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Biomedical subjects

J C Petit

Publications and source records attributed to J C Petit.

At least 55 records · Page 3Linked to original sources

Killing kinetics of meropenem against penicillin-resistant pneumococci.

The killing kinetics of meropenem against sixteen clinical isolates of pneumococci (12 penicillin-resistant, three penicillin-intermediate and one penicillin-sensitive) were studied. Meropenem was tested at 1x, 2x and 4x the MIC for each individual isolate. The results showed a good bactericidal activity with rapid killing of pneumococci (killing > 3 log10 cfu/mL was obtained for nine strains). This strategy needs clinical assessment and might prove to be a suitable alternative to penicillin and cephalosporins for the treatment of mixed infections involving multiresistant pneumococci.

Meropenem↗

Monitoring of cytomegalovirus infection and disease in bone marrow recipients by reverse transcription-PCR and comparison with PCR and blood and urine cultures.

Preemptive therapy is a promising strategy for the prevention of serious cytomegalovirus (CMV) disease after bone marrow (BM) transplantation but requires relevant diagnostic tests. We compared the clinical value of a reverse transcription (RT)-PCR method, which detected a late viral mRNA in peripheral blood leukocytes (PBL), with a PCR method that detected the viral DNA in PBL and with viral culture from leukocytes and urine for the diagnosis of symptomatic CMV infection after BM transplantation. Forty-five consecutive BM recipients were prospectively tested at weekly intervals by the four methods. CMV infection, demonstrated either by the culture of CMV or by repeated detection of viral DNA, was observed in 28 patients, but only 14 developed CMV-related clinical symptoms. The clinical sensitivity and specificity of each technique for detection of symptomatic infection were, respectively, 36 and 74% for urine culture, 43 and 84% for leukocyte culture, 100 and 65% for PCR, and 71 and 94% for RT-PCR. Although PCR detection of DNA in PBL was the earliest and most sensitive technique for the diagnosis of CMV infection, RT-PCR was more predictive of the onset of CMV-related clinical symptoms. These data suggest that both molecular methods should be used for identifying BM recipients at highest risk of CMV disease.

Adolescent↗

[In vitro study of the bacteriostatic and bactericidal activity of meropenem against strains of Pseudomonas aeruginosa multiresistant to antibiotics].

Meropenem is a new dehydropeptidase stable carbapenem which has an in vitro bacteriostatic activity superior to imipenem against Pseudomonas aeruginosa. Minimal inhibitory concentrations of meropenem (MEM) and imipenem (IPM) were determined on twelve strains: two were genetically characterized reference strains and ten isolated from patients. Killing curves were performed for MEM used at 1,2 and 4 fold the MIC and 32 mg/l; survivors were counted at baseline and after 5 and 24 hours of incubation by spiral plating. Five strains were susceptible to MEM and IPM; five were intermediate and two resistant to MEM; these seven strains were resistant to IPM. A weak bactericidal effect was obtained after 5 h at each concentration. Only one strain achieved a 3 log 10 reduction after 5 h at 2 x MIC. A regrowth of all the strains tested was observed after 24 h.

Dose-Response Relationship, Drug↗

Correlation between viral DNA load and serum anti p19 antibody concentration in symptomless human T-lymphotropic virus type-I (HTLV-I)-infected individuals.

In order to determine whether serum anti-human T-cell lymphotropic virus type I (HTLV-I) antibody concentration is correlated with cellular viral DNA load, these 2 biological parameters were established in 22 symptomless HTLV-I carriers. The proviral copy (PVC) number was determined through quantificative polymerase chain reaction. Specific antibody titers were determined by Western blot with the end-point dilution method; the quantification of each antibody was performed through ScanBlot by determination of the peak height of each Western-blot band. A positive correlation was observed between the PVC number and the titer of total antibodies. When the association between the peak height of each antibody and the PVC number was studied, a significant positive correlation was observed only with anti-p 19. Further evaluation through follow-up studies of symptomless HTLV-I individuals is needed to clarify the value of anti-HTLV-I antibody titer as a predictor of disease progression.

Adult↗

Serum anti-p24 antibody concentration has a predictive value on the decrease of CD4 lymphocyte count higher than acid-dissociated p24 antigen.

We studied the prognostic value on the decrease of CD4 lymphocyte count of anti-p24 antibody (ab) titer and compared this value with that of polyclonal and monoclonal p24 (ag) titer before and after immune complex dissociation (ICD); 53 human immunodeficiency virus (HIV)-infected patients having CD4+ counts above 400/mm3 when first examined were followed up over a 3-year period including at least four visits; HIV disease progressors (n = 18) were defined as having CD4+ counts below 200/mm3 and non-progressors (n = 35) as having CD4+ counts still above 400/mm3 at the end of follow-up. Sera were collected at each visit and assayed for p24 ag with and without ICD and for anti-p24 ab titer. The mean anti-p24 ab titer of progressors and of non-progressors at entry was significantly different. A threshold of anti-p24 ab titer indicating a HIV progression was determined at 1/300. The proportion of individuals with an anti-p24 ab titer lower than 1/300 at least once during the study period was 34% in non-progressors and 94% in progressors. The difference between progressors and non-progressors at entry was significant with monoclonal p24 ag without ICD and more significant with monoclonal p24 ag after ICD. The marker having the highest predictive value was the anti-p24 ab titer, then monoclonal p24 ag with ICD, then polyclonal p24 ag with ICD. Anti-p24 ab is an earlier and stronger marker of the decrease of CD4 lymphocyte count than p24 ag even after ICD.

Acids↗

Value of routine stool cultures in hospitalized patients with diarrhea.

In a prospective study conducted over a six-month period, the relative yield of 721 routine cultures of stool from adult inpatients as a function of the time after hospital admission was assessed. Salmonella, Campylobacter, Shigella or Yersinia spp. were recovered from 10.9% (41/377) of patients within three days of hospitalization and from only 1.5% (5/344) after three days. However, a review of these patients' charts did not suggest nosocomial transmission but rather a delay in stool collection or asymptomatic carriage. Clostridium difficile was isolated with a high frequency in patients both within and after three days of hospitalization (10.3% and 10.2%, respectively). Thus, stool specimens from adults hospitalized for more than three days should not be cultured except for Clostridium difficile unless there are plausible clinical or epidemiological reasons to do so.

Adult↗

Decreased transmission of Enterobacteriaceae with extended-spectrum beta-lactamases in an intensive care unit by nursing reorganization.

In our gastrointestinal surgical intensive care unit (SICU), the large number of patients with multiple enterostomies enhances the risk of nosocomial transmission of gut extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) by health care workers. A control study performed in our SICU from June-August 1992 showed an ESBLE gut colonization rate of 70%. To reduce this rate, nursing procedures were intensified or modified, particularly handwashing, single-use equipment and waste control. To test the efficiency of these procedures, 64 patients hospitalized for more than two days from September 1992-March 1993 were screened for gut acquisition of ESBLE. Rectal samples were taken within 48 h after admission and then weekly. After nursing reorganization, the ESBLE colonization rate dropped significantly to 40% (P < 0.001). Twenty patients (31.7%) acquired a gut ESBLE, after a mean of 24.3 +/- 13.7 days. Each patient was colonized with one, two or three ESBLE (Klebsiella pneumoniae, Escherichia coli and Enterobacter aerogenes). Baseline characteristics of the 20 colonized and 39 non-colonized patients showed no significant difference (Student's t-test, P > 0.05). The nursing workload, estimated as a omega index, was greater in the colonized group (P < 0.001). These findings show that strict observance of nursing procedures can significantly reduce ESBLE acquisition in a high-risk surgical unit.

Aged↗

[Thromboembolic accidents in postmenopausal patients with adjuvant treatment by tamoxifen. Frequency, risk factors and prevention possibilities].

Tamoxifen is the anti-estrogen the most widely used in breast cancer. The duration of its prescription, as adjuvant treatment, tends to increase (5 years, and even more) and now it is used in chemoprevention. A slight increase of thromboembolic complications was noted in some studies. This article evaluates the frequency of thromboembolic accidents (TEA) in 441 postmenopausal patients treated by an association of conservative radiosurgery, tamoxifen +/- chemotherapy, for a breast carcinoma T0, T1T2 < 4 cm. Nineteen patients (4.3%), all in remission, presented a TEA, between 1 and 44 months after the beginning of the tamoxifen treatment. We observed seven pulmonary embolisms (PE), 11 deep venous thromboses (DVT) and an acute arterial ischemia. Two patients aged 74 and 80 years died, the others had a favourable evolution under anticoagulant treatment. Among these 19 patients, six presented known risks factors (phlebitis, cardiovascular disorders) and ten had a "favouring circumstance" aggravating the risk of TEA (surgical operation, severe infection, fracture). Their median age was 65 years (61 for all the 441 patients). We noted eight cases of breast lobular cancer (42%) among these 19 patients (11% for all the patients). Among postmenopausal patients, the indication of tamoxifen must be evaluated according to the benefits expected in those with high risk factors of TEA (history of heart failure, obesity, spread varix, age > 65 years). In case of DVT and/or PE, this treatment seems contra-indicated. In case of "favouring circumstances", a hypocoagulant or systematic anticoagulant treatment must be proposed. In case of combined chemotherapy, it is better to start tamoxifen at the end of the treatment. These simple prophylactic measures should allow to reduce significantly the risk of TEA in postmenopausal patients with adjuvant anti-estrogenotherapy.

Aged↗

Comparison of two techniques for measurement of in vitro killing kinetics of five antibiotics against Pseudomonas aeruginosa.

The in vitro activity of ticarcillin, imipenem, gentamicin, amikacin and ciprofloxacin against six Pseudomonas aeruginosa isolates was evaluated by two time-killing curve methods: the conventional broth technique, and another method previously described which employs a transfer filter membrane. The patterns of the killing curves obtained over a 5 h period with the two techniques were similar. In contrast to the results obtained for beta-lactam agents, the reduction of inoculum was great and increased with the concentration for aminoglycosides and ciprofloxacin. After 5 h, regrowth of the six strains tested was observed in broth with all antibiotics, whereas a bactericidal effect was observed over 24 h with the filter membrane method. Further studies are warranted to determine the reasons for this difference.

Amikacin↗

Investigation of a nosocomial outbreak of Clostridium difficile-associated diarrhoea among AIDS patients by random amplified polymorphic DNA (RAPD) assay.

Clostridium difficile is now well-established as the main cause of antibiotic-associated diarrhoea or colitis. Nosocomial acquisition of C. difficile has been described among various immunocompromised patient populations. From January to December 1992, 19 cases of antibiotic-associated diarrhoea occurred among AIDS patients in the same ward of a hospital. They all harboured C. difficile in their stools. All the strains were retrospectively typed by the random amplified polymorphic DNA (RAPD) method using two different 10-mer oligonucleotides. Twenty-five C. difficile strains (isolated from 15 patients) yielded the same RAPD pattern, suggesting they were identical. The timing and location of infections indicated that transmission of this highly resistant spore-forming bacterium can occur not only by direct patient-patient contact but also at a distance in time and space. This is the first report of an outbreak of C. difficile-associated diarrhoea in AIDS patients. Epidemiological markers are needed to recognize and control common-source outbreaks; RAPD assay is a simple, rapid and effective way of distinguishing isolates of C. difficile.

Acquired Immunodeficiency Syndrome↗

Tissue segregation enhances calvarial osteogenesis in adult primates.

Calvarial defects of adult mammals have a limited potential for regeneration. Osteogenesis may be impaired by the intrusion within the defect of nonosteogenic tissues during healing, which inhibits centripetal bone deposition from the margins of the defects. Using a primate model, we evaluated bone regeneration in calvarial defects treated with demineralized bone matrix versus defects treated according to the strategy of guided tissue regeneration. Sixty-four defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). In each animal, 2 contralateral defects were covered with a template of porous polymer, 35 mm in diameter. Templates were positioned over the calvarial margins to prevent penetration of the pericranium and the temporalis muscle within the defects, thus maintaining tissue segregation during healing. The third defect was implanted with allogeneic demineralized bone matrix, as positive control. The fourth defect was left untreated and was used as negative control. Undecalcified bone sections (7 microns thick) were prepared from the harvested specimens 3 and 6 months after surgery. Although untreated defects showed limited osteogenesis after fusion of the pericranium with the dura, defects covered with the polymeric template often showed extensive bone deposition extending centripetally from the margins of the craniotomies. Histomorphometry demonstrated that defects treated with demineralized bone matrix and defects covered with the polymeric template had greater amounts of bone and osteoid when compared with untreated defects (p < 0.01). At 6 months, greater amounts of bone formed in demineralized bone matrix-treated defects when compared with defects covered with the polymeric template (p < 0.01). The results of this study show that calvarial membranous bones of adult primates retain the potential to regenerate when segregation between the different tissue components participating in the healing of the wound is maintained. In the same model, however, implantation of allogeneic demineralized bone matrix, used as a positive control provided the most effective treatment for the defects.

Age Factors↗

Endotoxemia and bacteremia in patients with sepsis syndrome in the intensive care unit.

STUDY OBJECTIVES: To study circulatory endotoxin (ET) in patients with sepsis syndrome (SS) in order to answer three questions: (a) How often and at which concentration is ET present in the plasma of patients with SS and is the presence of ET a prognostic marker in this situation? (b) Is detection of ET helpful in predicting Gram-negative bacterial infections with or without bacteremia? (c) What are the kinetics of clearance of ET concentrations in plasma? DESIGN: Prospective study of consecutive patients fulfilling Bone's criteria for SS. SETTING: Medical ICU in a teaching hospital. PATIENTS: The study included 93 patients. The simplified acute physiologic score was 19 +/- 6, 49 percent were in shock, and 54 percent were mechanically ventilated. The mortality at day 28 was 53 percent. MEASUREMENTS: Endotoxin determinations and blood cultures were performed simultaneously at the onset (day 1) of SS. Samples were collected on several days from 48 patients. Endotoxin concentration was determined using an end point chromogenic Limulus assay. For the first ET determination, the mean circulatory level (mean +/- SEM) was calculated among patients with detectable ET, thus excluding patients with a null value for ET. RESULTS: On day 1, ET was detected in 44 patients (47 percent; 60.2 +/- 16.5 pg/ml) and was statistically more frequent in patients with shock, elevated plasma lactate, and organ failure. There was no statistical difference for age, gender, ratio of PaO2 to fraction of inspired oxygen. Among patients with proven Gram-negative bacterial infection (n = 46), ET was detected in 67 percent as compared with 28 percent without Gram-negative bacterial infection (p = 0.0001). On day 1, among 19 patients who had positive blood cultures with Gram-negative bacteria (GNB), 15 had detectable ET (79 percent, 61 +/- 22 pg/ml). In 14 other patients whose blood cultures were positive for GNB but became negative on day 1, 9 had detectable ET (64 percent; 36 +/- 6.5 pg/ml). Endotoxin declined linearly between days 1 and 4. CONCLUSION: In our study, the plasma ET concentration predicts neither Gram-negative infection, with or without bacteremia, nor the outcome. However, when ET is present in the plasma of patients with SS it remains detectable for a long period of time as compared to its rapid disappearance from plasma of animals or healthy human volunteers receiving ET intravenously. This slow clearance of ET suggests either a continuous release or a defect in its clearance.

Bacteremia↗

Predicting progression of HIV disease: usefulness of acid-dissociated p24 antigen.

To ascertain whether immune complex dissociation (ICD) improves the value of p24 antigen as a prognostic marker for progression of HIV infection, 53 patients were followed over a 3-year period, including at least one visit per year. All had CD4+ counts at entry > 400/mm3; progressors (n = 18) were defined as having CD4+ counts < 200/mm3 and nonprogressors (n = 35) as having CD4+ counts still > 400/mm3 at the end of follow-up. Serum specimens were collected at each annual visit and assayed for p24 antigen with and without ICD treatment. At entry, the percentage of progressors positive for ICD p24 antigen was significantly higher than the percentage of positive nonprogressors (39% versus 3%, p < 0.01). The sensitivity of p24 antigen over all visits in terms of predicting the progression increased from 61% before ICD to 83% after. The specificity of p24 antigen in terms of predicting progression decreased from 97% before ICD to 89% after. The relative risk of progression in individuals positive for p24 antigen was 6.7 before ICD and increased after ICD to 12.7. When evaluating the respective prognostic value of the p24 antigen and of the ICD p24 antigen, only ICD p24 was significant (RR 10.2, 95% CI 2.2-46.9). ICD p24 antigen appears to be a marker of progression that may be detected earlier than p24 antigen without ICD.

Adult↗

Genomic fingerprinting of Clostridium difficile isolates by using a random amplified polymorphic DNA (RAPD) assay.

This study describes the use of a new and easy method called random amplified polymorphic DNA (RAPD) assay to distinguish strains of C. difficile. We used two single short primers (AP4 and AP5) with arbitrary nucleotide sequences in a polymerase chain reaction to amplify genomic DNA. The profiles observed after electrophoretic separation were able to distinguish 20 reference C. difficile strains previously serotyped by Delmée's method. The fingerprints of 11 epidemiologically unrelated C. difficile strains clearly yielded a DNA polymorphism between all the strains. Latterly, RAPD profiles of 11 C. difficile strains isolated from 2 independent suspected outbreaks showed, in each case, a predominant banding pattern corresponding to an epidemic strain. These results suggest that RAPD assay could be a valuable tool for epidemiological studies.

Base Sequence↗