Low awareness of COPD among physicians

Introduction: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. Objectives: The aim of this study was to determine the frequency of under‐diagnosed chronic obstructive lung diseases among current smokers. Materials and methods: The under‐diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. Results: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician‐diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. Conclusion: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage. Please cite this paper as: Sundblad B‐M, Larsson K and Nathell L. Low awareness of COPD among physicians. The Clinical Respiratory Journal 2008; 2: 11–16.     

Serous papillary carcinoma of the endometrium: A histopathological study of 22 cases

In a histological review of all 1985 cases of endometrial carcinoma in Norway diagnosed in the period 1970 through 1977, 22 patients (1.1%) with serous papillary carcinoma (ESPC) were identified. Mean age at diagnosis was 72 years, which was significantly higher than for patients with ordinary adenocarcinoma. All patients were followed at least 10 years. The crude 5- and 10-year survival rates were 27 and 14%. Only three patients survived longer than 10 years and all of these had had stage I tumors. In 19 available curettage specimens ESPC could be identified in 18. This could have implications regarding choice of therapy because this subtype of endometrial carcinoma is very aggressive. It is most often found in elderly women.     

ACCELERATED PAPER: Intermittent 50 Hz magnetic field and skin tumour promotion in SENCAR mice

A number of epidemiological studies have indicated associationbetween exposure to extremely low frequency electromagneticfields and a variety of cancers, including leukaemia and braintumours among residentially exposed children and among occupationallyexposed adults. In order to test if intermittent magnetic fields(MF) act as a tumour promoter, a long-term skin carcinogenicitystudy of 50 Hz sinusoidal MF with flux densities of 50 µTand 0.5 mT, continuous as well as with an intermittence of 15s on/off, was performed. Female SENCAR mice were divided intoeight groups of 50 animals in each and treated according toan initiation- promotion scheme. 7,12-dimethylbenz[a] anthracene(DMBA) in acetone was applied to the dorsal skin at a subcarcinogenicdose, as an initiator and exposure to MF was performed for 19–21h/day during 104 weeks starting 1 week after the initiator treatment.The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)was used as a positive control for skin tumour promoting activity.Two animals from each group were assigned for skin hyperplasiaanalysis at 2, 6, 12,18 and 21 months. The animals were observeddaily. The appearance of skin lesions and neoplasms were carefullyfollowed and histopathological diagnosis was made for all neoplasmspresent at death. The experiment was terminated after 105 weeks.DMBA-treatment alone yielded altogether two skin tumours intwo tumour-bearing animals and the animals exposed to acetonealone had one skin tumour. The animals exposed to continuousfields showed no skin tumour. Five animals exposed to 0.5 µTon/off had a total of 13 skin tumours and in the group exposedto 50 µT on/off four animals had a total of four skintumours. The on/off exposed groups differed significantly fromthe continuously exposed groups (P = 0.014) but the differencebetween the on/off exposure groups and the DMBA group was notstatistically significant when tumour-bearing animals and cumulatedskin tumours were compared. There was a statistically significantdose trend (P = 0.045) with flux density and Tesla-h for intermittentMF exposure for cumulated skin tumours per tumour-bearing animals.The epithelial thickness of DMBA + MF-treated animals was ofthe same magnitude as for DMBA-treated animals indicating that,in the case of a promoting effect being present, another mechanismthan one involving sustained hyperplasia may be involved.     

Annoyance and effects on work from environmental noise at school

The aim of this study is to investigate how students rate the annoyance and effects of noise in their working environment. 216 students, between the ages 13-15 years, and 12 teachers took part in this study. Sound level measurements were made for 20 minutes in the middle of a lesson for each class. On the measurement occasion the students were seated in a class room working on mathematics. Immediately after the sound level measurement, the students and the teachers filled in a questionnaire. The correlation between sound level and perceived annoyance and rated effect of noise on the students' schoolwork was poor. The correlation between the annoyance and rated effect of noise on the students' schoolwork was significant. Equivalent sound levels during mathematics lessons were 58-69 dB(A). Even though the sound levels were relatively high the students claimed that they were just moderately annoyed. More than 1/3 of the students claimed that the existing sound environment obstructed their work. No difference was found between boys and girls in rated annoyance and rated effect on their work. The younger students were more annoyed than the older ones. The participants claimed that chatter in the class room and scraping sounds from tables and chairs were the most annoying sound sources. The teachers shared this opinion. The concurrency between the students' rating of their annoyance and the teachers' rating of the students annoyance was remarkably low.     

Estrogens affect endothelin-1 mRNA expression in LNCaP human prostate carcinoma cells

OBJECTIVE: To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17beta (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer.METHODS: Cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2.RESULTS: ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2-4h but after 48 h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100 nM following 2-4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S.CONCLUSION: ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.     

Effect of Surgery on the Outcome of Midgut Carcinoid Disease with Lymph Node and Liver Metastases

We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.     

Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease

Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.     

A new screening model for safety evaluation of superantigen-antibody recombinant fusion proteins (mAb Fab-SEA/E) using telemetric monitoring in conscious rabbits

INTRODUCTION: Carcinoma recognising monoclonal antibodies (mAb) and mutated forms of the T-cell-activating bacterial staphylococcal enterotoxin A/E (SEA/E) have been combined in single hybrid constructs (mAb Fab-SEA/E). By introducing substitutions in an MHC class II binding site, these harmful toxins can be converted into tolerable immunotoxins. Rabbits and humans are sensitive to SE toxins, and cardiovascular effects in rabbits are similar to those seen in septic shock in man. A new screening model using telemetry in conscious rabbits was applied in the safety evaluation of different mAb Fab-SEA/E constructs administered intravenously. METHODS: Telemetry transmitters were implanted in the peritoneal cavity of animals with a pressure catheter in the aorta and electrodes for ECG recording subcutaneously following administration of mAb Fab-SEA/E constructs intravenously. RESULTS: The responses in body temperature, heart rate, and blood pressure varied depending on the treatment regimen and the mutations of the drug given. For example, 25 micro g/kg of C215 Fab-SEAmut9 were given as a first treatment cycle on days 1, 5, and 7 and as a second treatment cycle on days 13-15. The first dose induced high fever, whereas the second and third doses induced fever responses more rapidly and were of lower and shorter duration. The second treatment cycle, starting on day 13, did not induce any responses probably due to anti-SEA antibodies formed because of the treatment. Another construct, 5T4 Fab-SEA/E-11 at 50 micro g/kg, induced a similar response as C215 Fab-SEAmut9 on days 1, 5, and 7. In this case, the pharmacologic response was still present on days 13-15, though no clinical signs developed or no formation of anti-SEA antibodies occurred. When 50 micro g/kg of 5T4 Fab-SEA/E-11 was administered once daily for 4 days, body temperature after the first dose increased slowly during the first 24 h, whereas the second to fourth doses induced more rapid and higher responses. The fourth dose of another compound, K305 Fab-SEA/E-11 (50 micro g/kg), induced an even more pronounced response both in magnitude and in duration as well as in adverse clinical signs. DISCUSSION: By using continuous telemetric registration in the rabbit as a tool in superantigen-antibody (mAb Fab-SEA/E) drug selection, it has been possible to evaluate the dynamics of drug-induced immune effects (fever) and concomitant engagement of the cardiovascular system, conditions that are essential before clinical trials can be initiated.