Novel quinolone CHM‐1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line

Novel 2‐phenyl‐4‐quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20‐fluoro‐6,7‐methylenedioxy‐2‐phenyl‐4‐quinolone (CHM‐1) in human osterogenic sarcoma U‐2 OS cells. CHM‐1‐induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM‐1‐inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM‐1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM‐1 induced G2/M arrest and apoptosis at an IC₅₀ (3 µM) in U‐2 OS cells and caspase‐3, ‐8, and ‐9 were activated. Caspase inhibitors increased cell viability after exposure to CHM‐1. CHM‐1‐induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased ΔΨ_m levels, and promotion of mitochondrial cytochrome c release. CHM‐1 stimulated mRNA expression of caspase‐3, ‐8, and ‐9, AIF, and Endo G. In addition, CHM‐1 inhibited cell metastasis at a low concentration (<3 µM). CHM‐1 inhibited the cell metastasis through the inhibition of MMP‐2, ‐7, and ‐9. CHM‐1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM‐1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM‐1. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1637–1644, 2009     

Nonparallel cutaneous microcirculatory responses to pharmacologic alterations of systemic arterial pressure in rats

Both hypotension and hypertension aggravate the damage of reperfusion injury after reconstructive microsurgery. The purpose of this study is to establish a theoretical guide for postoperative blood pressure control in optimizing the cutaneous perfusion and flap survival. Systemic arterial pressure was altered by the intravenous infusion of saline, sodium nitroprusside, phentolamine, and phenylephrine in thirty‐two 280–350 g anesthetized Sprague Dawley rats. Power spectral analysis of systemic arterial pressure (SAP) and laser Doppler flowmetry (flux) of epigastric skin were used to reveal the blood pressure and cutaneous blood flow variabilities. Nonparallel responses of cutaneous perfusion and blood pressure were found. The baseline SAP and flux were 126.0 ± 1.4 mmHg and 57.2 ± 1.8 au, respectively. Sodium nitroprusside and phentolamine significantly decreased the SAP (71.1 ± 2.7 and 70.5 ± 1.5 mmHg, P < 0.0001). However, the corresponding responses in cutaneous perfusion were opposite (56.2 ± 3.1 au, P = 0.7389 and 36.2 ± 2.3 au, P < 0.0001). Phenylephrine significantly increased the SAP (171.7 ± 3.0 mmHg, P < 0.0001) but the flux of epigastric skin was decreased (44.4 ± 2.6 au, P < 0.0001). Phentolamine and phenylephrine showed negative effects on the systemic cardiac and vascular sympathetic modulations. Sodium nitroprusside had a trend in increasing systemic vasomotor activity. We suggested not using vasoconstrictors in treating intra and postoperative hypotension associated with free flap transfer. Nitric oxide donors are superior to α‐adrenoceptor antagonists in preserving the cutaneous flap perfusion when treating postoperative hypertension. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.     

Three‐dimensional reconstruction and visualization of the median nerve from serial tissue sections

The purpose of this study was to definitively implement the three‐dimensional visualization of sensory and motor fascicles in the human median nerve by means of acetylcholinesterase (AChe) histochemical staining and under the assistance of the computer technology. One fresh human median nerve was harvested from a male adult cadaver. The median nerve was fixed at a special holder. Then, the whole holder was embedded and rapidly frozen in the liquid nitrogen. The processed median nerve was then cut coronally every 100 μm at a 20 μm thickness along its long axis in a sliding freezing microtome. The total number of sections was 4,650 slices. All sections were stained with the AChe histochemical method. The stained sections were scanned and saved as Joint Photographic Experts Group files. These images with positively and negatively stained sections were acquired to an Intel dual Pentium computer. The Adobe Photoshop CS2 software was used to compare the reference points of images before and after staining. The two‐dimensional intraneural microstructure database of median nerve was then acquired. A software of 3D nerve visualization system was developed. With the 3D nerve visualization system, the 3D visualization result of intraneural microstructure of median nerve was created. The findings may provide more accurate and detailed anatomic information for nerve repairs, specifically for the fascicular nerve repairs. The 3D nerve visualization technique may have potential for future studies of topography of peripheral nerve. © 2009 Wiley‐Liss, Inc. Microsurgery, 2009.     

Dynamic contrast-enhanced subtraction and delayed MRI of gastric tumors: radiologic-pathologic correlation

PURPOSE: Our goal was to determine whether dynamic MR subtraction images could be used to detect and stage gastric tumors. METHOD: Dynamic MR subtraction images were prospectively performed in 20 patients without gastric lesions and in 39 patients with gastric tumors. The flat- or depressed-type early gastric cancers were excluded. The MR findings were assessed for layered pattern of the normal gastric wall, detectability of tumors, enhanced pattern of tumor, and depth of the tumor invasion. Surgical specimens were obtained from 30 of the patients with tumors, and histopathologic sections were made in the dynamic MR scanning direction. RESULTS: The three-layered structure of the normal gastric wall was apparent in more of the dynamic MR subtraction images (60%) than of the nonsubtraction images (30%) in the control group. All 39 gastric tumors were detected by MRI. The intact inner layers overlying stromal tumors and outer layers interrupted by advanced gastric cancers were clear on the subtracted images. MRI accurately T-staged 88% of the gastric cancers. CONCLUSION: Dynamic MR subtraction images can be used to identify gastric tumors and to stage gastric cancers.     

A novel surgical correction through a small transverse incision for pectus excavatum

Surgical correction of pectus excavatum (PE) has been well established since Ravitch's publication in 1949. However, Ravitch's procedure, even if modified, was associated with the relatively radical nature of the operation. The aim of this study was to report our early experience and results in treatment of PE by a novel less invasive surgical technique through a small skin incision. From 1998 to 2003, a novel surgical correction through a small transverse incision was performed for 11 patients with PE, including 9 males and 2 females. The mean age was 9.2 years (range, 3 to 17 years). The less invasive surgical technique consisted of a small transverse skin incision over the deepest part of the PE deformity, subcutaneous dissection to the margin of the depressed deformity, elevation of pectoralis musculature from the midline toward the lateral border of the operative field, subperichondrial resection of the short segment (1 to 2 cm) of the involved costal cartilages, detachment of the xiphoid process and elevation of the sternum with sharp or blunt dissection, retrosternal titanium miniplate strutting, placement of drainage tubes in the mediastinum or pleural spaces, and closure of the operative wound. No sternal osteotomy was performed in this series. The average length of the skin incision was 3.2 cm. The number of the resected cartilages varied from 3 to 6 ribs on each side. The average blood loss was 41 mL (range, 10 to 80 mL), and the operation time was 3.1 hours. The duration of hospitalization was 4.4 days on average. There was no surgical complication or mortality. All patients were satisfied with their cosmesis, and no migration of the retrosternal strut was found in chest radiographs until the date of analysis. This less invasive surgical technique, which did not require osteotomy, could be effectively performed through a small skin incision and was associated with steady recovery of chest wall deformity, as well as excellent cosmetic results.     

Distal ligament in human glans: a comparative study of penile architecture

To elucidate the anatomic distal ligament of the human glans penis and associated clinical implications, we compared the structures of the glans penis and corpora cavernosa in dogs, rats, and humans. From May 2001 to March 2003, gross dissection, microscopic examinations, and stains for elastic fibers and collagen subtypes were made in the penises of 11 adult human male cadavers, 7 dogs, and 5 rats. A distal ligament in the human glans penis replaces the os penis that is present in dogs or rats, also termed the baculum, but retains collagen types I and III as common structural and interlocking components, respectively. The intercavernosal septum is complete, and intracavernosal pillars (ICPs) are abundant in dogs, absent in rats, and moderately developed in humans. A tunica with numerous elastic fibers exists to fulfill the requirements of erectile function in humans but not in dogs or rats, since it is essential for establishing tissue strength to serve as a buttress. We may conclude that in dogs and rats, the strong os penis is designed for ready intromission and is associated with a pair of well-developed nonelastic corpora to serve as a buttress for the os penis. These structures are necessary for the rigorous coitus observed in dogs. The less compliant corpus cavernosum is suitable for the flipping action observed in a mating male rat. These specific anatomic designs may provide explanations for the individual requirements for the specific physiologic functions that differ from species to species. Although there is no os in the human glans, a strong equivalent distal ligament is arranged centrally and acts as a supporting trunk for the glans penis. Without this important structure, the glans could be too weak to bear the buckling pressure generated during coitus and too limber to serve as a patent passage for ejaculation, and it could be too difficult to transmit the intracavernosal pressure surge along the entire penis during ejaculation. Given the common histologic nature of the distal ligament, which is associated with the tunica albuginea and serves a similar function as the os penis observed in the dog and the rat, one may ask whether the healing process of a tunica may take as long as that required in a bony structure. Further research is required to answer this question.     

Effectiveness of urethral injection of botulinum A toxin in the treatment of voiding dysfunction after radical hysterectomy

OBJECTIVE: After radical hysterectomy for cervical cancer patients may have difficulty in urination due to detrusor underactivity and a non-relaxing urethral sphincter. This study evaluated the effectiveness of urethral injection of botulinum A toxin in treating voiding dysfunction in these patients. METHODS: Thirty patients with difficult urination after radical hysterectomy due to cervical cancer were enrolled to receive urethral injection of 100 units of botulinum A toxin (n=20) or medical treatment as controls (n=10). The clinical results and urodynamic parameters at baseline and after treatment were compared in the study group, and the quality of life (QOL) index was compared between the study and control groups. RESULTS: After urethral injection of botulinum A toxin, 8 patients had excellent results (40%) and 8 had improved results (40%) in the study group. Both voiding pressure (115.2+/-63.7 vs. 90.2+/-49.5 ml, p=0.025) and post-void residual volume (330.9+/-124.9 vs. 183.9+/-183.4 ml, p=0.011) improved significantly after treatment. The obstructive symptom score was significantly reduced (17.5+/-4.7 vs. 5.7+/-2.3 points, p=0.000) and the QOL index also improved (4.5+/-2.7 vs. 2.3+/-2.3 points, p=0.000) after treatment. The success rate was 80% in the study group. There were no significant changes in obstructive symptom scores or the QOL index in the control group. The maximal effect appeared about 1 week after treatment. The duration of the therapeutic effect ranged from 3 to 9 months. Mild stress urinary incontinence and nocturnal enuresis were noted in 7 patients (35%). CONCLUSION: Urethral injection of botulinum A toxin can be effectively used to treat patients with detrusor underactivity and non-relaxing urethral sphincter after radical hysterectomy with few adverse effects.     

Prognostic value of acute physiology and chronic health evaluation II and organ system failure in patients with acute renal failure requiring dialysis

BACKGROUND: Despite advances in modern technology of dialysis, prognosis of patients with acute renal failure (ARF) remains poor. To give the clinicians the most useful information, a model that accurately predicts outcome early in the course of ARF is required. However, because ARF is a heterogeneous syndrome and occurs in patients with diverse etiologies and some coexisting diseases, predicting outcome early is hard. The aim of this study is to evaluate prospectively the Acute Physiology and Chronic Health Evaluation (APACHE II) and organ system failure (OSF) models, evaluated prior to dialysis, in predicting hospital mortality. METHODS: From June 2002 to March 2004, ARF patients requiring dialysis at Chang Gung Memorial Hospital, Chiayi, were prospectively recruited for this study. The worst clinical and laboratory data in the 24 hours before initiation of dialysis were prospectively evaluated, and the patients' APACHE II score and OSF number were assessed. RESULTS: A total of 61 patients (40 male and 21 female) were enrolled, of whom 38 (62.3%) died before discharge. By multivariate logistic regression, the APACHE II score (odds ratio 1.3 per increase in one score; P<0.001), or OSF number (odds ratio 1.9 per increase in one OSF; P<0.01) and oliguria (odds ratio 4.2; P=0.04), were found to be statistically significant prognostic factors for hospital mortality. Mortality increased progressively and significantly as OSF number (chi-square for trend; P=0.001) or the APACHE II score (chi-square for trend; P < 0.001) increased. By using Youden's index, the best cut-off value for APACHE II was 24, with 63% sensitivity and 96% specificity. The best cut-off value for OSF number was 2, with a sensitivity of 81.6% and a specificity of 60.9%. The areas under the receiver operating characteristic curves for APACHE II and OSF number were 0.847 (95% confidence interval (CI)=0.752-0.942; P<0.01) and 0.769 (95% CI=0.646-892; P<0.001), respectively, indicating good model discrimination. CONCLUSIONS: This study concludes that APACHE II and OSF number measured prior to initiation of dialysis reliably predict outcomes of ARF patients requiring dialysis. The mortality rates increase as the APACHE II score or OSF number increases. For predicting mortality, the APACHE II score > or = 24 was found to have 63% sensitivity and 96% specificity, and OSF number> or = 2 had 81.6% sensitivity and 60.9% specificity.     

尿脱落细胞吖啶橙染色检查在膀胱癌诊断中的应用价值

目的 探讨尿脱落细胞吖啶橙荧光染色(AO-F)检查在膀胱癌诊断中的应用价值.方法 回顾性分析1016例膀胱癌患者资料,按临床分期、病理分级、肿瘤大小、数目、部位,手术治疗方式及有无血尿症状,分别计算AO-F阳性率,并进行统计学分析.结果 1016例患者尿样AO-F阳性率78.05%(793/1016),表浅癌和浸润癌患者阳性率分别为74.69%(611/818)和91.92%(182/198);病理分级≤Ⅱ级和Ⅲ级患者阳性率分别为67.24%(351/522)和90.37%(413/457);有无血尿症状患者阳性率分别为80.30%(750/934)和52.44%(43/82);肿瘤直径≥2 cm和<2 cm患者阳性率分别为79.87%(710/889)和65.35%(83/127);多发和单发肿瘤患者阳性率分别为83.07%(363/437)和74.27%(430/579);肿瘤累及膀胱三角区或膀胱颈部者阳性率为77.21%(105/136),累及其他部位者为78.07%(687/880);治疗方法TURBt、膀胱部分切除和膀胱全切除患者阳性率分别为69.68%(393/564),87.87%(268/305)和91.74%(100/109).AO-F阳性率与膀胱癌临床分期、病理分级、手术治疗方式、肿瘤大小、数目及有无血尿症状等因素有明显相关性,且与其临床分期、病理分级间存在正相关(r值分别为0.99和0.97);患者性别及肿瘤发生部位等因素与AO-F阳性率之间无相关性.结论 尿脱落细胞AO-F榆查诊断膀胱癌阳性率高,且简便、无创、经济、准确性高,可反复进行,可提高膀胱癌患者的早期诊断率,值得临床推广应用.     

Measurement of foot placement and its variability with inertial sensors

Gait parameters such as stride length, width, and period, as well as their respective variabilities, are widely used as indicators of mobility and walking function. Foot placement and its variability have thus been applied in areas such as aging, fall risk, spinal cord injury, diabetic neuropathy, and neurological conditions. But a drawback is that these measures are presently best obtained with specialized laboratory equipment such as motion capture systems and instrumented walkways, which may not be available in many clinics and certainly not during daily activities. One alternative is to fix inertial measurement units (IMUs) to the feet or body to gather motion data. However, few existing methods measure foot placement directly, due to drift associated with inertial data. We developed a method to measure stride-to-stride foot placement in unconstrained environments, and tested whether it can accurately quantify gait parameters over long walking distances. The method uses ground contact conditions to correct for drift, and state estimation algorithms to improve estimation of angular orientation. We tested the method with healthy adults walking over-ground, averaging 93 steps per trial, using a mobile motion capture system to provide reference data. We found IMU estimates of mean stride length and duration within 1% of motion capture, and standard deviations of length and width within 4% of motion capture. Step width cannot be directly estimated by IMUs, although lateral stride variability can. Inertial sensors measure walks over arbitrary distances, yielding estimates with good statistical confidence. Gait can thus be measured in a variety of environments, and even applied to long-term monitoring of everyday walking.