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Biomedical subjects

C Perret

Publications and source records attributed to C Perret.

At least 37 records · Page 2Linked to original sources

[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

Food habits and pancreatic cancer: a case-control study of the Francophone community in Montreal, Canada.

In a population-based case-control study of pancreatic cancer and nutrition among the Francophone population of Montreal (Quebec, Canada), a total of 179 cases and 239 controls matched for age, sex, and language (French) were interviewed between 1984 and 1988. Data on food habits, methods of food preparation and preservation, and related information were obtained through a questionnaire. The study found an increased risk of pancreatic cancer associated with a high consumption of salt [relative risk (RR) = 4.28; 95% confidence interval (CI) = 2.20-8.36], smoked meat (RR = 4.68; CI = 2.05-10.69), dehydrated food (RR = 3.10; 95% CI = 1.55-6.22), fried food (RR= 3.84; 95% CI = 1.74-8.48), and refined sugar (RR = 2.81; 95% CI = 0.94-8.45). An inverse association was found with the consumption of food with no preservatives or additives (RR = 0.08; 95% CI = 0.01-0.59), raw food (RR = 0.28; 95% CI = 0.10-0.75), and food prepared by presto or high-pressure cooking (RR = 0.35% 95% CI = 0.15-0.81), electricity (RR = 0.30; 95% CI = 0.90), or microwave oven (RR = 0.56; 95% CI = 0.34-0.92). Cooking with firewood was associated with a significantly higher risk for pancreatic cancer (RR = 4.63; 95% CI = 1.15-16.52). The results of this study suggest that food habits may play an important role in the etiology of cancer of the pancreas among French Canadians in Montreal, whereas other food habits may reduce the risk of this disease.

Adult

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

Calbindin-D9k gene expression in the uterus: study of the two messenger ribonucleic acid species and analysis of an imperfect estrogen-responsive element.

The calbindin D9k (CaBP9k) gene is under strict estrogen control in the rat uterus. This tissue contains two CaBP9k messenger RNA (mRNA) species. We have used primer extension analysis, reverse transcriptase associated with polymerase chain reaction, and RNase H digestion to show that these two mRNA species have the same structural features, including 5'- and 3'-ends, and poly(A) tail length. Our results suggest that the difference in electrophoretic mobilities of the two mRNA species might be due to interaction with another factor. We also analyzed the imperfect estrogen-responsive element (ERE) present on the first 5'-splice site of the rat CaBP9k gene. The oligonucleotide corresponding to the CaBP9k ERE was cloned in the plasmid pBLCAT2 (where the thymidine kinase promoter governs the expression of the chloramphenicol acetyl transferase gene) and transfected into MCF7 cells. This CaBP9k ERE was found to be a hormone-inducible enhancer that worked in an orientation-independent manner on a heterologous promoter and was functional at physiological hormone concentrations. One CaBP9k ERE conferred only weak (about 2-fold) estrogen induction, but two EREs cloned in tandem were strongly synergistic (14- to 16-fold). The CaBP9k ERE also bound to the partially purified estrogen receptor (ER) and to ER expressed in COS cells by gel shift assay. Methylation interference showed that all the guanine residues in both half-sites of the CaBP9k ERE were protected by ER binding. Thus, ER binds to the CaBP9k ERE in a way similar to other EREs. The gel shift assay results indicate that the strong synergistic effect of two EREs cloned in tandem is not due to cooperative binding between the two elements. As the CaBP9k gene is under strong estrogenic control in the uterus in vivo, the imperfect CaBP9k ERE may cooperate with another trans-acting factor to become fully efficient.

Animals

N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study.

OBJECTIVE: To determine the effects of intravenous N-acetylcysteine (NAC) on the development of severe adult respiratory distress syndrome (ARDS) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score. SETTING: Three university hospital ICUs and one regional ICU in Switzerland. PATIENTS: Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC, 40 mg/kg/d, or placebo intravenously for 3 days. MEASUREMENTS: Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2, the evolution of the lung injury score, and the PaO2/FIO2 ratio. The cardiovascular state, liver function, and kidney function were also monitored. Data were collected at admission (day 0), during the first 3 days, and on the day of discharge from the ICU. RESULTS: The NAC and placebo groups (32 and 29 patients, respectively) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score (SAPS) (10.8 +/- 4.6 vs 10.9 +/- 4.8) and lung injury score (LIS) (1.39 +/- 0.95 vs 1.11 +/- 1.08) (mean +/- SD). Three patients in each group developed ARDS. The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group (difference not statistically significant). At admission, 22 of 32 patients (69 percent) in the NAC group were mechanically ventilated compared with 22 of 29 (76 percent) in the placebo group. At the end of the treatment period (day 3), 5 of 29 (17 percent) in the NAC group and 12 of 25 (48 percent) in the placebo group were still receiving ventilatory support (p = 0.01), The FIO2 was 0.37 less than admission value (day 0) in the NAC group, and 0.20 less in the placebo group (p < 0.04); the oxygenation index (PaO2/FIO2) improved significantly (p < 0.05) from day 0 to day 3 only in the NAC-treated group. The LIS showed a significant regression (p = 0.003) in the NAC-treated group during the first 10 days of treatment: no change was observed in the placebo group. No adverse effects were observed during the treatment with NAC. CONCLUSIONS: Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases. Development of ARDS and mortality were not reduced significantly by this therapy.

Acetylcysteine

Malondialdehyde dosimetry in laser-irradiated tissues sensitized by hematoporphyrin derivative.

Photodynamic therapy (PDT) is based on the selective retention of a photosensitizer (hematoporphyrin derivative [HPD]) by tumor tissue and the subsequent irradiation of this tissue with light. Unsaturated phospholipids are important targets of membrane photodamage, and malondialdehyde (MDA), an ultimate marker of lipid peroxidation, can easily be measured by the fluorometric thiobarbituric acid (TBA) assay. To determine whether MDA content represents a reference for PDT intensity, tissue content in 7-week-old male nude mice was studied on biopsy samples after PDT (5 mg/kg HPD injected intravenously 24 hr before irradiation at 632 nm) with or without intraperitoneal injection of WR-2721 40 min before treatment. The FeCl3 method requiring only 15 min of incubation in a 95 degrees C waterbath proved most effective compared with the method involving phosphotungstic acid or the MDA-TBA determination using a commercially available kit. Whatever the method used, the best results were found using a 60-min interval between treatment and freezing. MDA concentration in HPD-PDT-treated samples was significantly higher than in HPD-tested controls (P < .01) and increased at laser irradiation doses ranging from 0 to 50 J/cm2. Administration of WR-2721 intraperitoneally significantly reduced MDA concentration (from 70% to 38%). A maximal effect was obtained with 100 mg/kg for brain (-70%) and 200 mg/kg for muscle (-47%). Higher doses produced no additional changes. The MDA assay is a simple tool for indirect evaluation of PDT, and WR-2721 can decrease MDA content in normal tissue, suggesting the possibility of good protection for normal tissue during PDT.

Amifostine

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction.

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eighty-nine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (+/- SEM) of 207 +/- 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = NS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

Adult

Cardiac arrest: prognostic factors and outcome at one year.

This study was designed to determine by multivariate statistical methods the influence of 38 variables on outcome after cardiopulmonary resuscitation (CPR) and to assess neuropsychological status in long-term survivors. The charts of 181 consecutive patients resuscitated in a 1,100-bed University Hospital over a 2-year period were analyzed retrospectively. Of the 181 resuscitated patients, 23 (13%) could be discharged. Outcome was significantly affected by the following variables: presence of shock or renal failure before cardiac arrest (CA) (odds ratio = 10.6; 95% confidence interval = 1.3-85.8 and odds ratio = 13.8; 95% confidence interval = 1.7-109.2, respectively), administration of epinephrine (odds ratio = 11.2; 95% confidence interval = 3.2-39.2) or prolonged CPR (> 15 min) (odds ratio = 4.9; 95% confidence interval = 1.7-13.7). By contrast, when CA occurred in uncomplicated acute myocardial infarction a significantly better prognosis could be demonstrated (odds ratio = 0.2; 95% confidence interval = 0.0-0.6). The 10 long-term survivors investigated lead an independent life and all returned to former occupation. The most common complaint was moderate memory disturbance (five patients). The conclusion is that this study confirms the critical influence of cellular anoxia on prognosis and allows the improved delineation of the situations in which cardiopulmonary resuscitation appears to be hopeless or likely to be successful. The follow up in a small number of survivors has shown a good quality of life and minor neuropsychological sequellae.

Cardiopulmonary Resuscitation

Colon cancer in seven siblings.

In a case-control study of cancer of the colon it was found that 96 out of 332 (29%) cases had a positive family history of cancer of the colon (2 cases and more) as compared with 19 out of 473 (4%) controls. 3 colon cancer cases reported that 6 of their respective relatives were also affected with the same cancer. We were able to do a complete follow-up study of one family where 7 out of 12 sibling (P < 0.05) had confirmed pathological diagnoses of cancer of the colon. The mean age at diagnosis among these familial colon cancer cases was 64 years (60 years for females and 73 years for males) and all tumours were located in the caecum or right colon (a common characteristic of colon cancer in this family). There was no history of familial adenomatous polyposis in this family. It is unlikely that the significantly high proportion of familial colon cancer found could be due to chance. This suggests that both environmental and genetic factors play an important role in the aetiology of colon cancer.

Adenocarcinoma