Determinants of Microscale pH in In Situ-Grown Dental Biofilms.

Dental biofilm pH is the most important determinant of virulence for the development of caries lesions. Confocal microscopy-based pH ratiometry allows monitoring biofilm pH with high spatial resolution. Experiments performed on simplified biofilm models under static conditions identified steep pH gradients as well as localized acidogenic foci that promote enamel demineralization. The present work used pH ratiometry to perform a comprehensive analysis of the effect of whole saliva flow on the microscale pH in complex, in situ-grown 48-h and 96-h biofilms (n = 54) from 9 healthy participants. pH was monitored in 12 areas at the biofilm bottom and top, and saliva flow with film thicknesses corresponding to those in the oral cavity was provided by an additively manufactured microfluidic flow cell. Biofilm pH was correlated to the bacterial composition, as determined by 16S rRNA gene sequencing. Biofilm acidogenicity varied considerably between participants and individual biofilms but also between different areas inside one biofilm, with pH gradients of up to 2 units. pH drops were more pronounced in 96-h than in 48-h biofilms (P = 0.0121) and virtually unaffected by unstimulated saliva flow (0.8 mm/min). Stimulated flow (8 mm/min) raised average biofilm pH to near-neutral values but it did not equilibrate vertical and horizontal pH gradients in the biofilms. pH was significantly lower at the biofilm base than at the top (P < 0.0001) and lower downstream than upstream (P = 0.0046), due to an accumulation of acids along the flow path. pH drops were positively correlated with biofilm thickness and negatively with the thickness of the saliva film covering the biofilm. Bacterial community composition was significantly different between biofilms with strong and weak pH responses but not their species richness. The present experimental study demonstrates that stimulated saliva flow, saliva film thickness, biofilm age, biofilm thickness, and bacterial composition are important modulators of microscale pH in dental biofilms.

Pulmonary function and blood gases after gastric bypass and lifestyle intervention: a comparative study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study to compare the effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary function improved to a greater extent after gastric bypass than after lifestyle intervention. The superiority of surgical treatment might be mediated by greater weight loss after gastric bypass. Impaired lung function associated with obesity improves with weight loss. The effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases have not previously been subjected to comparative examination. In this 1-year non-randomized controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139 morbidly obese subjects (19-66 years, mean [standard deviation] body mass index [BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes, gas diffusing capacity and arterial blood gases were measured. Compared with lifestyle intervention, surgery resulted in a significantly greater increase in forced vital capacity (mean [95% confidence interval] between-group difference, 7 [4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1-8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%), expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or diminished after adjusting for weight loss. Reduced central adiposity (waist circumference and waist-to-hip ratio) and systemic inflammation (C-reactive protein and adiponectin) had no effect on pulmonary function beyond the effect of reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass surgery is more effective than lifestyle intervention at improving arterial oxygenation and pulmonary function. The effect might be mediated by greater weight loss after surgical treatment.

Valvular dysfunction and left ventricular changes in Hodgkin's lymphoma survivors. A longitudinal study.

PURPOSE: Hodgkin's lymphoma survivors (HLSs) have an elevated risk for cardiovascular diseases that appear several years after radiotherapy. This study examined the time-dependent development and evolution of valvular and myocardial function related to treatment with mediastinal radiotherapy and anthracyclines in HLSs. PATIENTS AND METHODS: In 1993, echocardiography was performed in 116 HLSs median 10 years (range 6-13 years) after treatment with mediastinal radiotherapy. None of the 116 patients had valvular stenosis in 1993 whereas 36 (31%) had moderate valvular regurgitation. In 2005-2007, 51 of 57 invited patients were included in a second echocardiographic study - median 22 years (range 11-27 years) after treatment. Of these patients, 28 (55%) had also received anthracyclines. The patients were selected on the basis of the presence or absence of moderate valvular regurgitation in 1993. RESULTS: The second echocardiographic study demonstrated that 10 out of 27 (37%) patients with only mild or no aortic or mitral regurgitation in 1993 had developed moderate regurgitation in either or both the aortic or mitral valve. Of the 24 patients with moderate (n=23) or severe (n=1) regurgitation in the aortic or mitral valve in 1993, 8 (33%) had progressed to severe regurgitation, developed moderate regurgitation in a previously normal or mild regurgitant valve or had received valvular replacement. In total, of all patients, 20 (39%) had developed mild to severe aortic stenosis and 3 patients had received valvular replacement. In a multiple linear regression the use of anthracyclines predicted left ventricular remodelling between ECHO 1993 and 2005 as demonstrated by increased left ventricular end systolic diameter (beta =0.09 (95% CI 0.01-0.17), P=0.04) and reduced thickness of the left ventricular posterior wall (beta =-0.18 (95% CI -0.33 to -0.03), P=0.02) and interventricular septum (beta =-0.16 (95% CI -0.30 to -0.03), P=0.02). CONCLUSION: Given the progressive nature of valvular dysfunction and left ventricular remodelling 20-30 years after diagnosis, we recommend life-long cardiological follow-up of HLSs treated with mediastinal radiotherapy.

Severe chronic obstructive pulmonary disease: association with marginal bone loss in periodontitis.

An association between chronic marginal periodontitis and chronic obstructive pulmonary disease (COPD) has been suggested. The aim of this study was to investigate whether chronic marginal periodontitis is more prevalent in very severe COPD than in other very severe respiratory diseases, and whether periodontitis in COPD is related to risk factors for periodontitis that are often present in COPD subjects. Orthopantomograms were collected from 130 patients with COPD and 50 patients with non-COPD evaluated for lung transplantation. Chronic marginal periodontitis was defined as a general marginal bone level > or = 4 mm. The prevalence of periodontitis was 44% in the COPD group vs. 7.3% in the non-COPD group. All oral measurements differed significantly between the groups. The difference in mean marginal bone level remained statistically significant when adjusting for age, gender and pack years smoked. In logistic regression analysis mean marginal bone level > or = 4 mm was identified as a factor significantly associated with severe COPD. This study demonstrates that chronic marginal periodontitis is common in patients with severe COPD. The high prevalence of periodontitis in COPD patients appears to be independent of possible risk factors for periodontitis such as age, pack years smoked, body mass index, use of corticosteroids and bone mineral density.

Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins.

Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediate phenotypes of asthma. Using population-based data collected from a sample of twins, the present authors estimated the relative contribution of genes, family environment and nonshared environmental influences to variations in eNO and airway responsiveness (AR). In addition, the genetic and environmental sources of covariation between these two asthma-related phenotypes were investigated. The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. The main outcome variables were eNO and AR to methacholine. Genetic effects accounted for 60% of the variation in eNO. Family environment accounted for 30% of the variation in AR, while nonshared environmental influences explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects for atopy and smoking. The small, but significant association between eNO and AR was primarily explained by genetic factors. Sub-analyses restricted to atopic and nonsmoking twins strengthened the observation. In conclusion, variations in exhaled nitric oxide and airway responsiveness appear to be explained by different genetic and environmental variance structures. Variation in exhaled nitric oxide is explained by genetic and nonshared environmental effects, whereas an environmental model best explains the variation in airway responsiveness. Common genetic effects explain the small but significant association between exhaled nitric oxide and airway responsiveness.

Airway inflammation in aluminium potroom asthma.

AIMS: To examine whether asthma induced by exposure to aluminium potroom emissions (potroom asthma) is associated with inflammatory changes in the airways. METHODS: Bronchial biopsy specimens from 20 asthmatic workers (8 non-smokers and 12 smokers), 15 healthy workers (8 non-smokers and 7 smokers), and 10 non-exposed controls (all non-smokers) were analysed. Immunohistofluorescent staining was performed to identify mucosal total leucocytes (CD45+ leucocytes), neutrophils, and mast cells. RESULTS: Median RBM thickness was significantly increased in both asthmatic workers (8.2 microm) and healthy workers (7.4 microm) compared to non-exposed controls (6.7 microm). Non-smoking asthmatic workers had significantly increased median density of lamina propria CD45+ leucocytes (1519 cells/mm2 v 660 and 887 cells/mm2) and eosinophils (27 cells/mm2 v 10 and 3 cells/mm2) and significantly increased concentrations of exhaled NO (18.1 ppb v 6.5 and 5.1 ppb) compared to non-smoking healthy workers and non-exposed controls. Leucocyte counts and exhaled NO concentrations varied with smoking habits and fewer leucocytes were observed in asthmatic smokers than in non-smokers Asthmatic smokers had significantly increased numbers of eosinophils in lamina propria compared to non-exposed controls (10 v 3 cells/mm2). Both eosinophilic and non-eosinophilic phenotypes of asthma were recognised in the potroom workers and signs of airway inflammation were also observed in healthy workers. CONCLUSIONS: Airway inflammation is a central feature of potroom asthma and exposure to potroom emissions induces pathological alterations similar to those described in other types of asthma. Cigarette smoking seems to affect the underlying mechanisms involved in asthma, as the cellular composition of airway mucosa appears different in asthmatic smokers and non-smokers.

Lung function 5 yrs after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide.

Long-term data on lung function after bone marrow transplantation (BMT) are inconclusive. Previously, a persistent reduction in gas transfer 1 yr after allogeneic BMT with busulphan and cyclophosphamide conditioning was reported by the current authors. In the present study this reduction was examined to see if it was permanent, transient or progressive. Prospectively, 43 consecutive adult patients with malignant blood disorders undertook lung function measurements prior to BMT, at 3 month intervals during the 1st yr after BMT and finally after 5 yrs. Mean baseline lung function values were >90% predicted. Within the 1st yr after BMT a transient decline in lung volumes and a persistent reduction in gas transfer were observed. After 5 yrs, baseline values were restored for all variables, except in four patients who developed obliterative bronchiolitis. Acute leukaemia and smoking were independently associated with gas transfer reductions at baseline and during the 1st yr after BMT. Allogeneic bone marrow transplantation with busulphan and cyclophosphamide conditioning was associated with a reduction in gas transfer 1 yr after bone marrow transplantation but baseline values were usually restored after 5 yrs. Since recovery may be gradual and slow, an observation period >1 yr is required before drawing conclusions concerning the development of a permanent reduction in lung function after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide.

Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers.

OBJECTIVES: To examine whether underground construction workers exposed to tunnelling pollutants over a follow up period of 8 years have an increased risk of decline in lung function and respiratory symptoms compared with reference subjects working outside the tunnel atmosphere, and relate the findings to job groups and cumulative exposure to dust and gases. METHODS: 96 Tunnel workers and a reference group of 249 other heavy construction workers were examined in 1991 and re-examined in 1999. Exposure measurements were carried out to estimate personal cumulative exposure to total dust, respirable dust, alpha-quartz, oil mist, and nitrogen dioxide. The subjects answered a questionnaire on respiratory symptoms and smoking habits, performed spirometry, and had chest radiographs taken. Radiological signs of silicosis were evaluated (International Labour Organisation (ILO) classification). Atopy was determined by a multiple radioallergosorbent test (RAST). RESULTS: The mean exposure to respirable dust and alpha-quartz in tunnel workers varied from 1.2-3.6 mg/m3 (respirable dust) and 0.019-0.044 mg/m3 (alpha-quartz) depending on job task performed. Decrease in forced expiratory volume in 1 second (FEV1) was associated with cumulative exposure to respirable dust (p<0.001) and alpha-quartz (p=0.02). The multiple regression model predicted that in a worker 40 years of age, the annual decrease in FEV1 would be 25 ml in a non-exposed non-smoker, 35 ml in a non-exposed smoker, and 50-63 ml in a non-smoking tunnel worker (depending on job). Compared with the reference group the odds ratio for the occurrence of new respiratory symptoms during the follow up period was increased in the tunnel workers and associated with cumulative exposure to respirable dust. CONCLUSIONS: Cumulative exposures to respirable dust and alpha-quartz are the most important risk factors for airflow limitation in underground heavy construction workers, and cumulative exposure to respirable dust is the most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.

Effects of blasting fumes on exposure and short-term lung function changes in tunnel construction workers.

OBJECTIVES: This study attempts to determine the effects of exposure to blasting fumes and its influence on the lung function of tunnel workers. METHODS: Two groups of tunnel workers, one using ammonium nitrate fuel oil (ANFO) as the explosive and the other using size-sensitized emulsion (SSE), with 24 workers per group, were compared with a reference group (N=34) with low exposure. Spirometry was used to determine lung function. Personal exposure to total and respirable dust, alpha-quartz, volatile organic compounds, oil mist and vapors, formaldehyde, nitrogen dioxide, and carbon monoxide was measured. RESULTS: The ANFO workers were more exposed to all the agents than the reference group and more exposed than the SSE workers to all the agents except total dust and carbon monoxide. The SSE workers were significantly more exposed to total dust and alpha-quartz than the reference group. High peak exposures to nitrogen dioxide (up to 20 ppm) occurred for the ANFO workers in contrast to the SSE workers, whose exposure did not exceed 2 ppm. The lung function of the ANFO workers significantly decreased by 3% for forced vital capacity, 7% for forced expiratory volume in 1 second, and 8% for forced expiratory flow rate from 25% to 75% of the forced vital capacity over the 11-day period. The changes were reversible. There were no significant changes among the SSE workers and the outdoor workers. The ANFO workers had a significant decrease in FEV1.0 when compared with both the SSE and outdoor workers. CONCLUSIONS: Tunnel workers using ANFO explosive show a temporary reduction in lung function, whereas those using SSE do not. The most likely explanation for the observed changes is peak exposures to nitrogen dioxide.

Late medical complications and fatigue in Hodgkin's disease survivors.

PURPOSE: Long-term medical complications, such as cardiac, pulmonary, and thyroid dysfunction, are frequent among Hodgkin's disease survivors (HDSs). Chronic fatigue is also highly prevalent among HDSs. Few studies have explored possible etiologic explanations for fatigue. The aim of this study was to explore whether late cardiac, pulmonary, and thyroid complications after curative treatment for Hodgkin's disease (HD) may explain the high level of fatigue among HDSs. PATIENTS AND METHODS: Four-hundred fifty-nine patients treated for HD at the Norwegian Radium Hospital from 1971 to 1991 were included in a cross-sectional, follow-up study of subjective health status. Fatigue (physical [PF] and mental), was measured by the Fatigue Questionnaire. A subcohort of the HDSs (116 patients) treated from 1980 to 1988 were included in a separate study in which long-term cardiac, pulmonary, and thyroid complications were assessed. All patients had received radiotherapy, and 63 patients had received additional chemotherapy. The present study comprised 92 patients (mean age, 37 years; range, 23 to 56 years) who participated in both studies. RESULTS: HDSs with pulmonary dysfunction were more fatigued than HDSs with normal pulmonary function (PF 10.9 v 8.9; P <.05). Gas transfer impairment was the most prevalent pulmonary dysfunction, and three times as many patients with gas transfer impairment reported chronic fatigue (duration, 6 months or longer), compared with patients without pulmonary dysfunction (48% v 17%, P <.01). No associations were found between cardiac sequelae or hypothyroidism and fatigue. CONCLUSION: Pulmonary dysfunction is associated with fatigue in HDSs. Cardiac sequelae was not associated with fatigue in HDSs. We question the absence of an association between thyroid complications and fatigue.

Gas and dust exposure in underground construction is associated with signs of airway inflammation.

Exposure to gases and dust may induce airway inflammation. It was hypothesized that heavy construction workers who had been exposed to dust and gases in underground construction work for 1 yr, would have early signs of upper and lower airway inflammation, as compared to outdoor workers. A study group comprising 29 nonsmoking underground concrete workers (mean +/- SD age 44+/-12 yrs), and a reference group of 26 outdoor concrete workers (39+/-12 yrs) were examined by acoustic rhinometry, nasal and exhaled nitric oxide spirometry and a questionnaire on respiratory symptoms. Exposure measurements were carried out. The underground workers had higher exposure to total and respirable dust, alpha-quartz and nitrogen dioxide than the references (p<0.001). The occurrence of respiratory symptoms was higher in the underground workers than in the references (p<0.05). Exhaled nitric oxide (NO) (geometric mean+/-SEM) was higher in the underground workers than in the references (8.4+/-1.09 versus 5.6+/-1.07 parts per billion (ppb), p = 0.001), whereas spirometric values were comparable. The underground workers had smaller nasal cross-sectional area and volume than the references, and more pronounced increases after decongestion (p<0.001). To conclude the exposure in underground construction may cause nasal mucosal swelling and increased levels of exhaled nitric oxide, indicating signs of upper and lower airway inflammation.

Increased nitric oxide in exhaled air: an early marker of asthma in non-smoking aluminium potroom workers?

OBJECTIVES: To study exhaled nitric oxide (NO) as a marker of airway inflammation caused by potroom exposure, hypothesising that (a) workers exposed to potroom pollutants would have higher concentrations of NO in expired air than control subjects employed at the same plant but working outside of the potroom atmosphere, and (b) that concentrations of exhaled NO in potroom employees might be positively associated with concentrations of fluoride and exposure to dust. METHODS: A study group comprising 186 male subjects (aged 24-63 years), employed in the potrooms of one Norwegian aluminium smelter, and 40 comparable control subjects (aged 25-60 years) recruited from the same plant, were examined by measurements of exhaled and nasal concentrations of NO, spirometry, and a questionnaire on respiratory symptoms as a part of an annual health surveillance programme. Estimates of exposure to fluorides and dust for selected job categories were obtained by means of personal samplers carried by the workers. RESULTS: In the non-smokers, the concentrations of exhaled NO were higher in the potroom workers than in the controls (median (interquartile range) 9.3 (6.2-15.6) v 5.7 (4.6-8.3) ppb, p=0.001). The two groups did not differ in spirometry and asthma-like symptoms. Non-smoking potroom workers with asthma-like symptoms had higher concentrations of exhaled NO than those with no symptoms (median (interquartile range) 21.0 (19.3-41. 4) v 8.5 (5.9-12.8) ppb, p=0.001), but had comparable spirometric values. In subjects who smoked, the concentrations of exhaled NO did not differ significantly between potroom workers and controls (median (interquartile range) 4.6 (3.3-8.0) v 4.0 (3.4-5.1) ppb. Exhaled NO was not significantly associated with either duration of employment or routine measurements of dust and fluorides. CONCLUSIONS: Exposure to potroom pollutants is associated with increased concentrations of exhaled NO in non-smoking subjects. Nitric oxide in exhaled air may be an early marker of airway inflammation in aluminium potroom workers.

Health-related quality of life in lung transplant candidates and recipients.

BACKGROUND: Studies on the health-related quality of life in lung transplantation have used general questionnaires, although lung-specific instruments might be more sensitive to small differences. OBJECTIVES: To compare the health-related quality of life of lung transplant recipients with lung transplant candidates, using lung-specific and general instruments, and to assess the reliability and validity of these questionnaires. METHODS: The study is a cross-sectional postal survey of 31 lung transplant recipients and 15 candidates, using the following outcome measures: St. George's Respiratory Questionnaire (SGRQ), a lung-specific health status instrument; the Short Form 36 (SF-36), a general measure, and the Hospital Anxiety and Depression scale (HAD). RESULTS: The SGRQ showed a significantly better score (p < 0.05) for transplant recipients in the impacts and activity dimensions and the total score than for candidates. SF-36 scores showed a similar improvement in all subscales of the SF-36 except bodily pain. Cronbach's alpha for all dimensions of the SGRQ, SF-36, and HAD were 0.77-0.95. CONCLUSIONS: Patients surviving lung transplantations can expect a considerable improvement in most dimensions of health-related quality of life. This finding was consistent using both lung-specific and general measures. The reliability of the questionnaires was acceptable. The associations between scales support the validity of the questionnaires in this setting.

Increased risk of obstructive pulmonary disease in tunnel workers.

BACKGROUND: Tunnel workers are exposed to gases and particles from blasting and diesel exhausts. The aim of this study was to assess the occurrence of respiratory symptoms and airflow limitation in tunnel workers and to relate these findings to years of exposure. METHODS: Two hundred and twelve tunnel workers and a reference group of 205 other heavy construction workers participated in a cross sectional investigation. Exposure measurements were carried out to demonstrate the difference in exposure between the two occupational groups. Spirometric tests and a questionnaire on respiratory symptoms and smoking habits were applied. Atopy was determined by a multiple radioallergosorbent test (RAST). Radiological signs of silicosis were evaluated. Respiratory symptoms and lung function were studied in relation to years of exposure and adjusted for smoking habits and atopy. RESULTS: Compared with the reference subjects the tunnel workers had a significant decrease in forced vital capacity (FVC) % predicted and forced expiratory volume in one second (FEV(1)) % predicted when related to years of exposure. Adjusted FEV(1) decreased by 17 ml for each year of tunnel work exposure compared with 0.5 ml in outdoor heavy construction workers. The tunnel workers also reported significantly higher occurrence of respiratory symptoms. The prevalence of chronic obstructive pulmonary disease (COPD) was 14% in the tunnel workers compared with 8% in the reference subjects. CONCLUSION: Exposure to dust and gases from diesel exhaust, blasting, drilling and rock transport in tunnel work enhances the risk for accelerated decline in FEV(1), respiratory symptoms, and COPD in tunnel workers compared with other heavy construction workers.

Late medical sequelae after therapy for supradiaphragmatic Hodgkin's disease.

A total of 221 consecutive early stage Hodgkin's disease (HD) patients were given mantle field irradiation only or in combination with chemotherapy in 1971-1991. In 1994 these patients responded to a mailed self-report questionnaire covering items on late medical symptoms. Of 200 patients (91%) who reported that their thyroid function had been tested, 110 patients (55% of those tested) had thyroid hypofunction at follow-up in 1994. Ninety-five patients (86% of patients with biochemical hypothyreosis) had started hormonal substitution. In 1993 and 1994, 101 of these patients who had received mantle field irradiation in 1980-1988 were called in for interview, clinical examination and thyroid function tests. Eighteen patients (18%) had started hormonal substitution treatment earlier, but 58 (70%) of the other 83 patients were found to have biochemical hypothyreosis. Of the 221 patients who completed the questionnaire, 66 patients (30%) reported dyspnoea on exertion for more than 3 years after treatment, 8 patients (4%) reported a history of myocardial infarction, 6 patients (3%) reported pericardial disease and 25 patients (11%) heart valve disease. Increased expenses incurred for dental care were reported by 106 patients (48%), increasing to 55% when Waldeyer's ring had been irradiated. The consequences of late sequelae after mantle field irradiation for future treatment are discussed.

[Late complications after treatment of Hodgkin's disease]. / Senkomplikasjoner etter behandling for Hodgkins sykdom.

Treatment of Hodgkin's disease involves chemotherapy and radiation. Both modalities may cause cardiac, pulmonary and thyroid side-effects. In a cross-sectional study, we aimed to assess the occurrence and severity of such complications. From 1980 to 1989, 129 Norwegian patients (< 50 years old) had curative treatment for Hodgkin's disease 116 (90%) of them participated in the study (follow-up period 5-13 years). Methods included lung function tests, chest X-rays, bicycle exercise tests, echocardiography and thyroid function tests. Nearly 30% of the patients reported dyspnoea on exertion and had associated reductions in lung function. Evidence of fibrosis occurred in 68%, but was associated with reduced lung function in only 12%. Pathological left-sided heart valve regurgitations were detected in 24% of the patients, pericardial thickening in 15%, and coronary artery disease in 5%. Biochemical hypothyreosis was found in 67% of the patients. We conclude that cardiac, pulmonary and thyroid dysfunctions are frequent long-term side-effects after treatment for Hodgkin's disease. We recommend annual screening of thyroid function and echocardiographic examination in patients who have received standard mantle field radiotherapy without cardiac shielding. Lung function testing should be done in individuals who require further radiation, chemotherapy or thoracic surgery.

[Measurement of exhaled nitric oxide. A new lung function test?]. / Måling av nitrogenoksid i utåndingsluft. En ny lungefunksjonstest?

Nitric oxide (NO) is a gas molecule produced endogenously in the lungs. It can be detected in the exhaled air of animals and humans. Nitric oxide can be generated in the air passages by a synthase which is induced in several cell types by exposure to proinflammatory cytokines. Its induction is blocked by glucocorticoids. An increased concentration of nitric oxide can be found in the exhaled air of patients with asthma and other inflammatory lung disorders. Gas analysers for measuring nitric oxide in exhaled air have recently been made commercially available. The test is non-invasive, simple to perform, and can also be used in patients with reduced lung function. The method seems to provide a unique non-invasive means of diagnosing and monitoring inflammation of the air passages, and in the future the test may become a useful tool in a clinical setting. Preliminary recommendations for measurements and technical standardization have recently been proposed by the European Respiratory Society.

Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin's disease: an echocardiographic study.

OBJECTIVE: To assess by echocardiography the occurrence and degree of late cardiac sequelae after treatment for Hodgkin's disease by radiation and chemotherapy. PATIENTS AND METHODS: In Norway from 1980 to 1988, 129 patients < 50 years old with Hodgkin's disease had curative treatment with mediastinal radiation, with or without chemotherapy. 116 (90%) of these patients (mean (SD) age 37 (7) years, 67 males) were examined by echocardiography 5-13 years after treatment. 40 healthy individuals (mean (SD) age 40 (11), 20 males) were examined as controls. All those examined were in regular sinus rhythm. RESULTS: Grade > 1 (scale 0-3) aortic and/or mitral valvar regurgitation was found in 24% of the patients (15% aortic, 7% mitral, and 2% aortic+mitral), affecting 46% of the females v 16% of the males (P < 0.001). Female gender was a significant risk factor for aortic and mitral regurgitation (odds ratio 4.7, 95% confidence interval 2.0 to 11.2), whereas age, period of follow up, radiation dose, and chemotherapy were not. Thickened pericardium was diagnosed in 15% of the patients. No risk factors were identified. No cases of pericardial thickening or valvar regurgitation grade > 1 were recorded in the control group. Mean values for measured and calculated indices of systolic and diastolic function were within the normal range for patients and controls. The patients had reduced E/A ratio compared with the healthy controls (E/A 1.1 v 2.0, P < 0.001). CONCLUSIONS: Abnormal left sided valvar regurgitation was detected in one fourth of the patients, affecting the aortic valve in more than half of the cases. Females had an increased risk of valvar regurgitation. Echocardiographic screening after high-dose mediastinal radiation is recommended.