Biomedical subjects
Publications and source records attributed to B Georges.
Transrectal prostate biopsy represents the most accurate technique to diagnose prostate cancer. More vigilance is necessary when fluoroquinolones are given as prophylactic agents because of the increase in Escherichia coli resistant strains. We report a case of multiresistant E. coli meningitis after transrectal biopsy resulting in the death of the patient.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In burn patients it has been shown ([2]), that there is a correlation between the creatinine clearance (CL(CR)) and the clearance of inulin. * The CL(CR) has never been studied in burn patients who have normal serum creatinine. * The Robert, Kirkpatrick and sMDRD formulae have never been evaluated in burn patients. WHAT THIS STUDY ADDS: * Despite burn patients having normal serum creatinine concentrations, the study showed that there are large variations in CL(CR) which cannot be detected by single serum creatinine measurements, and which have important implications for drug therapy. * It showed that the formulae currently used to calculate creatinine clearance on the basis of serum creatinine are inadequate for use in burn patients, and they should be abandoned in favour of direct measurement from a 24 h urine collection. AIMS: The aim of this study was to evaluate whether the renal function of burn patients could be correctly assessed using a single serum creatinine measurement, within normal limits, and three prediction equations of glomerular filtration taking into account, serum creatinine, age, weight and sex. METHODS: This was a prospective study comprising 36 adult burn patients with a serum creatinine <120 micromol l(-1), within the second or third week following the burn injury. Renal function was assessed using serum creatinine, 24 h urinary CL(CR), and the Cockcroft-Gault, Robert, Kirkpatrick and simplified MDRD equations. RESULTS: Despite normal serum creatinine concentrations in all patients, a significant number had a decreased CL(CR). The urinary CL(CR) was <80 ml(-1) min(-1) 1.73 m(-2) in nine patients (25%), and <60 ml(-1) min(-1) 1.73 m(-2) in five patients (14%). Between the groups having a CL(CR) lower or greater than 80 ml(-1) min(-1) 1.73 m(-2) there were no differences in gender, burn indices, percentage of mechanically ventilated patients or length of hospital stay, but a difference in age. The highest CL(CR) (>140 ml(-1) min(-1) 1.73 m(-2)) was found in 13 patients younger than 40 years. Regression analysis, residual and Bland-Altman plots revealed that neither the Cockcroft-Gault, Robert, Kirkpatrick nor sMDRD equations were specific enough for the assessment of renal function. CONCLUSIONS: In burn patients with normal serum creatinine during the hypermetabolic phase, serum creatinine and creatine based predictive equations are imprecise in assessing renal function.
Altered pharmacokinetics in burn patients may affect antibiotic plasma concentrations. Typical once-daily dosing (ODD) of 15 mg/kg amikacin (AMK) in burn patients does not always produce peak concentrations (C(max)) reaching the therapeutic objective of six to eight times the minimal inhibitory concentration (MIC). We recorded plasma concentrations following administration of 20 mg/kg AMK in burn patients and studied factors affecting pharmacokinetics. Mean C(max) was 48.3+/-10.8 mg/L and the C(max)/MIC ratio was 6+/-1.35. Statistical analysis demonstrated a relationship between C(max) and the area of the burn and Unit Burn Standard, and between AMK clearance and creatinine clearance (Cl(CR)). We conclude that ODD regimens of AMK in patients with burns >15% body surface area and/or with Cl(CR) >120 mL/min could require doses >20 mg/kg to reach adequate C(max). In all cases, patient therapeutic drug monitoring is essential to ensure the safe usage of these dosing recommendations.
The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 x 2 g in combination with amikacin. Patient characteristics and the minimal inhibitory concentration (MIC) of the isolated bacteria were comparable. Clinical outcomes were assessed along with pharmacodynamic indices and compared in both groups (chi2 and Mann-Whitney U-tests). Mechanical ventilation, clinical outcome and bacteriological eradication did not significantly differ between the two groups. Also, the area under the plasma cefepime concentration curve at steady state (AUCss: 612 +/- 369 vs. 623 +/- 319 mg x 1(-1) x h), AUCss > MIC (595 +/- 364 vs. 606 +/- 316 mg x 1(-1) x h) and the area under the inhibitory concentration curve (AUICss: 4258 +/- 5819 vs. 5194 +/- 7465 mg x 1(-1) x h) were similar. If the time above MIC (t > MIC) was not significantly higher in Group 1 (100 +/- 0%) than in Group 2 (90 +/- 11%), t > five-fold MIC in Group 1 (100 +/- 0%) was significantly higher (p < 0.01) than in Group 2 (82 +/- 25%). The mean time over the French breakpoint (4 mg/l) was 100 +/- 0% and 72 +/- 27% in Group 1 and 2 (p < 0.001), respectively. In contrast to intermittent cefepime administration, continuous infusion of cefepime consistently maintained a serum concentration > 5 x the MIC of typical Gram-negative nosocomial pathogens. This results in greater bactericidal activity against organisms with a higher (2 mg/l) cefepime breakpoint even if the clinical outcome is not significantly modified.
The American Women's Health Initiative Study was stopped 2 years ago. Last year the British One Million Women Study was published. Both studies led to a critical discussion of hormone replacement therapy. Since then media, scientists and physicians have been discussing pros and cons. There is no agreement so far, but the German Senology Society and the German Society for Gynecology and Obstetrics declared their positions on this issue. The discussion focuses on the association between hormone replacement therapy and breast cancer. In vitro studies showed that estrogens stimulate the epithelium of the breast. Prolonged exposure to estrogens (e.g. early menarche and late onset of menopause) can promote breast cancer. Indications for hormone therapy are climacteric symptoms, prophylaxis of osteoporosis, improvement of cognitive functions as well as prophylaxis of dementia. These indications are discussed in the light of recent studies.
The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability.
UNLABELLED: Vancomycin is always the drug of choice for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in spite of his bactericidal kinetic. BACKGROUND: The aim of this study was to evaluate in vivo the improvement of bactericidal kinetic of vancomycin associated with cefpirome against MRSA infection in critically ill patients. METHODS: The prospective cross-over study was carried out in 20 patients with severe pneumonia or bacteremia. There were randomized to receive vancomycin 2 g per day (Group 1, n = 10) or vancomycin with cefpirome 2 g x 2 (Group 2, n = 10). Clinical recovery, bacteriologic parameters (bactericidal kinetic and bactericidal power in vivo at the peak and the valley), duration of ventilation and stay in ICU were comparatively explored in both groups. RESULTS: Clinical outcome did not significantly differ between Group 1 and 2. Bactericidal kinetics were better in the Group 2 (40% vs 60% after 6 hours to the dilution for 1/8e) but the difference was not significant. However, bactericidal power in sera was also better in the Group 2 with more bactericidal dilution at 1/16e (68% vs 88.8%: NS) and overall at 1/32e (10.5% vs 50%: p < 0.05) and CRP, an inflammatory marker, was significantly lower in the Group 2 than in the Group 1 (119.5 +/- 24 mg/l vs 198.6 +/- 78 mg/l: p < 0.05) on the third day.
We describe the highly conserved sequence 56-68 of the HIV Nef protein as the first promiscuous HLA-DQ HIV-derived peptide. The Nef peptide exhibits an albeit rare capacity to bind 6 different HLA-DQ molecules whereas no binding is observed with the 10 HLA-DR molecules tested. In agreement with these data, after immunization with the Nef peptide, HLA-DQ transgenic Abeta degrees mice display a vigorous cellular and humoral response while the specific immune response of HLA-DR expressing mice is minimal. The promiscuous potentiality of the Nef 56-68 peptide in humans has been confirmed by ex vivo immunization experiments with CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68 specific CD4+ T cells rapidly acquire a memory cell phenotype and are characterized by the preferential usage of the TCR Vbeta 6.1 gene segment and predominant production of IFN-gamma. Taken together, these data indicate that the Nef 56-68 peptide constitutes an attractive component of vaccines aiming at inducing or enhancing HIV-specific T cell immunity.
The aim of this study was to assess the influence of the physiological changes of gastric emptying on the simplified 14C-urea breath test. Thirty patients performed the test in fasting conditions. Patients were orally administered 0.074 mega Bq of 14C-urea, mixed with 0.0185 mega Bq of 99mTc-S colloids in 25 ml water. A breath sample was taken before and 10 min after intake of the tracers and followed by a 2 min planar anterior scintigraphic image of the abdomen to measure gastric activity. Gastric emptying was estimated by dividing the residual gastric activity at 10 min by the total activity in the abdomen. The procedure was performed twice for each patient after a 24 h interval. The repeatability of both the gastric emptying test and the urea breath test was assessed by the method described by Bland and Altman. The coefficient of repeatability of the urea breath test was 1.18 for a confidence interval of 95%. The coefficient of repeatability of gastric emptying was 27.4. There was no significant correlation (r= 0.08) between the plot of the individual modifications of urea breath test and residual gastric activity in two successive tests. It is concluded that the physiological changes of gastric emptying do not influence the results obtained by the simplified, single-sample 14C-urea breath test.
OBJECTIVE: Prognosis of rhabdomyosarcoma of the infratemporal fossa is generally poor. We report our experience. MATERIAL AND METHODS: Twenty-three children with rhabdomyosarcoma of the infratemporal fossa were treated at the Gustave Roussy and Curie Institutes between 1984 and 1999. Seventeen children received radiotherapy (group 1), four children were treated surgically with or without postoperative radiotherapy (group 2), and two children received no further treatment after chemotherapy (group 3). RESULTS: In group 1, there were 10 local recurrences and one metastatic failure; all 11 children died from their disease. Nodal recurrence was salvaged successfully in one other with chemotherapy and surgery. In group 2, three children were disease free at 3 years and one died of local recurrence. In group 3, one child experienced a local recurrence successfully salvaged with radiotherapy. This child was disease free at 3 years. The other child developed local recurrence and died. DISCUSSION: Overall survival rate in our patients was 50%. Local control remained the main prognostic factor for survival. Surgery has already been shown to improve local control in other localizations of rhabdomyosarcoma. If residual tumor tissue remains after neo-adjuvant chemotherapy, surgery should be considered in a multidisciplinary discussion of therapeutic options. Indications for postoperative radiotherapy depend on age and histological features of the surgical specimen.
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This study was performed to assess the impact of precise timing and the repeatability of the simplified 10-min 14C-urea breath test. Thirty-three patients underwent a 14C-urea breath test at 10 and 12 min (test I) and after 24 h (test II). The paired t-test was applied to assess differences between two successive measurements at 10 and 12 min, and the method of Bland and Altman was used to evaluate the repeatability of the test. Only test I (P = 0.004) showed a significant difference between two successive measurements at 10 and 12 min. The coefficients of repeatability at 10 and 12 min were 1.54 and 1.48, respectively. No bias was found. From this study, we can conclude that breath collections, delayed by 2 min (20% error), have no impact on the clinical interpretation of the results. The repeatability of the simplified 10-min 14C-urea breath test is sufficient for clinical use.
[18F]-2-(2-Nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide ([18F]-EF3) has been prepared, in 65% chemical yield and 5% radiochemical yield, by coupling 2,3,5,6-tetrafluorophenyl 2-(2-nitroimidazol-1-yl) acetate 1 with [18F]-3,3,3-trifluoropropylamine 7. This original radiolabelled key-synthon was obtained in 40% overall chemical yield by oxidative [18F]-fluorodesulfurization of ethyl N-phthalimido-3-aminopropane dithioate 4, followed by deprotection with hydrazine of the resulting [18F]-N-phthalimido-3,3,3-trifluoropropylamine 5. All the process was performed within 90 min, from the [18F]-HF production in the cyclotron to the purification of the final target.
The Na+-Ca2+ exchanger (NCX) is well known to regulate intracellular Ca2+ concentration in many excitable cells. To date, three members of the NCX exchanger gene family have been identified: NCX1, NCX2 and NCX3. In zona fasciculata of the bovine adrenal gland, a Na+-Ca2+ exchanger has been recently found to display biochemical similarities with the NCX1 exchanger of renal basolateral cells. Although a Na+-Ca2+ exchanger has already been characterized in zona medulla of adrenal gland, such an exchanger has never been studied in the adrenal cortex. Thus, we have used a reverse transcriptase-polymerase chain reaction (RT-PCR) assay with specific NCX primers on fasciculata cell cultures. The sequencing of the amplified fragment revealed, for the first time, the presence of a NACA3 isoform of the NCX1 exchanger in the adrenal cortex, similar to the one found in adrenal chromaffin cells and in renal cortex. This isoform is 92 and 94% identical in the portion compared with kidney Na+-Ca2+ exchanger NACA3 of rat and pig, respectively.
BACKGROUND: The recent identification of genes responsible for syndromes of periodic fever with amyloidosis has opened the way to a molecular diagnosis of hereditary AA amyloidosis. METHODS: A Belgian woman presented for genetic counseling. Three first-degree relatives had a diagnosis of renal amyloidosis with a history of recurrent fever and inflammatory episodes. Medical records and pathological specimens were obtained from all physicians who had been in charge of her three relatives. Immunohistochemical staining was performed on paraffin-embedded material. A mutation search was performed in the MEFV (Mediterranean fever) and tumor necrosis factor receptor 1 (TNFR1 or TNFRSF1A) genes causing familial Mediterranean fever (FMF) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), respectively. RESULTS: The family history was consistent with autosomal-dominant transmission of periodic fever with arthralgias, abdominal pain, and eventual AA amyloidosis involving the kidneys, digestive tract, and thyroid. Recurrent amyloidosis in kidney graft was demonstrated in one patient and was suspected in the other. A novel heterozygous mutation (C55S) in TNFRSF1A was identified in the affected patient available for genetic testing but not in the asymptomatic woman requiring counseling. No mutation was detected in MEFV. CONCLUSIONS: We report a novel mutation (C55S) in TNFRSF1A, resulting in autosomal-dominant periodic fever and AA amyloidosis. This condition, known as TRAPS, should be added to the differential diagnosis of hereditary renal amyloidosis, with obvious implications for management and genetic counseling.
OBJECTIVE: To assess management of acute respiratory distress syndrome (ARDS) in Midi-Pyrénées, France. METHODS: A prospective study using a questionnaire divided into 10 parts, definition, etiology, radiography, computed tomography, management, was conducted in 26 intensive care units in the Midi-Pyrénées. Management of ARDS in Midi-Pyrénées was comparted with management elsewhere as described in the literature. RESULTS: Overall participation rate was 73%. Disparities were found concerning the definition. Four etiologies accounted for 75% of all ARDS cases. Chest x-rays were used for positive diagnosis and thoracic scans for complications. Ventilatory and hemodynamic optimizations were the first line therapy used. Twenty-nine percent and 41% of the intensive care unites used nitric oxide and prone position respectively. CONCLUSIONS: There are differences between ARDS management in Midi-Pyrénées and that described in the current literature. Epidemiologic studies such as this one are necessary before publishing guidelines for the management of ARDS.
SDS-PAGE analyses of stable HLA-DR1 complexes indicate that the binding of T cell epitopes can lead to multiple conformational variants. Whereas short T epitopes (<14-mer) induce complexes with apparent MW ranging from 47 to 57 kDa, longer peptides form generally high mobility complexes (44-45 kDa). The generation of HLA-DR1 conformational variants appears dependent on core peptide residues fitting inside the groove but can additionally be attributed to the presence of N- and C-terminal flanking residues (PFRs) acting as a complementary mechanism. These PFRs can jointly affect major histocompatibility complex class II conformation and stability, supporting the existence of alternative contacts at a distance from the classical binding site.
Carnitine is involved in the transfer of fatty acids across mitochondrial membranes. Carnitine is found in dairy and meat products, but is also biosynthesized from lysine and methionine via a process that, in rat, takes place essentially in the liver. After intestinal absorption or hepatic biosynthesis, carnitine is transferred to organs whose metabolism is dependent on fatty acid oxidation, such as heart and skeletal muscle. In skeletal muscle, carnitine concentration was found to be 50 times higher than in the plasma, implicating an active transport system for carnitine. In this study, we characterized this transport in isolated rat myotubes, established mouse C2C12 myoblastic cells, and rat myotube plasma membranes and found that it was Na(+)-dependent and partly inhibited by a Na(+)/K(+) ATPase inhibitor. L-carnitine analogues such as D-carnitine and gamma-butyrobetaine interfere with this system as does acyl carnitine. Among these inhibitors, the most potent was mildronate (3-(2,2,2-trimethylhydrazinium)propionate), known as a gamma-butyrobetaine hydroxylase inhibitor. It also induced a marked decrease in carnitine transport into muscle cells. Removal of carnitine or treatment with mildronate induced growth inhibition of cultured C2C12 myoblastic cells. These data suggest that myoblast growth and/or differentiation is dependent upon the presence of carnitine.