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C Perret

Publications and source records attributed to C Perret.

At least 19 recordsLinked to original sources

Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine.

The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine (NAC) have been described in experimental and clinical ARDS. NAC could act in part by replenishing the intracellular stores of glutathione (GSH) in activated granulocytes, leading to detoxification of oxygen radicals produced by these cells. To test this hypothesis, 16 patients in the early phase of ARDS were randomized to receive either NAC (n = 8) or placebo (n = 8); granulocyte GSH, granulocyte oxygen radical production, and plasma levels of granulocyte elastase were measured in blood samples drawn sequentially within 8 h after the onset of ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) after the first sample; treatment with NAC or placebo was started immediately after day 0 and stopped just after day 3. Granulocyte GSH was significantly higher on days 1 and 3 when NAC was received by the patient. Unstimulated oxygen radical production, as measured ex vivo by luminol- and lucigenin-amplified chemiluminescence (CL), was higher in granulocytes from ARDS patients than from healthy control subjects, but was not influenced by NAC. The plasma levels of granulocyte elastase were five to eight times above the upper normal limit on day 0, decreased steadily until day 5, and were uninfluenced by NAC. In summary, parenteral NAC treatment started within 8 h of diagnosis increases the intracellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells. The mechanisms of the protective effects of this drug previously reported in experimental and clinical ARDS remain to be established.

Acetylcysteine

Contrasting effects of tamoxifen and ICI 182 780 on estrogen-induced calbindin-D 9k gene expression in the uterus and in primary culture of myometrial cells.

Antiestrogens have a large range of tissue- and promoter-specific actions, many of which still remain unclear, particularly in the uterus. Thus, we have analyzed the effects of two antiestrogens, tamoxifen (TAM) and ICI 182 780 (ICI) on the uterine estrogen-responsive gene calbindin-D9k (CaBP9k), in the ovariectomized rat uterus, and in primary cultures of myometrial cells. In the ovariectomized rat uterus, estradiol (E2) or E2 plus TAM induced CaBP9k mRNA to the same levels in 6h. Rats given TAM alone had the same mRNA concentration, but maximal induction was obtained later, 12h after injection. ICI alone did not induce CaBP9k gene expression. Rats given E2 plus ICI had low uterine CaBP9k mRNA levels at 6-12h that became undetectable at 24h. Thus ICI has a full antagonistic effect on E2-induced CaBP9k gene. Estradiol receptor (ER) assays showed that TAM had a partial antagonist effect, while ICI had a full antagonist effect on the ER. We also analyzed the effect of TAM and ICI on CaBP9k gene expression in primary cultures of myometrial cells. The effects were similar to those observed in whole uterus. Thus, TAM has mixed effects, being an agonist for CaBP9k gene induction, and an antagonist for ER. ICI antagonizes the effects of E2 on the CaBP9k gene in myometrial cells and in the intact uterus, but in a way that does not involve a decrease in the cellular content of ER. Instead, it interferes with at least one of the events leading to transcriptional activation.

Animals

[Aseptic meningitis. Demonstration of bacterial DNA in cerebrospinal fluid by gene amplification].

OBJECTIVE: To develop a diagnostic tool to recognize whether a postoperative meningitis occurring in neurosurgical patients is of bacteriological origin or not, in detecting in CSF bacterial DNA with the polymerase chain reaction (PCR) technique. STUDY DESIGN: Laboratory study. PATIENTS: Twenty-seven neurosurgical ICU patients associating, in the postoperative period, the CDC criteria of meningitis and a neutrophil polymorphonuclear count over 100 cells.mm-3 were allocated either into the MB+ group (n = 7) when their CSF culture was positive or in the MB- group (n = 20) when the culture was sterile. The CSF of 43 neurosurgical ICU patients without postoperative clinical and biological features of meningitis acted as controls. Sixteen specimens out of the 43 were inoculated with bacteria at a known concentration. METHODS: The CSF specimens of all patients were tested for the presence of eurcaryote DNA using the PCR technique. Beforehand its sensitivity had been assessed using the inoculated CSF of control group: a positive amplification at 20 cycles was equivalent to 10(5) CFU.mL-1 and a positive amplification at 25 cycles to 10(3) CFU.mL-1. RESULTS: In the 43 sterile control CSF specimens the amplification was negative in all at 20 cycles and in 42 at 25 cycles. In the 16 previously sterile control specimens supplemented with bacteria, as well as in the CSF of all 7 patients of MB+ group the amplification was positive at 20 and 25 cycles. In those of MB- group the amplification was negative in all at 20 cycles, but was positive in 19 out of 20 at 25 cycles. Southern blot with specific procaryote probes was positive with amplification products from CSF of MB+ and MB- groups and negative with control CSFs and human DNA. DISCUSSION: The presence of bacteria in CSF of patients sustaining a meningitis can be accurately detected through their DNA. Postoperative aseptic meningitides may have a bacterial origin. PCR can be used as a routine technique to provide a diagnosis of bacterial meningitis in less than 6 hours. Additionally specific oligonucleotides allow to identify the bacteria in less than 12 hours.

Adolescent

Accuracy of reports of familial breast cancer in a case-control series.

We examined pathology records to determine the accuracy of reports of breast cancer among 125 first-degree relatives by 414 breast cancer cases and 429 population-based controls. Cases who reported only one affected relative tended to overreport the occurrence of breast cancer to a slightly larger extent (4%) than controls (3%). One-third of reports by cases with at least two affected relatives were erroneous, compared with none in the control group. Both cases and controls committed absolute errors of approximately 2 years when reporting the age at diagnosis of relatives. These results indicate that some recall bias is introduced when self-reports of breast cancer occurrence in first-degree relatives are used in case-control studies.

Breast Neoplasms

Minor breakpoint cluster region (m-BCR) positive chronic myeloid leukaemia with an acute lymphoblastic leukaemia onset: a case report.

m-BCR chronic myeloid leukaemia (CML) is a rare entity. We report a patient presenting with Philadelphia (Ph)-positive, m-BCR-positive acute lymphoblastic leukaemia (ALL) who achieved complete remission after induction chemotherapy, but showed a majority of Ph-positive mitoses during this remission. A diagnosis of m-BCR CML was established and the patient was given interferon alpha therapy. This is the first m-BCR CML presenting as ab initio ALL. This report emphasizes the importance of karyotyping Ph-positive ALL during remission so as not to misdiagnose CML patients who can benefit from Interferon therapy.

Adult

Trehalase gene expression during postnatal development of rabbit intestine and kidney: effects of glucocorticoids.

Rabbit trehalase is a 75-kDa glycosyl phosphatidylinositol-anchored glycoprotein of the microvillus membrane of the enterocyte and kidney proximal tubule epithelial cells. The purpose of this work was to try to elucidate the molecular basis of trehalase gene expression in intestine and kidney during normal postnatal development and after hydrocortisone injection in suckling rabbits. Trehalase cDNA isolated, sequenced, and characterized by J. Ruf, H. Wacker, P. James. M. Maffia, P. Seiler, G. Galand, A. Kieckebusch, G. Semenza, and N. Mantei (J. Biol. Chem. 265: 15034-15039, 1990) was used to quantify trehalase mRNA. To measure the amount of trehalase mRNA encoding for trehalase, poly(A)+ mRNA was isolated and analyzed by Northern blot hybridization. This cDNA hybridized to a 1.8-kb mRNA in the small intestine and kidney. In developing rabbit intestine, after a slow decrease between 4 and 10 days, there is a sharp and parallel rise of both trehalase specific activity (28x) and mRNA (10x) between 10 and 30 days after birth. In contrast, in the kidney, between 4 and 30 days, the general developmental profile of both parameters is very different. There is an overall significant and parallel increase of both trehalase specific activity (3.3x) and mRNA (4.3x). In intestine the longitudinal gradient of trehalase activity and mRNA expression is different in adult and 16-day cortisol-treated suckling rabbits. In intestine, between 10 and 14 days, cortisol induces a coordinate increase of both trehalase activity (26x) and mRNA (19x), but at 16 days the two parameters diverge markedly. Daily injections of cortisol between 10 and 16 days do not induce significantly trehalase mRNA over controls at 16 days. In only 2 days, between 14 and 16 days, there is a clear loss of trehalase mRNA responsiveness to glucocorticoids. On the contrary, in the kidney, daily injections of cortisol between 10 and 16 days have no significant effect on trehalase mRNA but induce a small and significant increase of trehalase specific activity at 16 days (1.8x). Therefore we conclude that, with respect to the distribution along the small intestine, normal development in kidney and intestine, and after induction with glucocorticoid in intestine, alteration in the steady-state levels of trehalase mRNA is a major mechanism for the regulation of trehalase gene expression.

Aging

[Controlled hypercapnia: a new strategy in the treatment of severe respiratory insufficiency].

Permissive hypercapnia (PHY) represents an interesting approach in critically ill ventilated patients, because it allows to ensure adequate gas exchange while avoiding the adverse effects related to excessive airway pressures. Its objective is to improve oxygenation while reducing the risk of barotrauma and circulatory impairment. This concept is all the more important when considering that in majority of lung diseases for which MV is applied, lung involvement is highly inhomogeneous, meaning that the functionally normal or near normal areas are the most exposed to the deleterious effects of overdistension. Undesired physiological effects of non massive respiratory acidosis (PaCO2 < or = 80 mmHg, arterial pH > or = 7.15) are reversible and mostly minor. This good tolerance legitimizes two strategies: firstly to accept hypercapnia in conditions such as acute severe asthma for which enforced normalization of PaCO2 would imply potentially lethal complications, and secondly to deliberately induce respiratory acidosis while using very low airway pressures and alveolar ventilation to limit or prevent overdistension lung damage in injured as well as in normal areas. When the cerebral vasodilation induced by CO2 might aggravate a preexisting intracranial disorder, PHY is obviously contraindicated.

Humans

Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial.

OBJECTIVE: To assess three anti-stress ulcer prophylaxis regimens in mechanically ventilated patients for bacterial colonization, early- and late-onset nosocomial pneumonia, and gastrointestinal bleeding. DESIGN: Randomized controlled trial. PATIENTS: Consecutive eligible patients with mechanical ventilation and a nasogastric tube. Of 258 eligible patients, 244 were assessable. SETTING: Medical and surgical intensive care units. INTERVENTION: At intubation, patients were randomly assigned to receive one of the following: antacid (a suspension of aluminum hydroxide and magnesium hydroxide), 20 mL every 2 hours; ranitidine, 150 mg as a continuous intravenous infusion; or sucralfate, 1 g every 4 hours. MEASUREMENTS: Using predetermined criteria, the incidence of gastric bleeding, gastric colonization, early-onset pneumonia, and late-onset pneumonia was assessed in patients intubated for more than 24 hours. RESULTS: Of 244 assessable patients, macroscopic gastric bleeding was observed in 10%, 4%, and 6% of patients assigned to receive sucralfate, antacid, and ranitidine, respectively (P > 0.2). The incidence of early-onset pneumonia was not statistically different among the three treatment groups (P > 0.2). Among the 213 patients observed for more than 4 days, late-onset pneumonia was observed in 5% of the patients who received sucralfate compared with 16% and 21% of the patients who received antacid or ranitidine, respectively (P = 0.022). Mortality was not statistically different among the three treatment groups. Patients who received sucralfate had a lower median gastric pH (P < 0.001) and less frequent gastric colonization compared with the other groups (P = 0.015). Using molecular typing, 84% of the patients with late-onset gram-negative bacillary pneumonia were found to have gastric colonization with the same bacteria before pneumonia developed. CONCLUSION: Stress ulcer prophylaxis with sucralfate reduces the risk for late-onset pneumonia in ventilated patients compared with antacid or ranitidine.

Adult

[Value of D(-) lactate determination for the fast diagnosis of meningitis after craniotomy. An initial study].

The early diagnosis of postoperative bacterial meningitis (BM) may be difficult. CSF cultures may remain sterile. Clinical features and routine laboratory data often fail to give an evidence. As early antibiotic therapy is essential in such patients, a rapid diagnosis is required. Different authors proposed the D(-) isomer of lactic acid as an early and effective marker of infection in the body fluids (including CSF). D(-) lactate is produced by bacteriae and fungi; L(+) lactate may be produced also by human tissues in anaerobic situations. We conducted a prospective study in a neurosurgical intensive care unit to evaluate this technique for the diagnosis of meningitis following craniotomy. Fifty-four patients were included, 40 in group A (not infected or infected out of the CNS), 4 in group B (suspected BM), 10 in group C (BM with positive CSF cultures). No patient suffered from septicemia, haemodynamic or ventilatory instability, nor metabolic disorder. Clinical data, CSF and blood samples (cytology, conventional biochemistry, D(-) and L(+) lactate, bacteriology) were collected at inclusion and, in group B and C patients, at day 2, 5 and at clinical recovery. D(-) lactate measurements were performed with an enzymatic method adaptated from a Boehringer Mannheim kit (for determination in foodstuff). Statistics were based on the comparison of group A vs C patients. D(-) and L(+) lactate concentrations in the CSF were significantly higher in group C patients, and blood concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Regulation of inspiratory neuromuscular output during synchronized intermittent mechanical ventilation.

BACKGROUND: In synchronized intermittent mandatory ventilation, it is generally accepted that the work of the inspiratory muscles is decreased by the ventilator so that their activity can be modulated by the frequency of assisted breaths. We examined the validity of this concept, which recently has been questioned. METHODS: We studied five patients receiving synchronized intermittent mandatory ventilation because of an acute exacerbation of chronic obstructive pulmonary disease. The level of machine assistance, defined as the percentage of total ventilation delivered by the ventilator, was varied from a high (> 60%) to a medium (20-50%) and to the lowest tolerated value (0% in four patients). Esophageal pressure, air flow, and the electromyograms of the diaphragm and sternocleidomastoid muscles were recorded. At each level of machine assistance, distinguishing assisted from spontaneous breaths, the duration of electrical activation, the integrated electromyograms, and the work of breathing were computed. RESULTS: The durations of electrical activation and the integrated electromyograms of the diaphragm and sternocleidomastoid were similar in successive spontaneous and assisted breaths. At > 60% of machine assistance, the cumulative values per minute of the integrated electromyograms of the diaphragm and sternocleidomastoid and the work of breathing were reduced only by 38, 32, and 44%, respectively, compared with the lowest tolerated level of machine assistance. The durations of electrical activation did not change with increasing level of machine assistance. CONCLUSIONS: The degree of inspiratory muscle rest achieved by synchronized intermittent mandatory ventilation is not proportional to the level of machine assistance; furthermore, the inspiratory motor output is not regulated breath by breath but rather is constant for a given level of machine assistance.

Aged

CD11b/CD18 expression, adherence, and chemotaxis of granulocyte in adult respiratory distress syndrome.

The accumulation of granulocytes in the pulmonary microvasculature is generally thought a cardinal event in the pathology of adult respiratory distress syndrome (ARDS). However, the mechanism by which granulocytes are sequestered in the pulmonary vascular bed remains largely unknown. Because the CD11b/CD18 membrane receptors mediate various adhesion-dependent functions, their expression was investigated in granulocytes from patients during the course of ARDS development in relation to adherence and chemotaxis. CD11b expression of ARDS resting granulocytes was increased within 24 h of ARDS onset by a factor of two in comparison with control patients (p < 0.05) and remained significantly increased 72 to 120 h later. In contrast, the stimulated expression was significantly decreased only within 24 h of ARDS onset. Adherence was not modified within 8 h of the onset of ARDS, but was increased at Days 1, 3, and 5. The time course of granulocyte chemotaxis shows a decreased chemotaxis capacity during the first 3 d of ARDS, followed by normalization at Day 5. The dynamic changes observed in the various functions studied indicate a possible relationship between the modulation of the CD11b expression and a hyperadhesive state of granulocytes in ARDS. These sticky granulocytes may potentially contribute to the microvascular injury.

Adult