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271.
Degoey DA Grampovnik DJ Chen HJ Flosi WJ Klein LL Dekhtyar T Stoll V Mamo M Molla A Kempf DJ 《Journal of medicinal chemistry》2011,54(20):7094-7104
Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported. 相似文献
272.
Mengistu Legesse Gobena Ameni Gezahegne Mamo Girmay Medhin Gunnar Bjune Fekadu Abebe 《BMC public health》2011,11(1):157
Background
Infection with Mycobacterium bovis (Mb) predominantly causes cervical TB lymphadenitis (TBL). Raw milk is considered the main source of Mb infection and raw milk is a major food source for Afar pastoralists. The aim of this study was to assess Afar pastoralists' knowledge concerning cervical TBL and its treatment. 相似文献273.
Uchida H Takeuchi H Graff-Guerrero A Suzuki T Watanabe K Mamo DC 《Journal of clinical psychopharmacology》2011,31(4):497-502
Positron emission tomography (PET) studies proposed a therapeutic window of D2 receptor occupancy (65%-80%) of antipsychotics for the treatment of schizophrenia in young adults. However, this conclusion has been drawn from clinical PET studies using small sample sizes (<20). Prospective PET studies that measured D2 occupancy levels and assessed extrapyramidal side effects (EPS) and/or treatment response induced by antipsychotics (excluding partial agonists) were identified, using MEDLINE and EMBASE (last search: March 2010). Individual subjects were divided into 2 groups based on EPS status (ie, presence or lack of newly emergent EPS) and treatment response (ie, a ≥ 25% or ≥ 50% reduction in the Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale). To evaluate the performance of this binary classification, sensitivity, specificity, and accuracy of consecutive cutoff points in the D2 occupancy were calculated: Accuracy = (True Positive + True Negative) / Total N. Twelve studies, including a total of 82 subjects, were included in our analyses. The cutoff points associated with 0.5 or greater in both sensitivity and specificity with the greatest accuracy were 77% to 78% for EPS, 60% for a 25% or greater symptom reduction, and 72% for a 50% or greater symptom reduction. These findings support the presence of a therapeutic window of 60% to 78% D2 occupancy of antipsychotics in young adults with schizophrenia and may suggest the presence of a continuum of effectiveness with increasing occupancy within this therapeutic window. 相似文献
274.
Ismail Z Nguyen MQ Fischer CE Schweizer TA Mulsant BH Mamo D 《Current psychiatry reports》2011,13(3):211-218
Alzheimer’s disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including
psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from
hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions
in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles
of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to
a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities.
Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification
delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between
these two syndromes is essential to making progress in the area of delusions in AD. 相似文献
275.
Hiroyuki Uchida md phd Takefumi Suzuki md phd David C. Mamo md msc frcpc Benoit H. Mulsant md ms frcpc Kenichi Tsunoda md Hiroyoshi Takeuchi md Toshiaki Kikuchi md Shinichiro Nakajima md Kensuke Nomura md Masayuki Tomita md Koichiro Watanabe md phd Haruo Kashima md phd 《Psychiatry and clinical neurosciences》2009,63(2):244-246
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278.
Sturniolo G Bonanno L Gagliano E Tonante A Taranto F Mamo M De Salvo G Sturniolo G 《Chirurgia italiana》2007,59(6):781-787
This study describes the findings of a retrospective study of 57 medullary thyroid cancer patients observed at the main Sicilian centres for endocrine surgery. Six of these patients were observed locally in order to add a further dimension to the discussion of surgical therapies for medullary thyroid carcinoma. A review of the literature on sporadic forms of medullary thyroid carcinoma and hereditary neoplastic syndromes is followed by presentation of the authors' series. Diagnostic protocols, surgical therapies and pathological observations are discussed. Particular attention is paid to patterns of metastases of medullary thyroid carcinoma and to the differing opinions regarding the extent of lymph-node dissection required and the treatment of recurrent disease. Total extracapsular thyroidectomy with lymph-node dissection is identified as the gold standard of surgical therapies for this form of cancer. 相似文献
279.
Tonante A Bonanno L Taranto F Gagliano E Mamo M Sturniolo G De Salvo G Sturniolo G 《Il Giornale di chirurgia》2008,29(6-7):289-290
The Authors report a case of a spontaneous intestinal 'recanalization' after 1 year since the palliative surgery (definitive colostomy) for rectal cancer in a 79 years-old patient. 相似文献
280.