GG genotype of cyclin D1 G870A polymorphism is associated with increased risk and advanced colorectal cancer in patients in Singapore

Recent studies have implicated cyclin D1 G870A single-nucleotide polymorphism (SNP) in susceptibility to and early onset of colorectal cancers (CRC). We investigated the role of cyclin D1 G870A SNP in Singapore CRC patients without dominant family history by genotyping 254 patients and 101 controls. The risk of cancer for AA individuals was less than half that of GG individuals (odds ratio (OR) 0.41; 95% confidence interval (CI) 0.18-0.96). Furthermore, AA and AG patients whose tumours were Dukes C and D (OR 0.38; 95% CI 0.17-0.83), poorly differentiated (OR 0.28; 95% CI 0.09-0.84) and left-sided (OR 0.45; 95% CI 0.21-0.98) were associated with significantly lower risk than GG patients. Young (aged 50 years or less) GG patients had a 5-year lower mean age at onset than AA/AG patients (P=0.02). Young male GG patients had worse disease-specific survival than AA/AG patients (P=0.002). Thus, contrary to Caucasians, the GG (rather than AA) genotype is associated with increased susceptibility and advanced CRC in Singapore patients, suggesting a more complex relationship between the SNP and CRC risk, possibly modulated by population differences.     

A potent apoptosis-inducing activity of a sesquiterpene lactone, arucanolide, in HL60 cells: a crucial role of apoptosis-inducing factor

Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC(50) in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24 - 36 h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-kappaB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.     

Feasibility of baculovirus-expressed recombinant 10-kDa antigen in the serodiagnosis of Taenia solium neurocysticercosis

Bacterially expressed recombinant 10-kDa protein of Taenia solium metacestode (TsM) was previously found to be reliable in the diagnosis of active stage neurocysticercosis (NCC) by immunoblotting but not by ELISA. In this study, we evaluated the diagnostic feasibility of detecting eukaryote-expressed recombinant 10-kDa protein of TsM by ELISA (rTsM10-ELISA) in the serum and cerebrospinal fluid (CSF) from NCC patients. In 45 cases of active NCC, 91.1 and 97.8% cases showed positive reactions for serum and CSF by rTsM10-ELISA. ELISA employing the crude cyst fluid antigen (CF-ELISA) also revealed a similar result. Negligible cross-reactions were observed in serum samples from control subjects and from subjects with other helminthic diseases by rTsM10-ELISA (5/139 cases, 3.6%). By contrast, CF-ELISA demonstrated a high degree of cross-reactivity (24/139, 17.3%) especially from those patients with alveolar and cystic echinococcoses. The overall sensitivity and specificity of rTsM10-ELISA were 94.3 and 96.4%; and those of CF-ELISA were 95.7 and 84.5%, for serum and CSF, respectively. Antibody responses to rTsM10 were detected as early as 3 months after experimental infection of T. solium eggs in pigs. Our results show that ELISA with rTsM10 could be highly applicable in the serodiagnosis of NCC from early stage of infection.     

The Ratios of Individual Chemicals in a Mixture Determine the Degree of Joint Effect: The Climax Hypothesis

A new hypothesis, the Climax Hypothesis, is proposed to describe how the ratios of individual chemicals influence the joint effects of chemical mixtures. This hypothesis is derived from a generalized approach using “isobolograms.” With this hypothesis, one can predict that for a given mixture, a curvilinear correlation exists between the joint effects and the ratios of individual chemicals and that this curve has a climax at the equitoxic ratio. This prediction is supported by the observed toxicity to Vibrio fischeri of 18 mixtures (12 binary mixtures, 4 ternary mixtures, and 2 quaternary mixtures). With this prediction, the Climax Hypothesis has some promising applications such as controlling the discharge of effluents in environmental science, maximizing detoxifying effects in medicine, and optimizing combined pesticides in agriculture.     

Concealed mothball abuse prior to anesthesia: mothballs, inhalants, and their management

Mothballs are one of a number of volatile compounds including model airplane glue, spray paint, nail polish remover, room fresheners, and gasoline that are intentionally inhaled for the purpose of recreational self-intoxication. Their inhalation produces a rapid 'high' characterized by euphoria and generalized intoxication. Chronic abuse can be associated with significant organ impairment, and, in rare cases, cardiac dysrhythmias and deranged end-tidal gas monitoring. Mothballs contain the aromatic compound naphthalene and/or paradichlorobenzene. Prolonged exposure can cause hepatic failure and severe hemolytic anemia. We present a case of a young adult who initially concealed her chronic mothball inhalation. The literature regarding mothball abuse as well as inhalant abuse relevant to anesthesia is reviewed, and suggestions for the diagnosis and peri-operative management are offered.     

An unusual case of Dantrolene sodium-induced urinary retention in post-traumatic minimally responsive state

Introduction: An unusual case of urinary retention is reported occurring during the inpatient rehabilitation of minimally responsive state (MRS) following severe traumatic brain injury (TBI). Clinical picture: Urodynamic evaluation showed detrusor acontractility and subsequent management involved intermittent bladder catheterization and treatment of a single urinary tract infection. Treatment: Factors contributing to her bladder paralysis included severe immobility, tetraplegia and treatment of diffuse spasticity with oral Dantrolene sodium 250 mg per day. Constipation, diabetes and spinal cord injury were absent. In addition, she received unilateral partial sciatic neurolysis with 50% alcohol for severe knee flexor spasticity and intra-muscular Botulinum toxin A to both spastic upper limbs. Outcome: Bladder acontractility resolved completely when Dantrolene was reduced with subsequent achievement of a catheter-free status and small post-void residual volumes. Repeat urodynamics showed spontaneous detrusor contractions. Conclusion: A discussion of possible aetiologic factors for detrusor acontracility following TBI is presented including a brief review of the literature.     

泰素周疗和三周疗法作为卵巢癌一线化疗的多中心对照研究

目的比较泰素周疗和铂尔定联合化疗与泰素3周疗法和铂尔定联合化疗作为卵巢癌一线化疗的效果,观察两种联合方案的毒性作用及两种联合方案对卵巢癌患者两年生存期的影响。方法采用多中心对照研究的方法,将手术后病理学诊断为晚期卵巢上皮癌的125例患者分为两组。（1）周疗组：51例患者,泰素60—80mg／m^2,每周给药1次,共6次。铂尔定（药释曲线=5．0）仅在第1周,第4周用完泰素后给药。8周为1个疗程,化疗6周,休息2周。2个疗程（16周）后评价疗效。（2）3周疗法组：74例,泰素175mg／m^2,3h静脉滴注。铂尔定：（药释曲线面积为5．0）,每疗程的第一天联合应用泰素＋铂尔定,3周为1个疗程,用药6个疗程（18周）后评价疗效。结果（1）CAl25下降情况：经手术和化疗后102例（81．6％）患者CAl25呈现满意的下降,其中3周疗法组为58例（78．4％）,周疗组为44例（86．3％）,两组比较差异无统计学意义（P〉0．05）。（2）病情复发和未控情况：①总的复发和／或未控病例有32例,占26．4％。3周疗法组复发和／或未控病例有22例（29．7％）,其中停化疗〉6个月的复发有8例,停化疗〈6月的复发有9例,肿瘤持续进展为5例。周疗组复发和／或未控病例有10例（19．6％）,其中停化疗〉6个月的复发有2例,停化疗〈6个月的复发有6例,肿瘤持续进展为2例,两组在病情复发和未控发生率上差异无显著意义（P〉0．05）。②肿瘤复发平均时间：3周疗法组平均复发时问为15．7个月,周疗组平均复发时问为13．6个月（P〉0．05）。③无瘤生存时问（progress—free survival,PFS）3周疗法组平均复发时间为16．5个月,周疗组平均复发时问为15．6个月（P〉0．05）。④生存情况：3周疗法组1年生存率为95．2％,2年生存率为78．7％;周疗组1年生存率为93．9％,2年生存率为85．3％,两组在1年和2年生存率上差异无统计学意义意义（P〉0．05）。（3）毒副反应的情况：在血液毒性方面：3周疗法组,有34例发生3—4度骨髓抑制,发生率为45．9％,周疗组有14例发生3—4度骨髓抑制,发生率为27．5％,两组差异有统计学意义（P〈0．05）。在神经毒性方面3周疗法的发生率略低于周疗组,但差异无统计学意义（P〉0．05）。其他的毒性反应,两组比较差异无统计学意义（P〉0．05）。结论（1）泰素的临床疗效周疗与3周疗法相同。（2）泰素周疗的骨髓抑制发生率明显低于3周疗法,其他的毒性作用与3周疗法比较差异无统计学意义。（3）泰素周疗的毒副反应较轻,更适用于年迈体弱的患者和门诊化疗。