Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease: analysis of nationwide experience in Scotland (2004–2008)

Background  Adalimumab is a second generation humanized anti-tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn's disease (CD).
Aims  To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting.
Methods  We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4-year period (2004–2008).
Results  A total of 98 patients received adalimumab - 100.5 patient follow-up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1-year follow-up, with 30% and 55% requiring dose escalation to weekly therapy at 1-and 2-year follow-up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively).
Conclusions  Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy- and disease-related risks of serious complications.     

胰岛素瘤相关蛋白-2高表达对胰岛细胞增殖的影响

目的:探讨1型糖尿病自身抗原胰岛素瘤相关蛋白-2(IA鄄2)高表达对胰岛细胞系RIN5F细胞增殖、生长周期和细胞凋亡的影响。方法:利用分子克隆技术构建IA鄄2真核表达载体,转染RIN5F细胞后筛选稳定高表达IA鄄2的细胞系,采用3鄄(4,5鄄二甲基)鄄5鄄(3鄄羧甲基苯环)鄄2鄄(4鄄硫基苯)鄄2H鄄四唑盐复合物(MTS)检测法确定细胞增殖速率,运用流式细胞术检测细胞生长周期和细胞凋亡水平。结果:IA鄄2高表达细胞增殖速率显著低于载体对照组细胞(P<0.05)。IA鄄2高表达细胞的细胞凋亡数显著高于载体对照组细胞(P<0.01)。IA鄄2高表达细胞中位于S期的细胞比率显著增加,而G2/M期的细胞比率减少(P<0.05)。结论:IA鄄2在胰岛细胞内高表达可抑制胰岛细胞的增殖,促进细胞凋亡,在G2鄄M期细胞生长阻滞。     

18F-FDG及11C-乙酸盐PET/CT诊断原发及转移性肝细胞癌:一项前瞻性研究的价值与不足分析

肝细胞癌是亚洲地区发病率最高的肿瘤之一,因此有众多的研究涉及肝细胞癌.然而,在研究中所用统计学方法和技术等不当易得出不正确的概念和结论.作者就已发表在美国<核医学杂志>上的<18F-FDG及11C-乙酸盐PET/CT诊断原发及转移性肝细胞癌的前瞻性研究>一文提出了一些不同观点,希望这方面的研究者能掌握正确的统计学方法、诊断标准及样本人选标准.     

Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha-interferon with steroid priming

Background: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pre-treatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. Methods: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. Results: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. Conclusion: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.     

Gastric cytoprotection by amoxycillin in the rat

Abstract Amoxycillin in combination with anti-ulcer agents has been shown to prolong duodenal ulcer remission. While this effect can be related to the eradication of Helicobacter pylori , it is not known if amoxycillin might possess cytoprotective properties. Protection against ethanol-induced gastric mucosal damage by intragastric instillation of amoxycillin suspension (prepared from capsule form) and solution (from injection form, 100% pure amoxycillin), and by intraperitoneal injection of amoxycillin solution was studied using an ex vivo gastric chamber in the rat. Intragastric and intraperitoneal administration of amoxycillin dose-dependently protected the rat gastric mucosa from damage by absolute ethanol. This protection was lost when the rats were pretreated with indomethacin. Gastric mucosal blood flow as measured by laser Doppler flowmetry and gastric acid output were unaffected by amoxycillin. Amoxycillin imparts gastric cytoprotection, and one possible mechanism is by the release of prostaglandins.     

Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer

AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant therapy of superficial bladder transitional cell carcinoma, with respect to recurrence, progression and survival. Prognostic factors are also evaluated. METHODS: Between October 1991 and September 1999, all patients harboring superficial bladder cancers (Ta or T1) with any of the relevant criteria (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete transurethral resection were randomized to receive either 81 mg Connaught strain BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover, even repeatedly, until progression. Recurrence, progression and survival were analyzed in relation to initial treatment, patient characteristics and tumor characteristics. RESULTS: There were 209 patients included in the study, 149 men and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted of 102 patients and the epirubicin group contained 107 patients. Final analysis was made at a median follow up of 23, 47 and 61 months for recurrence, progression and survival, respectively. The 10-year Kaplan-Meier estimates for recurrence-free, progression-free and disease-specific survival were 61%, 78% and 80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and 92%, respectively, for the epirubicin group. Time to recurrence differed significantly between two treatment groups (P=0.0004). Multiplicity increased the risk of recurrence, while grading influenced recurrence, progression and disease specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to recurrence when compared with epirubicin. Grading was shown to be a universal prognostic factor for recurrence, progression and disease specific survival.     

Ureteral cancer associated with dermatomyositis

Dermatomyositis is a rare inflammatory myopathy that has characteristic cutaneous lesions. Although many malignancies are associated with dermatomyositis, urogenital malignancies have rarely been reported to be associated with dermatomyositis. We report here on the first case of ureteral cancer associated with dermatomyositis. A 42-year-old man presented to us with a skin rash. A clinical diagnosis of dermatomyositis was made due to the skin lesions, muscle weakness, arthralgia, the increased erythrocyte sedimentation rate and the increased creatine kinase level. The patient revealed microscopic hematuria and abnormal urine cytology during the investigation for the underlying malignancy. Retrograde pyelography demonstrated a suspicious lesion in the right mid-ureter, and the ureteroscopic biopsy revealed the urothelial carcinoma. Although an operation was recommended, the patient died of pneumonia associated with his interstitial lung disease, which is one of the poor prognostic indicators of dermatomyositis.     

Performance of Bordetella pertussis IS481 real-time PCR in a vaccine trial setting

A real-time PCR method targeting the Bordetella pertussis IS481 gene fragment was evaluated in a vaccine trial setting in which real-time PCR results could be validated against culture and serology results. Two commonly used DNA extraction methods, Amplicor Respiratory Preparation kit and the QIAamp DNA Mini Kit, were compared. An approximately 50-fold higher sensitivity was achieved using the Amplicor kit. 89 of 276 aspirates analysed with the IS481 real-time PCR were positive. Interestingly, six of these were culture negative and came from serology-negative patients. Defining true positive cases either as culture-positive or as PCR-positive cases that had been confirmed with a serology-positive result or verified with a newly constructed recA PCR, the sensitivity and specificity of the IS481 real-time PCR were 89% and 98%, respectively. This study confirms the specificity and high diagnostic sensitivity of IS481-based PCR methods for diagnosis of B. pertussis.     

PRIMARY HYPOTHYROIDISM AND ESSENTIAL HYPERNATREMIA IN A PATIENT WITH HISTIOCYTOSIS X

Abstract: :A 27 year old woman with histiocytosis X had an unusual initial presentation with features of primary hypothyroidism and a goitre. Diagnosis was made by lung and thyroid biopsies. Endocrine tests showed the presence of hypopituitarism and a discrete suprasellar mass, consistent with hypothalamic histiocytosis X, was demonstrated by computerised tomography. Radiotherapy and chemotherapy arrested the clinical progression of the disease.