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Statins are cholesterol-lowering agents and some of them, like simvastatin, have anti-inflammatory effects. In this study, we evaluated the effect of atorvastatin on nitric oxide (NO) release, leukocytes levels and alveolar diameter related to the inflammatory process associated with elastase-induced emphysema in rats. 32 rats were divided into 4 groups, n=8: control (C), atorvastatin (A), emphysema (E), and emphysema+atorvastatin (EA). On day 0 (zero), groups C and A received intratracheal instillation of saline (0.2 ml), and groups E and EA received elastase (0.2 ml). Groups A and EA received atorvastatin (20 mg/kg) and C and E received vehicle, by gavage, for 25 days. Animals were euthanized, slices of lung stained and the alveolar diameters measured. Data obtained show that the treatment with atorvastatin (EA group) did not reduce the alveolar diameter (35.3 vs. 32.3), NO (2.7 vs. 3.0 µM) or the leukocyte count (111 vs. 136) compared with the E group, indicating that different statins, like simvastatin or atorvastatin, have different behavior in inflammatory processes like in elastase-induced development of emphysema in rats.

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A mecoprop [(+/-)-2-(4-chloro-2-methylphenoxy)propionic acid; MCPP]-degrading bacterium identified as Stenotrophomonas maltophilia PM was isolated from a Danish aquifer. Besides mecoprop, the bacterium was also able to degrade MCPA [(4-chloro-2-methylphenoxy)acetic acid)], MCPB [(4-chloro-2-methylphenoxy)butyric acid], 4-CPA [(4-chlorophenoxy)acetic acid], 2, 4-D [(2, 4-dichlorophenoxy)acetic acid], 2, 4-DP [(+/-)-2-(2, 4-dichlorophenoxy)propionic acid] and 2, 4-DB [(2, 4-dichlorophenoxy)butyric acid]. The bacterium was able to grow using these individual phenoxyalkanoic acids as the sole source of carbon and energy. In addition, it was able to co-metabolically degrade the phenoxyalkanoic acid 2, 4, 5-T [(2, 4, 5-trichlorophenoxy)acetic acid)] in the presence of mecoprop. At high 2, 4, 5-T concentrations (100 and 52 mg/l), however, only partial degradation of both mecoprop and 2, 4, 5-T was obtained, thus indicating the production of toxic metabolites. Bacterial yields were highest when grown on the monochlorinated phenoxyalkanoic acids as compared to the dichlorinated analogues, an exception being growth on 4CPA, which resulted in the lowest yield at all. Using [ring-U-14C]-labeled herbicides it was shown that the lower yield on 2, 4-D than on mecoprop was accompanied by greater CO2 generation, thus indicating that less energy is available from the complete oxidation of the dichlorinated phenoxyalkanoic acids than the monochlorinated analogues.

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BACKGROUND: The Faroe Islands are a group of small islands in the north Atlantic. The population is well-defined and is therefore very suitable for epidemiological research, including dietary studies in relation to carcinogenesis. With the establishment of a cancer registry on January 1, 1994, with data from 1960, inspection of incidence rates and trends in cancer may give clues to areas for etiologic research. METHODS: We identified retrospectively all incident cases of colorectal cancer in the period 1979-1993, by reviewing all case reports and death certificates in the Faroe Islands. RESULTS: We found 242 cases of colorectal cancer: 166 colon cancers and 76 rectal cancer, of which 93% and 96% (respectively) were histologically confirmed. Colorectal cancer incidence was significantly lower than in Denmark, with standardised incidence ratios (SIRs) for colon cancer at 0.8 (95% CI = 0.7-1.0) in men and 0.7 (95% CI = 0.6-0.9) in women. For rectal cancer SIRs were 0.6 (95% CI = 0.5-0.9) in males and 0.6 (95% CI = 0.4-0.9) in females. CONCLUSIONS: This paper presents for the first time incidence rates of colorectal cancer in the Faroe Islands. For both cancer types the most recent standardised incidence rates, 1989-1993, were among the lowest in north western Europe and North America. This relatively low risk of colorectal cancer occurs in spite of a low intake of vegetables and a high intake of total fat. However, the Faroese diet is high in fish, calcium and vitamin D and the possibility therefore exist that the low rates are due to a protective effect of these nutrients and micronutrients.

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The National Health Insurance started to refund expenditure on selective serotonin reuptake inhibitors in 1994. Questions have been raised if a significant portion of benzodiazepine users would transfer to these new drugs when they were described in the literature as also being used for light anxiety, but not carrying the addiction risk associated with benzodiazepines. The study looks at changes over a four-year period in the prescription of benzodiazepines and selective serotonin reuptake inhibitors dispensed from two pharmacies in Vest-Agder County with a total customer base of 17,800. For four years we also followed the prescription of drugs in these two groups to 1,125 patients who had been prescribed benzodiazepines in 1994. Our data show that only 5% of those receiving benzodiazepines in 1994, whom we were able to track, changed to a selective serotonin reuptake inhibitor-only therapy. 18% used a combination of the two groups of drugs and 77% continued to use benzodiazepines as before. The increase in the number of patients receiving selective serotonin reuptake inhibitors during the study period is far greater than the increase measured by number of daily doses. Selective serotonin reuptake inhibitors seem to have little influence on the use of benzodiazepines in our pharmacies' area. Our findings indicate that instead of "from Valium to Prozac" the change during the years 1994-97 can be described as "from Valium to Valium and Prozac".

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The main purpose was to establish a cancer registry which could provide data for the treatment and control of cancer in the Faroe Islands. The registry should also be useful for epidemiological research in the future to pinpoint causes of cancer. The initiation of the registry is a result of a workgroup with members from the Faroes Hospital and Health System and from the Institute of Cancer Epidemiology at the Danish Cancer Society. The data items collected in the Faroes registry are identical with the data items in the Danish Cancer Registry. To provide a basis for the registry we have performed a retrospective data collection identifying all cancer cases in the Faroes for the 15 year period 1979-1993. All hospital records and death certificates in the period were scrutinized. The official initiation of the Faroes cancer registry was on 1, January 1994.

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Glucagon-like peptide 1 (GLP-1) has great potential in diabetes therapy due to its glucose-dependent stimulation of insulin secretion, but this is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. Four analogues, N-terminally substituted with threonine, glycine, serine or alpha-aminoisobutyric acid, were synthesised and tested for metabolic stability. All were more resistant to dipeptidyl peptidase IV in porcine plasma in vitro, ranging from a t1/2 of 159 min (Gly8 analogue) to undetectable degradation after 6 h (Aib8 analogue; t1/2 for GLP-1 (7-36) amide, 28 min). During i. v. infusion in anaesthetised pigs, over 50% of each analogue remained undegraded compared to 22.7 % for GLP-1 (7-36) amide. In vivo, analogues had longer N-terminal t1/2 (intact peptides: means, 3.3-3.9 min) than GLP-1 (7-36) amide (0.9 min; p < 0.01), but these did not exceed the C-terminal t1/2 (intact plus metabolite: analogues, 3.5-4.4 min; GLP-1 (7-36) amide, 4.1 min). Analogues were assessed for receptor binding using a cell line expressing the cloned receptor, and for ability to stimulate insulin or inhibit glucagon secretion from the isolated perfused porcine pancreas. All bound to the receptor, but only the Aib8 and Gly8 analogues had similar affinities to GLP-1 (7-36) amide (IC50; Aib8=0.45 nmol/l; Gly8=2.8 nmol/l; GLP-1 (7-36) amide=0.78 nmol/l). All analogues were active in the isolated pancreas, with the potency order reflecting receptor affinities (Aib8 > Gly8 > Ser8 > Thr8). N-terminal modification of GLP-1 confers resistance to dipeptidyl peptidase IV degradation. Such analogues are biologically active and have prolonged metabolic stability in vivo, which, if associated with greater potency and duration of action, may help to realise the potential of GLP-1 in diabetes therapy.

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The accuracy of the acoustic reflections method for the evaluation of human nasal airway geometry is determined by the physical limitations of the technique and also by the in vivo deviations from the assumptions of the technique. The present study 1) examines the sound loss caused by nonrigidity of the nasal mucosa and viscous loss caused by complex geometry and its influence on the estimation of the acoustic area-distance function; 2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathing He-O2 during the measurements on accuracy. Measurements made in eight plastic models, with cavities exactly identical to the "living" nasal cavities, revealed only minor effects of nonrigidity of the nasal mucosa. This was confirmed by an electrical analog model, based on laser vibrometry admittance measurements of the nasal mucosa, which indicated that the error in the acoustic measurements caused by wall motion is insignificant. The complex geometry of the nasal cavity per se (i.e., departure from circular) showed no significant effects on the measurements. Low-pass filtering of the signal is necessary to cut off cross modes arising in the nasal cavity. Computer simulations and measurements in models showed that the sampling frequency should be approximately four times the low-pass filtering frequency (i.e., twice the Nyquist frequency) to avoid influence on the result. No advantage was found for the the use of He-O2 vs. air in the nasal cavity.

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Ethylenethiourea is an important degradation product of ethylenebisdithiocarbamate fungicides, which are widely used in different kinds of crops. The ethylenebisdithiocarbamate group includes maneb, zineb and mancozeb. The ethylenebisdithiocarbamates are not highly toxic and degrade rapidly in the presence of moisture and oxygen, forming different compounds. One of these is the polar ethylenethiourea, which is relatively stable. Thus, this compound appears to be a potential contaminant for groundwater. Batch experiments were carried out under biotic as well as abiotic conditions to study the degradation dependence of concentration, temperature and organic matter. The decomposition of ethylenethiourea under abiotic conditions was found to be less than 5% of the degradation under biotic conditions. Further, ethylenethiourea showed to be stable over a period of 150 days at 20 degrees C in tap water as well as in batch with soil sterilized with NaN3. The degradation of ethylenethiourea depends on the concentration in the water implying first order reaction kinetics. The microbial degradation of ethylenethiourea is highly temperature dependent with aerobic Q10 between 2.9 and 4.2, and an anaerobic between 2.1 and 2.5. A minor increase in degradation rates was observed by application of nitrate and manure to the batches. The experiments show extremely complete degradation of ethylenethiourea in the presence of microbial nitrate reduction with pyrite which occurs in deeper parts of the aquifers.

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Resium, an old Spanish herb, is claimed to remove gallstone symptoms and to dissolve gallstones. Ten patients admitted for cholecystectomy because of intermittent bile cholics participated in a study for six months to evaluate the effects. None had had complications to their gallstone disease, and all had normal liver biochemistry and a normal well-functioning gallbladder before entry into the study. By ultrasonography minor changes in both directions in stone number and volume were seen. Five patients experienced some relief of symptoms, while the rest had unchanged, or worse symptoms. No adverse events to Resium were seen. In conclusion no effect of Resium upon gallstone size and volume was seen. The design of the study does not allow any conclusion about symptomatic effect to be drawn.

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Tertatolol is a noncardioselective beta-blocker without intrinsic sympathomimetic activity. In a preliminary 3-month open study, it was shown that T was devoid of any atherogenic effect since HDL-cholesterol (HDL-C) and apoprotein levels did not change for 3 months of therapy. To investigate the long-term effects of tertatolol on the lipid profile and its safety in hypertensive patients with peripheral arterial disease (PAD), a 9-month, randomized, double-blind, parallel group study was carried out in 40 patients. Tertatolol 5 mg once daily was compared with metoprolol 200 mg once daily. If BP was not controlled after 2 months, a vasodilatator agent, dihydralazine, was added at the lowest dose required to control BP (diastolic BP < 90 mm Hg). Lipoprotein fractions and apoproteins were assayed before (M0) and after 2, 6 and 9 months of therapy. At the same occasions, peripheral arterial disease (PAD) was evaluated on exercise tests carried out on a treadmill and on the regional blood flow measured in the ankle arteries by the Doppler technique. Four patients were not eligible for analysis. In the tertatolol group, 1 patient with a normal BP, and 2 patients who dropped out, 1 because of persistent nausea and 1 because of personal reasons. In the metoprolol group, 1 patient refused to take dihydralazine. In the 35 fully documented patients, BP control was achieved in both groups. The mean reductions in supine systolic/diastolic BP were 31.4/14.6 and 34.7/17.1 mm Hg in the tertatolol and metoprolol groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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All patients with ulcerative colitis referred to Rigshospitalet, Copenhagen, from 1 April 1964 to 1 January 1983 (18 years and 9 months) were studied from time of referral until death, proctocolectomy, or end of the study (1983). There were 759 patients, 423 females (56%) and 336 males (44%). None was lost to follow-up study. Median time from onset of disease until death, proctocolectomy, or end of the study was 11 years (range, 0-54 years). Median age at onset was 28 years (range, 0-83) among the males and 28 years (range, 4-83) among the females. Pancolitis was present in 312 patients (41%), left-sided colitis in 212 (28%), and haemorrhagic proctitis in 235 (31%). Surgical treatment was performed in 299 patients (39%): proctocolectomy in 197 (26%), colectomy with occluded rectal stump in 72 (9%), and colectomy with ileorectal anastomosis in 30 (4%). Altogether, 49 patients developed cancer, 20 being intestinal and 29 extraintestinal cancer. Compared with the general population matched for age, sex, and calendar time, there was an excessive number with intestinal cancer in both sexes (p less than 0.05). In females the number with extraintestinal cancer was higher than in the general population (p less than 0.01), a finding that has not been reported elsewhere. We found a similar, significantly increased incidence of extraintestinal cancer in females with Crohn's disease in a previous report. We found no increased risk of colorectal cancer in patients with early onset of ulcerative colitis. For all age classes we found that the age of appearance of colorectal cancer followed the equation: age at colorectal cancer = 14 + age at onset of ulcerative colitis. We found no higher potential for development of colorectal cancer in patients with pancolitis. In our series the incidence of colorectal cancer in pancolitis and left-sided colitis was equal. The incidence in patients with haemorrhagic proctitis was zero.

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Late complications have been examined in 96 patients consecutively treated for choledocholithiasis by endoscopic sphincterotomy in the years 1976 to 1980. Forty-four of the patients (46%) had the gallbladder in situ. Patients treated for short-term complications--that is, in the 1st month after sphincterotomy--are not included in this study. The mean length of follow-up study was 4.1 years (range, 2 months to 8 years and 9 months). Late bile duct symptoms occurred in seven patients (7%): three (6.8%) in patients with the gallbladder in situ and four (7.6%) in cholecystectomized patients. Stones were found in the common bile duct in three of these patients, one with and two without the gallbladder. The median duration from sphincterotomy to late complication was 8 months (range, 2 months to 5 years). Six of the patients had cholangitis, and the seventh had jaundice with abdominal pain. Two of the patients died of their complications. In conclusion, our results indicate that the frequency of late complications to endoscopic sphincterotomy is low and apparently independent of possible prior cholecystectomy.

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The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.

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The effect of the H2-receptor blocking agent cimetidine on jejunal effluent was examined in eight short-bowel patients with high-output jejunostomies. Stool mass and faecal excretion of sodium and potassium were significantly reduced by intravenous injection of 400 mg cimetidine four times a day. The amount of calcium, magnesium, phosphate, zinc, and fat in jejunostomy effluent did not change significantly. Cimetidine may be considered an antidiarrhoeal drug in extensively small-bowel-resected patients with a jejunostomy and may reduce the need for parenteral saline supply in these patients.

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In order to evaluate the clinical requirement for gastrin measurements, we examined all gastrin measurements requested over 1.5 years in a homogeneous population of 5.1 million inhabitants. Gastrin was quantitated with a radioimmunoassay that measured bioactive gastrins with equimolar potency. We received 1392 serum samples from 931 patients. In 394 samples from 121 patients the gastrin concentration was above the limit of the reference interval (50 pmol/l). Of the 121 patients, 19 were known Zollinger-Ellison patients followed for control of the therapy. In 11 previously unknown patients the gastrin analysis suggested presence of gastrin-producing tumours. Of these, four had classical Zollinger-Ellison syndromes, three had mixed endocrine tumours without peptic ulcer, and four were awaiting final confirmation of gastrinomas. Two vitiligo patients were hypergastrinaemic suggesting latent pernicious anaemia. Upon second measurement the plasma gastrin concentrations were within the reference interval in 14 previously hypergastrinaemic ulcer patients. In the remaining 75 patients the hypergastrinaemia was secondary to other gastrointestinal diseases. The results indicate that diagnosis, localization, and therapeutic control of gastrinomas require 200 gastrin measurements per million inhabitants per year. We suggest that this number be used in planning gastrin-assay services.

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The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24-hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5-ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed.

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The incidence of cancer in Crohn's disease has been evaluated in 473 patients admitted to Rigshospitalet during the period 1 April 1964 to 1 January 1983. The patients' condition at the end of the survey, their survival, and the number and location of cancers were registered. During the survey period 23 cancers (4.9%) were found. Five were intestinal (1.1%) and were split evenly among the two sexes, whereas among 18 patients with extraintestinal cancers there was only 1 man. There was no increased risk of developing cancer inside the gastrointestinal tract compared with a background population matched for age, sex, and calendar time. Extraintestinal cancer in women was, however, significantly in excess.

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