Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.     

腮腺良性和恶性多形性腺瘤的超声研究

目的研究腮腺良性和恶性多形性腺瘤的超声特点,为临床医师诊治提供有效依据。方法选取腮腺良性多形性腺瘤患者79例和恶性多形性腺瘤患者15例,对其肿块的大小、硬度、内部回声、彩色多普勒血流显像(CDFI)特点结合病理学诊断进行对照研究。结果恶性多形性腺瘤的声像图特点与良性多形性腺瘤相似,但其肿瘤相对较大,质地更硬,内部回声分布更紊乱。不同性质的肿瘤的大小和质地有显著性差异,(P<0.01)。结论多形性腺瘤的超声诊断主要依据二维图像之特点。当多形性腺瘤大于3.0 cm,硬度较硬,内部回声分布不均多提示恶性。     

大脑中动脉支架内血栓形成1例报告

支架内血栓形成是支架置入术后的一种常见并发症。术后血管内皮损伤、胶原组织暴露和作为异物的支架均为引发血栓形成的可能机制。不能及时识别处理则成为再狭窄的重要原因。我们报告1例发生在大脑中动脉（middle cerebral artery，MCA）支架内的血栓形成，探讨其识别处理过程和可能的机制。     

切开复位内固定治疗骨盆桶柄样Tilt骨折

目的探讨骨盆桶柄样Tilt骨折手术治疗方法。方法切开复位内固定治疗52例骨盆桶柄样Tilt骨折。前骨盆经Plan—nenstiel入路固定9例，Pfannenstiel入路结合部分髂腹般沟入路固定43例。37例行骨盆重建钢板固定，骨盆重建钢板固定结合耻骨上支髓内螺钉固定9例，6例2块骨盆重建钢板固定。后环37例经患侧髂嵴入路以骨盆重建钢板固定。8例骶骨骨折行骶髂关节螺钉固定。7例未行后骨盆固定。结果平均随访18个月。全部骨性愈合，无下肢不等长，骨盆畸形基本纠正。按Majeed疗效评定标准优良率为93．8％。结论通过前后联合入路，切开复位治疗骨盆桶柄样Tilt骨折疗效满意，并可防止远近期并发症的发生。     

ES05ROUTINE PARAFIBROMIN IMMUNOHISTOCHEMISTRY OF LARGE PARATHYROID ADENOMAS IS NOT AN EFFECTIVE SCREENING STRATEGY FOR CARCINOMA

Purpose Parathyroid carcinoma (PC) is rare and accounts for less than 1% of all cases of primary hyperparathyroidism (PHPT). The definitive histopathologic diagnosis of PC requires unequivocal invasion or metastasis which may be absent at first presentation. As a result, many cases of PC can only be diagnosed retrospectively. Parafibromin is the protein encoded by HRPT2 which is mutated and not expressed in many parathyroid carcinomas. Given that PCs generally weigh more than parathyroid adenomas (PA)s, we hypothesized that amongst large PAs there may be a high incidence of occult PC which could be identified by negative staining for parafibromin. Methodology 57 parathyroid glands weighing greater than 2 grams excised from 1998–2006 were identified from the University of Sydney Endocrine Surgical Database. Two specimens with a histopathologic diagnosis of PC were excluded. Immunohistochemical staining for parafibromin was performed on the remaining 55 PAs. Results Of the 55 specimens stained for parafibromin only one definite negative stain was detected. This case was originally classified as an “atypical adenoma” because it showed nuclear and architectural atypia without unequivocal evidence of invasive growth. In view of the negative staining for parafibromin it therefore probably represents occult carcinoma. There has been no evidence of recurrence or metastasis after 6.5 years. Conclusions Complete loss of staining for parafibromin is very rare in giant parathyroid adenomas suggesting that occult carcinoma is equally rare. As a result routine immunohistochemical staining for parafibromin does not appear to be an effective screening test for carcinoma in large PA without histopathologic features of PC.     

HP26PSEUDO‐ACHALASIA FOLLOWING A SLIPPED LAPAROSCOPICALLY PLACED ADJUSTABLE GASTRIC BAND: A CASE REPORT

Purpose To demonstrate that laparoscopic adjustable gastric banding may promote oesophageal dilatation or interfere with oesophageal motility. Methodology We report a case of a 67 year old female with a complex medical history who developed secondary achalasia from a slipped laparoscopic adjustable gastric band for weight loss. This led to recurring episodes of aspiration pneumonia requiring multiple admissions at North Shore Hospital, Auckland, New Zealand. Results A decision was made to remove the gastric band, five years after its initial insertion. At one month follow up, she was swallowing normally and oesophageal manometry had returned to normal. Conclusion Oesophageal dysmotility is sometimes seen in patients who have bands that are adjusted too tightly or in whom the band has slipped. This can lead to serious complications if unrecognized and incorrectly treated. Oesophageal symptoms in patients with adjustable bands must be considered secondary to the band until proven otherwise ie removal of the band or complete deflation.