99锝-亚甲基二磷酸盐治疗甲状腺相关眼病的Meta分析

背景 目前治疗甲状腺相关眼病(TAO)应用最广泛的方法为糖皮质激素的应用,其疗效显著,但不良反应较多.99锝-亚甲基二磷酸盐(99Tc-MDP)近年来在临床上的应用逐渐受到重视,但其与糖皮质激素治疗比较是否更为安全、有效尚未明确. 目的 系统评价99Tc-M DP治疗TAO的临床效果.方法 计算机检索The Cochrane Library、中国知网、PubMed、万方数据库、维普数据库,手工检索Google学术网,检索文献的发表时间为建库至2012年4月,收集99Tc-MDP治疗TAO的随机对照试验(RCT),根据研究的方法学评价纳入文献的质量,提取有效数据,评价指标包括主要结局指标,如治疗的总体有效率、眼球突出度和复发率,以及次要结局指标,如治疗的不良作用.采用RevMan 5.1软件进行Meta分析.结果 共纳入11个符合质量标准的RCTs,共706例.按测量指标和干预措施进行亚组分析.Meta分析结果显示,治疗TAO的总有效率比较,99Tc-MDP静脉推注法与免疫抑制疗法(甲强龙联合氨甲喋呤)治疗间差异无统计学意义[相对危险度(RR)=0.96,95％可信区间(CI):0.76 ～ 1.22,P=0.740],99Tc-MDP静脉推注法与口服泼尼松法间差异有统计学意义(RR=1.25,95％ CI:1.06 ～ 1.46,P=0.007),99Tc-MDP静脉推注法与空白对照组间差异有统计学意义(RR=2.53,95％ CI:1.68 ～3.81,P=0.000),99Tc-MDP静脉推注联合甲强龙冲击疗法与单用甲强龙组间差异有统计学意义(RR=1.27,95％ CI:1.05 ～ 1.53,P=0.010).治疗眼球突出度的有效率比较,99Tc-MDP静脉推注组与口服泼尼松组间的差异有统计学意义(RR=2.02,95％ CI:1.44～ 3.56,P=0.020);TAO治疗有效者1年后的复发率比较,99Tc-MDP静脉推注组与口服泼尼松组间的差异有统计学意义(RR=0.51,95％ CI:0.33 ～0.78,P=0.002).99Tc-MDP静脉推注组不良反应的发生率明显低于口服泼尼松组和免疫抑制疗法组.结论 99Tc-MDP静脉推注的治疗方案可以达到与甲强龙联合氨甲喋呤的免疫抑制疗法相同的治疗效果;99Tc-MDP静脉推注联合甲强龙冲击疗法较单用甲强龙冲击疗法可以达到更好的治疗效果,其全身不良反应明显减少.     

Focal MIBI uptake is a better indicator of active myeloma than diffuse uptake

PURPOSE: Technetium-99m 2-methoxyisobutylisonitrile (MIBI) imaging has been proposed as a front-line investigation to detect bone disease both before and after the treatment of myeloma. In this study, we have compared the pattern of MIBI uptake (focal and diffuse) between patients with proven myeloma and a cohort of patients without myeloma, in order to identify the uptake pattern that best correlates with disease activity. METHODS: Nineteen scans were taken in 16 consecutive patients (nine males and seven females: aged 39-71 yr) with active myeloma. A further 20 scans (10 subjects having MIBI myocardial perfusion scintigraphy and 10 subjects having MIBI parathyroid adenoma localisation studies), comprised the control (non-myeloma) cohort. Scans were evaluated in a double-blinded fashion by two observers for any diffuse skeletal MIBI uptake (homogeneous uptake in spine, sternum and/or long bones), and/or abnormal focal uptake (patchy, focal or tubular uptake in the skeleton or soft tissues). RESULTS: The pattern of MIBI uptake was significantly different in the myeloma-positive subjects and the control cohort. Focal uptake was highly discriminatory, being seen in 15 of 19 (79%) scans of the myeloma-positive group as opposed to one of 20 (5%) scans of the control group (P < 0.0001). In contrast, diffuse uptake was seen in 17 of 19 (89%) scans in patients with myeloma, and in 11 of 20 (55%) of the control cohort (P = 0.02). Using multiple logistic regression analysis, any focal uptake was significantly predictive for active myeloma (P = 0.0007) but diffuse uptake was not (P = 0.15). Diffuse uptake alone, without focal uptake, was found in four of 19 scans with myeloma and in 10 of 20 without active myeloma, but was not significantly associated with absence of active myeloma (P = 0.06). Using the criteria of Pace et al. for positivity (diffuse activity >50% myocardial activity), we demonstrated improved specificity from 45% to 100%, but significantly impaired sensitivity for presence of myeloma (79% vs. 37%, P = 0.02). CONCLUSION: Our study thus illustrates that the presence of any focal uptake of MIBI is useful in indicating active myeloma whereas diffuse uptake is not.     

Technetium 99m-diethylene triamine penta-acetic acid aerosol clearance in the evaluation of pulmonary involvement in sickle cell disease

BACKGROUND: Pulmonary clearance of inhaled technetium (Tc) 99m-labeled diethylene triamine penta-acetic acid (DTPA) aerosol is a sensitive non-invasive marker of alveolar permeability and patients with interstitial lung diseases show enhanced clearance. However, a previous study in adult patients with diabetes mellitus showed delayed clearance. OBJECTIVES: To investigate DTPA clearance in steady-state, otherwise healthy adult sickle cell disease (SCD) patients and correlate it with pulmonary function tests (PFTs), hematologic and clinical parameters. MATERIALS AND METHODS: The subjects were randomly selected from the Hematology Clinic of Mubarak Hospital, Kuwait. Hematologic and pulmonary function data were collected with standard methods. DTPA radio-aerosol clearance studies were performed using ultrafine nebulizer containing 35 mCi (1295 MBq) of Tc 99m-DTPA in its reservoir and t(1/2) clearance in minutes was determined. Average values for both lungs were calculated and compared with normal values for our population. RESULTS: Forty-three subjects (24 SS and 19 S-beta(0)thal) aged between 16 and 45 yr (mean of 27.1 +/- 9.7) were studied. Twenty-two subjects (51.2%) had delayed, while only 10 (23.3%) showed enhanced DTPA clearance. Patients with enhanced clearance showed better PFTs than those with normal or delayed clearance. There was significant negative correlation of DTPA clearance with forced expiratory volume in 1 s, forced vital capacity and total lung capacity and significant positive correlation with age. CONCLUSIONS: Majority of adult SCD patients have delayed DTPA clearance unlike in inflammatory lung diseases, but similar to diabetes mellitus. DTPA clearance may be a useful modality for monitoring pulmonary involvement in SCD.     

The prevalence and significance of increased gastric wall radiotracer uptake in sestamibi myocardial perfusion SPECT

Background: Limited available data indicate that a specific pattern of increased gastric wall radiotracer uptake is associated with dyspepsia. Our purpose was to evaluate the frequency of this finding and its relation with dyspeptic evidences. Method: 1056 consecutive outpatients referred for myocardial perfusion SPECT were interviewed concerning the dyspeptic symptoms, current gastric medications and previous gastroduodenal interventions. The intensity of gastric wall activity was graded qualitatively as G1 or hyperactive gastric wall (equivalent to the patient’s heart activity) and G2 (less than heart activity). Results: The pattern of gastric wall hyperactivity was identified in 1.9% of patients. Dyspeptic symptoms were present in 80 and 18.6% of G1 and G2 patients, respectively (p<0.001). The dyspeptic symptoms were classified as ulcer-like in 37.5%, dysmotility-like in 43.75% and GERD-like in 18.75% of the dyspeptic G1 patients. Considering the classification of dyspepsia, there was no significant difference between the dyspeptic patients of groups. The history of previous gastroduodenal interventions and current use of gastric medications was significantly higher among G1 patients. Conclusion: The infrequent pattern of gastric wall hyperactivity could be clinically important and can identify a category of patients, who require additional diagnostic gastrointestinal investigation to specify another possible noncardiac origin of complaints.     

Abnormal bone remodelling and increased levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) in Waldenström macroglobulinaemia

Serum levels of macrophage inflammatory protein‐1 alpha (MIP‐1α) and bone remodelling markers were evaluated in 38 patients with Waldenström macroglobulinaemia (WM) and correlated with clinical and laboratory variables. MIP‐1α was elevated in WM; untreated patients had higher MIP‐1α levels than patients in remission or with active disease after treatment. MIP‐1α correlated with increased bone resorption, β₂‐microglobulin and splenomegaly. Receptor activator of nuclear factor‐κB ligand serum levels were elevated in WM patients; the subsequent increased bone resorption was balanced by a comparable elevation of osteoprotegerin production and bone formation. These findings may explain the absence of lytic lesions in WM patients and suggest a potential role of MIP‐1α in WM.     

Proteomic classification of pancreatic adenocarcinoma tissue using protein chip technology

BACKGROUND & AIMS: Pancreatic adenocarcinoma is a most devastating cancer that presents late and is rapidly progressive. This study aimed to identify unique, tissue-specific protein biomarkers capable of differentiating pancreatic adenocarcinoma (PC) from adjacent uninvolved pancreatic tissue (AP), benign pancreatic disease (B), and nonmalignant tumor tissue (NM). METHODS: Tissue samples representing PC (n = 31), AP (n = 44), and B (n = 19) tissue were analyzed on hydrophobic protein chip arrays by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Training models were developed using logistic regression and validated using the 10-fold cross-validation approach. RESULTS: The hydrophobic protein chip array revealed 13 protein peaks differentially expressed between PC and AP (receiver operating characteristic [ROC] area under the curve [AUC], 0.64-0.85), 8 between PC and B (ROC AUC, 0.67-0.78), and 12 between PC and NM tissue (ROC AUC, 0.63-0.81). Logistic regression and cross-validation identified overlapping panels of peaks to develop a training model that distinguished PC from AP (77.4% sensitivity, 84.1% specificity), B (83.9% sensitivity, 78.9% specificity), and NM tissue (58.1% sensitivity, 90.5% specificity). The final panels selected correctly classified 80.6% of PC and 88.6% of AP samples (ROC AUC, 0.92), 93.5% of PC and 89.5% of B samples (ROC AUC, 0.99), and 71.0% of PC and 92.1% of NM samples (ROC AUC, 0.91). CONCLUSIONS: This study used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to discover a number of protein panels that can distinguish effectively between pancreatic adenocarcinoma, benign, and adjacent pancreatic tissue. Identification of these proteins will add to our understanding of the biology of pancreatic cancer. Furthermore, these protein panels may have important diagnostic implications.     

Genomic and transcriptional analysis of protein heterogeneity of the honeybee venom allergen Api m 6

Several components of honeybee venom are known to cause allergenic responses in humans and other vertebrates. One such component, the minor allergen Api m 6, has been known to show amino acid variation but the genetic mechanism for this variation is unknown. Here we show that Api m 6 is derived from a single locus, and that substantial protein-level variation has a simple genome-level cause, without the need to invoke multiple loci or alternatively spliced exons. Api m 6 sits near a misassembled section of the honeybee genome sequence, and we propose that a substantial number of indels at and near Api m 6 might be the root cause of this misassembly. We suggest that genes such as Api m 6 with coding-region or untranslated region indels might have had a strong effect on the assembly of this draft of the honeybee genome.     

De novo COX2 mutation in a LHON family of Caucasian origin: implication for the role of mtDNA polymorphism in human pathology

Recent studies suggest that certain mutations with phylogeographic importance as haplogroup markers may also influence the phenotypic expression of particular mitochondrial disorders. One such disorder, Lebers hereditary optic neuropathy (LHON), demonstrates a clear expression bias in mtDNAs belonging to haplogroup J, a West Eurasian maternal lineage defined by polymorphic markers that have been called secondary disease mutations. In this report, we present evidence for a de novo heteroplasmic COX2 mutation associated with a LHON clinical phenotype. This particular mutation—at nucleotide position 7,598—occurs in West Eurasian haplogroup H, the most common maternal lineage among individuals of European descent, whereas previous studies have detected this mutation only in East Eurasian haplogroup E. A review of the available mtDNA sequence data indicates that the COX2 7598 mutation occurs as a homoplasic event at the tips of these phylogenetic branches, suggesting that it could be a variant that is rapidly eliminated by selection. This finding points to the potential background influence of polymorphisms on the expression of mild deleterious mutations such as LHON mtDNA defects and further highlights the difficulties in distinguishing deleterious mtDNA changes from neutral polymorphisms and their significance in the development of mitochondriopathies.     

Biological properties of chimeric West Nile viruses

Recently, we have described a lineage 2 attenuated WN virus suitable for the development of a live WN vaccine. To design vaccine candidates with an improved immunogenicity, we assembled an infectious clone of the NY99 strain and created several chimeric constructs with reciprocal exchanges of structural protein genes between attenuated W956 and virulent NY99 and investigated their biological properties. Our data indicated that, while the growth rates of NY99 and chimeric viruses in tissue culture are determined primarily by properties of the structural proteins, determinants responsible for a highly cytopathic phenotype of NY99 or lack thereof for W956 are located within the nonstructural protein region of the WN genome. The high virulence of NY99 and the attenuated phenotype of W956 were found to be associated with determinants in the nonstructural region. Chimeric viruses carrying the NY99 structural proteins were attenuated in neuroinvasiveness and demonstrated an immunogenicity superior to W956.     

Electromyographic activity of m. longissimus and the kinematics of the vertebral column during level and downslope treadmill walking in cats

Electromyographic (EMG) burst patterns of m. longissimus and the kinematics of the vertebral column were assessed in cats during treadmill walking for six downslope grades (5 degrees-30 degrees). The EMG bursts during downslope walking were weak between 5 degrees and 20 degrees. At steeper grades (>20 degrees), EMG bursts were large. Bursts at T10 facilitated inward movements, and those at L1 decreased forward movements, while those at L5 decreased backward movements during downslope walking at steeper grades.