Biomedical subjects
N Bernard
Publications and source records attributed to N Bernard.
Cyclooxygenases 1 and 2 and thromboxane synthase in kidneys of Lyon hypertensive rats.
Compared with their two normotensive (LN and LL) controls, genetically hypertensive rats of the Lyon strain (LH) exhibit increased renal vascular resistance and a blunted pressure natriuresis function as well as an increased urinary excretion of vasoconstrictor prostanoids. The aim of this study was to assess in the kidneys of these animals the synthesis of vasoconstrictor or sodium-retaining prostanoids. The relative abundance of the mRNAs of cyclooxygenases (COX) 1 and 2 and of thromboxane A2 synthase (TXS), was measured by reverse-transcription polymerase chain reaction (RT-PCR) in renal cortex and medulla dissected in groups of male LH, LN, and LL rats either in baseline conditions or after 1 week of salt loading (1.5% NaCl in the drinking water). In basal conditions, at 3 and 11 weeks of age COX1 was expressed in the kidneys of all rats more markedly in medulla than in cortex. COX2 was poorly expressed in the whole kidney. TXS expression was usually too low to be quantified. No difference could be observed among LH, LN, and LL rats. After salt loading, the expression of COX1 was enhanced in the medulla and that of COX2 reduced in the cortex. LH rats differed from controls by a significantly more marked increase in medullary COX1 expression. The present work excludes any primary generalized increase in the renal expression of the genes that control the synthesis of vasoconstrictor prostanoids in LH rats, but suggests that medullary COX1 is upregulated by salt in these animals.
A possible association between Chlamydiae psittacci infection and temporal arteritis.
Some arguments are in favor of the role of Chlamydia in the pathogenesis of atherosclerosis and some vasculitis. Illustrating this possible relation, we report the case of a patient developing consecutively a Chlamydia psittacci infection and a temporal arteritis. A 73-year-old woman, with no significant medical history, was hospitalized for constitutional symptoms. Three weeks before, she had described fever and sore throat of two days' duration. Since that time, she had remained exhausted and developed a mild intermittent claudication of the jaws. Clinical examination was poor. A biological inflammatory syndrome was noticed. Chest X-ray revealed bilateral interstitial opacities. The titer of anti-C. psittaci antibodies was significant (positive 1g G at 1/2048). Soon after initiation of doxycycline, a temporal arteritis biopsy was performed, due to the persistence of clinical symptoms and high inflammatory syndrome, conclusive for the diagnosis of temporal arteritis. Corticotherapy was added to antibiotic therapy, resulting in the decrease of inflammatory syndrome and an improvement in the general status of the patient. X-ray opacities decreased in three weeks. Serological control after three months showed a decrease of the titer of anti-C. psittacci antibodies to 1/256, confirming the initial diagnosis of Chlamydia pneumopathy. Our observation could provide one more argument for the role of bacteria-like Chlamydia in the pathogenesis of vascular diseases. Prospective seroepidemiological and molecular biology studies could allow us to clarify the association between Chlamydia infections and inflammatory vasculitis-like temporal arteritis.
Prognostic factors of survival of HIV-infected patients with cytomegalovirus disease: Aquitaine Cohort, 1986-1997. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA).
OBJECTIVE: To analyse survival of HIV-infected patients who developed cytomegalovirus (CMV) disease and to identify prognostic factors of their survival. METHODS: Cases of CMV disease diagnosed in the Aquitaine Cohort of HIV-infected patients (n = 4297) during the 1986-1996 period, were reviewed using standardised definitions. Follow-up was extended to December 1997. Cox model was used to determine factors associated with survival after the initial manifestations of CMV disease, considering protease inhibitor (PI) prescription and anti-CMV treatment as time dependent covariates. RESULTS: 253 patients presented a CMV disease of which 221 (87.3%) died (median survival: 7 months). A better prognosis for survival was associated with: PI prescription [relative hazard (RH): 0.26; 95% confidence interval (CI): 0.11-0.59], anti-CMV treatment (RH: 0.37; CI: 0.25-0.54), CD4+ lymphocyte cell count > 50/mm3 (RH: 0.66; CI: 0.47-0.94) and absence of neoplasia (RH: 0.70; CI: 0.52-0.94) whereas the disseminated CMV disease worsened prognosis (RH: 1.83; CI: 1.20-2.80). CONCLUSION: Antiretroviral treatment including PI, improved short-term prognosis of CMV disease regardless of its clinical manifestations.
Extrarenal renin-angiotensin systems are unable to maintain blood pressure in sheep.
1. The present study was designed to assess the participation of extrarenal tissue renin-angiotensin systems (RAS) in pressure homeostasis in sheep. 2. The effect of the administration of an angiotensin II type 1 receptor antagonist (losartan; 30 mg/kg, i.v.) on mean arterial blood pressure (MABP) was investigated in eight intact (controls) and 10 binephrectomized sheep haemodialysed every 2 days for 10 days. 3. In control sheep, losartan decreased blood pressure and this decrease was significantly more marked after furosemide-induced water and salt depletion. After nephrectomy and throughout the anephric period, losartan lost its hypotensive effect, while the plasma renin concentration fell to undetectable levels. Baseline MABP became significantly lower than at the beginning of the anephric period after 7 days. The inability to maintain blood pressure after several volume-depleting haemodialysis sessions proved that an efficient system for blood pressure regulation was lacking after nephrectomy. 4. Renin gene expression measured by reverse transcription-polymerase chain reaction was found in liver, adrenal and arterial wall tissue. Neither nephrectomy nor sodium depletion enhanced this tissue renin gene expression. 5. In conclusion, the present work allows us to exclude an active role of extrarenal RAS in the maintenance of blood pressure. In addition, haemodialysis technology in nephrectomized sheep can be used as a good model for the study of extrarenal control of blood pressure.
[Nitrogen dioxide and ozone exposures in a population sample from Ile-de-France].
BACKGROUND: Individual exposure to NO(2)and O(3) has been estimated in an urban population sample in southern France and the determinants identified. The present study was conducted to evaluated individual exposure to NO(2) and O(3) and to identify the environmental determinants of exposure in a larger population living in different environmental conditions. METHODS: Two hundred ninety-four volunteers were recruited from the SUVIMAX sample in Ile-de-France. The study covered 2 periods of 5 consecutive days, one in winter and the other in the fall of 1998. Passive monitors were used to estimate individual exposure and indoor concentration at the participant's dwelling. Background atmosphere concentrations were obtained for the AIRPARIF surveillance network. Single and multiple ANOVA were used for statistical analysis. RESULTS: Individual exposures were low, especially for O(3) in the considered periods of time. Mean NO(2) and O(3)concentrations were 41 microg/m(3)/h and 16 microg/m(3)/h, respectively. The NO(2) individual exposure increased with the time spent in traffic and indoor concentration. The correlation coefficient between indoor and individual levels was r=0.73, and indoor concentration explained 50% of the variance in individual exposure. The site of the dwelling with regard to high traffic street, and most strongly, the presence of a gas stove influenced indoor concentration. However, mechanical air extraction decreased the mean indoor NO(2) level of the dwellings. CONCLUSION: This study allowed identification of the environmental determinants of NO(2) exposure in an urban sample. These data, together with those obtained previously, well be used to establish an exposure matrix for NO(2).
Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe dEpidémiologie Clinique de Sida en Aquitaine (GECSA).
OBJECTIVE: To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 to 100, level 2: 101 to 200), hepatitis B and C co-infection. RESULTS: Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence was 164 days for HAART-treated patients and 252 days for those treated with two NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively). CONCLUSION: Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.
20-Hydroxyeicosatetraenoic acid and renal function in Lyon hypertensive rats.
To evaluate the contribution of cytochrome P450 (CYP450) metabolites of arachidonic acid in the increased renal vascular resistance and blunted pressure-natriuresis response exhibited by Lyon hypertensive (LH) rats, the effects of an intrarenal infusion of 17-octadecynoic acid (3 microM), an inhibitor of the formation of epoxyeicosatrienoic and 20-hydroxyeicosatetraenoic acids, were compared in 8-week-old LH and low blood pressure (LL) control rats. 17-Octadecynoic acid failed to affect renal function in LL rats. In contrast, it reduced renal vascular resistance and shifted the pressure-natriuresis relationship to lower pressures in LH rats. Blockade of thromboxane-endoperoxide (TP) receptors with GR 32191B prevented the renal vasodilator response to 17-octadecynoic acid but not its natriuretic action. Miconazole (1 microM), an inhibitor of epoxygenase activity, had no effect on renal function in LH rats. These results indicate that CYP450 metabolites of arachidonic acid, likely 20-hydroxyeicosatetraenoic acid, contribute to the resetting of the pressure-natriuresis relation in LH rats and that the renal vasoconstrictor effects of 20-hydroxyeicosatetraenoic acid in LH rats may be related to activation of TP receptors.
Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.
BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.
Prevalence and underestimation of pain in HIV-infected patients by physicians: a cross-sectional study in a day care hospital.
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Cytochrome P-450 arachidonate metabolite inhibition improves renal function in Lyon hypertensive rats.
The present study evaluated the effects of miconazole, a selective inhibitor of epoxygenase activity, on renal hemodynamics and the pressure-natriuresis response of saline-drinking, uninephrectomized Lyon hypertensive (LH) and Lyon low blood pressure (LL) rats. Infusion of miconazole (final concentration, 1 micromol/L) into the renal artery had no effect on the renal function of LL rats over a range of renal perfusion pressures (RPP) from 100 to 140 mm Hg. In contrast, miconazole lowered renal vascular resistance (RVR, 17.9 +/- 1.1 v 26.3 +/- 1.5 mm Hg/mL/min/g, P < .01) and increased urinary sodium excretion (6.4 +/- 1.2 v 4.2 +/- 0.8 micromol/min/g, P < .05) in LH rats at a RPP of 140 mm Hg. To determine whether the effects of epoxyeicosatrienoic acids were dependent on activation of the thromboxane A2-prostaglandin H2 (TP) receptor, we studied the effects of a TP receptor antagonist, GR 32191B (0.1 mg/kg/min), on the renal response to an infusion of miconazole into the renal artery in LH rats. GR 32191B decreased basal RVR and prevented the dilation induced by miconazole. It did not, however, alter its natriuretic effect. The renal metabolism of arachidonic acid was also compared in LH and LL rats. The production of epoxygenase metabolites was 25% lower in microsomes prepared from the renal cortex of LH versus LL rats. Miconazole (1 micromol/L) reduced epoxygenase activity similarly, by approximately 60%, in both strains. These results suggest that endogenously formed P450 metabolites of arachidonic acid may serve as a substrate for the formation of vasoconstrictor endoperoxides that interact with TP receptors in LH rats and contribute to the enhanced renal vascular tone but not the blunted pressure-natriuresis response.
Effects of L-type calcium channel activation on renal vascular resistances in the Lyon hypertensive rat.
This study aimed to evaluate the role of L-type calcium channels in the increased renal vascular resistance (RVR) of the Lyon hypertensive (LH) rat before and after normalization of its blood pressure (BP) by angiotensin-converting enzyme inhibition with perindopril. Concentration-response curves to Bay K 8644 (from 0.1 nM to 1 microM), a selective agonist of L-type calcium channels, were obtained in single-pass perfused kidneys isolated from groups of eight untreated or perindopril-treated (3 mg/kg/day, p.o., from age 3 to 7 weeks) LH and low-BP (LL) control rats. In untreated rats, the negative logarithm of the molar concentration of Bay K 8644 required to produce a half-maximal effect (pD2) values for Bay K 8644 did not differ between the two strains, whereas the maximal RVR response was higher in LH than in LL kidneys (28.0+/-4.9 vs. 12.9+/-0.8 mm Hg/ml/min/g, respectively). Perindopril normalized BP and RVR in LH rats and suppressed the interstrain differences in the maximal RVR responses (11.4+/-0.6 vs. 10.5+/-1.2 mm Hg/ml/min/g in LH and LL rats, respectively). These results demonstrate that LH rats exhibit an increased maximal contractile response to Bay K 8644 compared with LL controls, and that this alteration is not a primary defect because it disappears after normalization of BP level.
The novel and nursing history: a consideration of potential sources.
The use of novels in general as a historical source is discussed in this paper. The author shows that, while they must be used with extreme caution, a novel can provide insight for the historian. Literature concerning the role of novels for informing nursing history is reviewed in the paper. The novel Jean Becomes a Nurse by Yvonne Trewin is considered in detail. The novel's aim, stated in its Introduction, of encouraging readers to become nurses, is highlighted. Aspects of the book's content are analyzed including clinical detail, nursing as a vocation and the use of Nightingale motifs. The task-oriented approach to care depicted in the book is also mentioned. The novel is seen to provide insight into the perception and attitudes of nurses towards nursing in the 1950s in the UK. The paper ends by suggesting areas for future research.
Survival of HIV-infected patients with cytomegalovirus retinitis under highly active antiretroviral therapy. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.
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Predictive factors of occurrence of cytomegalovirus disease and impact on survival in the Aquitaine Cohort in France, 1985 to 1994. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.
Our objectives were to determine the factors associated with the occurrence of a first episode of cytomegalovirus (CMV) disease in an HIV-infected population and to estimate the overall impact of CMV disease on survival. The study population consisted of the 3525 patients included in the Aquitaine Cohort between 1985 and December 31, 1993. Eligible patients (n = 1868) must have had at least one CD4+ lymphocyte count of <200 cells/mm3 during follow-up, which represents the baseline period. CMV disease manifestations were investigated using standardized definitions. A Cox proportional hazards regression analysis was used to determine the factors independently associated with the probability of developing a first episode of CMV infection and the probability of death. During follow-up, 111 patients presented with a first episode of CMV disease. Four factors were independently associated with the onset of CMV disease: older age at baseline (risk ratio [RR] = 1.03 by a 1-year increase; 95% confidence interval [CI] = 1.02-1.05), homosexuality (RR = 1.90; CI = 1.18-3.02), the progression to a CD4+ lymphocyte count <50/mm3 (RR = 10.58; CI = 5.58-20.05), and the occurrence of toxoplasmosis (RR = 3.00; CI = 1.97-4.57) or a neurologic disease (RR = 2.59; CI = 1.38-4.86) during follow-up. After other predictors were controlled for, CMV disease was associated with a high risk of death in the cohort (RR = 1.58; CI = 1.24-1.94). The development of prophylactic strategies for CMV disease for selected groups of HIV-infected patients must be a priority to improve their quality of life.
[Continuous analgesia with a femoral catheter: plexus or femoral block?].
OBJECTIVE: To evaluate the spread and quality of sensitive blockade produced by continuous and prolonged use of a femoral catheter inserted for postoperative analgesia. STUDY DESIGN: Prospective non comparative evaluation. PATIENTS: The study included 20 consecutive patients undergoing major knee surgery with postoperative analgesia obtained with a femoral catheter, a technique commonly used in our department. METHODS: Regional analgesia was induced after surgery with a bolus injection of 30 mL of 2% lidocaine with 1:200,000 epinephrine 1 in 200,000, maintained by continuous infusion of 1% lidocaine + morphine 0.03 mg.mL-1 + clonidine 2 micrograms.mL-1 for 48 h. The infusion rate was 0.1 mL.kg-1.h-1. The evaluation was based on: 1) the quality of analgesia at rest, at 30 min, h1, h3, h6, h12, h24 and h48; 2) the sensitive and motor blockade at the same time intervals. RESULTS: A "3 in 1" block was only observed in 50% of patients after the initial bolus via the femoral catheter. During the maintenance of analgesia with a continuous infusion a blockade of the three main nerves of the lumbar plexus occurred in less than 20% of patients after 6 h and was limited to the territory of the femoral nerve in 45 to 50% of patients after 12 to 48 h. In all cases the median values of VAS were below 42 mm. CONCLUSION: In most patients, a local anaesthetic administered continuously via a femoral catheter produces a blockade limited to the femoral nerve. These data do not substantiate the conclusions by those who consider they are producing a continuous "3 in 1" block with this technique. However, it is obviously not essential to produce a sensitive blockade of the three main nerves of the lumbar plexus to obtain an effective analgesia after knee surgery.
Mechanical correlations derived from segmental histologic study of the equine superficial digital flexor tendon, from foal to adult.
OBJECTIVE: To assess histologic variations of the equine superficial digital flexor tendon (SDFT) according to site and to horse age and activity, and to correlate these data with reported segmental mechanical results. SAMPLE POPULATION: Superficial digital flexor tendons isolated from 42 horses 0.5 hour to 23 years old. PROCEDURE: 7 segments of each SDFT were delimited and submitted for conventional histologic examination. Each segment was examined and graded for fiber undulation, cellularity, number and size of interfascicular connective spaces (ICS), presence or absence of focal and diffuse chondroid metaplasia, and differentiation of the dorsal (DB) and palmar (PB) borders of the tendon. RESULTS: Fiber undulation and cellularity significantly decreased with age. The proximal and middle metacarpal segment fibers were significantly less undulated and their ICS were smaller than those of the other segments, especially in old horses. Focal chondroid metaplasia developed from 5 years onward, mainly in the sesamoidean segments. Diffuse chondroid metaplasia was characteristic of the digital region in horses > 6 years old. The DB of the metacarpodigital region tended to differentiate into fibrocartilage in association with age. The PB was generally differentiated as nonfascicular dense connective tissue. Activity induced a decrease in the number and size of the ICS. CONCLUSIONS: The lesser undulation of the proximal and middle metacarpal segments fibers can be correlated to their mechanical behavior (stress-strain curve) and relative weakness within the SDFT. Focal chondroid metaplasia and fibrocartilage on the DB are normal features, related to the compression stresses undergone by the sesamoidean region of the tendon.
D-2-hydroxy-4-methylvalerate dehydrogenase from Lactobacillus delbrueckii subsp. bulgaricus. I. Kinetic mechanism and pH dependence of kinetic parameters, coenzyme binding and substrate inhibition.
The steady-state kinetics of D-2-hydroxy-4-methylvalerate dehydrogenase have been studied at pH 8.0 by initial velocity, product inhibition, and dead-end inhibition techniques. The mechanism is rapid-equilibrium ordered in the NAD+ plus D-2-hydroxy-4-methylvalerate direction, and steady-state ordered in the other direction. In both cases coenzyme is the first substrate added and both the E-NADH-D-2-hydroxy-4-methylvalerate and E-NAD+-2-oxo-4-methylvalerate give rise to abortive complexes which cause excess substrate inhibition. Steady-state measurements show that the rate-limiting step in both directions at pH 8.0 is between formation of the enzyme-coenzyme-substrate ternary complex and the release of the first product of the reaction. Transient kinetics combined with primary kinetic deuterium isotope effects show that in the NADH-->NAD+ direction there is a slow, rate-limiting rearrangement of the E-NADH-oxoacid complex while hydride transfer is very fast. The release of NAD+ at pH 8.0 is 200-times faster than Kcat (NADH-->NAD+) whereas the release of NADH is only 5-times faster than Kcat (NAD+-->NADH). The pH dependence of NADH binding depends upon the presence of two ionizable residues with a pKa of about 5.9. The pH dependence of kinetic parameters is explained by a third ionizable residue with pKa values 7.2 (in the E-NADH complex) and < or = 6.4 (in the E-NAD+ complex) which may be the proton donor and acceptor for the chemical reaction. At pH 6.5 the mechanism changes in the NADH-->NAD+ direction to be partly limited by the chemical step with a measured primary kinetic isotope effect of 5.7 and partly by an only slightly faster dissociation of NAD+. In addition the inhibition by excess oxo-4-methylvalerate is more pronounced. The mechanism implies that removing the positive charges created by the two groups which control coenzyme affinity could both enhance the catalytic rate at pH 6.5 and diminish excess substrate inhibition to provide an enzyme better suited to the bulk synthesis of D-2-hydroxyacids.