Quinolone-resistant Neisseria gonorrhoeae: correlation of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV with antimicrobial susceptibility profiles.

Fifty-five clinical strains of Neisseria gonorrhoeae were examined for mutations in the gyrA and parC genes and for antimicrobial susceptibility profiles. The MICs of quinolones for 31 strains with alterations in GyrA were significantly higher than the MICs for 24 strains without such alterations. Eleven strains with alterations in both GyrA and ParC were significantly more resistant to fluoroquinolones than those with alterations in GyrA alone. The MICs of cephalosporins for these strains were also significantly higher than those for other strains.     

Cardiac disease in pregnancy

Pregnancy produces many hemodynamic alterations of the cardiovascular system. Consideration of these alterations must be given in the management of pregnant patients with cardiac disease. This article reviews the cardiovascular hemodynamic alterations of pregnancy, and the management of pregnant patients with specific cardiac lesions.     

骨髓增生异常综合征的表观遗传改变

表观遗传改变是指不涉及DNA序列变化但影响细胞基因表达的一些可遗传的改变,主要包括DNA启动子的甲基化和组蛋白的各种共价修饰。表观遗传改变与肿瘤的发生密切相关,在多种表观遗传相关分子共同参与下,组蛋白氨基酸残基去乙酰化或甲基化,抑癌基因启动子甲基化,使各种转录因子无法与DNA结合而导致抑癌基因失活。目前已知,骨髓增生异常综合征(MDS)存在多种抑癌基因的表观遗传改变,也存在着表观遗传调节蛋白PcG的表达异常,这些都与MDS的进展和预后有着密切的关系,提示了它们可作为新的疾病标志物应用于临床。本文就MDS的存在的表观遗传改变分子机制、抑癌基因失活和PcG蛋白异常作一综述。     

冠脉旁路移植术后心电图改变的临床评价

目的 探讨冠脉旁路移植术(coronary artery bypass grafting，CABG)后各种缺血性心电图改变的临床意义，评价其围术期心梗和心肌缺血的早期诊断价值及与术后早期预后的相关性。方法 108例患者于CABG术后2—10d进行2次／d的12标准导联心电图检查，术后第7天、第14天常规12导联心电图检查1次。依据急性心梗及心肌缺血的心电图诊断标准记录阳性改变。根据有无心电图阳性改变将本组患者分为研究组和对照组，进行手术前后超声心动图EF值及室壁运动情况、术后心肌酶、血流动力学情况和相关并发症等的比较及统计学分析。结果 单纯ST-T改变者51例(研究组1)，出现Q波者15例(研究组2)，无阳性改变者42例(对照组)，各研究组与对照组在以上观察指标的比较中无显著差别。结论 CABG术后心电图的缺血性改变并非围术期心梗和心肌缺血的特异性诊断指标及术后早期顸后的判断指标。     

Metabolic derangements in sepsis and septic shock

This article examines the spectrum of metabolic alterations in sepsis and septic shock. The clinical manifestations, neuroendocrine control, and bioenergetics of the "ebb" and "flow" phases of sepsis are reviewed. Characteristic alterations in carbohydrate, fat, and protein metabolism induced by sepsis are outlined. Finally, the implications of these metabolic alterations for the nutritional support of patients with sepsis are discussed.     

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity in Human Sensory Neuron Somata Parallel Alterations Described in Spontaneously Active Rodent Nociceptors

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. These include enhancement of depolarizing spontaneous fluctuations of membrane potential (DSFs), which were analyzed quantitatively for the first time in human DRG neurons. The functional alterations were indistinguishable from SA-driving alterations reported for nociceptors in rodent chronic pain models. Irregular, low-frequency DSFs in human DRG neurons closely resemble DSFs described in rodent nociceptors while differing substantially from the high-frequency sinusoidal oscillations described in rodent LTMRs. These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons.PerspectiveElectrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.     

Immunologic changes in obesity

A growing body of literature suggests multifaceted alterations to the immune function in obese patients compared with a lean cohort. Although treatment in the intensive care unit has an associated risk of infectious complications, which, if any, of these immunologic alterations are causal is unclear. Obesity clearly causes abundant alterations to the immune system. Overall, the aggregate effect seems to be chronic activation of inflammatory mediators.     

Fluid and electrolyte imbalances after cardiac surgery.

Patients having cardiac surgery experience a myriad of fluid and electrolyte disorders. Cardiopulmonary bypass (CPB) can cause multiple physiologic alterations, including electrolyte disturbances, acid-base imbalances, atelectasis, diminished pulmonary compliance, hemolysis, and thromboembolism. Cardioplegic solutions and induced hypothermia impose alterations in potassium metabolism and pH. The stress of surgery increases catecholamine circulation and augments antidiuretic hormone release, both of which affect fluid and electrolyte equilibrium. Dilution of the circulating blood volume from pump perfusate and volume resuscitation with crystalloid and colloid solutions produce fluid, electrolyte, and hemostatic disorders. Nonpulsatile flow produced by CPB can alter renal function. This article describes the metabolic alterations that are iatrogenically produced by cardiac surgery and the nursing and medical therapies aimed at correcting such alterations.     

COMPARATIVE STUDIES OF THE ISOZYMES OF LACTIC DEHYDROGENASE IN RABBIT AND MAN : OBSERVATIONS DURING DEVELOPMENT AND IN TISSUE CULTURE

During development of rabbit tissues, characteristic sequential alterations in the LDH isozyme pattern occur, and consist for liver and muscle in loss of the most rapidly migrating anodal bands, and increased activity in the cathodal bands and slower migrating anodal bands. In heart the reverse changes were observed. Comparison of the isozyme patterns observed in various fetal and adult human tissues suggests that these same sequential alterations probably occur. A species-specific isozyme pattern is obtained in long term culture of rabbit, chick, and human cells. The alterations in tissue culture are characterized by a gradual redistribution of total LDH activity in which there is decreased intensity of rapidly migrating anodal bands. These sequential alterations are independent of the organ of origin. The number of bands observed in the starch gel is partly dependent upon the total activities applied. Isozymes may provide a convenient method for determining the species of origin of cell lines in common use and for investigating the effects of various alterations in the in vitro environment on cells grown in tissue culture.     

Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates. Therefore, gray matter density (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy control subjects (HC) were examined in a three-step approach using cross-sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of structural alterations irrespective of symptomatology; (2) subdivision of the patient sample according to a three-dimensional factor model of the PANSS and investigation of structural differences between these subsamples and healthy controls; (3) analysis of a common pattern of structural alterations present in all patient subsamples compared to healthy controls. Significant GMD reductions in patients compared to controls were identified within the prefrontal, limbic, paralimbic, temporal and thalamic regions. The disorganized symptom dimension was associated with bilateral alterations in temporal, insular and medial prefrontal cortices. Positive symptoms were associated with left-pronounced alterations in perisylvian regions and extended thalamic GMD losses. Negative symptoms were linked to the most extended alterations within orbitofrontal, medial prefrontal, lateral prefrontal and temporal cortices as well as limbic and subcortical structures. Thus, structural heterogeneity in schizophrenia may relate to specific patterns of GMD reductions that possibly share a common prefrontal-perisylvian pattern of structural brain alterations.     

Complications of menopause. Nutritional implications

In this article, the authors analyze the pathological alterations which women suffer in which menopause is assumed to be a risk factor leading to the outbreak of these pathologies. Taken together, all of these alterations present some clear nutritional considerations; therefore, adequate dietetical care, followed by women during this phase, could help in their prevention and control. These alterations are: osteoporosis, obesity, arterial hypertension, arteriosclerosis and cardiovascular diseases.     

Imaging HDACs In Vivo: Cross-Validation of the [11C]Martinostat Radioligand in the Pig Brain

Molecular Imaging and Biology - With the emerging knowledge about the impact of epigenetic alterations on behavior and brain disorders, the ability to measure epigenetic alterations in brain tissue...     

Transformation of human kidney proximal tubule cells by ras-containing retroviruses. Implications for tumor progression

Normal human kidney proximal tubule cells into which a ras oncogene was inserted undergo a series of transformation-related alterations that are characteristic of renal carcinomas. These include changes in morphology, growth potential, anchorage dependence, antigen expression, growth factor production, and chromosomal stability. Further, there are spontaneous progressive alterations in vitro in the karyotype and antigenic profile of the transformed cells. Cytogenetic analyses suggest that alterations of chromosome 21 may play an early and pivotal role in the development of transformed proximal tubule cells.     

Taste alterations among patients with cancer

Patients with cancer frequently develop taste alterations, which are manifested by food aversions and decreased caloric intake. Many etiologies are recognized, including the effect of tumors, cancer cell mitosis, vitamin deficiencies, and cytokine involvement. Preventing or improving taste alterations in patients with cancer is challenging. Clinicians play an important role in assessing, educating, and referring (when indicated) patients experiencing potential or actual taste alterations. Directions for further nursing research include the development of assessment tools and preventative strategies.     

CO2气腹对腹腔内环境的影响

腹腔镜手术中应用CO2气腹可导致腹膜表面发生超微结构、代谢以及免疫的改变。这些改变包括腹膜间皮层结构改变、局部pH紊乱和腹膜巨噬细胞反应性的变化。这可能是恶性肿瘤腹腔镜手术后穿刺孔转移和广泛腹膜转移的原因。     

Pathogenesis of Posttraumatic Headache and Migraine: A Common Headache Pathway?

In recent years, research implicating biochemical abnormalities in various pathological conditions has spiraled. Headache is an area in which numerous research studies have been conducted examining biochemical alterations. We have noticed several similarities in biochemical changes reported to occur in migraine and in experimental traumatic brain injury. The most common symptom in mild head injury or mild traumatic brain injury is headache which, in many instances, resembles migraine but has a poorly understood pathophysiology. Biochemical mechanisms believed to be similar in both conditions include: increased extracellular potassium and intracellular sodium, calcium, and chloride; excessive release of excitatory amino acids; alterations in serotonin; abnormalities in catecholamines and endogenous opioids; decline in magnesium levels and increase in intracellular calcium; impaired glucose utilization; abnormalities in nitric oxide formation and function; and alterations in neuropeptides. In this paper, these preposed biochemical alterations will be reviewed and compared. Very similar alterations suggest posttraumatic headache associated with mild head injury and migraine may share a common headache pathway.     

Molecular changes in smoking-related lung cancer

To elucidate the effect of cigarette smoke on developing lung cancer among individuals, numerous genetic and epigenetic factors related to cigarette smoke-induced lung cancers have been widely investigated and a various genes, loci and pathways have been identified as candidates to date. However, the importance of these molecular alterations in the initiation and progression of lung cancer still remains imprecise and different molecules altered in lung cancer are being used for stratification of patients for targeted therapy. There are a number of molecular pathways involved in the development of lung cancer, and environmental factors related to these alterations are still unclear. Furthermore, various genetic alterations determined by candidate gene approach have not been re-evaluated for their functional significance together with epigenetic alterations in the same population. Accumulated evidence suggested that lung cancer in ever smokers and never smokers follow distinct molecular pathways and may therefore respond to distinct therapy. Therefore, additional studies will be essential to re-evaluate the individual risk of developing lung cancer based on the combination of genetic and epigenetic alterations and to set up a guideline to assess the individual risk for lung cancer and for its prevention.     

白术对大鼠脑出血后小肠粘膜形态学变化的影响

目的：评价白术对脑出血大鼠小肠粘膜形态学的影响。方法：56只SD大鼠随机分为模型组24只、治疗组24只及对照组8只,对照组不予任何处理,模型组和治疗组制备脑出血大鼠模型后分别采用灌胃法每天灌注生理盐水和白术液（0.2 g/mL）。检测并分析对照组及脑出血后第1、7、14天模型组、治疗组（每时间点各取8只）小肠粘膜的形态学参数。结果：与对照组比较,模型组脑出血后绒毛面积降低最快最明显,绒毛高度及粘膜厚度逐渐降低,肠腺密度和深度先降低后增高。与模型组比较,治疗组于脑出血后第1天小肠绒毛高度、粘膜厚度明显降低（P0.01）,绒毛面积略降,肠腺密度及深度略增;第7天小肠绒毛高度、绒毛面积及粘膜厚度略降,肠腺密度及深度明显增大（P0.01）;第14天小肠绒毛高度、绒毛面积及粘膜厚度明显增加（P0.01）,肠腺密度及深度略降。结论：脑出血可以引起小肠粘膜萎缩;白术可改变脑出血大鼠的小肠粘膜形态,从而促进大鼠肠道功能的恢复。     

Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays

Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.     

Conjunctival and pulmonary hemodynamic properties in sickle cell disease subjects with and without pulmonary hypertension

Conjunctival microvascular hemodynamic alterations were reported for the first time in sickle cell subjects with and without pulmonary hypertension. Assessment of the conjunctival microcirculation using noninvasive imaging may improve understanding of microvascular hemodynamic alterations that occur due to pulmonary hypertension in sickle cell disease.