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PubMedDate not supplied

[Dr. John Baptiste Edouard Gélineau].

With this brief review we honor the memory of the great French doctor Jean Baptiste Edouard Gélineau. Dr. Gélineau was born on December 23, 1828 at Blaye, Gironde, close to the Bordeaux region. His name is connected with the first clinical description of the disease for which he, both by the right of the primacy as well as ad valorem of his first two names, coined the name "narcolepsy". He was the first to notice the intrinsically evanescent symptoms of narcolepsy, such as excessive daytime somnolence, imperative sleep habits and cataplexy or "astasia" as he called it, and incorporate them into a single clinical syndrome. In 1881 Gélineau discussed Kaffe's case of "maladie du sommeil" as a proof of the existence of the new disease described a year before. As a good clinical observer Gélineau noticed the close relation of emotional engagement and astasia. His attitude was that narcolepsy was a nosologic entity, a disease sui generis, but admitted that it could appear purely as a symptom only. This was in discordance with the views in England where (in 1928) Dr. Samuel Alexander Kinnier Wilson repudiated such convictions; in 1930 Lhermitte still shared the same opinion. Gélineau differentiated narcolepsy from epilepsy with the elegance of clinical reasoning. Overall, Gélineau described three elements of the narcoleptic pentade. Sleep paralyses were first described by Mitchell in 1876, and were first attributed to narcolepsy by Wilson in 1928; in 1930 Lhermitte first described hypnapompic, and Daniels, in 1934, hypnagogic sleep paralysis. Hypnagogic hallucinations were described by Maury in 1848 and subsequently by de Saint Denis in 1867. In twenties they were thoroughly studiesed during the epidemic encephalitis and after the Big War in 1922 by Levy. The life story of Dr. Gélineau covers multivarious activities. As a young student of the Rochefort Navy Medical School he took part in the fight against colera which deluged the city of La Rochelle. In 1849 he became the "Intern" of the Navy Hospital and next year a "Surgeon of the Third Class". As a Navy surgeon he visited French colonies in the Indian ocean: first the Reunion island and then Mayotte island of the Commores Archipelago. Of this period he wrote "Voyage a i'lle de la Réunion", memoirs published much later, in 1905, in which he described colonial life and abolition of slavery. The story of Elise, a beauteous Creole woman, a concubine of a young naval Commander, who delivered a child that soon died, inexorably points to the autobiographic character of his work. He defended a doctoral thesis "Aperçu Medical de I'lle de Mayotte" at Montpellier University School of Medicine in 1858, using the data collected during his year-and-a-half stay on a Mayotte island; at that time he was a "Navy Surgeon of the Second Class". For his dedication in fighting against epidemics that broke out during the French-German war in 1870 he was nominated for the Legion of Honor, but received it only later. In 1871 Gélineau introduced "Doctor Gélineau's tablets" for the treatment of epilepsy (contained bromide and arsenic). He was a member of the Société de Médicine, Société d' Hypnologie, La-Société Française d' Hygiène, and a few others. After retirement at the age of 72, Gélineau switched to wine production, continuing the family tradition; for the quality of his Bordeaux wines he was awarded gold medals at the Anvers and Paris Exhibitions. Dr. Gélineau died on March 2, 1906, at Argeles Gazost in Pyrnees honored by the titles of Chevalier de la Légion d' Honneur, Officier d'Academie and Commander of Nichan of the Ottoman Empire.

Epilepsy↗
PubMed1994

A phase I study of swainsonine in patients with advanced malignancies.

Swainsonine, an alpha-mannosidase inhibitor which blocks Golgi oligosaccharide processing, represents a new class of compounds that inhibit both rate of tumor growth, and metastasis, in murine experimental tumor models. In this first phase I study, the quantitative and qualitative toxicities of swainsonine have been studied in patients given a continuous i.v. infusion over 5 days, repeated at 28-day intervals. Dose levels were escalated in increments of 100 micrograms/kg/day from 50-550 micrograms/kg/day. Nineteen patients with both solid tumor and hematological malignancies were given a total of 31 courses. Hepatotoxicity, particularly in patients with liver metastases, was the dose-limiting toxicity. The maximum tolerated dose (MTD) and the recommended starting dose (MTD -1 level) were 550 and 450 micrograms/kg/day, respectively. Common side effects included edema, mild liver dysfunction, a rise in serum amylase, and decreased serum retinol. Acute respiratory distress syndrome possibly precipitated by swainsonine resulted in a treatment-related death in a patient with significant pretreatment hepatic dysfunction. One patient with head and neck cancer showed > 50% shrinkage of tumor mass for 6 weeks after treatment. Two patients with lymphangitis carcinomatosis on chest X-ray noted improvement in cough and shortness of breath during the infusion of swainsonine and for 1 week thereafter. Clearance and serum half-life for swainsonine were determined to be approximately 2 ml/h/kg, and 0.5 day, respectively. Golgi oligosaccharide processing, a putative anticancer target for swainsonine was inhibited in peripheral blood lymphocytes as evidenced by a marked decrease in leukoagglutinin binding after 5 days of treatment. Oligomannosides in patient urine increased 5-to 10-fold over the 5 days of treatment, indicating that tissue lysosomal alpha-mannosidases were also blocked by swainsonine. Urine oligomannoside accumulation reached steady state at 3 days, approximately 1 day after serum drug levels reached steady state. The fraction of HLA-DR-positive cells in peripheral blood lymphocytes increased following 5 days of swainsonine treatment, an effect similar to that observed for peripheral blood lymphocytes from normal subjects cultured with swainsonine. No significant changes in CD3, CD4, CD8, CD16, and CD25 were observed. Swainsonine produces minimal toxicity when administered i.v. to cancer patients at dosages that inhibit both Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. Detection of hepatic metastases or liver enzyme abnormalities prior to treatment predict for more significant toxicity.

Adult↗
PubMed2006

Effect of bacterial symbionts Xenorhabdus on mortality of infective juveniles of two Steinernema species.

Steinernema species are entomopathogenic nematodes associated with Xenorhabdus bacteria. The life cycle of these associations is composed of two stages: (1) a free stage in the soil, where infective juveniles (IJs), which carry bacteria in their guts, search for new insect hosts; and (2) a parasitic stage, where the IJs infect insects, release their Xenorhabdus symbionts and reproduce in order to produce new IJs. Previous studies clearly showed benefits to the association for several Steinernema species during the parasitic stage. Nevertheless, no study has so far explored, during the free stage, the existence of costs or benefits to the association for different Steinernema. Here, we compared the survival of both symbiotic and aposymbiotic IJs in two nematode species: (1) Steinernema carpocapsae-exhibiting IJs that carry a high number of Xenorhabdus cells in their guts; and (2) its closely relative species, S. scapterisci-exhibiting IJs, that carry very few Xenorhabdus cells in their guts. We showed that the bacterial symbionts were costly for S. carpocapsae by increasing IJs' mortality but not for S. scapterisci. This difference in cost induced by bacteria to IJs during the free stage could be correlated with the difference in the numbers of bacteria carried by IJs of each nematode species.

Animals↗
PubMed2003

Structural genomics of highly conserved microbial genes of unknown function in search of new antibacterial targets.

With more than 100 antibacterial drugs at our disposal in the 1980's, the problem of bacterial infection was considered solved. Today, however, most hospital infections are insensitive to several classes of antibacterial drugs, and deadly strains of Staphylococcus aureus resistant to vancomycin--the last resort antibiotic--have recently begin to appear. Other life-threatening microbes, such as Enterococcus faecalis and Mycobacterium tuberculosis are already able to resist every available antibiotic. There is thus an urgent, and continuous need for new, preferably large-spectrum, antibacterial molecules, ideally targeting new biochemical pathways. Here we report on the progress of our structural genomics program aiming at the discovery of new antibacterial gene targets among evolutionary conserved genes of uncharacterized function. A series of bioinformatic and comparative genomics analyses were used to identify a set of 221 candidate genes common to Gram-positive and Gram-negative bacteria. These genes were split between two laboratories. They are now submitted to a systematic 3-D structure determination protocol including cloning, protein expression and purification, crystallization, X-ray diffraction, structure interpretation, and function prediction. We describe here our strategies for the 111 genes processed in our laboratory. Bioinformatics is used at most stages of the production process and out of 111 genes processed--and 17 months into the project--108 have been successfully cloned, 103 have exhibited detectable expression, 84 have led to the production of soluble protein, 46 have been purified, 12 have led to usable crystals, and 7 structures have been determined.

Acid Anhydride Hydrolases↗
PubMed2025

Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. METHODS: This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. CONCLUSIONS: The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.

Aged↗
PubMed2004

Technology to promote safe mobility in the elderly.

New technologies designed to help prevent adverse events related to the mobility of geriatric patients (ie, patient falls, bed-rail entrapment, patient handling, and wandering) are described. Technology offers the potential to eliminate or mitigate preventable adverse events that interfere with treatment, delay rehabilitation, potentiate impairment, and compromise patient safety. Unchecked, these adverse events can have a negative impact on patient health, functional status, and quality of life. It is not surprising that the elderly constitute the population at highest risk for adverse events, based on poor health, chronic conditions, long hospitalizations, and institutional care. Patient falls are a high-risk, high-volume, and high-cost adverse event. Key technologies to prevent falls and fall-related injuries include hip protectors, wheelchair/scooter safety features, intelligent walkers, fall alarms, and environmental aids. Bed-rail entrapment is a serious adverse event, which includes patients being trapped, entangled, or strangled in beds. New technologies to prevent bed-rail entrapment include new hospital bed designs, height-adjustable low beds, devices to close gaps in legacy beds, and bedside floor mats. Patients with mobility impairments necessitate physical assistance in transfers and other patient-handling tasks, which increases risk for the caregiver and the patient. Featured technologies to prevent patient handling injuries include innovations in floor-based lifts, new ceiling-mounted patient lifts, and improvements in powered standing lifts, new friction-reducing devices, and new patient transport technology. Wandering affects 39% of cognitively impaired nursing home residents and up to 70% of community-residing elderly persons with cognitive impairments. New technologies to prevent adverse events associated with wandering include door alarms and signal-transmitting devices. Nurses in geriatric settings would benefit from exposure to technologies that could improve patient and caregiver safety. To maximize the benefits of technology, it is critical that front-line nursing staff be involved in the testing and selection of devices that will be used in their practice. Further, to reap the full benefits of technology, a careful plan for implementation needs to be developed that would include integrating the new technology with existing infrastructure. Training needs to be provided for all staff who will be using the technology, and efforts to ensure competency over time is needed. A major barrier to widespread use of new technology is cost. Further research is needed to demonstrate the cost effectiveness of these devices. Results from these studies will help to build a business case, demonstrating that initial capital investments will result in cost savings, improved quality of care, and other benefits.

Accident Prevention↗