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Biomedical subjects

P Lagrange

Publications and source records attributed to P Lagrange.

At least 37 records · Page 2Linked to original sources

The superoxide production mediated by the redox cycling of xenobiotics in rat brain microsomes is dependent on their reduction potential.

Several exogenous molecules undergo enzymatic one-electron reduction leading to radicals which can rapidly react with molecular oxygen to form superoxide anions. We have previously shown that under aerobic conditions a significant superoxide anion production occurred during the NADPH-dependent one-electron reduction of some drugs and xenobiotics by rat brain preparations. We report here for several compounds a fairly good correlation between the reduction potentials (Epc vs. SCE) which ranged between - 230 and - 700 mV in aqueous medium (pH 7.4) or between -700 mV and -1100 mV in the aprotic solvent N,N-dimethylformamide, and the rate of superoxide anion production during their metabolism by rat brain microsomes. The data obtained suggest that the redox potential of most of the molecules assayed was related to their ability to undergo one-electron reduction mediated by flavoenzymes in the rat brain. The main range of reduction potentials corresponding to a large superoxide anion production suggests that the redox cycling of these chemicals was mediated by NADPH-cytochrome P-450 reductase. Therefore the measurement of reduction potentials of drugs and xenobiotics able to reach the brain, and chemically related to quinones, nitroaromatics, nitroheterocyclics and iminiums, may provide information both on their electron affinity and the possibility of one-electron transfer in vivo, and thus on their possible neurotoxicity due to the production of oxygenated free radicals.

Animals↗

Routine transesophageal echocardiography for the diagnosis of aortic disruption in trauma patients without enlarged mediastinum.

OBJECTIVE: To assess the value of routine transesophageal echocardiography (TEE) in diagnosing traumatic disruption of the aorta (TDA) in trauma patients presenting without enlarged mediastinum on chest x-ray films. DESIGN: Prospective study. MATERIALS AND METHODS: TEE was routinely performed to exclude the presence of TDA in patients who sustained severe trauma secondary to abrupt deceleration collisions and presented with an upper mediastinum of fewer than 8 cm on supine chest x-ray films. Patients were divided into two groups according to the presence (group I) or absence (group II) of mediastinal hematoma diagnosed during TEE examination. Radiographic signs regarded as indicators of the presence of TDA were evaluated in both groups. RESULTS: Among the 40 consecutive patients studied, TEE demonstrated two cases of TDA associated with a mediastinal hematoma that were confirmed by both aortography and surgery. One of the patients had a normal mediastinum on presentation chest x-ray films, and the other only exhibited a blurred aortic knob. Radiographic mediastinal abnormalities suggestive of TDA were observed in 13 patients, but chest x-ray films were unremarkable in 12 patients. Twenty patients had multiple rib fractures. The frequency of chest radiographic abnormalities was not significantly higher in group I (n = 6) when compared with group II patients (n = 34). TEE examination demonstrated a normal thoracic aorta in 35 patients and was nondiagnostic in 3 patients (normal aortography). CONCLUSION: TEE should be routinely performed in victims of violent deceleration collisions, even in patients presenting apparently normal mediastinum on supine chest radiography.

Accidents, Traffic↗

Role of transesophageal echocardiography in the diagnosis and management of traumatic aortic disruption.

BACKGROUND: Traumatic disruption of the aorta (TDA) is a life-threatening injury that requires rapid diagnosis and treatment. Emergency aortography, which is the current standard diagnostic imaging modality, is invasive, time-consuming, and difficult to perform in hemodynamically unstable patients with multiple trauma. We performed transesophageal echocardiography (TEE) in patients with suspected TDA to determine the diagnostic accuracy and impact on patient management of this alternative, portable imaging modality. METHODS AND RESULTS: Thirty-two consecutive trauma patients (mean age, 40 +/- 16 years) with suspected TDA (violent deceleration accident and mediastinum > 8 cm on admission chest x-ray) prospectively underwent a TEE examination in the emergency room. Findings during TEE were compared with those encountered during aortography, surgery, or necropsy. Two subsets of traumatic aortic injuries with distinct echocardiographic signs were observed: (1) subadventitial TDA (n = 10) and (2) traumatic intimal tears (n = 3). Eighteen patients had normal TEE confirmed by aortography. One 2-mm medial tear was missed by TEE (necropsy). The sensitivity and specificity of TEE for the diagnosis of subadventitial TDA were 91% and 100%, respectively. Patients with subadventitial TDA were taken to surgery immediately, whereas patients with intimal aortic tears were treated conservatively. Eighteen patients (mean age, 57 +/- 15 years) with confirmed acute aortic dissection involving the aortic isthmus were also included to establish the echocardiographic differential diagnostic criteria between this entity and TDA. CONCLUSIONS: TEE should be considered the first-line imaging modality for the evaluation of trauma patients with suspected injuries of the thoracic aorta because of its portability, safety, diagnostic accuracy, and potential impact on patient management.

Adult↗

Escherichia hermannii: susceptibility pattern to beta-lactams and production of beta-lactamase.

The susceptibility pattern of Escherichia hermannii, although closely related to Escherichia coli according to its biochemical patterns, was clearly distinguishable by its susceptibility to beta-lactams by both diffusion and dilution methods from E. coli penicillinase producing or non-producing strains, Citrobacter diversus, Klebsiella pneumoniae, and Klebsiella oxytoca. Beta-lactamase clavulanate-sensitive activity was localized with various isoelectric points from 7.0 to 8.5. No cross hybridization with DNA intragenic probes (blaTEM, blaSHV, blaCARB and blaOXY) was observed by dot blot procedure.

Anti-Bacterial Agents↗

Campylobacter infections in HIV-infected patients: clinical and bacteriological features.

OBJECTIVE: To study the clinical and bacteriological features of Campylobacter infections in HIV-infected patients. DESIGN: A retrospective analysis (1989-1992), followed by a prospective analysis (1992-1994). SETTING: Hospital HIV inpatient unit. PATIENTS AND METHODS: All patients with Campylobacter spp. identified by the laboratory of microbiology at Saint-Louis Hospital, Paris were studied, and their clinical features as well as their response to therapy recorded. RESULTS: During the study period, Campylobacter infection was documented in 38 HIV-infected patients, 76% of whom had AIDS. Campylobacter spp. was isolated from stools in 36 cases and from blood cultures in four cases. Species identification yielded C. jejuni (84%) and C. coli (16%). High-level resistance to quinolones was frequently observed (21%), but resistance to erythromycin (3%) and tetracycline (5%) was rare. Diarrhoea, fever and abdominal pain were the main clinical features of infection. Other intestinal pathogens were found in 42% of patients. Most patients had an acute illness with rapid resolution under appropriate antimicrobial therapy. However, eight patients (21%), experienced chronic diarrhoea with persistent isolation of Campylobacter and in vivo selection of resistant strains, requiring multiple courses of antibiotics. CONCLUSIONS: Campylobacter usually cause acute diarrhoea in patients with HIV infection. Antimicrobial therapy should be guided on in vitro susceptibility testing because of the prevalence of antibiotic resistance. Despite appropriate therapy, some patients will present with prolonged diarrhoea and in vivo selection of multiresistant isolates.

AIDS-Related Opportunistic Infections↗

[Effects of intraperitoneal insufflation on hematogenous seeding of abdominal infections. Preliminary results of an experimental study in rats].

Most laparoscopic procedures require the creation of a pneumoperitoneum. In order to evaluate the potential hazards of bacteriemia related to insufflation, we conducted a study in the rat. Two groups of 20 Wistar rats were used for this study. Peritonitis was induced by opening the terminal ileum. Twenty-four hours later, 20 rats were insufflated at a mean pressure of 6 mm Hg (Group I). After one hour of insufflation, an hemoculture was performed via direct intracardiac puncture and in the other group of 20 non-insufflated rats (Group NI). Five of the 18 hemoculture were positive in the Gr. I (27.7%) and 6 out of 20 in the Gr. NI (30%) (chi 2 = 0.238 p = 0.62 non significant difference). These results suggest that insufflation does not facilitate hematogenous dissemination of bacteria from intraperitoneal sepsis in this animal model.

Animals↗

[Critical analysis of tests for rapid detection of Staphylococcus aureus, Pastorex Staph plus, Slidex Staph-kit and Staph aureus in clinical isolates].

One hundred and seventy three clinical isolates of mannitol fermenter staphylococci, including 120 S. aureus (38% methicillin resistant) and 53 coagulase negative staphylococci were assayed for direct detection of S. aureus on colonies. Three new rapid slide agglutination tests were compared: Pastorex Staph Plus, Slidex Staph Kit and Staph aureus. Each one detects fibrinogen receptor and protein A. According to the addition of monoclonal antibodies, Pastorex Staph plus is intended to detect capsular antigens 5 and 8, and Slidex Staph kit to detect a surface glycopolysaccharide. Sensitivities of these tests were equal, Pastorex Staph plus 95%, Slidex Staph kit 94.2%, Staph aureus 95.8%. Among meticillin-resistant S. aureus, sensitivities reached 91.3%, 87% and 91.3% respectively. Specificities over coagulase negative staphylococci which gave conclusive results were 92.5%, 90.2% and 90.4% respectively. The validity of these results was checked over 100 staphylococcal primary isolates of medical samples in April 1994. Over 62 S. aureus (29% methicillin-resistant) Pastorex Staph plus and Staph aureus sensitivities were 96.8% and 98.4% respectively and specificities were 94.6% and 91.9% over 37 coagulase negative staphylococci which gave conclusive results. Staph aureus test sensitivity is at least equivalent to second generation tests as well in primary cultures as in subcultures The best specifity is achieved with Pastorex Staph plus, which contains latex particles without red blood cells.

Humans↗

Superoxide anion production during monoelectronic reduction of xenobiotics by preparations of rat brain cortex, microvessels, and choroid plexus.

Brain microsomes may produce reactive metabolites during the reductive metabolism of some xenobiotics including drugs. These reactive species can, in turn, react with molecular oxygen to form superoxide radicals (O2.-). We measured the rates of superoxide production by homogenates obtained from three cerebral structures, cortex plus cerebellum, choroid plexus, and microvessels. The molecules assayed were related to quinone, nitroheterocycle, and iminium chemical families. The results we obtained showed a significant correlation between the rate of superoxide anion production and the apparent kinetic parameters (log Km/Vmax) of NADPH-cytochrome P450 reductase activity for these molecules, suggesting the involvement of this enzyme in xenobiotic-induced superoxide production.

Animals↗

[Frequency of angiographic restenosis after 6 months and long-term outcome of coronary angioplasty].

Five hundred patients with a mean age of 59 years were followed up for an average of 32 months after coronary angioplasty. All patients were included in a prospective study comprising coronary angiography at 6 months for 379 patients (91% primary successes). The long-term outcome was evaluated by a questionnaire or telephone interview in all cases. The global primary success rate was 84.4% in this series. The primary failures include 1.8 fatalities, 0.6% myocardial infarction, 2% emergency coronary bypass surgery and 11.2% without immediate clinical consequences. At 6 months, there were 48% of restenoses (182/379 patients) and 28% underwent immediate repeat angioplasty (141/500 patients) with a primary success rate of 91%. After the repeat angioplasty, the restenosis rate was 43% but this varied according to the time from the first restenosis: 60% when the interval was short (under 2 months) compared with 21% when the interval was 6 months (p < 0.01). The actuarial survival rates at 4 years were 95% after successful angioplasty 96% after uncomplicated failures or medically treated restenosis and 98% after bypass surgery. The predictive factors for secondary death were age of over 70 years, previous non-thrombolized myocardial infarction and complications of angioplasty. The long-term outcome was good despite the 48% 6 months restenosis rate requiring revascularisation procedure in 73% of cases.

Actuarial Analysis↗

[Diagnostic value of transesophageal echocardiography in traumatic rupture of the thoracic aorta].

Traumatic rupture of the aorta (TRA) usually occurs at the isthmus. It is rapidly lethal without early surgery and, therefore, diagnosis must not be delayed. The reference diagnostic investigation is aortography but it is invasive in a patient with multiple trauma whose haemodynamic status is often precarious. Transoesophageal echocardiography, a non-invasive investigation which can be undertaken rapidly at the bedside has been proposed recently for the diagnosis of this condition because it gives excellent views of the aortic isthmus. The authors report their experience of transoesophageal echocardiography in 3 victims of severe road traffic accidents with thoracic trauma and who were operated for traumatic rupture of the aorta. Echocardiographic diagnosis of TRA is based on the recording of the association of a thick and mobile intraluminal echo corresponding to the torn intima and media and localised dilatation of the aorta, the wall of which is reduced to the adventitia under tension. On Doppler colour flow mapping the velocities are similar on both sides of the tear but turbulence at the site of rupture may give rise to aliasing. It is important to recognise the echocardiographic features of TRA to differentiate it from dissection of the aorta. Transoesophageal echocardiography also allows diagnosis of any associated traumatic cardiovascular lesions. Its limitations are due to the inability to visualise the proximal portion of the transverse aorta and the supra aortic vessels. Aortography remains essential when a lesion of these vessels is suspected and when the echocardiographic features of the aorta are atypical.

Accidents, Traffic↗

[Syncopal angina caused by sinus arrest; cured by transluminal coronary angioplasty and calcium inhibitor].

The authors report the case of a 42 year old man who smoked and who presented with recurrent spontaneous anginal chest pain followed by syncope due to sinus arrest. The mechanism underlying these symptoms was spasm of the left circumflex artery at the site of severe stenosis of its middle segment just before the origin of the sinus node artery. Treatment with a calcium antagonist with transluminal coronary angioplasty of the narrowed segment of the circumflex artery resulted in complete regression of all symptoms with a follow-up of 15 months. Seven other reports of the same type were found in the literature concerning 6 men and 1 woman, with an average age of 49 years, presenting with the same symptoms and sinus arrest associated with the minimal coronary artery disease. The proof of coronary spasm was documented in 6 of the 7 cases by a positive ergometrine stress test or by the observation of spontaneous spasm during coronary angiography or rapid atrial pacing. The outcome was good with calcium antagonist therapy in 5 cases, and with slow release nitrate derivatives in 1 case. One patient, treated by betablockers, died. It is useful to investigate some sino-atrial blocks to diagnose the underlying ischaemic mechanism as the patients may be treated simply with calcium antagonists rather than undergo implantation of a pacemaker.

Adult↗

[Extended spectrum beta-lactamases].

At least 30 extended-spectrum beta-lactamases (ESB) have emerged responsible for resistance to indigestible beta-lactams (C3G) since their discovery in West Germany in 1983. Most of them are produced by enterobacteria and essentially K. pneumoniae which appeared susceptible to oxyimino-beta-lactams. A double-disk test was useful to detect such nosocomial isolates of enterobacteria (urines, blood, wound, sputum cultures) mostly recovered from patients in intensive care units. These have spread through hospital and outbreaks were described. Because plasmid-encoded this resistance mechanism was spreading among enterobacteria with other resistance markers (e.g. netilmicin, amikacin). It seems highly likely that the use of newer antibiotics favors the appearance of ESB obtained by selection of mutated genes coding for penicillinases (TEM, SHV). Treatment including a beta-lactam is still possible because of the stability of some beta-lactams e.g. cefamycins, carbapenems and the sensitivity to beta-lactam inhibitors. Digestive selective decontamination may overcome outbreak.

Adult↗

Detection of human T lymphotropic virus type I tax gene in salivary gland epithelium from two patients with Sjögren's syndrome.

OBJECTIVE: To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjögren's syndrome (SS). METHODS: Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present. RESULTS: Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients. CONCLUSION: None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.

Antibodies, Viral↗

Intestinal microsporidiosis in human immunodeficiency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biologic features.

Eighteen patients infected with human immunodeficiency virus and with chronic unexplained diarrhea were prospectively studied to investigate the prevalence and clinical and biologic features of intestinal microsporidiosis. All patients underwent extensive evaluation for bacterial, viral, and parasitic pathogens. Enterocytozoon bieneusi was found in 9 patients (50%; 95% confidence interval, 27-73) in stools and duodenal and jejunal biopsies. In 8 patients, it was the sole pathogen found. Other pathogens were also isolated from the intestinal tracts of 4 patients, but diarrhea remained unexplained in 6. Patients with intestinal microsporidiosis had significantly lower mean Karnofsky scores (69.4 vs. 85.5, P = .009), CD4 cell counts (18.6 vs. 209.8/microL, P = .02), and D-xylose absorption tests (0.13 vs. 0.36 g/L, P < .001) than did patients without intestinal microsporidiosis. Intestinal microsporidiosis appears to be a frequent cause of unexplained chronic diarrhea in patients with AIDS and is associated with diminished D-xylose absorption.

AIDS-Related Opportunistic Infections↗

Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected patients.

OBJECTIVE: To identify risk factors associated with a first episode of Clostridium difficile-associated diarrhoea (CDAD) in patients with HIV infection. DESIGN: A case-control study. SETTING: University teaching hospital HIV inpatient unit. PATIENTS AND METHODS: Nineteen HIV-infected patients with CDAD, defined as diarrhoea with positive stool culture for Clostridium difficile (CD) and positive stool cytotoxin B assay, were compared with 38 randomly selected controls (HIV-infected patients hospitalized on the ward on the day the matched case was diagnosed). CD isolates were phenotyped by electrophoretic protein patterns. RESULTS: The incidence of CDAD among HIV-infected patients was 4.1/100 of patient-admissions. On univariate analysis, cases were more likely to have used clindamycin [11 out of 19 compared with four out of 38; odds ratio (OR) 19; 95% confidence interval (CI), 2-160; P = 0.0007], and pyrimethamine (14 out of 19 compared with 13 out of 38; OR, 4.8; 95% CI, 1.4-16, P = 0.02) in the month before diagnosis, and to have had cerebral toxoplasmosis (12 out of 19 compared with 13 out of 38; OR, 2.8; 95% CI, 0.9-8.6; P = 0.09). There was also a significant increase of the risk of CDAD as duration of hospitalization in the ward increased (chi 2 for trend, P = 0.007). Multivariate models associated two risk factors with CDAD: clindamycin use (OR, 42; 95% CI, 2-813; P = 0.01), and prolonged hospitalization in the ward (OR, 3.6 per week in the ward; 95% CI, 1-13, P = 0.048). Of 18 available CD isolates, 15 (83%) had identical electrophoretic protein pattern. CONCLUSIONS: Clindamycin use and prolonged hospitalization in the ward were the main risk factors associated with CDAD in this study. These observations, together with the occurrence of one major phenotype of CD, suggest nosocomial transmission of CD in the ward.

Adult↗

Interaction between human immunodeficiency virus and Toxoplasma gondii replication in dually infected monocytoid cells.

THP-1 monocytoid cells, either not infected or chronically infected with human immunodeficiency virus type 1 (HIV-1), were challenged with Toxoplasma gondii. Parasitic growth, as assessed by trophozoite counting and measurement of supernatant p30 membrane antigen, was similar in HIV-infected and noninfected THP-1 cells. Also, T. gondii did not affect HIV replication. These experiments therefore failed to demonstrate any interaction between HIV-1 and T. gondii replication in concurrently infected monocytoid cells.

Animals↗

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.

Adolescent↗