Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand

In Thailand, smoking of commercial cigarettes and of handmadecigarettes has drastically increased in recent decades. Cancerof the lung and of the upper aerodigestive tract have also increasedin Thailand as they have in many other countries. It is ourworking hypothesis that the increase of primary cancer of theliver, especially of cholangiocarcinoma in the north-easternprovinces of Thailand is associated with the use of tobaccoin men infested with the liver fluke Opisthorchis viverrini(OV). Bioassays have shown that volatile nitrosamines and tobacco-specificnitrosamines induce cholangiocarcinoma in laboratory animalsand that the hepatocarcinogenic action of nitrosodimethylaminein hamsters is significantly increased by infestation with theliver fluke OV. The endogenous formation of nitrosamines issignificantly increased by OV infestation. This report presentsanalytical data on the concentration of volatile nitrosaminesand tobacco-specific nitrosamines in mainstream smoke of nineleading brands of commercially produced Thai cigarettes whichrepresent ~85% of the market share in Thailand. Observed ranges(ng/cigarette) were 8.5–31.9 for nitrosodimethylamine,8.8–49.6 for nitrosopyrrolidine and 4.2–18.9 fornitrosodi-n-butylamine. These values are exceptionally highcompared with the smoke of light and blended cigarettes fromNorth America and Western Europe. Among the tobacco-specificnitrosamines, the range was 28–730 for nitrosonornicotineand 16–370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.There was a correla-tion between volatile and tobacco-specificnitrosamines, and tar and nicotine deliveries in the mainstreamsmoke. The analytical data are in line with the rate for lungcancer and support our working hypothesis that nitrosamines,and especially the tobacco-specific nitrosamines, are associatedwith the increased risk for primary liver cancer among thoseThai people who smoke cigarettes and also carry OV infestation.     

Physical examination and radiographic interpretation of carpal anatomy in orthopedic residents and emergency medicine physicians

The purpose of this study was to evaluate carpal anatomy proficiency in orthopedic residents as well as emergency medicine physicians. Orthopedic surgery residents and emergency medicine physicians were tested on their understanding of normal carpal anatomy using a Wrist Anatomy Assessment (WAA) score, which consists of both palpation of carpal bony landmarks and radiographic interpretation of the carpal bones. There were 89 participants in this study. Cohorts of orthopedic residents (n = 20), emergency medicine residents (n = 21), emergency medicine attending physicians (n = 26), and 4th-year medical students (22) were used. Group size was based on 100% orthopedic resident involvement. Total WAA scores (score of 17 = 100% correct) ranged from 2 to 16, with a mean of 8.6. Carpal palpation and radiographic interpretation means were both significantly better in the orthopedic resident cohort (total WAA score, 13.8), compared with either of the emergency medicine groups (resident total WAA score, 7.5; attending total WAA score, 7.2). Orthopedic residents have a better understanding of the clinical and radiographic anatomy of the carpal bones than emergency medicine residents and attending physicians. Future research to test educational interventions to improve carpal anatomy education is warranted.     

A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

Background

Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres.

Patients and methods

Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire.

Results

Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9–79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8–63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9–27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m² oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p?=?0.031, RR?=?8.3 95%CI?=?1.2–57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p?=?0.051; RR?=?1.7 95%CI 1.0–2.8).

Conclusion

Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports.     

Treatment of acute myelogenous leukemia with outpatient azacitidine

BACKGROUND: Patients older than 55 years of age with acute myelogenous leukemia (AML) are less likely to achieve complete remission and more likely to experience toxicity with conventional induction chemotherapy than younger patients. Azacitidine administered in the outpatient setting is well tolerated and can induce complete hematological remission in patients with myelodysplastic syndromes (MDS). At higher doses, azacitidine has activity in AML. METHODS: Twenty patients were retrospectively identified who had been treated with azacitidine with bone marrow blast counts between 21 and 38%. Patients with blast counts up to 29% were initially treated as MDS, but by WHO now meet criteria for AML. Patients with blast counts over 29% were treated with azacitidine after being deemed poor candidates for induction chemotherapy. Azacitidine 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle. RESULTS: The overall response rate was 60% (12/20): complete response (CR; n = 4; 20%); partial response (PR; n = 5; 25%); hematologic improvement (HI; n = 3; 15%). The median survival of responders was 15+ months compared with 2.5 months for nonresponders (P = .009). During therapy, responders had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0. The most common toxic event was infection (n = 8). Four patients were hospitalized during the first cycle of treatment. CONCLUSIONS: Azacitidine administered in the outpatient setting can induce remission in AML. The therapy is well tolerated and might be an alternative for patients unlikely to tolerate standard induction chemotherapy.     

Molecular identification of Trichinella papuae from a Thai patient with imported trichinellosis

Previously, we reported the presence of imported trichinellosis in a Thai worker returning from Malaysia, who presented with progressive generalized muscle hypertrophy and weakness after eating wild boar meat. This work analyzed a partial small subunit of a mitochondrial ribosomal RNA gene of Trichinella larvae isolated from the patient. The results showed complete identity with a mitochondrial RNA gene of Trichinella papuae (GenBank accession no. EF517130). This is the first report of imported trichinellosis in Thailand caused by T. papuae. It is possible that T. papuae is widely distributed in the wildlife of Southeast Asia.     

Identification and characterization of a cathepsin L-like cysteine protease from Gnathostoma spinigerum

Gnathostoma spinigerum is a causative agent of human gnathostomiasis, a common parasitic disease involving skin and visceral organs, especially the central nervous system. In this study, we identified a cDNA encoding a cathepsin L-like cysteine protease (GsCL1) from the lambdaZAP cDNA library of G. spinigerum advanced third-stage larva (aL3) and characterized the biochemical properties of the recombinant enzyme. The cloned cDNA of 1484bp encoded 398 amino acids which contained a typical signal peptide sequence (23 amino acids), a pro-domain (156 amino acids), and a mature domain (219 amino acids) with an approximate molecular weight of 24kDa. The deduced amino acid sequence of GsCL1 gene showed 53-64% identity to cathepsin L proteases of various organisms including a cathepsin L family member (cpl-1) of Caenorhabditis elegans. Recombinant proGsCL1 expressed in Pichia pastoris showed typical biochemical characteristics of cysteine proteases. The expressed enzyme displayed optimal protease activity toward Z-Phe-Arg-AMC substrate at pH 6.0 but not toward Z-Arg-Arg-AMC. The activity was sensitive to cysteine protease inhibitors E-64 and K11777. The preference for large hydrophilic and aromatic residues in the P2 position (I, L, F, W, U, V) was typical of cathepsin L proteases. Mouse anti-GST-proGsCL1 serum showed reactivity with 35-, 38- and 45-kDa proteins in the aL3 extracts. These proteins were shown to localize inside the intestinal cells of aL3.