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Biomedical subjects

G Humbert

Publications and source records attributed to G Humbert.

At least 55 records · Page 3Linked to original sources

[Celioscopic cholecystectomy. 2 cases of infectious complications].

Despite the low morbidity and mortality of laparoscopic cholecystectomy, trauma and infection have been reported. Such complications can produce a misleading clinical picture, as in two cases we observed. Case 1. A symptomatic 56-year-old female patient underwent laparoscopic cholecystectomy. During the operation, the gall bladder ruptured and the contents had to be aspirated from the abdominal cavity. The patient complained of hepatalgia 2 weeks after the operation, then was not seen again for more than 1 year when fever and hepatalgia did not respond to symptomatic treatment. An inter-hepato-renal collection (6 cm in diameter) was punctured under echography. Aspirate culture yielded Pseudomonas aeruginosa. Adapted antibiotic therapy was unsuccessful and surgery was required to empty the abscess then remove a fibrous conjunctive tissue formation. Case 2. A 55-year-old female patient with a history of complete remission after mammectomy for breast cancer underwent laparoscopic cholecystectomy in 1991. Two days after the operation, fever (39 degrees C) was accompanied by abdominal defence. Biliary peritonitis due to imperfect suture of the bile duct was repaired followed by peritoneal lavage-drainage. Per-operative blood samples revealed type 6 Pseudomonas aeruginosa. Despite adapted parenteral antibiotics, fever persisted at 39 degrees C and intense jaundice was observed. A second laparoscopy 14 days later showed inflammatory narrowing of the main bile duct which was drained into a small bowel loop. Eight days later computed tomography revealed multiple abscess in the liver. Transparietal cholangiography was performed and showed that the contrast medium entered the abscesses via the biliary canals. The state of sepsis persisted, jaundice worsened and hepatic encephalopathy developed with obnubilation and flapping tremor. After 1 month of general antibiotherapy, no improvement was seen on computed tomography images and needle biopsy of an abscess led to the identification of resistant type 6 P. aeruginosa. Antibiotics were adapted and administered iv with no clinical improvement. Selective catheterism of the hepatic artery via the femoral access was performed to allow intra-hepatic antibiotic delivery. Three weeks later clinical situation remained unchanged when acute respiratory distress highly suggestive of pulmonary embolism led to death. Autopsy was not performed. In both of these rare cases of infectious complications due to P. aeruginosa after laparoscopic cholecystectomy, the source of contamination remained unknown. Nosocomial infection was suspected.

Anti-Bacterial Agents↗

The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation.

In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection.

Antibodies, Monoclonal↗

Triple combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a highly penicillin-and glycopeptide-resistant isolate of Enterococcus faecium.

A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.

Animals↗

A non-comparative, multicentre study of cefepime in the treatment of serious bacterial infections.

Multi-resistant strains of Gram-negative bacteria are rapidly emerging as a frequent cause of serious bacterial infection in the hospital environment. Effective treatment must include an antibiotic with activity against these organisms. In an open multicentre study, cefepime was evaluated as empirical therapy in 156 hospitalized patients (mean age 57 years) with serious infection of the urinary tract (n = 43), lower respiratory tract (n = 101) and skin and soft tissue (n = 12). In 18 patients, septicaemia/bacteraemia was also diagnosed. Cefepime, 2 g bd, was administered for a maximum of 16 days (mean 8). Of 98 pathogens isolated, 75 were Gram-negative and 23 were Gram-positive species. Ninety-four of the pathogens were susceptible to cefepime, including multi-resistant isolates such as Pseudomonas aeruginosa and Enterobacter cloacae. The overall clinical cure rate, excluding septicaemia/bacteraemia, was 92% (94/102); the corresponding bacterial eradication rate was 95% (52/55). In patients with septicaemia/bacteraemia, the clinical cure rate was 87% (13/15) despite eradication of 100% (11/11) of the assessable pathogens. Cefepime was well-tolerated, although 14 (9%) patients experienced local intolerance at the infusion site. Other drug-related adverse events were reported in six (4%) patients and included diarrhoea, pruritus, rash and urticaria. Cefepime is safe and effective as empirical treatment for serious infections commonly found in the hospital setting. Clinical cure and bacterial eradication can be achieved with a convenient bd dosing schedule.

Adolescent↗

[Effect of ketoprofen on the pharmacokinetics of two fluoroquinolones in males].

The influence of a non steroidal antiinflammatory drug (NSAID), ketoprofen, on the pharmacokinetics of two fluoroquinolone derivatives, pefloxacin (P) and ofloxacin (O), was studied in ten healthy adult male volunteers. The subjects were given orally for three days the quinolone alone (P: 400 mg q 12 h and O: 200 mg q 12 h), with at least a one week interval between the two quinolone studies. On day 4, the first kinetic study of pefloxacin and ofloxacin was performed. During the three following days, the quinolone was administered in association with ketoprofen (100 mg daily). Another pharmacokinetic study of P and O was performed on day 8 and the kinetic data obtained were compared to those found on day 4. During the two kinetic studies (D4 and D8), blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 et 24 h and urine was collected during the time-periods 0-4 h, 4-8 h, 8-12 h and 12 24 h. Plasma and urine concentrations of the active P and O drug were measured by microbiological assay. Ketoprofen administered for three days with the fluoroquinolone derivative induced no statistical modification in the kinetic parameters of both P and O: peak plasma levels, time to peak level, areas under the curve, apparent volume of distribution, total and renal clearances.

Adult↗

[Evaluation of the carriage of Staphylococcus aureus in patients and the personnel of a hemodialysis center for the prevention of infections].

With the aim of improving the prevention of Staphylococcus aureus infections in hemodialysis patients, an evaluation of S. aureus nasal carriage was carried out at the hemodialysis center of CHU-Rouen between the 1st of January, 1991 and the 30th of June, 1991. The S. aureus strains were classified according to their antibiotypes, serotypes and lysotypes. The carriage rate appears to be similar to that of the general population but inferior to what has been previously reported in hemodialysis centers. We report our findings on nasal carriage strains. The risk of infection is low. The standards of hygiene, adopted by hospital personnel, seem to be effective although cross colonization may have possibly occurred. Taking into account the different epidemiologic circumstances encountered in each hemodialysis center it is, therefore, necessary to determine the rate of carriage and identify the personnel at risk (persistent carriers, patients with a previous history of S. aureus septicemia, meti-R strains) in order to implement prophylaxis accordingly to epidemic characteristics of each center.

Hemodialysis Units, Hospital↗

Adult onset Still's disease and pregnancy.

The interactions between pregnancy and adult onset Still's disease (AOSD) are unclear. Between 1983 and 1990, 5 pregnancies occurred in 4 women with AOSD. AOSD occurred at the 5th and 6th month of the 1st pregnancy in 2 patients; a 2nd pregnancy occurring in one of them was not associated with a flare. In the other 2 patients pregnancy occurred 36 and 44 months after the AOSD; during gestation only transient arthralgia were observed in both cases. Pregnancy seems to have no effect on AOSD, and conversely, in our experience, AOSD has no influence on pregnancy, fetal growth or infant health.

Adult↗

[Evaluation and utilization patterns of antibiotic therapy. A study in 4 hospital departments].

The use of antibiotics in 480 cases in 4 hospital wards during 1988 was assessed by examination of medical records. Only the first antibiotic therapy administered during the first stay in the ward for each patient was included. Antibiotics were administered to 163 in-patients (37% of hospitalizations) for infections in 113 (26%) cases. Amoxycillin and macrolides were the drugs most frequently used. Sixty-eight percent of the treatments were administered in the absence of microbiological data. Single drug therapy was used in 60% of treatments. Fifty in-patients (11% overall; 41% of patients undergoing surgery) received antibiotics for prophylaxis. The exact indication(s) for the choice of therapy was not given in the medical records of 39% of cases. Treatment started within 48 hours of infection in 15% of the cases. Overall, 93% of the treatments given were indicated, but 53% were inappropriate because they were too expensive, unlikely to be effective or were multiple drug therapy without justification. There are a variety of factors that cause such inappropriate administration of antibiotics.

Adult↗

Penetration of lomefloxacin into human prostatic tissue.

Serum and prostatic tissue concentrations of lomefloxacin were measured in 12 elderly patients who underwent transurethral resection of the prostate after receiving a single oral dose of 400 mg. The peak serum concentration of lomefloxacin was 2.5-10.0 micrograms/mL (mean, 5.2 +/- 1.9 micrograms/mL). During surgery, serum and tissue concentrations averaged 4.6 +/- 2.2 micrograms/mL and 6.5 +/- 2.7 micrograms/g, respectively. The ratio of tissue to serum concentrations was 1.53 +/- 0.54. The levels of lomefloxacin in serum and prostatic tissue were found to be higher than the minimum inhibitory concentration (MIC) values for most urinary tract pathogens.

Administration, Oral↗

Pharmacokinetics of meropenem in subjects with renal insufficiency.

The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 micrograms.ml-1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.

Adult↗

Short-term treatment of urinary tract infections: the French concept.

The indications for short-term treatment to cure urinary tract infections (UTIs) have been recently clarified in France by a "Consensus Conference". Short-term treatment essentially concerns young, non-pregnant women with symptomatic uncomplicated lower UTI of less than three days duration, with no other underlying severe illness or previous uro-nephrological history, and who accept the idea of clinical and possibly bacteriological control after treatment. Only antibiotics with prolonged urinary excretion are recommended, i.e. co-trimoxazole, fluoroquinolones or fosfomycin-trometamol. In pregnancy, in children, or in the elderly, indications for short-term treatment still remain controversial. As compared with conventional therapeutic strategies using urine cultures, the use of test strips for nitrite and leukocyte esterase for deciding on treatment and assessing its efficacy should allow considerable financial savings.

Anti-Infective Agents, Urinary↗

Pharmacokinetics of meropenem (ICI 194,660) and its metabolite (ICI 213,689) in healthy subjects and in patients with renal impairment.

The pharmacokinetics of meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-life of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are linearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, significantly increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 +/- 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.

Adult↗

Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers.

The influence of ketoprofen (K), a non steroidal antiinflammatory drug (NSAID) on the pharmacokinetics of two fluoroquinolone derivatives: ofloxacin (O) and pefloxacin (P) was studied in ten healthy adult male volunteers. All subjects orally received every 12 h the fluoroquinolone derivative (either O or P) for three days and the combination of the quinolone and ketoprofen (once a day) during the three following days. Two pharmacokinetic studies were performed for each quinolone, on days four and eight of the treatment. Blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after dosing. Urine was collected during 4 time-periods: 0-4 h, 4-8 h, 8-12 h and 12-24 h. Plasma and urine concentrations of the active drug of O and P were measured by microbiological assay. Ketoprofen did not significantly modify the pharmacokinetic parameters of the two fluoroquinolones studied in terms of peak plasma levels, time to peak, area under the curve, elimination half-life, volume of distribution and total and renal clearances.

Administration, Oral↗