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Biomedical subjects

C Perret

Publications and source records attributed to C Perret.

At least 145 records · Page 8Linked to original sources

Plasma levels of tumor necrosis factor in the adult respiratory distress syndrome.

The purpose of the study was to evaluate the role of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of acute lung injury in critically ill patients. An immunoradiometric assay with an upper normal limit of 9 pg/ml was used to measure plasma TNF alpha levels (pl-TNF alpha) in 34 patients with adult respiratory distress syndrome (ARDS) and in 16 patients in whom, despite the presence of risk factors, ARDS did not develop. Pl-TNF alpha was elevated in 76% of the patients with ARDS (71 +/- 104 pg/ml) and in 48% of the at-risk patients (47 +/- 73 pg/ml); the difference between the two groups was not statistically significant. In 13 patients studied serially from the onset (Day 0) to the fifth day of ARDS, the peak pl-TNF alpha occurred later than Day 0 in seven subjects. Although the highest pl-TNF alpha levels were found in septic patients, moderately elevated values were also observed in 56% of nonseptic subjects. We conclude that plasma TNF alpha level is not a marker of ARDS but rather of shock and sepsis. These results do not exclude a pathogenic role of TNF alpha in acute lung injury since this cytokine could be produced and exert its effects within the lungs. The large incidence of abnormally high could be produced and exert its effects within the lungs. The large incidence of abnormally high plasma TNF alpha levels raises important questions on the role of this toxic cytokine in other disorders occurring in critically ill patients.

Adult↗

Maximal sniff mouth pressure compared with maximal inspiratory pressure in acute respiratory failure.

Inspiratory muscle strength most often is better reflected by sniff Pes than PImax against occlusion. Furthermore, sniff Pes can be estimated noninvasively by the measurement of sniff Pmo in normal subjects and in patients with respiratory muscle weakness. The aim of this study was to compare sniff Pmo and P.PImax to assess inspiratory muscle strength in patients with acute respiratory failure. The highest pressure was produced by P.PImax in 61 percent of measurements, and by sniff Pmo in 39 percent. Above 35 cm H2O P.PImax yielded the highest pressure in 55 percent of cases and the ratio sniff Pmo/P.PImax was 1.20 +/- 0.54. Below 35 cm H2O, P.PImax yielded the highest pressure in 75 percent of cases and the ratio sniff Pmo/P.PImax was 0.76 +/- 0.35 (p less than 0.02). Thus, measurements of sniff Pmo and P.PImax complement one another for assessing inspiratory muscle strength. However, sniff Pmo underestimates inspiratory muscle strength in patients with severe inspiratory muscle weakness.

Acute Disease↗

[Survival of HIV-positive patients hospitalized in intensive care for respiratory insufficiency and pneumocystis carinii pneumonia].

Respiratory failure secondary to Pneumocystis carinii pneumonia (PCP) is associated with high mortality in AIDS patients. In a search for prognostic indicators, we reviewed hospital charts of 13 AIDS patients admitted to our intensive care service from 1982 to 1989. Mortality rate was higher from 1982 to 1987 (4/5 patients) than later (3/8 patients). There was no significant difference between survivors and non survivors of this acute episode with regard to sex. HIV risk factors, time elapsed since AIDS diagnosis, vital signs (blood pressure, heart rate, respiratory rate), hemoglobin, white blood cell count, platelets, total and T4 lymphocytes, electrolytes, lactate dehydrogenase, P24 antigen Apache II and SAPS scores and corticosteroid treatment. Higher mortality was associated with more advanced age and an oxygen alveolar-arterial gradient greater than 65 mm Hg with an inspired fraction of oxygen of 0.21. We conclude that only the alveolo-arterial gradient could represent a prognostic indicator of practical interest. It is our belief that improvement since 1988 can be explained by earlier diagnosis and prompt treatment before development of severe lung alterations.

Acquired Immunodeficiency Syndrome↗

[Lactic acidosis and hyperlactatemia].

Lactic acidosis is a relatively frequent acid-base disorder in a hospital setting. It is defined by the association of an arterial pH inferior to 7.35 and an arterial lactate level superior to 5 mmol/l. Classically, 2 types of acidosis are distinguished on the basis of their mechanisms of onset: the type A, with evident clinical signs of tissue hypoperfusion and the type B, more are, without apparent hypoxia. This last category is observed in various circumstances such as diabetes, acute liver failure, poisoning and, more rarely, inborn errors of carbohydrate metabolism. Treatment aims primarily at the correction of the cause. The efficacy of sodium bicarbonate is presently debated, considering the risk to worsen hyperlactatemia and to induce hyperosmolarity or rebound alkalosis. The administration of dichloroacetate, an activator of pyruvate dehydrogenase, permits to correct partially the lactic acidosis but is not harmless especially in case of prolonged administration. Other therapeutic modalities are evoked. Arterial lactate level is a reliable prognostic index of shock, because blood values do not depend only of the oxygen debt but also of the efficacy of hepatic and renal lactate uptake. Sequential measurements are recommended.

Acidosis, Lactic↗

[Hospital morbidity and mortality of acute opiate intoxication].

The records of 188 consecutive patients admitted for acute opiate intoxication were analyzed retrospectively to evaluate the morbidity and mortality of opiates. The most frequently used of these drugs were heroin (127 cases) and methadone (41 cases). In 79 cases the opiate was associated with another psychodepressant, usually benzodiazepines, alcohol or barbiturates. Forty-seven percent of the patients were admitted in deep coma, with respiratory arrest in almost every case. The complications observed in 49 patients were: aspiration of gastric contents (n = 24), rhabdomyolysis (n = 22), often associated with myocarditis (n = 13), pulmonary edema (n = 16), convulsions (n = 10), left ventricular dysfunction (n = 5) and lesions of the peripheral nervous system (n = 4). All patients survived, except one who died of cardiac arrest before admission. It is concluded that acute opiate intoxication treated in hospital has an excellent prognosis for life provided no cardiac arrest occurs prior to admission. One quarter of the patients require prolonged stay in an intensive care unit because of complications. The other patients, even when deeply comatose on admission, spend less than 1 day in hospital owing to the specific antagonist available.

Acute Disease↗

Molecular cloning and characterization of a rat intestinal sucrase-isomaltase cDNA. Regulation of sucrase-isomaltase gene expression by sucrose feeding.

To investigate the regulation of expression of intestinal sucrase-isomaltase (SI) complex in response to sucrose feeding, we isolated a cDNA (RPSI1) encoding partially the pro-SI of rat intestinal mucosa. The clone consists of 1929 mRNA-derived nucleotides, which covered the region including the C-terminal part of the isomaltase and the N-terminal part of the sucrase in the final SI complex. Nucleotide and amino-acid sequences of RPSI1 were compared with their corresponding regions in rabbit pro-SI. A greater similarity was found in sucrase parts than in isomaltase parts of the two species. Northern blot analysis revealed that the mRNA levels of SI increased rapidly after sucrose force feeding, while those of rats fed a carbohydrate-free diet did not. These changes in mRNA levels correlated with the corresponding enzyme activities. The results demonstrate that the induction of SI activities is directly associated with an increase in SI mRNA levels. Our results also suggest that circadian modulation of SI transcription may occur in basic SI gene expression.

Amino Acid Sequence↗

Respiratory failure and unilateral caudal brainstem infarction.

We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (PaCO2 62 mm Hg, PaO2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses.

Aged↗

Interlimb coordination during fictive locomotion in the thalamic cat.

Efferent discharges in muscle nerves of the four limbs were recorded simultaneously during spontaneous fictive locomotion in thalamic cats with the goal of understanding how the central nervous system controls interlimb coordination during stepping. The onset of the bursts of activity in the nerve of a selected flexor muscle in each limb allowed the temporal and the phase relationships between the fictive step cycle of a pair of limbs to be determined. Our main results are the following: 1) the fictive step cycles of the two forelimbs are always strictly alternated whereas the phasing of the step cycles of either the two hindlimbs or pairs of homolateral or diagonal limbs is more variable; 2) the time interval between the onsets of the flexor bursts of one of the two pairs of diagonal limbs is independent of the step cycle duration; 3) distinct patterns of interlimb coordination exist during fictive locomotion; a small number of patterns of coordination involving all four limbs, which correspond to the walking and the trotting gaits in the intact cat, occur very frequently. The results demonstrate that the central nervous system deprived of phasic afferent inputs from the periphery has the capacity to generate most of the patterns of interlimb coordination which occur during real locomotion. They further support the view that the central pattern of interlimb coordination essentially results from diagonal interaction between a forelimb generator for locomotion and a hindlimb one.

Afferent Pathways↗

Experimental study on the fractionation schedule for proton irradiation of uveal melanoma.

Greene melanoma in the anterior chamber of rabbits was irradiated by protons to find the isoeffect curve for proton irradiation fractionated into one, two, three or four doses. The isoeffect curve for tumor tissue remained constant between one- and three-dose fractionations and rose with four-dose fractionation. The isoeffect curve for normal tissue approximately followed the Ellis equation. Therefore, the optimal irradiation schedule should be in the range of three fractions because this best spares normal tissue while delivering a tumoricidal dose to the lesion. The relative reduction of the total dose from four- to one-dose fractions of intraoperative irradiation should be 20%.

Animals↗

17 beta-estradiol stimulates the calbindin-D9k (CaBP9k) gene expression at the transcriptional and posttranscriptional levels in the rat uterus.

The 9 kilodalton vitamin D-dependent calcium-binding protein (CaBP9k), calbindin-D9k, is expressed in the intestine and uterus of mammals. Rat intestinal CaBP9k is a well documented expression of the steroid hormone like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). In contrast exogenous 1,25-(OH)2D3 does not affect the concentration of uterine CaBP9k which is dependent on estrogen. We have analyzed the effect of 17 beta-estradiol on the regulation of CaBP9k gene expression in the uterus of mature ovariectomized rats. CaBP9k mRNA is undetectable in the uterus of mature ovariectomized rats. A single dose of 17 beta-estradiol results in a detectable level of CaBP9k mRNA at 1 h and a significant increase 3 h after injection. The maximal CaBP9k mRNA level is reached 6 to 12 h post injection. These results show that 17 beta-estradiol increases CaBP9k production by increasing CaBP9k gene transcription. Chronic 17 beta-estradiol administration results in a plateau of CaBP9k mRNA but in a large increase in CaBP9k concentration. The kinetic response to a single estradiol injection was similar in immature rats. This result shows that no cellular differentiation is required for the control of CaBP9k gene expression by 17 beta-estradiol. The uterine cells of immature rats are already competent to respond optimally to estradiol. There is a single 0.5 kilobase CaBP9k gene transcript in the rat duodenum. In contrast there are two estrogen-inducible CaBP9k mRNA species in the uterus of both the mature ovariectomized and the immature rats. The smallest species corresponds to the duodenal CaBP9k mRNA species, while the larger species is at least 50 nucleotides larger. However, a unique CaBP9k identical to that in the duodenum is expressed in the uterus.

Animals↗

[Structure, expression and control of calbindins-D].

The Calbindins-D (CaBP9K and 28K), like calmodulin, belong to a group of intracellular proteins that bind calcium with high affinity. Each protein is encoded by a separate gene and there is no direct filiation between the two genes. We have demonstrated the tissue-specific expression and regulation of CaBP9K gene. This gene is expressed in the intestine, placenta and uterus of the rat as a single 0.5kb long transcript. Exogenous 1,25(OH)2D3 triggers the rapid synthesis of CaBP9K mRNA and accumulation of translatable CaBP9K mRNA in the duodenum of vitamin D-deficient rats. Calcium also stimulates CaBP9K gene expression in this tissue. In contrast 1,25(OH)2D3 does not change the uterine concentration of CaBP9K but estrogen stimulates the transcription of the CaBP9K gene in the uterus. The promoter region of rat CaBP9K gene contains 1 TATA box and 4 CAAT box-type sequences and several steroid hormone regulatory elements. The CaBP9K gene is therefore a suitable model for studying the tissue-specific regulation of gene expression by steroid hormones.

Animals↗

Acute heart failure in myocardial infarction: principles of treatment.

Congestive heart failure after acute myocardial infarction can extend the area of infarction by worsening the oxygen supply-demand balance. Appropriate treatment requires insight into this pathophysiologic condition and knowledge of the effects of the various therapies available. Understanding of the role of vasodilating and inotropic agents and of mechanical interventions such as ventilation with PEEP is an important aspect of treatment.

Acute Disease↗

Cloning and analysis of calbindin-D28K cDNA and its expression in the central nervous system.

The vitamin D-dependent calcium-binding protein (CaBP), calbindin-D28K (CaBP28K), is present in the central nervous system (CNS), the sensory system, and kidneys of mammals and birds. Recent studies have indicated that several other CaBPs of very similar Mrs are also present in the CNS. This study was carried out to establish the relationship between CaBP28K and other CaBP, particularly spot 35, to provide a basis for further studies on the tissue-specific regulation and distribution of CaBP28K. A cloned pC28 cDNA was isolated from a rat brain expression library using synthetic oligodeoxyribonucleotides (oligos) complementary to rat spot-35 mRNA. This pC28 cDNA had an open reading frame (ORF) of 783 nucleotides (nt) coding for a 261-aa, 30-kDa protein. There was 100% homology between the pC28 sequence and that of the CaBP28K isolated from rat brain cDNA library using a chicken intestinal CaBP28K probe (Hunziker and Schrickel, 1988). Thus the aa and nt sequences of rat CaBP28K and spot 35 are identical. Primer extension studies and Northern analyses show that the major species of CaBP28K mRNA contains a 5'-untranslated region of 132 nt, a coding region of 261 codons and a 3'-untranslated region of 804 nt without the poly(A) tail. The rat CaBP28K probe hybridizes to one major RNA species (1.9 kb) and two minor ones (2.8 and 3.2 kb) in the cerebellum, hippocampus, retina and kidney. This distribution correlates well with the distribution of CaBP28K itself in these organs. Comparison of the genomic organization of the CaBP28K gene with that of other members of the 'EF-hand' CaBP family emphasizes that the CaBP28K gene diverged from the others at the first duplication of the gene encoding one CaBP domain. All the members of the 'EF-hand' gene CaBP family evolved by exon shuffling and specific genomic rearrangements.

Amino Acid Sequence↗

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells. The increase in the beating rate was accompanied by a frequency-dependent decrease in the amplitude of contraction. In electrically driven cells (1 Hz), endothelin-1 increased the amplitude of contraction dose-dependently, with an EC50 of 0.3 nmol/l, smaller than that of the calcium channel blocker BAY K 8644 (EC50 3.3 nmol/l), and with an efficacy close to that of BAY K 8644 and isoproterenol. Nicardipine (100 nmol/l) shifted to the right, by two orders of magnitude, the dose-response curve of endothelin-1 for inotropism. These results indicate that endothelin-1 is one of the most potent inotropic agents in cultured cardiac myocytes, and suggest that this effect involves, at least in part, a calcium ion influx through voltage-sensitive calcium channels.

Animals↗