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Biomedical subjects

J L Michaud

Publications and source records attributed to J L Michaud.

At least 19 recordsLinked to original sources
PubMed2005

[Recent progress in treatment of malignant pleural mesothelioma].

Incidence of malignant pleural mesothelioma will rise until 2030-2040 because the elapsed time between exposure and diagnostic is up to several decades. Prognosis remains very poor with median survival less than one year and five-year survival not exceeding 5%. As compared to 1999, standart treatment adds chemotherapy with cisplatin and pemetrexed to local radiotherapy for prevention of local seeding after invasive diagnostic procedures. Despite various growth factors and their receptors are involved in malignant mesothelioma, first clinical trials of targeted therapies reported poor results. Multimodality therapy with extrapleural pneumonectomy and radiation therapy (+/-chemotherapy) can be of benefit in subgroups of patients but it cannot be recommended in a routine approach. As compared to bronchial carcinoma, inclusion of patients in clinical trials (using intensity-modulated radiation therapy) is the only way to somewhat improve results.

Chemotherapy, Adjuvant↗
PubMed2004

Fat chance: genetic syndromes with obesity.

Although obesity shows high heritability, we are aware of only a small number of genes that affect adipose mass in humans. Genetic syndromes with obesity represent unique opportunities to gain insight into the control of energy balance. The majority of obesity syndromes can be distinguished by the presence of mental retardation. We performed a systematic search of such syndromes and reviewed the literature with a focus on distinguishing clinical features, the characteristics of their obesity, and the underlying pathogenetic mechanisms. We predict that the study of these conditions will shed light on common forms of obesity.

Chromosome Aberrations↗
PubMed2002

Retrospective clinical comparison of Celsior solution to modified blood Wallwork solution in lung transplantation for cystic fibrosis.

OBJECTIVE: To compare the preservative effects of Celsior solution and modified blood Wallwork solution in lung transplantation. METHODS: From 1989 to 2000, 44 lung transplantations for cystic fibrosis were performed: 26 grafts were preserved with modified blood Wallwork solution and 18 with Celsior solution. RESULTS: Preoperative status of the 2 groups was similar. The ratio of arterial oxygen to fraction of inspired oxygen and the pulmonary vascular resistance on the first postoperative day did not differ significantly between the 2 groups. Early death was 4% (SD, 20%) in the Wallwork group versus 11% (SD, 32%) in the Celsior group (not significant). No death was related to graft failure. The forced expiratory volume in 1 second during the first month after transplantation was 63% (SD, 19%) in the Wallwork group versus 63% (SD, 16%) in the Celsior group (not significant). CONCLUSION: Because the solution does not need to be prepared on site and does not require blood from the donor, Celsior seems better than Wallwork solution for preserving lung grafts.

Albumins↗
PubMed2001

Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus.

The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.

Adipose Tissue↗
PubMed2001

Isolated mitral valve replacement with St. Jude medical prosthesis: long-term results: a follow-up of 19 years.

BACKGROUND: In this retrospective study, approximately 440 patients received mitral valve replacements with the St Jude Medical prosthesis. The last patient was operated on 10 years before the beginning of the follow-up. The extended follow-up was 19 years. METHODS AND RESULTS: Four hundred forty patients (sex ratio, 1.32 [men to women]; age, 60+/-11.4 years; age range, 7 to 75 years) were operated on from 1979 to 1987. All patients underwent isolated mitral valve replacement. Tricuspid plasty was the only associated procedure. The follow-up at 19 years was 98% complete. The overall actuarial survival rate was 63+/-3.3% at 19 years, and the actuarial survival rate (only valve related) was 83+/-2.7%. The operative mortality rate (0 to 30 days) was 4.09%. We found that 89.4% of the patients alive at 19 years were in NYHA class I/II. Multivariate analysis showed that age and sex were significantly correlated with valve-related mortality and that age, sex, NYHA class, and atrial fibrillation were significantly correlated with overall mortality. The linearized rates (percent patient-years) of thromboembolism, thrombosis, and hemorrhage were 0.69, 0.2, and 1, respectively. At 19 years, freedom from endocarditis and reoperation was 98.6+/-1% and 90+/-3%, respectively. CONCLUSIONS: In this study, the very-long-term results confirm the excellent durability of the St Jude Medical prosthesis in the mitral position and show the difficulty of adjusting the anticoagulation protocol, even after long-term treatment.

Adolescent↗
PubMed2001

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Adolescent↗
PubMed2001

The developmental program of the hypothalamus and its disorders.

The hypothalamus integrates physiological processes essential for survival and reproduction. Recent studies have shown that developmental events can affect these processes. Pathways required for the induction of the ventral midline of the hypothalamus or for the differentiation of specific hypothalamic lineages have the potential of causing endocrine and metabolic disorders, including obesity. Also, some genes with paternal monoallelic expression are involved in the development of hypothalamic centers that are critical physiological regulators. Developmental defects affecting the hypothalamus might represent a more frequent cause of clinical disorders than previously suspected.

Animals↗
PubMed2001

Left bronchial disruption and aortic rupture after blunt chest trauma.

A 25-year-old male who had been involved in a traffic accident presented with a neurological disorder, bilateral pneumothoraces, and pneumomediastinum. Bronchoscopy revealed a complex rupture of the left bronchial tract. MRI revealed a sinus valsalva aneurysm. The bronchial lesion was first repaired via left thoracotomy. 10 days later, the aorta was repaired via sternotomy. In cases of combined bronchial and aortic lesion, a concomitant repair is not mandatory, at least when the aortic lesion appears limited and shows no signs of dissection.

Adult↗
PubMed2001

[Mid-term results of stentless bioprosthesis for aortic valve replacement. Experience in a series of 97 patients].

Stentless bioprostheses have been described as valve substitutes of interest for aortic valvular replacement. We studied 97 consecutive patients with a mean age of 72.2 years (40-84) who underwent aortic valvular replacement with 80 Toronto SPV and 17 Freestyle prostheses. Operative mortality was 6.2. With a mean follow-up of 19 +/- 10 months (1-46), 87.2% of the surviving 86 patients underwent an echocardiography performed by the same operator. Mean gradient was 10.9 +/- 3.6 mmHg (4.2-22.6) and effective orifice area was 1.8 +/- 0.5 cm2 (0.8-3.0) for the 75 controlled stentless valves. The best haemodynamic data were obtained with the 25 mm diameter prostheses. One asymptomatic partial dehiscence was observed during monitoring. None of the 15 detected aortic leaks was significant. We observed a significant reduction of the ventricular mass in 41 patients who had undergone pre- and postoperative evaluation (p < 0.0014). Overall survival was 86.8 +/- 4.4% at 2 years. Stentless bioprostheses offered satisfactory haemodynamic results in our series. They however require an implantation technique learning curve as well as a thorough knowledge of the aortic root anatomy and physiology.

Adult↗
PubMed2000

ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus.

One major function of the hypothalamus is to maintain homeostasis by modulating the secretion of pituitary hormones. The paraventricular (PVN) and supraoptic (SON) nuclei are major integration centers for the output of the hypothalamus to the pituitary. The bHLH-PAS transcription factor SIM1 is crucial for the development of several neuroendocrine lineages within the PVN and SON. bHLH-PAS proteins require heterodimerization for their function. ARNT, ARNT2, and BMAL1 are the three known general heterodimerization partners for bHLH-PAS proteins. Here, we provide evidence that Sim1 and Arnt2 form dimers in vitro, that they are co-expressed in the PVN and SON, and that their loss of function affects the development of the same sets of neuroendocrine cell types within the PVN and SON. Together, these results implicate ARNT2 as the in vivo dimerization partner of SIM1 in controlling the development of these neuroendocrine lineages.

ARNTL Transcription Factors↗
PubMed2000

Members of the bHLH-PAS family regulate Shh transcription in forebrain regions of the mouse CNS.

The secreted protein sonic hedgehog (Shh) is required to establish patterns of cellular growth and differentiation within ventral regions of the developing CNS. The expression of Shh in the two tissue sources responsible for this activity, the axial mesoderm and the ventral midline of the neural tube, is regulated along the anteroposterior neuraxis. Separate cis-acting regulatory sequences have been identified which direct Shh expression to distinct regions of the neural tube, supporting the view that multiple genes are involved in activating Shh transcription along the length of the CNS. We show here that the activity of one Shh enhancer, which directs reporter expression to portions of the ventral midbrain and diencephalon, overlaps both temporally and spatially with the expression of Sim2. Sim2 encodes a basic helix-loop-helix (bHLH-PAS) PAS domain containing transcriptional regulator whose Drosophila homolog, single-minded, is a master regulator of ventral midline development. Both vertebrate and invertebrate Sim family members were found sufficient for the activation of the Shh reporter as well as endogenous Shh mRNA. Although Shh expression is maintained in Sim2(-)(/)(-) embryos, it was determined to be absent from the rostral midbrain and caudal diencephalon of embryos carrying a dominant-negative transgene that disrupts the function of bHLH-PAS proteins. Together, these results suggest that bHLH-PAS family members are required for the regulation of Shh transcription within aspects of the ventral midbrain and diencephalon.

Animals↗
PubMed2000

[Late cerebrovascular complications of cardiac transplantation].

The occurrence of stroke after the post-operative period of cardiac transplantation is a rare event, and the role of the cardiac transplant in these patients, who often have various vascular risk factors, is unclear. We reviewed the clinical records of 303 consecutive patients with orthotopic cardiac transplantation performed from March 1985 to December 1996 and selected those who developed a stroke over the first 2 months postoperatively, in order to evaluate the frequency and the mechanisms of late cerebrovascular complications. Four patients had presented cerebral infarct and two intracranial hemorrhage. The overall risk of late cerebrovascular complications was 2.6p.100 at 5 years. Ischemic stroke was related to cardiac embolus in one patient, lacunar infarction in another, and was of undetermined etiology in two cases. In addition to vascular risk factors prior to transplantation and the development of intracardiac thrombus, immunosuppressive therapy, the surgical procedure and cardiac rejection may play a role in the occurrence of stroke in such patients.

Aged↗
PubMed1999

[Mucoviscidosis: lung transplantation is always in order].

THE ONLY SOLUTION: Despite significant progress in the management of patients with multiple sclerosis, lung transplantation remains the only chance for survival in those with severe respiratory failure. WAITING LIST INCLUSION CRITERIA: Lung function tests, the patientís general states and psychological and familial factors all contribute to determining inscription on lung transplantation waiting lists. TECHNICAL ASPECTS: Heart-lung, monoblock two-lung and sequential two-lung transplantations are detailed according to the respective advantages and disadvantages. RESULTS: Hospital mortality is about 5% and 5-year survival about 50%. However, only 10% of the patients on waiting lists due to the lack of organs survive for 2 years. PERSPECTIVES: The number of grafts must be increased by developing lobular grafts from live donors using the bipartition technique. Nevertheless, xenografts remain the most promising perspective for increasing the number of patients who can benefit from this therapy.

Adolescent↗
PubMed1999

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗
PubMed1999

Alström syndrome: further evidence for linkage to human chromosome 2p13.

Alström syndrome is a rare autosomal recessive disorder characterized by retinal degeneration, sensorineural hearing loss, early-onset obesity, and non-insulin-dependent diabetes mellitus. The gene for Alström syndrome (ALMS1) has been previously localized to human chromosome 2p13 by homozygosity mapping in two distinct isolated populations - French Acadian and North African. Pair-wise analyses resulted in maximum lod (logarithm of the odds ratio) scores of 3.84 and 2.9, respectively. To confirm these findings, a large linkage study was performed in twelve additional families segregating for Alström syndrome. A maximum two-point lod score of 7.13 (theta = 0.00) for marker D2S2110 and a maximum cumulative multipoint lod score of 9.16 for marker D2S2110 were observed, further supporting linkage to chromosome 2p13. No evidence of genetic heterogeneity was observed in these families. Meiotic recombination events have localized the critical region containing ALMS1 to a 6.1-cM interval flanked by markers D2S327 and D2S286. A fine resolution radiation hybrid map of 31 genes and markers has been constructed.

Base Sequence↗
PubMed1999

Early and late outcome after elective cardiac surgery in patients with cirrhosis.

BACKGROUND: A prospective study was performed to evaluate the early and late outcome after elective cardiac surgery in patients with cirrhosis. METHODS: All patients who underwent elective cardiac surgery between 1995 and 1997, and were suspected of having a history of cirrhosis, were followed in the intensive care unit (ICU), during hospitalization and after hospital discharge. All patients received high doses of aprotinin during surgery. RESULTS: Ten patients of Child-Pugh class A and 2 patients of Child-Pugh class B were studied. All patients had signs of portal hypertension, and 11 of 12 patients had thrombocytopenia. In the first 24 h after operation, the median chest tube output was 810 mL (range 350 to 1,500 mL). Median ICU and hospital stays were 3 and 15 days, respectively (range 2 to 10 and 7 to 36 days, respectively). Seven patients experienced postoperative morbidity and 7 patients had significant complications after their hospital discharge. One death occurred in the ICU. Two deaths occurred after hospital discharge and were related to further hepatic damage. CONCLUSIONS: These results suggest that, in patients with mild or moderate cirrhosis, the incidence of significant complications was high after elective cardiac surgery, increasing the length of stay in ICU and overall hospitalization time and compromising the health status, even well after the operation.

Aged↗
PubMed1999

Closure of the bronchial stump by manual suture and incidence of bronchopleural fistula in a series of 209 pneumonectomies for lung cancer.

OBJECTIVE: Bronchopleural fistula after pneumonectomy is a very serious complication, occurring in 1-4% of cases, regardless of the bronchial stump closure technique adopted. The objective of this study was to report a bronchial stump closure technique in pneumonectomy by manual suture (polypropylene running suture) and to study the incidence of bronchopleural fistula. METHODS: Between January 1988 and December 1997, 209 patients (186 men and 23 women, mean age = 60.5 years) were operated by the same operator. The indication for surgery was lung cancer in all cases. RESULTS: The incidence of bronchopleural fistula was 2.4%; four fistulas during the first postoperative month and another occurred at 6 months; four were located on the left side and one was situated on the right. The bronchial stulnp was covered in only two of these five cases; 40% died of this complication. Neoadjuvant treatment (chemotherapy and/or radiotherapy) was found to increase the risk of development of bronchopleural fistula (40% vs. 7.2%) and this difference was statistically significant (P = 0.046). CONCLUSIONS: Manual closure of the bronchial stump by running suture, performed on an open bronchus, is a reliable technique with a low incidence of bronchopleural fistula. Those results could be further improved by systematically covering the right and the left bronchial stumps.

Adenocarcinoma↗