Prevalence of smoking in a diabetic population: the need for action

Smoking habits in insulin-treated diabetics in Nottinghamshire (UK) and clinic-attending diabetics in Nottingham have been analysed. Compared with the general population, the prevalence of current cigarette smoking is significantly less (p less than 0.001) in both diabetic men and women older than 50 years. Fewer diabetic men over 60 years have ever smoked than in the general population (p less than 0.001) but this finding does not apply to diabetic women. While intervention probably plays some part in this lower prevalence, the most likely explanation is the multiplicative effect of both smoking and diabetes to produce high mortality risks. Actuarial analysis of insulin-treated clinic attenders diagnosed after 1970 showed that at most 14% (95% confidence interval [Cl] 9-18%) of the 183 who smoked at diagnosis had given up 5 years later while a minimum of 8% (95% Cl, 6-11%) of the 313 who were non-smokers had started smoking. Information about the patterns of smoking in patients with chronic disease is incomplete and it appears that too little is being done in clinical services which provide long-term management for these patients to either discourage smoking or determine why some patients give up smoking but others do not.     

A comprehensive study of smoking in primary school children in Hong Kong: implications for prevention.

STUDY OBJECTIVE: To identify factors associated with smoking behaviour in primary school children in Hong Kong. DESIGN: A cross sectional survey in which both children and parents completed questionnaires. The main outcome measure was the smoking status of the children; and risk factors (knowledge of and attitude to smoking and demographic and socioeconomic background) were identified as predictors of ever/never smoking. SETTING AND SUBJECTS: Altogether 9598 primary school children, aged 8-13 years, and attending 27 schools from two districts in Hong Kong participated. MAIN RESULTS: The prevalence of ever-smoking was 12% (1119)-15% (760) in boys and 7% (359) in girls. It ranged from 3% in 8 year old girls to 52% in 13 year old boys. The factors associated with ever-smoking included the following: being a boy (adjusted odds ratio 2.21; 95% confidence interval 1.89, 2.59), increasing age per year (1.48; 1.40, 1.57), living in Kwai Tsing district (1.29; 1.10, 1.50), having one or more smokers at home (2.07; 1.78, 2.39), and having a father who was not working (1.41; 1.19, 1.67). Children who were ever-smokers had both seen and approved of their friends' smoking (8.79; 5.33, 14.50), had a more positive attitude towards smoking (3.35; 2.21, 5.09), and were more successful in recognising cigarette brand names and logos (1.67; 1.42, 1.96), but they lacked confidence (1.78; 1.32, 2.39). CONCLUSIONS: The influences on child smoking are multifactorial and programmes in Hong Kong are falling to curb them. The control of these risk factors must be incorporated in the smoking prevention policy of Hong Kong and supported by future enforced legislation.     

Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1

Injection of microparticle-encapsulated DNA elicits immune responses to plasmid-encoded antigens in mice and humans. Cytochrome P450 CYP1B1 (CYP1B1) is a member of the CYP1 P450 enzyme family that is overexpressed in a variety of solid tumors. The work described herein was performed to study the kinetics of stimulating T cell responsiveness with an encapsulated DNA encoding CYP1B1 and provides support for the clinical development of this formulation. Immunization of HLA-A2/Kb transgenic mice with human CYP1B1 encoding plasmid DNA formulated in poly(lactide-co-glycolide) (PLG) microparticles elicits CD8+ T cells that respond to human CYP1B1-positive target cells. The duration of the immune response, the effect on the immune response of multiple injections, and the safety of repeated injections were studied. These results show that the PLG-encapsulated DNA therapeutic elicits durable immune responses to CYP1B1, the responses are dependent on repeat immunization, and that the formulation is well tolerated.     

T-cell frequency analysis does not predict the incidence of graft-versus-host disease in HLA-matched sibling bone marrow transplantation

BACKGROUND: Graft-versus-host disease (GVHD) is a major and sometimes fatal complication of allogeneic bone marrow transplantation (BMT). The prediction of GVHD remains an important issue in preventing morbidity and mortality after allogeneic BMT. In the past 10 years, there has been great interest in using the frequency analysis of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp and CTLp) to detect recipient-specific alloreactivity and thus predict GVHD in HLA-matched related and unrelated BMT. However, the results remain controversial. The intention of the present study was to investigate whether alloreactive HTLp and CTLp frequencies measured in donor peripheral blood before BMT would be a useful predictor for the occurrence of acute GVHD after HLA-matched sibling BMT. METHOD: A combined limiting dilution assay was used to determine alloreactive HTLp and CTLp frequencies for 42 HLA-matched sibling patient/donor pairs. The pretransplantation host-reactive HTLp and CTLp frequencies were then correlated with post-transplantation clinical outcomes of acute GVHD. The association between HTLp/CTLp frequencies and the incidence of acute GVHD was determined using the Fisher's exact test. RESULTS: The mean values of HTLp and CTLp frequencies for this cohort of HLA-matched sibling patient/donor pairs were 1:321,322 (range 1:71,000 to 1:1000,000) and 1:195,260 (range 1:3,717 to 1:1000,000), respectively. Acute GVHD (> or =II) was observed in one of four patients with high (>1:100,000) HTLp frequencies and 20 of 36 patients with low (<1:100,000) HTLp frequencies. Similarly, 6 of 10 patients with high (>1: 100,000) CTLp frequencies and 14 of 29 patients with low (<1:100,000) CTLp frequencies developed acute GVHD (> or =II). The overall correlation between hostreactive HTLp/CTLp frequencies and the incidence of acute GVHD in this cohort of patients was 42.5% and 53.9%, respectively. There was no significant difference in the incidence of acute GVHD between the patients with either high or low host-reactive HTLp/ CTLp frequencies (P=0.331 and 0.716, respectively). The data were also analyzed separately for the adult patient group based on GVHD prophylaxis with either cyclosporine alone or the combination of cyclosporine and methotrexate. Within these two prophylaxis groups, neither HTLp nor CTLp frequencies correlated with acute GVHD. CONCLUSION: Host-reactive HTLp and CTLp frequency analysis did not provide informative prediction for the occurrence of acute GVHD after HLA-matched sibling BMT.     

Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas.

PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors, including cervical carcinomas. Direct pO(2) measurement requires specialized equipment and expertise that is not generally available. Immunohistochemical measurement of intrinsic tissue markers of hypoxia is an alternative approach. Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy. Tissue sections were labeled using an immunofluorescence technique and CA IX expression in the viable tumor area measured using a semiautomated fluorescence image analysis technique. Results were compared with direct pO(2) values obtained using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA IX expression was examined in a subgroup of patient who underwent multiple biopsies. RESULTS: The median percentage of tumor area staining for CA IX was 3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf pO(2) measurements. Whereas the latter values were predictive of patient outcome, the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated that intratumoral heterogeneity accounted for 41% of the total variance in the data set. CONCLUSIONS: In contrast to some recent studies, we did not find significant associations between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. Probable explanations relate to the problems of sampling error using single biopsies and the existence of biological factors other than hypoxia that influence CA IX levels.     

Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial.

PURPOSE: Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. PATIENTS AND METHODS: Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8. RESULTS: Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. CONCLUSION: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.     

Validation of a clinical decision rule: chest X-ray in patients with chest pain and possible acute coronary syndrome

Current literature suggests that a large proportion of chest X-rays (CXRs) performed in emergency department (ED) patients with chest pain and suspected acute coronary syndrome (ACS) are unnecessary. The Canadian ACS Guidelines aim to guide clinicians in the appropriate use of CXR within this patient population. This study determined the prevalence of clinically significant CXR abnormalities and assessed the utility of the guidelines in a population of ED patients with chest pain and suspected ACS. Included in the study were participants over the age of 18 who presented to an Australian metropolitan ED, over a 1-year period, with a primary complaint of chest pain and who had a CXR and troponin level ordered in the ED (N?=?760). We retrospectively compared their radiographic findings with their recommendations for CXR according to the ACS Guidelines. We found that 12 % of the participants had a clinically significant chest X-ray. The guidelines had a sensitivity of 80 % (95 % CI 0.70–0.87) and specificity of 50 % (95 % CI 0.47–0.54). The positive predictive value was 18 % (95 % CI 0.15–0.22) with a 95 % negative predictive value (95 % CI 0.92–0.97). Had the ACS guidelines been applied to our patient population, the number of CXR performed would have been reduced by 47 %. This study suggests that the ACS Guidelines has the potential to reduce the numbers of unnecessary CXR performed in ED patients. However, this would come at the expense of missing a minority of significant CXR abnormalities.