A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

人骨髓间质干细胞体外扩增和向内皮细胞定向诱导分化的研究

目的：体外分离、扩增成人骨髓间质干细胞（MSCs）和向内皮细胞（ECs）定向诱导分化，开辟心血管组织工程种子细胞的新来源。 方法： 采用Percoll(1 073 g/L)从正常成人骨髓中分离出MSCs，纯化和扩增后流式细胞仪鉴定其纯度；用血管内皮生长因子(VEGF)诱导MSCs向ECs分化，Ⅷ因子(vWF)免疫组化和透射电镜(TEM)鉴定细胞性质。 结果： 5.0×105个MSCs在体外扩增15代后，获得8.0×1012个MSCs，扩增了约1.6×107倍；MSCs在加入VEGF诱导培养大约14-21 d，80%-90%的诱导细胞对Ⅷ因子相关抗原呈阳性反应；TEM可观察到胞浆内有Weible-palade小体，证实为ECs。 结论： 成人骨髓MSCs在体外具有定向诱导分化为ECs的潜能，这为心脏组织工程瓣体外构建, 尤其是在小儿先天性心脏病组织工程研究中种子细胞的来源提供了可能性。     

Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.     

Comparison of the effects of pentagastrin and meal-stimulated gastrin on plasma calcitonin in normal man

We compared the effects of exogenous pentagastrin and meal-stimulated gastrin on plasma immunoreactive calcitonin (iCT) in various studies of 13 normal adult men. Bolus intravenous injection of pentagastrin (0.5 μg/kg) produced increases of iCT in 8 of 9 men. There was a linearly increasing response of iCT concentrations to increasing doses of pentagastrin (0.0625, 0.125, 0.25, and 0.5 μg/kg) and to achieved serum immunoreactive pentagastrin concentrations (r=0.72, P<0.01). To determine the effects of endogenous gastrin upon peripheral iCT concentrations, we measured serum immunoreactive gastrin (iG) and plasma iCT in four men at frequent intervals for 240 min after ingestion of low-(100 mg) and high- (400 mg) calcium meals. Serum iG increased in all subjects, with a peak at ～30 min. However, plasma iCT levels were unchanged from basal throughout the study. The increase of pentagastrin (0.3 pmol/ml) which caused a barely detectable increase of iCT was five-to tenfold greater than the mean maximal increases of gastrin after low- and high-calcium meals (0.04 and 0.06 pmol/ml, respectively). These results suggest that increases of plasma iCT concentrations after administration of pentagastrin in man reflect pharmacologic phenomena and that postprandial gastrin secretion may be insufficient to affect peripheral iCT concentrations.     

改良第二掌背动脉皮瓣修复示中指中末节套脱伤

Objective To investigate the operative procedure and the clinical results of the modified reversed island flap based on the second dorsal metacarpal artery (SDMA) for repairing index or long finger degloving defects.Methods From May 2004 to January 2010, circumferential soft tissue defect in the middle and distal phalanx of the index or long fingers in 17 patients were repaired by the modified reversed island flaps based on SDMA.The dorsal digital nerve in the flap was coapted to the severed proper digital nerve.The area of the flaps ranged from 2.5 cm × 5.6 cm to 5.0 cm × 6.5 cm.The donor sites were closed by skin graft.Results Postoperatively blister and necrosis of the distal flap occurred in 2 cases which was cured by dressing change.All the other flaps survived uneventfully.Primary healing of the flaps and donor sites was achieved.All 17 patients were follow-up for 4 to 27 months with an average of 15.3 months.The flaps were pliable, full but not bulky.Two-point discrimination was 7 to 11 mm (mean 8.6 mm).Hand function as judged by the total active range of motion of the fingers was excellent in 8 fingers, good in 7 fingers and fair in 2 fingers.The satisfactory rate was 88.2%.Conclusion Modified SDMA reversed island flap transfer with dorsal digital nerve coaptation is an ideal procedure to repair index or long finger degloving injuries.The area of the harvested flap is large enough to cover the circumferential soft tissue defect in the middle and distal phalanx.The surgery is safe due to the reliable flap circulation.     

Aetiology and management of children with acute fever of unknown origin

This is part I of a 2-part paper on fever of unknown origin (FUO) in children. FUO is best defined as fever without obvious source on initial clinical examination and then classified into acute (illness of < or =1 week's duration) and prolonged (>7 to 10 days' duration). Aetiologically, there is a marked overlap between acute and prolonged FUO, and infections are major players in both. Age, climate, local epidemiology and host factors are the major aetiological factors that should be considered in the choice of definitive tests. Depending on age, serious bacterial infections (including bacteraemia, meningitis and urinary tract infection) occur in 3 to 20% of cases of acute FUO. Prevention of mortality and sequelae from these infections, particularly bacteraemia and meningitis, is of particular concern in acute FUO. An individualised approach, based on clinical evaluation supplemented with screening and definitive laboratory tests to determine the need for empiric antibiotic therapy and hospitalisation, seems to be the best approach to acute FUO (although this may be less applicable to neonates and infants younger than 90 days, particularly those aged 0 to 7 days). The place of laboratory tests, empiric antibiotic therapy and hospitalisation are important issues that are likely to remain so for some time.     

Thoracoscopic Radiofrequency Ablation of the Myocardium

Radiofrequency (RF) catheter ablation has been used for the treatment of ventricular tachycardia (VT), however, in some patients VT might result from subepicardiai macroreentry that could be successfully terminated by epicardial approach. This study examined the feasibility of thoracoscopic RF ablation of myocardium from epicardium using a custom made electrode. In five mongrel dogs, the thoracoscope was introduced through the 7th intercostal space. A 500-kHz continuous wave RF energy was connected to a custom made multiple electrode probe. Under thoracoscopic guidance, the heart was exposed and the RF probe was introduced. RF ablation was performed on the nonvascular ventricular wall of the beating heart. The left ventricular free wall and right ventricular outflow tract were satisfactorily visualized and ablated. The total dose of RF energy ranged from 50 to 500 J. and the estimated volume of ablated lesions ranged from 41.0–799 mm³. There were significant correlations between the RF discharge output and the irradiated lesion volume (P < 0.01), and the depth of the lesions (P < 0.01). Grossly, after RF ablation the ventricular myocardium demonstrated a circular, well-demarcated area of thermal injury. Volume and depth of the lesion depended upon the total dose of delivered RF energy. Thoracoscopic RF ablation appears to be a minimally invasive and useful method for creating irradiated myocardial lesions from epicardial surface. This method could he technically feasible for the treatment of Vts for which endocardial RF ablation is ineffective.     

Cardiopulmonary exercise variables in diastolic versus systolic heart failure

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p <0.08), with more women (p <0.006) and with greater body mass indexes (p <0.02), than those in the systolic HF group. There was no significant difference in the use of beta blockers or the incidence of coronary artery disease. Patients with diastolic HF had decreased E/A ratios (0.9 +/- 0.4 vs 1.4 +/- 1.1, p <0.02, diastolic HF vs systolic HF) and increased filling times (30.4 +/- 3.2 vs 26.5 +/- 4.7 ms, p <0.01, diastolic HF vs systolic HF). No significant differences in peak VO(2) (14.4 +/- 1.9 vs 15.6 +/- 3.2 ml/kg/min, p = 0.06, diastolic HF vs systolic HF) were observed. The VE/VCO(2) ratios for the 2 groups were abnormal and comparable (32 2 +/- 7.5 vs 34.0 +/- 8.3, p = 0.3, diastolic HF vs systolic HF). In conclusion, the CPX response in patients with diastolic HF and systolic HF is markedly abnormal and indistinguishable with regard to peak VO(2) and ventilation despite marked differences in the LV EF.     

Perception of voluntary screening for paediatric HIV and response to post-test counselling by Nigerian parents

Nigeria may be taken to represent countries with an evolving HIV/AIDS epidemic. With particular reference to paediatric HIV, the voluntary testing of young children and their parents may provide an important entry point for the institution of control measures. However, there is a paucity of knowledge about how individuals perceive voluntary testing. This knowledge is important to the development of guidelines for counselling. To reduce this gap, 258 parents of hospitalized children (> 1 month to 15 years of age) were interviewed using a structured questionnaire. In addition, to complement the data, four examples of seropositive mother's responses during post-test counselling are presented and analyzed. In the survey, 223 (86%) parents were HIV/AIDS aware but only 88 (39%) of these parents could describe one or more route(s) of transmission and none described vertical transmission. Among the respondents, 153 (62%) of 248 would consent to the screening of self, and 195 (85%) of 230 to the screening of a hospitalized child if based on his/her clinical condition. Perceptions of good health and lack of exposure, and despair owing to lack of a specific treatment, were the common reasons for refusing consent. These represent some of the issues which would need to be addressed to increase the acceptance of voluntary testing. The fear of a break up of families with seropositive mothers but seronegative fathers was a major concern expressed during post-test counselling. HIV-discordance among couples may be frequent and should be considered in the formulation of policies on counselling and voluntary testing.