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Biomedical subjects

P Leclercq

Publications and source records attributed to P Leclercq.

At least 19 recordsLinked to original sources

Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats.

Sepsis or endotoxaemia inhibits gluconeogenesis from various substrates, the main effect being related to a change in the phosphoenolpyruvate carboxykinase transcription rate. In addition, sepsis has been reported to affect the oxidative phosphorylation pathway. We have studied glycerol metabolism in hepatocytes isolated from rats fasted and injected 16 h previously with lipopolysaccharide from Escherichia coli. Endotoxin inhibited glycerol metabolism and led to a very large accumulation of glycerol 3-phosphate; the cytosolic reducing state was increased. Furthermore glycerol kinase activity was increased by 33% (P<<0.01). The respiratory rate of intact cells was significantly decreased by sepsis, with glycerol or octanoate as exogenous substrates, whereas oxidative phosphorylation (ATP-to-O ratio or respirations in state 4, state 3 and the oligomycin-insensitive state as well as the uncoupled state) was unchanged in permeabilized hepatocytes. Hence the effect on energy metabolism seems to be present only in intact hepatocytes. An additional important feature was the observation of a significant increase in cellular volume in cells from endotoxic animals, which might account for the alterations induced by sepsis.

Adenine Nucleotides

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Acquired Immunodeficiency Syndrome

Diagnosis of 22 new cases of Bartonella endocarditis.

BACKGROUND: Bartonella species are emerging pathogens that are seldom reported as a cause of blood culture-negative endocarditis. OBJECTIVE: To report the occurrence of, risk factors for, and clinical features of Bartonella endocarditis and to evaluate the diagnostic tools available for this condition. DESIGN: Case series and comparison with past series. SETTING: Multicenter international study in Halifax, Nova Scotia, Canada; Lyon, France; and Marseille, France. PATIENTS: 22 patients from France, England, Canada, and South Africa were investigated for blood culture-negative endocarditis. MEASUREMENTS: Titer of antibodies to Bartonella species by microimmunofluorescence assay, blood or vegetation culture, and amplification of Bartonella DNA from valvular tissue by polymerase chain reaction. Cross-adsorption was done for patients with antibodies to Chlamydia species. RESULTS: 22 patients had definite endocarditis. Five were infected with B. quintana, 4 with B. henselae, and 13 with an undetermined Bartonella species. These cases were compared with the 11 previously reported cases. Of the patients with the newly reported cases, 19 had valvular surgery and 6 died. Nine were homeless, 11 were alcoholic, 4 owned cats, and 13 had preexisting valvular heart disease. Bartonella species caused 3% of the cases of endocarditis seen in the three study centers. The patients with these cases could have previously received a diagnosis of chlamydial endocarditis because of apparently high levels of cross-reacting antibodies to Chlamydia species. CONCLUSIONS: Bartonella species are an important cause of blood culture-negative endocarditis and can be identified by culture, serologic studies, or molecular biology techniques. Alcoholism and homelessness without previous valvular heart disease are risk factors for B. quintana infection but not for infection with other Bartonella species.

Adult

Sexually dimorphic expression of calcitonin gene-related peptide (CGRP) immunoreactivity by rat mediobasal hypothalamic neurons.

Although the hypothalamic arcuate nucleus is a sexually dimorphic region of the rat brain, there are no reports of sex differences in the number of neurons containing specific neuropeptides within this structure. As cells synthesizing calcitonin gene-related peptide (CGRP) have been shown to exhibit sex differences in other steroid-receptive regions of the rat brain, we examined whether the CGRP-immunoreactive cells located in the mediobasal hypothalamus may also be sexually dimorphic. Immunostaining of sections from male and female colchicine-treated rats revealed a small population of CGRP-immunoreactive cells distributed throughout the arcuate nucleus. Immunoreactive cells were also detected in the lateral hypothalamic perifornical region, dorsomedial, posterior periventricular and ventral tuberomammillary nuclei, and zona incerta. Cell count analysis revealed approximately twice as many CGRP-immunoreactive cell profiles in the rostral (P < 0.01), middle (P < 0.001), and caudal (P < 0.01) thirds of the arcuate nucleus of male rats compared with females. A significant sex difference in immunoreactive cell numbers (male > female) was also detected within the caudal dorsomedial nucleus (P < 0.05) but not in the posterior periventricular nucleus, perifornical region and zona incerta. Although fibers immunoreactive for CGRP were identified in low density throughout the mediobasal hypothalamus, only female rats displayed prominent fiber staining in the periventricular region. Double-labelling immunofluorescence experiments revealed that the CGRP-immunoreactive cells within the zona incerta, but not the hypothalamus, were also immunoreactive for tyrosine hydroxylase; at least 60% of the A13 dopaminergic neurons co-express CGRP. These results provide evidence that sex differences exist in the number of specific neuropeptide-synthesizing cells within the hypothalamic arcuate nucleus and provide further examples of cell populations expressing CGRP immunoreactivity in a sexually dimorphic manner.

Animals

[Visceral localizations of cat-scratch disease in an immunocompetent patient].

Locoregional expression of cat scratch disease is well known, but despite advances in microbiology over the last 10 years leading to the description of two new bacteria (Afipia felis, Bartonella henselae) the infective agent responsible for cat scratch syndrome remains unknown. Until the 80s, only one systemic disease was attributed to infection with a germ in the Bartonella genus: trench fever. With the onset of the AIDS epidemic, new clinical syndromes caused by Bartonella bacteria have been described: bacillary angiomatosis, hepatic peliosis, cases of recurrent septicemia, cases of endocarditis, etc. More recently, atypical forms of cat scratch disease including systemic diseases have been reported in immunocompetent subjects. Although quite rare (1% of the cases), such types of expression can raise questions as to diagnosis both in terms of clinical signs and in terms of bacteriological findings. Clinical and experimental data do not provide a clear direction for treatment but would suggest that prolonged use of aminoglycosides is useful.

Adult

Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency.

We have investigated whether nutritional status and peroxidation process are associated with the degree of development of HIV infection. This was done by measuring the status of vitamins (E, A and beta-carotene), of antioxidant trace elements (zinc, selenium) and lipid peroxide levels (lipid hydroperoxides and thiobarbituric acid reactants) in HIV-seropositive patients at CDC II and CDC IV stages and in comparison with normal subjects. There was a decrease in vitamin and trace element levels related to the severity of disease. The most dramatic decrease, however, was seen for carotenoids (0.94 +/- 0.46 mumol/l) and beta-carotene (0.24 +/- 0.14 mumol/l vs. 0.56 +/- 0.29 mumol/l) whose stage II levels were only half the normal value. Paradoxically, lipid peroxidation was higher at stage II than at stage IV. This can be attributed to an overproduction of oxygen radicals by polymorphonuclears in stage II. This deficiency in antioxidant status, often found in patients suffering from peroxidative diseases, may have important consequences on cellular immunity. Furthermore, the concomitant overproduction of free radicals may also affect HIV multiplication.

Adult

Autologous blood donation before myocardial revascularization: a Holter-electrocardiographic analysis.

The influence of preoperative autologous blood donation on myocardial ischemia and arrhythmias was evaluated in 24 patients scheduled for coronary artery bypass grafting (CABG). All had a Holter recorder placed 24 hours before predonation (day 1), the cassette was changed prior to donation, and the recording continued for 24 hours thereafter (day 2). Each patient served as his or her own control, and observations made on day 2 were compared with those of day 1. Ischemia was quantitated by calculating the duration (C.Dur.) and the area (C. Area) of ischemic ST segment depressions, and ventricular premature beats (VPB) were classified according to the Lown grading system. Twenty-one men and 3 women were monitored. On day 1, 9 patients had 20 ischemic events, 3 being symptomatic. Nine patients demonstrated ischemia on day 2, representing a total of 3 symptomatic and 26 silent events. When comparing the two monitoring periods, 7 patients had longer or more severe ST segment depression whereas 6 other patients presented with more severe VPBs on day 2. Three patients had less ischemia on day 2, one remained stable, and 13 had no ischemia throughout the study. Silent ischemia was significantly more prolonged (C.Dur.Sil 316 v 152 sec, P < 0.05) and more intense (C. Area Sil 8 v 3.8 mm.min, P < 0.05) on day 2. Moreover, on top of a normal circadian distribution of ischemic events in the morning and in the evening, 40% of events were related to the donation or to a trip to the hospital. No preoperative characteristic helped to detect patients at risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

AIDS-Related Opportunistic Infections

Massive ketonuria during sedation with propofol in a 12 year old girl with severe head trauma.

Severe ketonuria developed during sedation with propofol in a 12 year old girl with brain injury. Deep sedation with propofol (5.1 mg/kg/h) was required because of agitation and severe intracranial hypertension; as a part of our management protocol, glucose intake was restricted to 5 Kcal/h. After 18 hours of propofol infusion there was intense ketonuria (8+ by Ketostix) without any evidence of metabolic acidosis (pH, HCO3- and anion gap were within normal values). At this time, indirect calorimetry (Deltatrac) confirmed that energy expenditure was principally based on fat consumption (70% of energy expenditure). Lowering the propofol infusion rate and increasing glucose intake reduced fat consumption to 39% within 8 hours: at this time, Ketostix was negative for ketone bodies. This case illustrates a potential risk of ketonuria during prolonged sedation with propofol (a 10% solution of intralipid), particularly if glucose intake is restricted. Monitoring urinary ketone bodies is recommended under these circumstances.

Brain Injuries

HIV-1 in blood monocytes: frequency of detection of proviral DNA using PCR and comparison with the total CD4 count.

In vivo infection of monocytes/macrophages by the human immunodeficiency virus (HIV) has been investigated in many studies since these cells were suggested to provide a reservoir for the virus. In this study, we wanted to find out whether HIV provirus could be detected in circulating monocytes and whether it could be compared with the provirus found in T lymphocytes (T-Ly). Twenty-one seropositive subjects were studied. The amplification method (PCR) was used with three different primer pairs (in gag, env, and long terminal repeat regions of the viral genome) to detect the HIV-1 genome in monocytes and T-Ly separated by an immunomagnetic isolation technique. Of 21 monocyte samples, 13 (61.9%) were positive with at least one primer pair. Furthermore, the provirus harboured in 9 of those 13 monocyte-positive samples differed, with respect to pattern of primer response, from the provirus found in T-Ly. When comparing primer responses of monocytes and T-Ly, most of the differences were found to have occurred with the env primers (8 of 9 cases). Dilution experiments with the 8 E5 cell line revealed that 9 of 12 T-Ly contained 15-150 HIV DNA copies per 150,000 cells while 8 of 11 positive monocytes contained less than 15 copies. However, monocyte samples from two asymptomatic individuals and an AIDS patient showed high levels of HIV DNA, comparable to those obtained in T-Ly. Finally, it was also found that the monocyte-positive subjects were more immunosuppressed than the negative ones, as shown by the total CD4 count of both groups (means of 269 T4/mm3 and 573 T4/mm3, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes

A new semiautomated algorithm to quantify Holter-detected myocardial ischemia: preliminary experience in the Trimetazidine European Multicenter trial (TEMS).

Holter-detected myocardial ischemia, either painful or painless, is an important issue in the functional and prognostic evaluation of coronary patients. This paper describes one of the first attempts to reliably quantify the duration and severity of the ischemic ST-segment changes over a given period of time; the algorithm described here provides physicians with a global index of ischemia that is the total ischemic area, namely, the integral of ST-segment depression or elevation over time (expressed in mm x min). The diagnostic and prognostic power of this new index remains to be established and to be compared with the actually used simple measurements, i.e., the number and duration of ischemic events.

Algorithms

[Prosthetic possibilities with the Denar "Steri-Oss" implant].

Implantology, very frequently presented under only the surgical angle, must in fact be approached from a biological and functional point of view. The analysis of the future prosthetic situation will allow an overall treatment scheme to be established, in which periodontics, surgery, prosthodontics and occlusal equilibration will follow each other in order to achieve the functional rehabilitation. In the first part of this article, the various steps which make up the treatment scheme are briefly and quickly described. It is imperative to approach them according to this chronological order when there is any treatment involving implants. While implantology involved only one surgical session a few years ago, it now involves two: the first, consisting of placing the implant in the living tissues, and the second, at some months interval from the first, allowing the endo-osseous portion to be attached to the future prosthesis. These two surgical acts are inter-dependent. Given the wide array of systems proposed and the quantity of "Implant-Prosthesis" connections produced in each system, the practitioner does not always know which kind of connection to choose or how to use it. The second part of the article is devoted to the study of the various connection possibilities between the Steri-oss implants and the prosthesis. The methods for lining up the cores in relation to the others are studied in detail, as are the different possibilities for stabilising removable prosthesis. Some of the methods described can be used with other implant systems.

Dental Implantation, Endosseous