Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort.

BACKGROUND: The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients. METHODS: A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves. RESULTS: High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03-1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively. CONCLUSIONS: This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.

Controlled trial of nicotine polacrilex gum with supportive measures.

In a placebo-controlled, double-blind, 2-year prospective study, 182 smokers were given either nicotine polacrilex gum containing 4 mg of nicotine (n = 92) or a placebo (n = 90). The number of participants abstinent at 2-year follow-up was 41 (44.6%) of 92 in the nicotine group vs 28 (31.1%) of 90 in the placebo group. Abstinence rates for daily nicotine gum users (n = 64) at 12 months and again at 24 months remained 48.4%, as compared with 26.1% and 31.9% for the daily placebo gum users (n = 69). Of participants with a high nicotine-dependence score, those allotted to the nicotine group rather than to the placebo group were 13 times more likely to be abstaining at the 2-year follow-up. Use of nicotine polacrilex gum, therefore, can substantially aid in stopping smoking, particularly among highly dependent smokers.

Long PCR detection of the C4A null allele in B8-C4AQ0-C4B1-DR3.

The genes coding for the two components of complement 4 (C4), C4A and C4B, are located within the major histocompatibility complex (MHC) on the short arm of chromosome 6. Several studies have shown that deficiency of C4A is associated with systemic lupus erythematosus (SLE), rheumatoid arthritis and scleroderma. A large deletion covering most of the C4A gene and the 21-hydroxylase-A (21-OHA) pseudogene found on the extended haplotype B8-C4AQ0-C4B1-DR3 is estimated to account for approximately two-thirds of C4A deficiency in Caucasian SLE patients. Detection of this C4A null allele has been technically difficult due to the high degree of homology between C4A and C4B, with protein analysis and restriction fragment length polymorphism (RFLP) analysis using Southern blotting being the only approaches available. In this study, a long PCR strategy was used to rapidly genotype for the C4A deletion through specific primer design. The methodology makes use of the unique sequence of the G11 gene upstream of C4A and the sequence of a 6.4 kb retrotransposon, the human endogenous retrovirus HERV-K(C4), which is present in intron 9 of C4A but absent in the case of the deletion.

Argyrophil carcinoid tumors of the lung. Incidence, clinical study, and follow-up of 46 patients.

Forty-nine patients with lung tumors initially diagnosed as carcinoids from their cellular appearance and arrangement were originally included in the study. The tumors of 46 of these patients showed an argyrophil reaction with the Grimelius silver stain. The three nonargyrophil tumors were reclassified as noncarcinoid tumors at further examination. The use of the argyrophil technique in characterization of the lung carcinoid tumors is discussed. The incidence of lung carcinoid tumors in the County of Uppsala was 0.7 patients per 100,000 inhabitants per year. Eleven patients with detected disease were symptom-free. The doctor's delay in 9 patients was 3 to 13.8 years. Yet, the prognosis was good, with 5-year survival in 91 percent, 10-year survival in 91 percent, and 15-year survival in 86 percent of the 46 surgically-treated patients. It is concluded that the surgical treatment should at least comprise a lobectomy.

Cloning, sequence analysis and overexpression of a rhodothermus marinus gene encoding a thermostable thymidine kinase.

Thymidine kinase type II is an important part of the pyrimidine salvage pathway. The thymidine kinase gene from the thermophilic eubacterium Rhodothermus marinus was cloned, sequenced and overexpressed. The gene is 639 bp and encodes a protein of 213 amino acids with a calculated molecular mass of 23.6 kDa. It shows homology to other thymidine kinase proteins from eukaryotic and prokaryotic organisms. The recombinant protein is inhibited by dNTPs but not by dNDPs. It is a tetramer in its native state. Its optimum temperature of activity is 65 degrees C and it has a half life of 15 min at 90 degrees C. This is the first thymidine kinase to be described from a thermophilic bacterium.

The choice of operation for bronchial carcinoids.

In a review of the literature, 1,392 patients with bronchial carcinoids were found. Of these, there were 313 patients for whom individual data with regard to type of operation, follow-up period, and outcome were given. Actuarial curves for proportions of patients who had not died of the disease or who had not undergone reoperation for residual disease were constructed for each type of operation. The prognosis up to 20 years after surgical treatment for bronchial carcinoids is excellent. For 15 to 20 years postoperatively, the prognosis after a lobectomy is excellent and after a pneumonectomy, slightly worse. The prognosis after a lung parenchyma-saving operation (wedge or segmental resection and bronchoplastic procedures) is similar to that after a lobectomy up to 7 years postoperatively. After that, the proportion of disease-free patients declines precipitously. At 20 years the difference in comparison with a lobectomy is statistically significant for both wedge or segmental resections and bronchoplastic procedures. Parenchyma-saving operations cannot therefore be said to be radical. A policy for decision-making at the operating table is formulated.

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.

AIMS: Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A smoker's cessation clinic. PARTICIPANTS: One hundred volunteers smoking 10 cigarettes/day or more. INTERVENTIONS: Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months. MEASUREMENTS: Continuous abstinence rates recorded at various time points up to 12 months from the quit date. FINDINGS: The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action. CONCLUSIONS: We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.

DNA ploidy in small cell carcinoma of the lung.

Fluorometric single cell DNA analysis was performed on 123 tumour samples from 33 patients who had died of small cell carcinoma of the lung (SCCL). In 36% (12 patients) the modal DNA profile was hypodiploid or near diploid and the median survival time was 16.3 months, as opposed to 9.5 months for the 21 patients with hyperdiploid DNA profile, who also seemed to have a lower response rate to chemotherapy. It is suggested that an estimation of the modal DNA ploidy before the start of the treatment in SCCL might be used as a cellular parameter to obtain more comparable treatment study groups and for the prediction of survival.

Nuclear DNA measurements in squamous cell carcinoma of the lung: a guide for prognostic evaluation.

Cytophotometric analysis of nuclear DNA in 30 squamous cell carcinomas showed in most tumours a peak value near 2c (diploid) or 3 c (aneuploid), and a wide distribution of other nuclear DNA values. A follow-up study showed that the prognosis was best for patients with diploid tumour cells and worst for patients with aneuploid tumour cells. The DNA histogram patterns give information about the dominating DNA ploidy of the tumour cells; in some tumours information about the tumour proliferation activity is also provided. These data are useful in prognostic evaluation and may prove useful as adjuncts in the diagnosis and in selection of treatment.

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up.

OBJECTIVE: To evaluate the efficacy of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year. DESIGN: Placebo controlled, double blind trial. SETTING: Reykjavik health centre. SUBJECTS: 237 smokers aged 22-66 years living in or around Reykjavik. INTERVENTIONS: Nicotine patch for 5 months with nicotine nasal spray for 1 year (n=118) or nicotine patch with placebo spray (n=119). Treatment with patches included 15 mg of nicotine for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, whereas nicotine in the nasal spray was available for up to 1 year. Both groups received supportive treatment. MAIN OUTCOME MEASURE: Sustained abstinence from smoking. RESULTS: Sustained abstinence rates for the patch and nasal spray group and patch only group were 51% v 35% after 6 weeks (odds ratio 1.97, 95% confidence interval 1.17% to 3.32; P=0.011(chi2), 37% v 25% after 3 months (1.76, 1.01 to 3.08; P=0.045), 31% v 16% after 6 months (2.40, 1.27 to 4.50; P=0.005), 27% v 11% after 12 months (3.03, 1.50 to 6.14; P=0.001), and 16% v 9% after 6 years (2.09, 0.93 to 4.72; P=0.08) [corrected]. CONCLUSIONS: Short and long term abstinence rates show that the combination of using a nicotine patch for 5 months with a nicotine nasal spray for 1 year is a more effective method of stopping smoking than using a patch only. The low percentage of participants using the nasal spray at 1 year, and the few relapses during the second year, suggest that it is not cost effective to use a nasal spray for longer than 7 months after stopping a patch.

Fluorescence cytophotometric measurements of nuclear DNA in adenocarcinoma of the lung; relation of proliferative activity and DNA ploidy to prognosis.

Nuclear DNA measurements on specimens of adenocarcinomas of the lung obtained at surgery from 22 patients showed that in 8 tumors the cells were near diploid and slowly proliferating. These 8 tumors displayed a higher degree of histopathologic differentiation than did the remaining 14 adenocarcinomas. In 3 of the 14 more poorly differentiated tumors the cells were also near diploid but had more S-phase DNA values, indicating increased proliferative activity. In 11 tumors aneuploid DNA stem line or lines were noted. Among patients with slowly growing near-diploid tumors the frequency of tumor recurrence and/or metastases (1 of 8) was lower than among those with more rapidly proliferating near-diploid tumors and aneuploid tumors (9 of 14). Nuclear DNA histogram patterns yielded information about the tumor proliferation activity, modal DNA value and occurrence of aneuploid DNA values. Furthermore, prognostic information about the likelihood of tumor recurrence after surgical treatment was obtained. This information can be utilized in the choice of therapy and in prognostic evaluation.

Circulating IgE levels in patients with bronchial carcinoma.

Serum IgE measurements in 107 patients with bronchial carcinoma revealed statistically significant elevations when compared to a control population. Serum IgE elevation was seen in 21.5% of the sample (23 of 107) and in all histological types at all clinical stages of the disease. It appears to occur early in the disease or possibly before the development of the carcinoma.

Diagnostic application of nuclear DNA measurements on bronchial secretions.

Bronchial washings from 254 patients with suspected pulmonary malignancy were investigated independently by two methods: bronchial cytologic examination and DNA measurements. For the latter, aneuploidy was used as a criterion of malignancy. At the time of the clinical follow-up, pulmonary malignancy had been verified by histopathologic examination in 91 of these 254 patients. For bronchial cytology the sensitivity was 40% and the specificity was 98%; for the DNA measurements the sensitivity was 37% and the specificity was 99%. Used in combination, the two methods showed a sensitivity of 46% and a specificity of 98%.

Hypersomnia and periodic breathing. Report of a case and review of the literature.

A patient with hypersomnia and periodic breathing has been studied. Both airflow obstruction and an abnormally of the respiratory control mechanism were implicated in the pathogenesis of the ventilatory arrhythmia. It is suggested that the older terms "Pickwick" syndrome and primary alveolar hypoventilation are abandoned for more descriptive terms, e.g. "hypersomnia with periodic breathing".

A double-blind randomized trial of nicotine nasal spray as an aid in smoking cessation.

The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution (NNS) for smoking cessation from the stopping day up to 3 months. We also followed the participants for 2 yrs after ceasing smoking to assess what happens after stopping using NNS. In a placebo-controlled, double-blind, 2 yr prospective study, 157 smokers were given either NNS, one dose containing 1 mg of nicotine per 100 microL (n=79), or placebo (n=78). Treatment was continued for up to 1 yr. One day after quitting smoking, the average number of daily doses was 11 in the group assigned NNS and 14 in the group assigned the placebo, and after 6 weeks, 14 and 6 doses, respectively, among abstinent participants still using spray. After 3 months, 65% of the abstainers in the nicotine group were still using the NNS. The abstinence rates were 51, 39 and 29% after 6 weeks, 3 and 6 months, respectively, as compared to 24, 19 and 18% in the placebo group (p=0.0003; p=0.003; p=0.050). The proportion abstinent at the 1 yr (25 vs 17%) and 2 yr follow-ups (19 vs 14%) was higher among those assigned to the nicotine than to the placebo group, but not significantly so for the numbers used in the study. In conclusion, the use of nicotine nasal spray significantly increased the abstinence rate during the first 6 months following the quitting day.

The diagnosis of cancer from body fluids. A comparison of cytology, DNA measurement, tissue culture, scanning and transmission microscopy.

A consecutive series of 70 exudates from 45 patients with clinically suspected malignancy was examined by cytology, cytophotometric measurement of DNA, short-term cell culture, scanning and transmission electron microscopy. In seven patients (21 fluids), the presence of malignant disease was verified. Malignant and benign cases were correctly diagnosed by combination of cytology and DNA analyses. An abnormal DNA profile defined by greater than 10 per cent cells with greater than 2c DNA or single cells with greater than 8c DNA was only seen in malignant exudates. Short-term cell culture with scanning electron microscopy could distinguish between lymphoid cells, histiocytes, fibroblasts, mesothelial cells and cancer cells. Only cancer cells had prominent microvilli on their surface. A future larger series will explore whether a combination of cytology and cytophotometric DNA estimation alone will improve the diagnostic accuracy to the same substantial degree as this pilot study would suggest.

[Tuberculous infection and tuberculosis in the foreign born in Iceland.].

OBJECTIVE: The purpose of the study was to find the incidence and prevalence of tuberculosis among the foreign-born in Iceland. MATERIAL AND METHODS: The study material was obtained from (a) the National TB register and (b) the files of the Immigration Office on recidency applicants in 1995. RESULTS: In 1975-1996 there were 32 cases of TB in the foreign-born out of a total of 468. The proportion of cases among the foreign-born rose significantly during the period (p<0.001). In 22 years the incidence of TB among the foreign-born was 18.0 but 8.4 among those born in Iceland (p<0.001). The incidence of TB in Asian-born was 173.7, or 21 times that among those born in Iceland (p<0.001). The second highest incidence (18.8) was in those born in North and South America. Tuberculosis usually appeared within five years of immigration. During 1995 the 559 applicants for recidence permit provided health certificates. Of these 363 had a tuberculin skin test (TST) and 42% were positive. The corresponding figure for those born in Africa was 68%, in Asia 58% and in East Europa 50%. Most of those with positive TST had a chest x-ray but also 23% of the others. 26.2% had neither a TST nor a chest x-ray but still received a health certificate. Only 33% of those positive received isoniazide to eliminate infection and 88% of these completed at least six months of isoniazide treatment. CONCLUSION: A TST is an indispensable part of health screening for immigrants and also a chest x-ray when appropriate. Treatment of TB infection should be used more often.

[Bronchial asthma and respiratory symptoms among Icelanders 20-44 years of age.].

OBJECTIVE: To estimate the prevalence of asthma and respiratory symptoms in an urban population. MATERIAL: Eight hundred men and women aged 20-44 years, living in the capital Reykjavik and suburbs. METHODS: Participants answered a questionnaire, underwent skin prick testing for atopy, spirometry and a test for bronchial hyperresponsiveness (BHR) by methacholine challenge. RESULTS: There was 77% attendance. Altogether 16.6% reported wheezing or whistling at any time in the last 12 months. Altogether 32 (5.6%)answered yes to "Have you ever had asthma?" and the diagnosis had been confirmed by a doctor in all but four. Fourteen (2.5%) had suffered from an attack of asthma in the last 12 months wheras only 0.9% were currently using anti asthmatic drugs. BHR was found among 8.7% and atopy on skin testing among 20.5%. BHR was more common among those with airflow obstruction and three times more common among the atopic participants (18% vs. 6%, p%lt;0.01). By using a history of wheezing during the last 12 months together with BHR and/or a history of doctor confirmed asthma the prevalence of current asthma was found to be 5% in our sample. The main predictive factors for asthma were a history of breathlessness and nighttime breathing symptoms, but also atopy, airflow obstruction and a maternal history of asthma. CONCLUSION: Even by using a conservative defination, asthma is a common disorder among 20-44 years old Icelanders whereas the use of asthma medication is rather uncommon in this population.