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Biomedical subjects

J M Michel

Publications and source records attributed to J M Michel.

At least 19 recordsLinked to original sources

[Primary surgical care of pelvic fractures associated with perineal laceration].

Unstable fractures of the pelvic ring, associated to perineal lacerations are severe injuries occurring during high-energy trauma. High rates of septic complications and mortality have been reported with these injuries. Current treatment guidelines, while dealing with open pelvic fractures or dislocations are discussed, based on a current review of the literature and on our local experience. At our institution, 55 unstable type B or C fractures of the pelvic ring were treated by osteosynthesis between 1991 and 1997. Of these, 11 patients presented with an associated perineal laceration (20%). Simultaneously to the immediate pelvic ring fixation, a diversion colostomy was performed in all these patients. Repeated wound debridements and wide spectrum antibioprophylaxis were associated. Of these 11 patients presenting an open pelvic fracture, only one died of pelvic sepsis at three weeks. 10 patients survived (91%) and went on to bony union, without any local infectious complications. Aggressive multidisciplinary initial surgical management is a rule when dealing with this type of injuries, immediate colostomy and careful wound debridement must be associated to the initial osteosynthesis.

Adult

cAMP-mediated long-term modulation of voltage-dependent K+ channels in cultured colliculi neurons.

Previously, we have described prolonged cAMP-induced inhibition of a K+ current in cultured colliculi neurons. The aim of the present study was to characterize the channel responsible for this cAMP-dependent effect. We detected the presence of a non-inactivating voltage-dependent 16-pS K+ channel that displayed long-lasting inhibition upon a brief application of cAMP and greater sensitivity to tetraethylammonium than to 4-aminopyridine. In addition to this channel, colliculi neurons express two other voltage-sensitive, non-inactivating K+ channels (8 and 49 pS) whose activity is facilitated by a brief application of cAMP, the effect of which is also long-lasting. These results suggest the presence of common sustained cAMP-dependent processes responsible for both up- and down-regulation of these channels in the neurons studied. They indicate that the 16-pS, but not the 8-pS or the 49-pS channels, participates in the cAMP-inhibited macroscopic K+ current.

4-Aminopyridine

Targeted gene inactivation for the elucidation of deoxysugar biosynthesis in the erythromycin producer Saccharopolyspora erythraea.

The production of erythromycin A by Saccharopolyspora erythraea requires the synthesis of dTDP-D-desosamine and dTDP-L-mycarose, which serve as substrates for the transfer of the two sugar residues onto the macrolactone ring. The enzymatic activities involved in this process are largely encoded within the ery gene cluster, by two sets of genes flanking the eryA locus that encodes the polyketide synthase. We report here the nucleotide sequence of three such ORFs located immediately downstream of eryA, ORFs 7, 8 and 9. Chromosomal mutants carrying a deletion either in ORF7 or in one of the previously sequenced ORFs 13 and 14 have been constructed and shown to accumulate erythronolide B, as expected for eryB mutants. Similarly, chromosomal mutants carrying a deletion in either ORF8, ORF9, or one of the previously sequenced ORFs 17 and 18 have been constructed and shown to accumulate 3-alpha-mycarosyl erythronolide B, as expected for eryC mutants. The ORF13 (eryBIV), ORF17 (eryCIV) and ORF7 (eryBII) mutants also synthesised small amounts of macrolide shunt metabolites, as shown by mass spectrometry. These results considerably strengthen previous tentative proposals for the pathways for the biosynthesis of dTDP-D-desosamine and dTDP-L-mycarose in Sac. erythraea and reveal that at least some of these enzymes can accommodate alternative substrates.

Amino Acid Sequence

Analysis of a Streptomyces antibioticus chromosomal region involved in oleandomycin biosynthesis, which encodes two glycosyltransferases responsible for glycosylation of the macrolactone ring.

A 6-kb region from the chromosome of Streptomyces antibioticus, an oleandomycin producer, was cloned and sequenced. This region was located between the 3' end of the gene encoding the third subunit of the oleandomycin type I polyketide synthase and the oleP and oleB genes, which encode a cytochrome P450 monooxygenase and an oleandomycin resistance gene, respectively. Analysis of the nucleotide sequence revealed the presence of five genes encoding a cytochrome P450-like protein (oleP1), two glycosyltransferases (oleG1 and oleG2) involved in the transfer of the two 6-deoxysugars (L-oleandrose and D-desosamine) to the oleandomycin macrolactone ring, a methyltransferase (oleM1), and a gene (oleY) of unknown function. Insertional inactivation of this region by gene disruption generated an oleandomycin non-producing mutant which accumulated a compound that, according to mass spectrometry analysis, could correspond to the oleandomycin macrolactone ring (oleandolide), suggesting that the mutation affects oleandrosyl glycosyltransferase.

Amino Acid Sequence

Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons.

As metabotropic glutamate receptor type 1 (mGluR1) is known to couple L-type Ca2+ channels and ryanodine receptors (RyR, Chavis et al., 1996) in cerebellar granule cells, we examined if such a coupling could activate a Ca2+-sensitive K+ channel, the big K+ (BK) channel, in cultured cerebellar granule cells. We observed that (+/-)-1-amino-cyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) and quisqualate (QA) stimulated the activity of BK channels. On the other hand, (2S, 3S, 4S)-alpha-carboxycyclopropyl-glycine (L-CCG-I) and L-(+)-2-amino-4-phosphonobutyrate (L-AP4) had no effect on BK channels, indicating a specific activation by group I mGluRs. Group I mGluRs stimulation of the basal BK channel activity was mimicked by caffeine and both effects were blocked by ryanodine and nifedipine. Interestingly, carbachol stimulated BK channel activity but through a pertussis toxin (PTX)-sensitive pathway that was independent of L-type Ca2+ channel activity. Our report indicates that unlike the muscarinic receptors, group I mGluRs activate BK channels by mobilizing an additional pathway involving RyR and L-type Ca2+ channels.

Animals

[Traumatic lesions of the anorectum].

Injuries of the colon and rectum are common surgical problems. Lesions can be classified into four groups according to the site of damage and the presence of sphincter tears: 1. intraperitoneal perforation without sphincter damage 2. intraperitoneal perforation with sphincter damage 3. extraperitoneal perforation without sphincter damage 4. extraperitoneal perforation with sphincter damage From 1990 to 1998, 11 patients, 7 males and 4 females presenting an anal and/or rectal trauma were admitted in Geneva University Hospital. 8 patients were admitted as an emergency, the 3 others had been transferred to correct an incontinent post traumatic pathology. No mortality. A terminal colostomy was performed in all patients with intraperitoneal injury and in 5 patients with combined extraperitoneal and anal sphincter injury. All sphincter lesions were sutured as an emergency (6 cases). In 3 patients we performed an overlapping sphincteroplasty. 2 patients with persisting incontinence were cured by a dynamic stimulated graciloplasty. The choice of treatment of anorectal trauma includes broad spectrum antibiotherapy, cleaning of the rectum, sphincter repair. A terminal diverting colostomy and laparotomy must be achieved in case of intraperitoneal injury, large extraperitoneal lesion, severe perineal laceration with or without pelvic fracture.

Anal Canal

Metabotropic glutamate receptors in the rat nucleus accumbens.

The effects of glutamate metabotropic receptors (mGluRs) on excitatory transmission in the nucleus accumbens were investigated using electrophysiological techniques in rat nucleus accumbens slices. The broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentyl-1,3-dicarboxylate, the mGluR group 2 selective agonists (S)-4-carboxy-3-hydroxyphenylglycine, (1S,3S)-ACPD) and (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1), and the mGluR group 3 specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) all reversibly inhibited evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)-3,5-dihydroxyphenylglycine [(R,S)-DHPG] did not depress transmission. Dose-response curves showed that the rank order of agonist potencies was: L-CCG1 > L-AP4 > (1S,3S)-ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic mechanism, as they increased paired-pulse facilitation, decreased the frequency of miniature excitatory postsynaptic currents and had no effect on their amplitude. The mGluRs did not inhibit transmitter release by reducing voltage-dependent Ca2+ currents through N- or P-type Ca2+ channels, as inhibition persisted in the presence of omega-conotoxin-GVIA or omega-Aga-IVA. The depression induced by mGluRs was not affected by specific antagonists of dopamine D1, GABA-B or adenosine A1 receptors, indicating direct effects. Finally, (R,S)-DHPG specifically blocked the postsynaptic afterhyperpolarization current (I(AHP)). Our results represent the first direct demonstration of functional mGluRs in the nucleus accumbens of the rat.

Adenosine

Swan-Ganz catheter induced pulmonary artery perforation during cardiac surgery concerning two cases.

Two case reports describing patients having cardiac operations under extra corporeal circulation are presented. At the completion of the operation, a massive hemoptysis occurred in both patients after a Swan-Ganz catheter had perforated the pulmonary artery. A hemostasis lobectomy was then immediately required. The immediate and long term prognosis seems satisfactory. This is an unusual but serious complication. The incidence of this complication varies between 0.06 and 0.2%. The more frequently related risk factors include people over the age of 60, pulmonary artery hypertension, anticoagulant therapy, hypothermia and manipulation of the heart by the surgeon. When this accident occurs, many authors suspect the balloon. An early diagnosis is essential in the case of a major or even a minor hemoptysis, because this complication may be a lethal one as the mortality rate may reach 50%. According to us, the appropriate therapy which would reduce this mortality is a surgical one (hemostasis lobectomy).

Aged

[Results of surgical treatment of hepatic metastasis of colorectal origin].

Surgery is the only treatment which can achieve long-term survival of patients with colorectal liver secondaries. This study reports the results in 71 patients with liver metastases who underwent hepatic resection from January 1980 to December 1994. The mean age was 60 years (range 37 and 80 years). Operations included 33 right hepatectomies, 5 extended right hepatectomies, 6 left hepatectomies, 11 left lobectomies,. Surgery was macroscopically and microscopically curative in 61 patients. Information was not available in 2 patients. Significant morbidity was observed in 37% of patients. Actuarial survival at 1, 3 and 5 years was 83%, 27% and 20% respectively. At the end of the follow-up, 50 patients had died and 6 were lost to follow-up. Techniques of hepatic resection for secondaries are well established and postoperative mortality is low. Pending advances in chemotherapy, we recommend surgery as being the only way of improving long-term survival in patients with colorectal hepatic metastases.

Adult

[Propofol in the surgery of the aortic bifurcation. Comparison with isoflurane].

Two groups of nine patients each, all undergoing surgery for aorto-bifemoral prosthesis, were studied. They were premedicated with 10 mg morphine and 1 mg flunitrazepam. A Swan-Ganz catheter was then inserted. Cardiac output was measured by thermodilution. Haemodynamic parameters were measured before induction (t0), 15 min after intubation (t1), 10 min after the start of the surgical procedure (t2), 5 min before clamping the aorta (t3), whilst the aorta was clamped (t4), and a few minutes after unclamping. Group A received 2 mg X kg-1 propofol at induction, anaesthesia being maintained with 100 micrograms X kg-1 X min-1 propofol. Group B received 4 mg X kg-1 thiopentone, followed by isoflurane at the dose of 0.9 vol. %. Both groups received 5 micrograms X kg-1 fentanyl and 0.1 mg X kg-1 vecuronium to ease intubation. Artificial respiration was carried out with a mixture of 40% oxygen and 60% nitrous oxide. The fall in blood pressure between t2 and t3 was significantly more important in the propofol group (-16%). In the same group, the systolic blood pressure and heart rate fell by 23 and 19% respectively after induction (p less than 0.05); the cardiac index fell by 20% and the systemic vascular resistances did not change. The fall in blood pressure, heart rate and cardiac index were not significant for group B. The haemodynamic changes due to clamping of the aorta were not significant between or within groups. In group A, one patient presented with bradycardia, hypotension and myocardial ischaemia, and another died of postoperative ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Phonomechanographic evaluation of left ventricular function in hyperthyroid states].

Hyperthyroidism is associated with a hyperkinetic syndrome, the mechanisms of which are not fully understood but which include an increase in heart rate, a reduction in systemic arterial resistance and a debatable increase in myocardial contractility. The limitations of radioimmunological assay of the hormonal mediators underline the diagnostic value of an atraumatic method of quantifying left ventricular systolic function. In view of the variable sensitivity of phonomechanographic and echocardiographic indices with respect to changes in heart rate, pre- and after load, we studied apex cardiographic indices during the phase of isovolumetric contraction. Fifty-eight patients with hyperthyroidism but without patent cardiovascular disease were divided into two subgroups: Grave's disease: 38 cases, and toxic adenoma: 22 cases. The results of the measurements of systolic time intervals and the calculation of "indices of contractility" obtained from the apex cardiogram and its first derivative, were compared with those of 36 young, normal subjects. The results show that: the pre-ejection period of the study population was much shorter than normal (65,7 ms +/- 2,5 vs 84,6 ms +/- 3,4; p less than 0,001); this was clearly related to the chronotropic factor (p less than 0,05). The pre-ejection/ejection period ratio did not differentiate hyperthyroid from normal subjects (0,265 vs 0,283, p greater than 0,20), except in Graves' disease (0,249, p less than 0,02). On the other hand, measurements made from the apex cardiogram showed significant differences in both types of hyperthyroidism. (Formula: see text). In conclusion, phonomechanography may be used to quantify the increase in left ventricular function in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Must acute carotid thrombosis be surgically treated? 1962-1973: long-term results].

A study of long-term results (mean follow-up: 10.6 years) in 22 patients operated on for acute carotid thrombosis between 1962 and 1973 is reported. In most instances, surgery was performed at the acute phase of a massive cerebrovascular occlusion, usually more than 8 hours after onset (10 cases). Five of these patients (22%) died in the postoperative period. Eight (35%) recovered without residual disease. In six, the condition improved, while it remained unchanged or worsened in three (14%). There were ten delayed deaths, including two from a recurrent cerebrovascular episode and four from cardiac disease. The actuarial survival curve does not differ from that of patients treated conservatively, with rates being 60% at five years, 36% at ten years and 28% at thirteen years. The quality of certain postoperative results suggests that surgical indications at the acute stage of carotid occlusion be reviewed. The study of thirty series from the literature (1 046 cases) shows a 17% mortality rate, while 50% of patients recover or improve. This mortality is significantly lower in recent statistics, under 10%: this improvement may be ascribable to more rigid surgical indications (delay under 6 hours, operation in variable neurologic deficiencies, early diagnosis by the Doppler procedure, better postoperative management). The authors conclude that surgical management of acute carotid thrombosis should no longer be systematically dismissed.

Acute Disease