Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.
Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity. 相似文献
BackgroundThe optimal management of community acquired pneumonia (CAP) depends on the clinical and microbiological profile in the locality.ObjectivesTo determine the clinical and microbiological profile of patients admitted with CAP in Ilorin, Nigeria.MethodsOne hundred and two consenting consecutively selected patients with clinical and radiologic confirmation of CAP were recruited in 12 months. The socio-demographic, physical examination and laboratory/radiologic parameters were documented in a questionnaire. Microbiological evaluation of their sputum was done and blood samples were taken for complete blood count, culture, serum urea and serological evaluation for atypical bacteria and some viral pathogens.ResultsCAP constituted 5.9% of the total medical admissions during the one-year study period. The mean age of the patients was 49 ± 22 years with the largest frequency in those aged 65 years and above. The commonest symptoms were shortness of breath (96.1%) and cough (94.1%), with a median duration of 3 days from symptom onset to admission. Systemic hypertension was the commonest comorbid illness (25/102; 24.5%). Klebsiella pneumoniae was the predominant pathogen isolated (20/102; 28.1%). The susceptible antibiotics were Imipenem, Ceftazidime and Ceftriaxone. Intra-hospital mortality was 17.6%. CURB – 65 score of ≥ 2 and the presence of complications of CAP were the independent predictors of mortality.ConclusionCAP constitutes a significant disease burden in Ilorin, Nigeria. Typical bacteria accounted for over half of the pathogens isolated from the patients with gram negative agents predominating. This highlights a possible shift in the microbiological profile which could guide empirical treatment. 相似文献
ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I2 = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I2 = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I2 = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I2 = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I2 = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I2 = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I2 = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I2 = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I2 = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I2 = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol. 相似文献
Current screening batteries for assessing neuropsychological function are not specific for Amyotrophic Lateral Sclerosis (ALS) and are considered as limited tools due to the physical disabilities associated with ALS. The Edinburgh Cognitive and Behavioural ALS screen (ECAS) was developed to detect the specific cognitive and behavioral changes that may occur among ALS patients. This study presents the ECAS developed for Arabic-speaking ALS patients (ECAS-AR) for use by healthcare professionals. ECAS was translated and modified to refined variety of Arabic language. Eighty-five ALS patients were included. Normative data were collected from 200 healthy controls (among them 97 were matched). Subjects were administered the ECAS-AR and two conventional cognitive screening batteries, Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE). ECAS-AR discriminated well between healthy controls and ALS patients. Significant differences were noted in language, executive functions, memory, and visuospatial domains between the two groups. The most prevalent deficit occurred in language and executive functions in ALS-specific functions. Whereas memory was more readily impaired in the lower and middle education groups concerning ALS non-specific functions. Verbal fluency tended to be preserved. Positive correlations were found between ECAS-AR and the standard cognitive tests supporting its full validity. The ECAS-AR version proposed will provide rapid, efficient and sensitive tools for healthcare professional to determine the cognitive-behavioural profile in Arabic-speaking ALS patients. 相似文献
We developed a semiautomatic method termed “cortical circumferential profiling” for objective analysis of cerebral cortex function in emission tomographic neuroimaging studies. This method treats cortex as a continuous ring near the outer brain edge. A computer algorithm samples the cortex at 60 contiguous, equiangular locations, using 1-cm2 samples. These values are plotted as a function of cortical angle to produce the cortical circumferential profile. This method was used in a study of regional cerebral perfusion in 15 patients with Alzheimer's disease and 8 elderly control subjects using N-isopropyl [I-123]-iodoamphetamine. Cortical circumferential profiling decreases variability, examines the entire cortex within slices at preselected levels above the orbital-meatal line, and facilitates intrasubject and intersubject comparisons. 相似文献
Recently, Korean people are consuming seaweeds almost 3.5 times more now than three decades ago. It is well known that seaweeds contain lots of soluble dietary fiber in addition to micronutrients such as β-carotene, iodine and some bioactive components. Seaweeds are considered to be effective for preventing chronic diseases including obesity, diabetes mellitus, atherosclerosis, cancer or constipation. This study was conducted to investigate the effect of seamustard intake on body weight gain, blood glucose level and lipid profiles in rats fed diets with different energy nutrient composition. Male Sprague-Dawley rats (average initial weight 103.7 g) were divided into groups for two experiments as follows; Control, M2.5 & M5 groups (Exp. I) and M5, M10, HCM5, HCM10, HFM5 & HFM10 groups (Exp. II). The rats were fed diet and water ad libitum for 4 weeks. In general, there was no significant difference in blood glucose and triglyceride concentration among groups. In Exp. I, serum LDL-cholesterol level of rats fed diet with 5% seamustard powder (M5) was significantly lower than that of control group, while HDL-cholesterol level, TC/LDL ratio and weight of adrenal gland were higher. In Exp. II, food intake, body weight gain and EER of high fat diet with 10% seamustard group (HFM10) were the lowest among groups. Except gastrocnemius muscle, all organ weights of HFM10 group were the lowest. Fecal cholesterol excretion and serum LDL-cholesterol concentration of HFM10 group were the highest, while serum HDL-cholesterol level was the lowest among groups. Interestingly, HDL-cholesterol concentration was the highest in HCM5 group among groups. From these results, it was suggested that seamustard intake might be more effective for body weight control, but not for improving blood lipid profiles in high fat diet than in high carbohydrate diet. 相似文献
An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models. 相似文献
A new MRI method is described to acquire a T(2)-weighted image from a single slice in a single shot. The technique is based on rapid acquisition by sequential excitation and refocusing (RASER). RASER avoids relaxation-related blurring because the magnetization is sequentially refocused in a manner that effectively creates a series of spin echoes with a constant echo time. RASER uses the quadratic phase produced by a frequency-swept chirp pulse to time-encode one dimension of the image. In another implementation the pulse can be used to excite multiple slices with phase-encoding and frequency-encoding in the other two dimensions. The RASER imaging sequence is presented along with single-shot and multislice images, and is compared to conventional spin-echo and echo-planar imaging sequences. A theoretical and empirical analysis of the spatial resolution is presented, and factors in choosing the spatial resolution for different applications are discussed. RASER produces high-quality single-shot images that are expected to be advantageous for a wide range of applications. 相似文献
Anorectal function was evaluated in eight patients who had low anterior resection of the rectum with a low anastomotic line,
using an EEA™ stapler, with determination of function based on periodic manometric studies and clinical symptoms. Immediately following
surgery all patients suffered from frequent bowel actions and soiling. These symptoms improved with time and most patients
could enjoy almost normal daily life by the sixth postoperative month. One month after surgery, anal canal resting pressure
and maximum squeeze pressure were significantly reduced and rectoanal inhibitory reflex was absent; neither showed a distinct
tendency to improve thereafter. Rectal sensation and reservoir capacity, which also were seriously impaired, recovered satisfactorily
by the time of the six-month examination. This suggests that an improvement of clinical symptoms following this operation
is dependent upon the recovery of reservoir capacity and sensation of the neorectum, and that this operative procedure is
a functionally acceptable option for low rectal cancer. 相似文献