含栅栏状肉芽肿样小体(巨菊形团)的低度恶性纤维肉瘤--报道1例转移病例

自Ｌａｎｅ等 1997年详细报道了ＨＳＣＴＧＲ后 ,一直没有该肿瘤转移潜能的证据 ,该文报道 1例 2 8岁女性右上臂三角肌内ＨＳＣＴＧＲ(8 7ｃｍ× 5 5ｃｍ× 4 0ｃｍ大小 ) ,术后 4年右肺转移 ,并于 6年后行肺部手术 ,取出 0 6ｃｍ～ 1 2ｃｍ大小转移性结节 3枚。肿瘤从大体形态到超微结构及免疫组化表现与前文相似。本文总结出该病光镜下由梭形细胞为主 ,构成 3种图像 :①纤维瘤样区 ,为肿瘤的主要成分 ,无核分裂象 ;②细胞区 ,细胞丰富 ,核浓染 ,胶原减少 ,罕见核分裂象 ;③特征性病变 (有诊断意义 ) ,即由丰富细胞核环绕的玻璃样变小体 …     

Patel S,Turner PR,Stubberfield C,Barry E,Rohlff CR,Stamps A,McKenzie E,Young K,Tyson K,Terrett J,Box G,Eccles S,Page MJ. Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer. International Journal of Cancer 2002;97(4): 416–424.

The original article to which this Erratum refers was published in International Journal of Cancer; 2002; 97(4) 416–422.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.     

Case Report: Congenital Radioulnar Synostosis and Its Embryological Correlation and Functional Assessment

Congenital radioulnar synostosis(CRS) is a rare anomaly and approximately 400 cases were reported worldwide so far. CRS is the failure of the longitudinal segmentation and the persistence of the cartilaginous anlage between the radius and ulna during the seventh week of development that results in a persistent bridge of tissue. Here we are discussing on a case of 25yrs old, male patient with bilateral congenital synostosis. On the left hand the pronation and supination movements are restricted completely where as on right side 10 degree of supination and 20 degree of pronation is possible. Radiologically in our patient synostosis is classified as type II variety by Wilkie(1914)1 classification and type IV by the Cleary and Omer classification(1985). The position of forearm was not found to be related to subjective functional limitation, or employment status. Main line of treatment is surgical mainly rotational osteotomy but is rarely indicated. Our patient is not able to rotate his forearm especially on the left side still he has no functional limitation so he has refused for the operative treatment. No study has objectively compared the preoperative functional limitation of the patients with their postoperative functional improvement in order to justify surgical intervention In the authors opinion the only major factor that is to be taken into consideration of operative treatment is functional limitation to the patient.     

Amyotrophic Lateral Sclerosis, 2016: existing therapies and the ongoing search for neuroprotection

Introduction: Amyotrophic lateral sclerosis (ALS), one in a family of age-related neurodegenerative disorders, is marked by predominantly cryptogenic causes, partially elucidated pathophysiology, and elusive treatments. The challenges of ALS are illustrated by two decades of negative drug trials.

Areas covered: In this article, we lay out the current understanding of disease genesis and physiology in relation to drug development in ALS, stressing important accomplishments and gaps in knowledge. We briefly consider clinical ALS, the ongoing search for biomarkers, and the latest in trial design, highlighting major recent and ongoing clinical trials; and we discuss, in a concluding section on future directions, the prion-protein hypothesis of neurodegeneration and what steps can be taken to end the drought that has characterized drug discovery in ALS.

Expert opinion: Age-related neurodegenerative disorders are fast becoming major public health problems for the world’s aging populations. Several agents offer promise in the near-term, but drug development is hampered by an interrelated cycle of obstacles surrounding etiological, physiological, and biomarkers discovery. It is time for the type of government-funded, public-supported offensive on neurodegenerative disease that has been effective in other fields.     

Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease

This study aimed to explore the therapeutic mechanism of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). Peripheral blood lymphocytes (PBLs) obtained from 26 children with KD and 20 age-matched healthy children were stimulated with anti-CD3 monoclonal antibody (mAb), and the percentage of apoptotic cells and DNA fragmentation were assayed at 0, 12, 24, 48 and 72 h in vitro. The patients were divided into two groups: one treated with aspirin combined with IVIG (n = 16) and one treated with aspirin alone (n = 10). PBLs were stimulated by phytohaemagglutinin to evaluate the lymphocyte proliferative response. Compared with normal controls, the apoptotic cell percentage and the DNA fragmentation were markedly decreased (p < 0.001) and delayed in PBLs from KD patients. After IVIG treatment, the decreased percentage of apoptotic cell and delayed DNA fragmentation were restored to the state of the normal controls, accompanied by a fast clinical remission compared with the aspirin-alone group. The lymphocyte proliferative response was also decreased 3-5 d after IVIG therapy (p < 0.001). Conclusion: The results suggest that decreased PBL apoptosis may be involved in the pathogenesis of KD. The therapeutic mechanism of IVIG in KD may be partially due to the reversal of the inhibited lymphocyte apoptosis, and may have implications for other autoimmune diseases with inefficient lymphocyte apoptosis.     

Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis

The serotonin (5HT3) antagonist ondansetron was compared in a randomised study with metoclopramide and dexamethasone for the prevention of chemotherapy induced emesis. Thirty children aged 1-15 years with acute lymphoblastic leukaemia received 'intensification modules' according to the MRC United Kingdom acute lymphoblastic leukaemia regimen UKALL XI. This contains the moderately emetogenic drugs daunorubicin, etoposide, and cytarabine. Fifteen children received an intravenous loading dose of ondansetron followed by intravenous or oral doses 12 hourly for five days. Fifteen children received intravenous metoclopramide every six hours for three days with a loading dose of dexamethasone, repeated every eight hours for three days intravenously or orally. Efficacy was assessed by a diary card documenting the incidence of nausea, retching, or vomiting. In the 24 hour period after starting chemotherapy, ondansetron was more effective, with a complete or major response rate of 93%, compared with 33% using metoclopramide/dexamethasone.