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571.
Treatment of human African trypanosomiasis--present situation and needs for research and development
Legros D Ollivier G Gastellu-Etchegorry M Paquet C Burri C Jannin J Büscher P 《The Lancet infectious diseases》2002,2(7):437-440
Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs. 相似文献
572.
Sunthorn H Hasija P Burri H Shah D 《Pacing and clinical electrophysiology : PACE》2005,28(11):1247-1249
We report the case of an elderly patient who presented with poorly tolerated episodes of atrial arrhythmia refractory to medical treatment. AV node ablation was identified as the only alternative expected to be efficacious for symptom relief. However, this usually simple intervention failed. The goal of creating a complete AV block was finally achieved through ablation of the anterior fascicle of the His bundle, which represented the only pathway for residual conduction in this patient. 相似文献
573.
Background
Genetic factors have been implicated in the etiology of female sexual dysfunction. Yet, how much the dynamic nature of sexual functioning is influenced by changes in genetic and/or environmental factors remains unknown.Aim
To explore temporal stability of genetic and environmental influences on female sexual functioning over a 4-year period.Methods
Data on desire, arousal, lubrication, orgasm, satisfaction, and pain were collected in 2009 and 2013 using the Female Sexual Function Index and were available for 1,209 British twin women.Outcomes
To track the stability of genetic influences the Female Sexual Function Index sub-domain and total scores were subject to multivariate twin analyses for repeated measures.Results
Desire showed a lower heritability at follow-up (37% vs 14%) whereas for arousal and sexual pain the heritability at follow-up was higher compared to baseline (28% vs 34% and 30% vs 45%, respectively). The heritability of lubrication remained stable at 27%. According to the best-fitting additive environmental (AE) Cholesky model for all domains except for sexual pain there were no new genetic factors expressing themselves over the 4-year period, but an addition of new, unique environmental determinants could be observed. For sexual pain an additional genetic factor could be observed at follow-up, explaining 39% of the phenotypic variance.Clinical Translation
The biological pre-disposition to sexual problems seems to remain relatively stable over time.Conclusions
This is the first study to investigate the genetic stability of female sexual functioning in a large population sample of women. White ethnicity and the relatively high mean age of women asks for caution in extrapolating the findings to other ethnic and age groups. The findings highlight the value of more in-depth exploration of the non-shared environmental influences that could provide clues to the mechanisms behind remittance and/or persistence of sexual problems. Integration of these findings may provide a useful conceptual framework for the treatment and prevention of certain types of sexual problems.Burri A, Ogata S. Stability of Genetic and Environmental Influences on Female Sexual Functioning. J Sex Med 2018;15:550–557. 相似文献574.
575.
Elizabeth Barba Emanuel Burri Sergio Quiroga Anna Accarino Fernando Azpiroz 《Neurogastroenterology and motility》2023,35(2):e14466
Background
Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation).Methods
A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35.Key Results
(A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent).Conclusions and Inferences
In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity. 相似文献576.
577.
Bao Ying Chen Jessica R. Salas Alyssa O. Trias Arely Perez Rodriguez Jonathan E. Tsang Miriam Guemes Thuc M. Le Zoran Galic H. Michael Shepard Lawrence Steinman David A. Nathanson Johannes Czernin Owen N. Witte Caius G. Radu Kenneth A. Schultz Peter M. Clark 《Immunology》2023,168(1):152-169
Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate-limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35–55 and MOG1–125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE-515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE-515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE-515 blocks activation-induced B and T cell proliferation and MOG35–55-specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35–55-specific lymphocyte activation-induced proliferation. 相似文献
578.