Management of the droopy tip: a comparison of three alar cartilage-modifying techniques

The droopy tip is a common nasal deformity in which the tip is inferiorly rotated. Five hundred consecutive rhinoplasty cases were studied to assess the incidence and causes of the droopy tip deformity and to evaluate the role of three alar cartilage-modifying techniques--lateral crural steal, lateral crural overlay, and tongue in groove--in correcting such a deformity. The external rhinoplasty approach was used in all cases. Only one of the three alar cartilage-modifying techniques was used in each case, and the degree of tip rotation and projection was measured both preoperatively and postoperatively. The incidence of droopy tip was 72 percent, and the use of an alar cartilage-modifying technique was required in 85 percent of these cases to achieve the desired degree of rotation. The main causes of droopy tip included inferiorly oriented alar cartilages (85 percent), overdeveloped scrolls of upper lateral cartilages (73 percent), high anterior septal angle (65 percent), and thick skin of the nasal lobule (56 percent). The lateral crural steal technique increased nasal tip rotation and projection, the lateral crural overlay technique increased tip rotation and decreased tip projection, and the tongue-in-groove technique increased tip rotation without significantly changing the amount of projection. The lateral crural overlay technique resulted in the highest degrees of rotation, followed by the lateral crural steal and finally the tongue-in-groove technique. According to these results, the lateral crural steal technique is best indicated in cases with droopy underprojected nasal tip, the lateral crural overlay technique in cases of droopy overprojected nasal tip, and the tongue-in-groove technique in cases where the droopy nasal tip is associated with an adequate amount of projection.     

Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis

Background

The Thrombolysis in Myocardial Infarction (TIMI) risk score uses clinical data to predict the short-term risk of acute myocardial infarction, coronary revascularization or death from any cause. It was originally developed for use in patients with unstable angina or non–ST-elevation myocardial infarction. We sought to expand the clinical application of the TIMI risk score by assessing its prognostic accuracy in patients in the emergency department with potential acute coronary syndromes.

Methods

We searched five electronic databases, hand-searched reference lists of included studies and contacted content experts to identify articles for review. We included prospective cohort studies that validated the TIMI risk score in emergency department patients. We performed a meta-regression to determine whether a linear relation exists between TIMI risk score and the cumulative incidence of cardiac events.

Results

We included 10 prospective cohort studies (with a total of 17 265 patients) in our systematic review. Data were available for meta-analysis in 8 of the 10 studies. Of patients with a score of zero, 1.8% had a cardiac event within 30 days (sensitivity 97.2%, 95% CI 96.4–97.8; specificity 25.0%, 95% CI 24.3–25.7; positive likelihood ratio 1.30, 95% CI 1.28–1.31; negative likelihood ratio 0.11, 95% CI 0.09–0.15). Meta-regression analysis revealed a strong linear relation between TIMI risk score (p < 0.001) and the cumulative incidence of cardiac events.

Interpretation

Although the TIMI risk score is an effective risk stratification tool for patients in the emergency department with potential acute coronary syndromes, it should not be used as the sole means of determining patient disposition.Chest pain is a common presenting complaint in the emergency department that requires efficient risk stratification, timely initiation of treatment in high-risk patients and safe determination of patient disposition. Several studies have been published that stratify the risk of patients in the emergency department with chest pain.^1–5 However, only the Thrombolysis in Myocardial Infarction (TIMI) risk score, which was initially developed for use in patients with unstable angina or non–ST-segment elevation myocardial infarction or both,⁶ has been broadly validated in several independent emergency department populations with chest pain and thus constitutes the highest level of evidence available.The TIMI risk score assigns each of seven predictors a value of one point, allowing stratification of patients into one of eight prognostic categories (Box 1).⁶ The clinical end points are acute myocardial infarction, coronary revascularization and death from any cause.

Box 1.?Predictor variables included in the TIMI risk score^*

• Age of more than 65 years
• Three or more risk factors for atherosclerosis
• Known coronary artery disease
• Two or more episodes of anginal chest pain in the preceding 24 hours
• Acetylsalicylic acid use in the seven days before hospitalization
• ST-segment deviation of 0.05 mV or more
• Elevated cardiac markers

A robust estimate of the performance of the TIMI risk score obtained from a systematic review may prove useful to both clinicians and researchers. Clinicians would have a reliable quantitative estimate of a patient’s short-term risk of a cardiac event. This could be used as an adjunct to clinical acumen and as a tool to communicate risk to patients in a shared decision-making model of care.⁷ Researchers would also have an estimate of the prognostic accuracy of the TIMI risk score derived from different practice settings and patient populations that represent a wide variety of ethnic backgrounds. This estimate may serve as a useful baseline for comparison as emerging clinical prediction rules and imaging modalities continue to refine our approach to diagnosis and risk stratification in patients in the emergency department with potential acute coronary syndromes.We conducted a comprehensive systematic review and meta-analysis to assess the methodological quality and prognostic performance of studies that had prospectively validated the TIMI risk score in patients in the emergency department.     

阿托伐他汀对高血压肾脏并发症炎性损伤的治疗作用(英文)

通过考察阿托伐他汀(atorvastatin, ATO) 对自发性高血压大鼠(spontaneously hypertensive rats, SHR) 肾脏炎性损害的影响, 探讨了 ATO 对高血压肾脏并发症的防治作用。将4周龄SHR分为高血压模型组和ATO治疗组(8mg/kg),以同周龄的Wistar-Kyoto大鼠为正常对照。灌胃给药8周后, 采用酶联免疫法(enzyme linked immunosorbent assay)测定血浆和肾组织血管紧张素Ⅱ(angiotensin, AngⅡ)含量;测定诱导性一氧化氮合酶(inducible nitric oxide synthase, iNOS)及细胞间粘附分子-1(intercellular adhesion molecule-1, ICAM-1) 的蛋白表达和亚硝酸阴离子(nitrite, NO2-)含量,以评价肾脏炎症状态; 以苏木素伊红(hematoxylin and eosin)和过碘酸六胺银染色(periodic acid-silver metheramine) 染色示SHR肾小球和肾间质形态学病变,并以尿蛋白含量为指标衡量肾脏功能。结果显示...     

NO-cGMP Signaling and Regenerative Medicine Involving Stem Cells

Nitric oxide (NO) is a short lived diatomic free radical species synthesized by nitric oxide synthases (NOS). The physiological roles of NO depend on its local concentrations as well as availability and the nature of downstream target molecules. At low nanomolar concentrations, activation of soluble guanylyl cyclase (sGC) is the major event initiated by NO. The resulting elevation in the intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse cellular and physiological processes. The participation of NO and cGMP in diverse physiological processes is made possible through cell type specific spatio-temporal regulation of NO and cGMP synthesis and signal diversity downstream of cGMP achieved through specific target selection. Thus cyclic GMP directly regulates the activities of its downstream effectors such as Protein Kinase G (PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide phosphodiesterases, which in turn regulate the activities of a number of proteins that are involved in regulating diverse cellular and physiological processes. Localization and activity of the NO-cGMP signaling pathway components are regulated by G-protein coupled receptors, receptor and non receptor tyrosine kinases, phosphatases and other signaling molecules. NO also serves as a powerful paracrine factor. At micromolar concentrations, NO reacts with superoxide anion to form reactive peroxinitrite, thereby leading to the oxidation of important cellular proteins. Extensive research efforts over the past two decades have shown that NO is an important modulator of axon outgrowth and guidance, synaptic plasticity, neural precursor proliferation as well as neuronal survival. Excessive NO production as that evoked by inflammatory signals has been identified as one of the major causative reasons for the pathogenesis of a number of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases. Regenerative therapies involving transplantation of embryonic stem cells (ES cells) and ES cell derived lineage committed neural precursor cells have recently shown promising results in animal models of Parkinson disease (PD). Recent studies from our laboratory have shown that a functional NO-cGMP signaling system is operative early during the differentiation of embryonic stem cells. The cell type specific, spatio-temporally regulated NO-cGMP signaling pathways are well suited for inductive signals to use them for important cell fate decision making and lineage commitment processes. We believe that manipulating the NO-cGMP signaling system will be an important tool for large scale generation of lineage committed precursor cells to be used for regenerative therapies. Special issue dedicated to John P. Blass.     

Enzyme inhibition activities of the extracts from rhizomes of Gloriosa superba Linn (Colchicaceae)

An alcoholic extract obtained from the rhizomes of Gloriosa superba Linn (Colchicaceae) was screened for enzyme inhibition activities. The crude extract and its subsequent fractions including chloroform, ethyl acetate, n-butanol and aqueous were screened against lipoxygenase, actylcholinesterase, butyrylcholinesterase and urease. An outstanding inhibition on lipoxygenase was observed. The highest enzyme inhibition potency was expressed by the chloroform fraction (90%) among the tested fractions on lipoxygenase. Overall 67-90% inhibition was found for lipoxygenase, 46-69% for acetylcholinesterase and 10-33% for butyrylcholinesterase, while urease was not inhibited.     

Expression of functional recombinant human growth hormone in transgenic soybean seeds

We produced human growth hormone (hGH), a protein that stimulates growth and cell reproduction, in genetically engineered soybean [Glycine max (L.) Merrill] seeds. Utilising the alpha prime (α') subunit of β-conglycinin tissue-specific promoter from soybean and the α-Coixin signal peptide from Coix lacryma-jobi, we obtained transgenic soybean lines that expressed the mature form of hGH in their seeds. Expression levels of bioactive hGH up to 2.9% of the total soluble seed protein content (corresponding to approximately 9?g?kg(-1)) were measured in mature dry soybean seeds. The results of ultrastructural immunocytochemistry assays indicated that the recombinant hGH in seed cotyledonary cells was efficiently directed to protein storage vacuoles. Specific bioassays demonstrated that the hGH expressed in the soybean seeds was fully active. The recombinant hGH protein sequence was confirmed by mass spectrometry characterisation. These results demonstrate that the utilisation of tissue-specific regulatory sequences is an attractive and viable option for achieving high-yield production of recombinant proteins in stable transgenic soybean seeds.     

An effective extracellular protein secretion by an ABC transporter system in <Emphasis Type="Italic">Escherichia coli</Emphasis>: statistical modeling and optimization of cyclodextrin glucanotransferase secretory production

Direct transport of recombinant protein from cytosol to extracellular medium offers great advantages, such as high specific activity and a simple purification step. This work presents an investigation on the potential of an ABC (ATP-binding cassette) transporter system, the hemolysin transport system, for efficient protein secretion in Escherichia coli (E. coli). A higher secretory production of recombinant cyclodextrin glucanotransferase (CGTase) was achieved by a new plasmid design and subsequently by optimization of culture conditions via central composite design. An improvement of at least fourfold extracellular recombinant CGTase was obtained using the new plasmid design. The optimization process consisted of 20 experiments involving six star points and six replicates at the central point. The predicted optimum culture conditions for maximum recombinant CGTase secretion were found to be 25.76 μM IPTG, 1.0% (w/v) arabinose and 34.7°C post-induction temperature, with a predicted extracellular CGTase activity of 68.76 U/ml. Validation of the model gave an extracellular CGTase activity of 69.15 ± 0.71 U/ml, resulting in a 3.45-fold increase compared to the initial conditions. This corresponded to an extracellular CGTase yield of about 0.58 mg/l. We showed that a synergistic balance of transported protein and secretory pathway is important for efficient protein transport. In addition, we also demonstrated the first successful removal of the C-terminal secretion signal from the transported fusion protein by thrombin proteolytic cleavage.