Diagnostic value of ischaemia-modified albumin in pulmonary contusion in rats

BackgroundPatients with pulmonary contusion (PC) are at increased risk of development of complications and death after trauma. The early diagnosis and determination of severity of PC could improve clinical outcomes. The aim of the study was to determine the diagnostic value of ischaemia-modified albumin (IMA) in a PC model in rats.MethodsThirty-two Sprague-Dawley rats were randomly allocated to four groups; the uninjured control Group I (n = 7) and the uninjured control Group II (n = 7) were euthanised at 2 and 6 h, respectively, and PC groups III (n = 9) and IV (n = 9) were euthanised at 2 and 6 h after trauma, respectively. The serum level of IMA, tissue and serum malondialdehyde (MDA) levels, and histopathological damage scores of the lung tissue were determined.ResultsSerum IMA and lung tissue MDA levels in the PC groups were not significantly different to those of the control groups (p = 0.555; p = 0.086, respectively). Serum MDA levels were significantly higher in the PC groups than in the control groups (p = 0.011). When histopathological changes in lung parenchyma were evaluated, there was a statistical difference between the injured and uninjured groups for inflammation and lung injury (p = 0.017; p = 0.001, respectively). However, there was no significant correlation between the histopathological score and biochemical parameters.ConclusionOur preliminary findings suggest that there is no significant change of serum IMA levels in the acute phase of PC induced by blunt chest trauma.     

Revision of genera in Asterinales

The order Asterinales comprises a single family, Asterinaceae. In this study, types or specimens of 41 genera of Asterinaceae are re-examined and re-described and illustrated by micrographs. Seventeen genera, namely Asterina (type genus), Asterinella, Asterotexis, Batistinula, Cirsosia, Echidnodella, Halbania, Lembosia, Meliolaster, Parasterinopsis, Platypeltella, Prillieuxina, Schenckiella (=Allothyrium), Trichasterina, Trichopeltospora, Uleothyrium and Vizellopsis, are maintained within Asterinaceae. Echidnodes, Lembosiella, Lembosina, Morenoina, and Thyriopsis are transferred to Aulographaceae based on morphological and molecular characteristics. Anariste is transferred to Micropeltidaceae, while Lembosiopsis is transferred to Mycosphaerellaceae. Placoasterella and Placosoma are morphologically close to taxa in Parmulariaceae, where they are transferred. Aulographina is placed in Teratosphaeriaceae, while Asterodothis, Asterinema, Dothidasteromella, Leveillella, Petrakina and Stephanotheca are transferred to Dothideomycetes, genera incertae sedis. Eupelte, Macowaniella, Maheshwaramyces, Parasterinella, and Vishnumyces are treated as doubtful genera, because of lack of morphological and molecular data. Aphanopeltis, Asterolibertia, Neostomella, Placoasterina, and Symphaster are synonyms of Asterina based on morphology, while Trichamelia, Viegasia, and Yamamotoa are synonyms of Lembosia. The characteristics of each family are discussed and a phylogenetic tree is included.     

Reassessment of the importance of mucins in determining sputum properties in cystic fibrosis

BackgroundThere is conflicting evidence about the importance of airway mucins (MUC5AC and MUC5B) in determining physical properties of sputum in cystic fibrosis (CF). We studied the effects of endogenous degradation of mucins on CF sputum elasticity and apparent mucin concentrations.MethodsElastic shear moduli (G′) and mucin concentrations in sputum of 12 CF patients were measured before and after incubation at 37 °C for 60 min.ResultsG′ fell from a median of 5.98 to 4.70 Pa (p = 0.01). There were significant falls in MUC5AC (8.2 to 5.2 μg/ml, p = 0.02) and MUC5B (17.3 to 12.5 μg/ml, p = 0.02) over the same period, and associated decrease in molecular weight and size.ConclusionsSputum is not inert and degradation reduces apparent mucin concentrations and sputum elasticity. Even if care is taken to process samples rapidly, sputum may therefore differ from secretions retained in airways. Previous studies may have underestimated the role of mucins in CF sputum.     

Comparison between in vivo and in vitro pharmacokinetics of succinylcholine in humans

Purpose. To compare the in vivo and in vitro pharma-cokinetics of succinylcholine (SCh) in humans. Methods. A bolus of SCh 1 mg·kg⁻¹ (n = 7) or 2 mg·kg⁻¹ (n = 11) was given to 18 patients anesthetized with thiopental. Arterial blood samples for determination of in vivo SCh concentrations were collected every 30 s for 5 min. Another 20-ml blood sample was obtained before induction of anes-thesia for determination of in vitro SCh. Concentrations of SCh were measured by high-performance liquid chromato-graphy. In vivo and in vitro concentrations of SCh vs time data were analyzed by the one-compartment model. Results. The respective in vivo and in vitro pharmacokinetic parameters (SCh 1 mg·kg⁻¹ vs SCh 2 mg·kg⁻¹) were as follows: Plasma clearance was 4.17 ± 2.37 and 1.85 ± 0.28 l·min⁻¹, P < 0.05, vs 2.91 ± 2.01 and 1.27 ± 0.43 l·min⁻¹, P < 0.05. Elimination half-life was 25.4 ± 10.6 and 47.4 ± 5.4 s, P < 0.002 vs 26.3 ± 10.0 and 75.2 ± 21.8 s, P < 0.00005. Conclusion. These results suggest that the rapid disap-pearance of SCh from the circulation is due to diffusion out of the blood vessels rather than to enzymatic hydrolysis. Received for publication on August 31, 1998; accepted on May 11, 1999     

The role of histamine in control of gastric mucosal blood flow in dogs

The role of the histamine receptors in the control of gastric mucosal blood flow was evaluated in dogs utilizing [¹⁴C]aminopyrine ([¹⁴C]AP) clearance techniques. Because of the importance of maintaining a low intragastric pH to prevent dissociation of AP and back diffusion through the gastric mucosa, AP was traped in the stomach lumen by intragastric perfusion of a marker solution with a pH of 1.16. Results obtained utilizing a marker to determine gastric secretory volume and gastric juice [¹⁴C]AP concentration correlated well with those values obtained from direct measurements from fluid collected from a gastric fistula. Histamine base administration increased [¹⁴C]AP clearance. Cimetidine, an H₂ receptor antagonist, did not significantly change basal [¹⁴C]AP clearance and inhibited [¹⁴C]AP clearance at low doses of histamine administration. An H₂ receptor agonist (4-methylhistamine) and an H₁ receptor agonist (2-methylhistamine) each increased mucosal blood flow approximately 30% and 70%, respectively, of the response produced by histamine base. Blood flow stimulated by 2-methylhistamine was inhibited by the H₁ receptor antagonist diphenhydramine. The results suggest that histamine H₁ and H₂ receptors are involved in the control of canine gastric mucosal blood flow.     

Stereoselective in vitro degradation pattern of mivacurium in human plasma

Background. Mivacurium is a mixture of three isomers, two ofwhich are rapidly broken down in vivo by plasma cholinesterases.This study investigates the stereospecificity of mivacuriumin vitro degradation to determine if it accounts for its invivo behaviour. Methods. The in vitro rate of degradation of each isomer ofmivacurium and the in vitro rate of formation of their primary(monoesters and alcohols) and secondary (alcohols) metaboliteswere examined using human plasma from six healthy volunteers.The in vitro rate of degradation of the monoester metaboliteswas also assessed. All these determinations were made usinga stereospecific high-performance liquid chromatography assay. Results. The in vitro rate of disappearance of the two activeisomers of mivacurium was very rapid, with mean values for thetrans trans and cis trans isomers of 0.803 and 0.921 min^–1respectively. These values are twofold faster than publishedin vivo data. The in vitro rate of disappearance was much slowerfor the cis cis isomer, with a mean value of 0.0106 min^–1.The cis trans isomer was converted exclusively to cis monoesterand trans alcohol, while only metabolites in the trans and cisconfiguration were found for the trans trans and cis cis isomersrespectively. Mean in vitro rates of disappearance for the transand cis monoester were 0.00750 and 0.000633 min^–1respectively. Conclusions. The in vitro rates of hydrolysis of the activeisomers of mivacurium confirm that plasma cholinesterases playa major role in their in vivo degradation, but that in vivoelimination is slowed by extravascular distribution. Mivacuriumhydrolysis is stereoselective, the ester group in the transconfiguration being more accessible to enzymatic attack. Thisstereoselective pattern, along with the relatively slow breakdownof the cis cis isomer, sheds light on the in vivo dispositionof the cis alcohol metabolite. Br J Anaesth 2002; 89: 832–8     

Role of Bcl2 in Osteoclastogenesis and PTH Anabolic Actions in Bone

Introduction : B‐cell leukemia/lymphoma 2 (Bcl2) is a proto‐oncogene best known for its ability to suppress cell death. However, the role of Bcl2 in the skeletal system is unknown. Bcl2 has been hypothesized to play an important anti‐apoptotic role in osteoblasts during anabolic actions of PTH. Although rational, this has not been validated in vivo; hence, the impact of Bcl2 in bone remains unknown. Materials and Methods : The bone phenotype of Bcl2 homozygous mutant (Bcl2^?/?) mice was analyzed with histomorphometry and μCT. Calvarial osteoblasts were isolated and evaluated for their cellular activity. Osteoclastogenesis was induced from bone marrow cells using RANKL and macrophage‐colony stimulating factor (M‐CSF), and their differentiation was analyzed. PTH(1–3;34) (50 μg/kg) or vehicle was administered daily to Bcl2^+/+ and Bcl2^?/? mice (4 days old) for 9 days to clarify the influence of Bcl2 ablation on PTH anabolic actions. Western blotting and real‐time PCR were performed to detect Bcl2 expression in calvarial osteoblasts in response to PTH ex vivo. Results : There were reduced numbers of osteoclasts in Bcl2^?/? mice, with a resultant increase in bone mass. Bcl2^?/? bone marrow–derived osteoclasts ex vivo were significantly larger in size and short‐lived compared with wildtype, suggesting a pro‐apoptotic nature of Bcl2^?/? osteoclasts. In contrast, osteoblasts were entirely normal in their proliferation, differentiation, and mineralization. Intermittent administration of PTH increased bone mass similarly in Bcl2^+/+ and Bcl2^?/? mice. Finally, Western blotting and real‐time PCR showed that Bcl2 levels were not induced in response to PTH in calvarial osteoblasts. Conclusions : Bcl2 is critical in osteoclasts but not osteoblasts. Osteoclast suppression is at least in part responsible for increased bone mass of Bcl2^?/? mice, and Bcl2 is dispensable in PTH anabolic actions during bone growth.     

华东地区健康成人颈椎椎间孔影像学参数测量

目的 观测华东地区健康成人颈椎椎间孔形态及三维空间下各相关参数的变化.方法 选择华东地区来本院体检的191名健康成人作为研究对象,其中男95名、女96名.对所有研究对象行颈椎CT检查并进行三维重建,观察颈椎各节段椎间孔形态,并测量最佳角度下的纵径、上前后径、下前后径、横径均值和横截面积等,比较各节段椎间孔之间及性别之间...     

Lack of prostanoid receptor involvement in ischemic acute renal failure in mice

Background. Thromboxane (TX) A₂ inhibition or prostaglardin (PGI₂) infusion prevents ischemic acute renal failure (ARF) in animal models. However, the pathophysiological roles of the prostanoid receptors in the development of ischemic ARF are not fully understood, partly because of the limited specificity of their inhibitors or antagonists. Methods. We investigated whether targeted disruption of the PGI₂ receptor (IP) or TXA₂ receptor (TP) genes conferred susceptibility to renal ischemic-reperfusion injury, using IP and TP knockout mice. Results. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no significant differences from the wild-type controls in regard to creatinine concentration or histological damage. Conclusions. Lack of TP or IP had no influence on postischemic ARF in mice, indicating that receptors for TXA₂ or PGI₂ may have minimal roles in the development of this mouse model of ischemic ARF. Received: July 5, 2001 / Accepted: April 8, 2002     

Investigation of the mechanism of nicotine induced relaxation in rabbit corpus cavernosum in vitro

In order to determine whether nicotine acts on corporal smooth muscle, the mechanism of its effect on strips of rabbit corpus cavernosum was studied in vitro. Rabbit corpus cavernosum muscle strips were mounted in an organ bath with modified Krebs-Henseleit solution and aerated with 95% O₂ and 5% CO₂. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease of precontraction induced by phenylephrine. Nicotine produced concentration dependent relaxation when preparations were precontracted by phenylephrine (10^–5 M). The maximum nicotine-induced relaxation was 60.4±4.2% of the phenylephrine contraction and was not affected by indomethacin (10^–5 M), N^w-nitro L-arginine methyl ester (3×10^–5 M), methylene blue (10^–5 M), glibenclamide (10^–5 M), clotrimazole (10^-6 M), tetraethylammonium (3×10^–4 M), or 4-aminopyridine (10^–3 M). Nicotine did not exhibit a calcium antagonizing effect. From these results, we conclude that nicotine-induced relaxation of the rabbit corpus cavernosum is not mediated by the release of nitric oxide, prostaglandins or a related substance, by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of the action by which nicotine acts on corporal smooth muscle.     

Ecological aspects of Hymenochaetaceae in an area of Caatinga (semi-arid) in Northeast Brazil

The diversity of Hymenochaetaceae and its relationship with native plants of the Caatinga were investigated in two stands (56 km² each) in the Parque Nacional do Catimbau, State of Pernambuco, Northeast Brazil. The basidiomata collected on both live and dead trees represented 14 species of Hymenochaetaceae. Eleven of them belonged to Phellinus, six of which were new records to the Brazilian semi-arid area (P. grenadensis, P. linteus, P. maxonii, P. melleoporus, P. rimosus, and P. rhytyphloeus). Hymenochaetaceae diversity was not influenced by differences between stands, caused mostly by agriculture (subsistence farming), logging and tourism. The occurrence of taxa of Hymenochaetaceae was not significantly related to humidity, although P. piptadeniae and P. rimosus were more frequently sampled during the dry season. Even if most of the specimens of Hymenochaetaceae, Phellinus and P. piptadeniae have been found on live hosts, this observation was not statistically supported. On the other hand, P. rimosus occurred only on live hosts. The occurrence on live hosts may indicate a parasitic relationship, but they may be colonizing dead tissues of the live plants. Plants of Piptadenia and P. moniliformis had high incidence of Hymenochaetaceae, Phellinus and P. piptadeniae, while Caesalpinia microphylla had high incidence of Hymenochaetaceae, Phellinus and P. rimosus, suggesting that P. piptadeniae is host-recurrent and P. rimosus is host-specific on species of Fabaceae in the studied area. The results indicate that, at least when analysing Hymenochaetaceae, the biome Caatinga differs from other tropical forests where higher species richness is observed on decaying rather than live substrata, and where host-specificity/recurrence have been shown to be low.     

A comparison of methods for in vivo assessment of cortical porosity in the human appendicular skeleton

The recent advent of high-resolution peripheral quantitative computed tomography (HR-pQCT) provides new opportunities to measure in vivo human bone microarchitecture. Increasingly, cortical porosity (CtPo) is of particular interest due to its relationship with bone quality and turnover. The two approaches that have emerged to measure CtPo from HR-pQCT are threshold-based and density-based methods, and the purpose of this work was to compare the performance of each against a gold-standard synchrotron radiation micro-computed tomography (SRμCT) measurement. Human cadaveric cortical bone specimens (N = 23) were measured by SRμCT and HR-pQCT, and high correlations were found for both methods. The density-based approach had an r² = 0.939 (95% confidence interval (CI) of + 6.17% to + 20.99%) and consistently overestimated porosity as measured by SRμCT, while the threshold-based approach had an r² = 0.977 and consistently underestimated porosity (95% CI of − 2.60% to − 10.76%). The density-based approach is prone to beam hardening artifacts and susceptible to natural variations of tissue mineral density (TMD), but is less affected by motion artifacts that may occur in in vivo scans. The threshold-based method has the advantage that it provides structural information that complements the cortical porosity measure, such as number of pores and connectivity, and can accurately detect the larger pores which are the most relevant to bone biomechanical strength. With the first generation HR-pQCT systems the accuracy of detecting pores larger than 140 μm diameter is excellent (r² = 0.983; 95% CI of − 4.88% to + 2.45%). The accuracy of the threshold-based method will improve as new HR-pQCT systems emerge and provide a robust quantitative approach to measure cortical porosity.     

Changes in osteopontin and in biomarkers of bone turnover during human endotoxemia

Systemic infection and inflammation in men are associated with bone loss. Rodent studies have elucidated the pathways mediating the effects of bacterial lipopolysaccharide (LPS), activated immune cells and hormones on bone. Here we investigate the changes in biochemical parameters of bone turnover following human endotoxemia, an experimental model of self-limiting systemic infection and inflammation.Ten healthy men received in a randomised, placebo-controlled, cross-over trial once placebo and once 2 ng/kg Escherichia coli endotoxin (LPS). During the following 6 h we monitored parathyoid hormone (PTH) and osteopontin (OPN), a multifunctional protein related to bone pathophysiology, as well as biochemical markers of bone turnover: C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). In LPS sessions there was a transient fall in PTH at 3 h (p = 0.009) and a nearly two-fold increase in OPN levels after 6 h (LPS: 155 ± 19 pg/ml; placebo: 85 ± 13 pg/ml, p < 0.001). LPS gradually reduced CTX levels (LPS: 0.44 ± 0.4 pg/ml; placebo: 0.59 ± 0.06 pg/ml, p = 0.003), P1NP showed a peak at 4 h (LPS: 89.9 ± 14.7 pg/ml; placebo: 75 ± 9.7 pg/ml, p = 0.028) and circulating OC did not change.The early human response to systemic endotoxemia boosts osteopontin levels and modifies bone biomarkers, indicating a decrease in the lytic activity of osteoclasts, accompanied by an increase in the activity of immature osteoblasts. These changes might present the acute phase response of immune and bone cells to bacterial stimuli in men.     

Evaluation of salt supplementation in CF infants

BackgroundCF infants may be at increased risk of sodium depletion which may lead to impaired growth. The objective of this study was to evaluate their sodium supplementation requirements.MethodsTen CF infants had serial measurements of weight and plasma/urine sodium and creatinine. Sodium supplementation was adjusted with the aim of maintaining fractional excretion (FENa) between 0.5% and 1.5% and urinary sodium > 10 mmol/L.ResultsUrine sodium:creatinine (UNa:Cr) ratio strongly correlated with FENa [UNa:Cr (mmol/mmol) = 35.0 × FENa (r = 0.99)]. The FENa target range corresponded to UNa:Cr 17–52 mmol/mmol. All infants required sodium supplementation to achieve UNa:Cr >17 mmol/mmol. Sodium supplement requirements (mean ± SD) at ages 0–3, 3–6, 6–9 and 9–12 months were 1.9 ± 0.5, 1.8 ± 0.8, 1.9 ± 0.9 and 0.8 ± 0.4 mmol/kg/d. No infant required calorie supplementation to achieve expected weight gain.ConclusionsUsing current UK guidelines, many cases of sodium depletion may be overlooked. Some infants require more than the recommended 1–2 mmol/kg/d. UNa:Cr ratio is a useful non-invasive measure to monitor sodium supplementation.     

Prediction of Outcomes in Crescentic IgA Nephropathy in a Multicenter Cohort Study

Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients≥14 years old with crescentic IgAN who were followed ≥12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3±3.4 mg/dl, and the mean percentage of crescents was 66.4%±15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%±4.7%, 45.8%±5.1%, and 30.4%±6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.IgA nephropathy (IgAN) is one of the most common GN worldwide.¹ On immunohistological examination, it is characterized by the presence of glomerular IgA deposition.² IgAN is now recognized as an autoimmune renal disease that occurs as a consequence of increased circulating levels of IgA1 with galactose-deficient hinge region O-glycans and antiglycan autoantibodies.³ The clinical and pathologic manifestations of IgAN are diverse. The clinical course of the disease ranges from isolated hematuria to rapidly progressive renal failure,⁴ and kidney biopsy findings vary from mild mesangial proliferation to diffuse crescent formation.² Extracapillary proliferation, usually characterized by noncircumferential crescents, occurs in up to 20%–30% of IgAN patients.^2,5 Crescentic IgAN, usually defined as the presence of crescents in over 50% of the glomeruli, is a rare phenotype, and it often presents as rapidly progressively kidney failure.^2,6Crescentic IgAN affects only a minority of IgAN patients and has not been widely investigated, except in a few small studies.^5,7,8 The recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for GN recommended that crescentic IgAN be treated using an immunosuppressive therapy regimen analogous to the regimen used for ANCA vasculitis.⁶ Until now, most studies on crescentic IgAN have been case series or small studies with less than 30 patients.^7,8 Little is known about the long-term outcomes and risk factors that influence kidney recovery in patients with crescentic IgAN,⁹ especially those patients who have undergone initial aggressive immunosuppressive therapy. We, therefore, examined the long-term outcomes of a large cohort of 113 patients who were diagnosed with crescentic IgAN using the criterion of crescents in more than 50% of glomeruli on biopsy specimens. In addition, we developed a concise model for predicting recovery from kidney failure.     

Standardized reporting of appendicitis-related findings improves reliability of ultrasound in diagnosing appendicitis in children

Purpose

Our objective was to increase ultrasound reliability for diagnosing appendicitis in an academic children's hospital emergency department (ED) through a multidisciplinary quality improvement initiative.