerged as the most suitable enzyme for pulsed-field electrophoresis by providing an adequate number of clearly separated DNA fragments. Field inversion gel electrophoresis confirmed the differences among strains already discriminated by conventional electrophoresis, and furthermore, differentiated strains which had previously appeared identical. Among the species that were studied, S. epidermidis showed great genomic diversity with a few common bands. On the contrary, S. haemolyticus, S. lugdunensis and S. schleiferi showed less diversity. Although these minor variations may be epidemiologically significant, this question has to be investigated on a larger number of strains.
The complete nucleotide sequence of the 3877-bp segment spanning the 3' region of intron-6 to the 5' region of intron-9 of the human lipoprotein lipase (LPL)-encoding ten-exon gene, LPL, is reported. An Alu repeat present in intron-7 was found by sequence analysis to belong to the 40-55-million-year-old Alu-Se subclass.
UNLABELLED: OBJECTIVE--To evaluate the efficacy and safety of ceftriaxone sodium in the treatment of streptococcal endocarditis. DESIGN--An open, multicenter, noncomparative study with a follow-up of patients for 4 months to 5 years. SETTING--Internal medicine wards and outpatient clinics of hospitals of various sizes in three European countries. PATIENTS--Fifty-nine patients with defined criteria for streptococcal endocarditis. INTERVENTION--Ceftriaxone sodium administered at a once-daily dose of 2 g for 4 weeks. MAIN OUTCOME MEASURES--Clinical outcome and microbiological cure rate. RESULTS--Among the 59 patients, 55 completed the treatment and were followed up for 4 months to 5 years. No patients showed evidence of relapse. Treatment was completely uneventful in 42 patients (71%). A cardiac valve was replaced in four patients (7%) receiving antimicrobial therapy and in six patients (10%) who had completed antimicrobial therapy. One of the 10 valves taken for culture at surgery was positive, but only for microorganisms that were different from the microorganism isolated before the treatment. The treatment had to be interrupted in four patients because of drug allergy. Other side effects were mild except for two cases of reversible neutropenia. The treatment was easy to administer: 27 patients (46%) had no permanent intravenous catheter at any time, seven patients (12%) had such a catheter for less than 4 days. Twenty-three patients (39%) were discharged from the hospital less than 2 weeks after admission. CONCLUSIONS: --Ceftriaxone sodium administered at a once-daily dose of 2 g appears to be an effective and safe treatment of streptococcal endocarditis. In hospitals, this agent may be more convenient to administer than penicillin G with or without aminoglycosides. Some patients may even be treated as outpatients.
Based on measurements carried out in water in two lithotriptor systems, the authors have made an attempt to reconstruct numerically amplitudes and shapes of shock wave pulses penetrating into kidney which differ from those in water. The difference between these pulses and those observed in water was analyzed and was also demonstrated experimentally. The amplitude and the steepness of the reconstructed pulse front were shown to be much lower than in water depending on the distance of the kidney stone from the patient's body surface. For a distance equal to 4 cm, the shock wave pulse amplitude of 40 MPa in water was estimated to decrease in the kidney by a factor of about two and the steepness of the positive shock pulse front to decrease several times. The analysis was carried out by considering the possible changes of absorption and attenuation in tissues which increase in an unknown way with the wave amplitude. It was shown that the temperature elevation caused by the increase of nonlinear high amplitude absorption is limited due to a corresponding increase in attenuation of the shock wave penetrating soft tissues. The temperature elevation was estimated on the basis of this work to be at most 1.8 times that one estimated in the case of two considered lithotripsy systems when assuming small amplitude absorption and attenuation coefficients.
1. Intralipid is a suitable substrate for measuring lipoprotein lipase activity in the presence of other triacylglycerol lipases in heart and myocytes. 2. Triacylglycerol lipase activity in heart and myocytes was increased 10-fold in the presence of serum at pH 7.4 and 8.1. The serum-stimulated activity in myocytes was 95% inhibited by saturating concentrations of antiserum to lipoprotein lipase. 3. Both heparin-releasable and non-releasable lipoprotein lipase fractions had similar Km values for Intralipid and a similar pattern of inhibition by high density lipoprotein but different responses to heparin. 4. Isoproterenol did not alter lipoprotein lipase activity in cardiac myocytes.
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Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a result of Chlamydia were seen. All patients were men, with a mean age of 42 years, and none had a history of exposure to Chlamydia psittaci. Symptoms, such as weight loss and anorexia, with fever in eight cases, had persisted for at least 2 months before admission. Haemodynamic failure was present in seven patients, and neurological signs in four. The aortic valve was involved in seven cases, the mitral valve in one and both valves in two. Vegetations, often fingerlike, were observed by echocardiography in nine cases. All patients required valve replacement, and three died in the year following diagnosis. Blood cultures were consistently negative in all cases, and no antibiotics had been given before admission. Significant titres of complement fixing anti-chlamydial antibodies were present in six cases, and micro-immunofluorescence using the three chlamydial species showed cross-reacting antibodies in all nine cases studied, with transient IgM positivity in six cases. Histologically, the leaflets were fibrosed and infiltrated by large macrophages containing dark red granules after Machiavello staining. These granules were specifically stained by immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not by that specific for C. pneumoniae. No organisms were seen after Gram staining, and no positive chlamydial immunofluorescence was seen on sections of valves from patients with staphylococcal or streptococcal endocarditis.