Re-recurrence and pain 12 years after laparoscopic transabdominal preperitoneal (TAPP) or Lichtenstein's repair for a recurrent inguinal hernia: a multi-centre single-blinded randomised clinical trial.

BACKGROUND: Long-term clinical outcome after a recurrent inguinal hernia repair may be associated with the type of repair, that is, laparoscopic or open. The results from previous randomised controlled trials are inconclusive regarding the long-term risk of re-recurrence chronic pain. Accordingly, this trial compared laparoscopic transabdominal preperitoneal repair (TAPP) with Lichtenstein's repair. The primary outcome was repair for a re-recurrence. The secondary outcome was chronic pain. METHODS: Multi-centre single-blinded, randomised trial on TAPP vs Lichtenstein's repair in male patients operated for a recurrent inguinal hernia after a primary open inguinal hernia repair. Follow-up for repair for a re-recurrence was registered in the Danish Hernia Database. Prospective follow-up data were achieved by a structured questionnaire on pain-related functional impairment using the Activities Assessment Scale (AAS-pain). RESULT: A total of 360 patients were randomised, 297 were mailed the follow-up questionnaire (63 excluded) after median 12 years (range 9-15). A total of 265 patients responded to the questionnaire (response rate 89%). The cumulative rate of repair for re-recurrence after 12 years was 10% (95% confidence interval (CI) 5.3-15.1%) vs 10% (5.6-14.7%) after TAPP or Lichtenstein, respectively (p = 0.764). Moderate/severe AAS-pain was reported by 4% (95% CI 1-8%) vs 7% (95% CI 3-11%) patients after TAPP or Lichtenstein, respectively (p = 0.698) CONCLUSION: Long-term re-recurrence rate and incidence of chronic pain was surprisingly high respectless of surgical approach and neither TAPP nor Lichtenstein's procedure was superior to improve surgical results.

Nationwide Results on Chronic Pain After Bilateral Transabdominal Preperitoneal Inguinal Hernia Repair.

BACKGROUND: Majority of studies on chronic postoperative inguinal pain has described the occurrence after unilateral inguinal hernia repair. Endo-laparoscopic repair, for example, laparoscopic transabdominal preperitoneal inguinal hernia repair, has been recommended for primary bilateral symptomatic inguinal hernias, although the literature on chronic postoperative inguinal pain among this type of patients is limited. The present study analyzed chronic postoperative inguinal pain following bilateral transabdominal preperitoneal inguinal hernia repair. METHODS: Nationwide consecutive patients who underwent bilateral transabdominal preperitoneal inguinal hernia repair (July 2012-June 2013) were recruited from the Danish Inguinal Hernia Database and cross-checked with hospital files and the National Patient Registry. A prospective follow-up was performed with a standardized postal questionnaire including questions on functional performance status assessed by a modified version of the Activity Assessment Scale. The primary outcome was incidence of chronic postoperative inguinal pain defined as moderate to severe pain-related impairment of everyday activities. Pain was registered according to the two individual groin areas. Furthermore, the overall incidence of chronic postoperative inguinal pain per operated inguinal hernia was calculated. Intensity of experienced pain (Activity Assessment Scale score) was compared between patients reporting pain from one versus both groin areas. RESULTS: In total, 209 patients (418 hernia repairs) were analyzed (questionnaire response rate 83%). The median follow-up time was 27 months (22-34 months). In total, 27 of 209 patients (13%) complained of chronic postoperative inguinal pain from either one (n = 17) or both (n = 10) groin areas after bilateral transabdominal preperitoneal inguinal hernia repair. The incidence of chronic inguinal pain per operated hernia was 9%. The intensity of impairment due to pain (Activity Assessment Scale score) did not differ significantly between patients with chronic postoperative inguinal pain in one (19%) versus both sides (30%), p = 0.056. CONCLUSION: Bilateral transabdominal preperitoneal inguinal hernia repair for symptomatic inguinal hernias was related to a high incidence (13%) of chronic postoperative inguinal pain and decreased functional performance status.

Pouch failures following ileal pouch-anal anastomosis for ulcerative colitis.

AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes.

BACKGROUND: Visceral fat plays an important role in the development of metabolic disease independently of the effect of overall abdominal fat. Ultrasonography is an accessible method of accurately assessing abdominal fat distribution in epidemiological studies, but few details about the reproducibility of this method have been published. OBJECTIVE: The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes. DESIGN AND METHODS: Ultrasonography was used to estimate visceral and subcutaneous abdominal fat. Intra- and interobserver variation, short-term variation and variation between estimates in the fasting and non-fasting state were examined in three samples of 30, 33 and 23 participants from the ADDITION-PRO study. A variance components model was used to calculate intra- and interobserver variation, and Bland-Altman plots were drawn for all three substudies. RESULTS: Coefficients of variation for intra- and interobserver variation were in the range 3.4-6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient of variation of 15%. The effect of a meal was primarily on the visceral estimates and did not extend beyond the first postprandial hour. Non-fasting visceral estimates were larger than fasting estimates. CONCLUSION: Both visceral and subcutaneous fat can be estimated with ultrasonography with adequate intra- and interobserver reproducibility by clinical researchers with limited training, making it a feasible method of assessing abdominal fat distribution in epidemiological studies.

Life cycle assessment of three water systems in Copenhagen--a management tool of the future.

Environmental life-cycle assessment (LCA) was applied to evaluate three different water systems of the water sector in Copenhagen, Denmark, including technologies within water supply, facilities recycling water and treatment of sewer overflow. In these three water systems LCA was used to evaluate the environmental impacts of each of the processes involved. The overall conclusion was that LCA is suitable as a decision support tool in the water sector as it provides a holistic evaluation platform of the considered alternatives categorised in environmental impact categories. The use of LCA in the water sector of this region has limitations since it does not yet consider impact categories assessing freshwater scarcity and ecological sustainability.

Incidence and remission of specific IgE aeroallergen sensitization from age of 40 to 60 years, and association with alcohol consumption.

BACKGROUND: Data on incidence and long-term persistence of IgE aeroallergen sensitization in older adults are limited. Alcohol consumption is a strong immune-modulator with a significant impact on the IgE response. OBJECTIVES: We aimed to assess the incidence and remission of aeroallergen sensitization from the age of 40 to 60 years. Furthermore, we examined the relationship of alcohol consumption to the prevalence and incidence of aeroallergen sensitization. METHODS: In 1976-1977, a total of 1,200 people born in 1936 and randomly selected from the general population were invited for a health examination (1,052 were examined). At 60 years, they were invited for a re-examination (695 were examined). Stored serum samples from both examinations were analyzed consecutively for serum-specific IgE to aeroallergens by using a qualitative multi-allergen immunoassay. RESULTS: We observed a total of 32 (7.1% of those not sensitized at 40 years) incident cases and 35 (41.1% of those sensitized at 40 years) remittent cases of aeroallergen sensitization over this 20 year period. Persistent as well as incident sensitization was significantly associated with self-reported atopic disease at 60 years. Alcohol consumption (>14 drinks per week) at 40 years was significantly associated with a higher prevalence of sensitization at 40 years, but not with the incidence of sensitization. CONCLUSIONS: In older adults, aeroallergen sensitization as reflected by serum-specific IgE positivity to aeroallergens is a dynamic process. Both persistent and incident sensitization was associated with atopic disease. Further studies are needed to clarify the influence of alcohol on the allergen-specific IgE response.

Combining asymmetrical flow field-flow fractionation with light-scattering and inductively coupled plasma mass spectrometric detection for characterization of nanoclay used in biopolymer nanocomposites.

It is expected that biopolymers obtained from renewable resources will in due course become fully competitive with fossil fuel-derived plastics as food-packaging materials. In this context, biopolymer nanocomposites are a field of emerging interest since such materials can exhibit improved mechanical and barrier properties and be more suitable for a wider range of food-packaging applications. Natural or synthetic clay nanofillers are being investigated for this purpose in a project called NanoPack funded by the Danish Strategic Research Council. In order to detect and characterize the size of clay nanoparticulates, an analytical system combining asymmetrical flow field-flow fractionation (AF(4)) with multi-angle light-scattering detection (MALS) and inductively coupled plasma mass spectrometry (ICP-MS) is presented. In a migration study, we tested a biopolymer nanocomposite consisting of polylactide (PLA) with 5% Cloisite30B (a derivatized montmorillonite clay) as a filler. Based on AF(4)-MALS analyses, we found that particles ranging from 50 to 800 nm in radius indeed migrated into the 95% ethanol used as a food simulant. The full hyphenated AF(4)-MALS-ICP-MS system showed, however, that none of the characteristic clay minerals was detectable, and it is concluded that clay nanoparticles were absent in the migrate. Finally, by means of centrifugation experiments, a platelet aspect ratio of 320 was calculated for montmorillonite clay using AF(4)-MALS for platelet size measurements.

Fermented feed for laying hens: effects on egg production, egg quality, plumage condition and composition and activity of the intestinal microflora.

1. An experiment with a total of 480 hens (Babcock) was carried out from 16 to 38 weeks of age to evaluate the suitability of wet fermented feed (feed water ratio, 1:1.2-1:1.4) for layers, taking aspects of nutrition and gastrointestinal health into consideration. The production performance, egg shell quality, plumage condition, litter dry matter (DM) content, as well as the composition and activity of the intestinal microbial flora were analysed. 2. Fermented feed was characterised by a high concentration of lactic acid (160-250 mmol/kg feed) and a moderate level of acetic acid (20-30 mmol/kg feed), high numbers of lactic acid bacteria (log 9-10 CFU/g feed) and a pH of approximately 4.5. Feed fermentation reduced the concentration of dietary sugar from 32.1 to 7.3 g/kg DM and the phytate bound phosphorus from 2.7 to 1.9 g/kg DM. 3. Fermented feed seemed to loose attractiveness for the birds quite rapidly, resulting in a more aggressive behaviour and a poorer plumage condition than in birds given dry feed. The use of fermented feed reduced the litter DM content. 4. During the experimental period, the body weight gain of hens receiving fermented feed was 80 g higher than of hens fed the dry mash. Presumably because of an extended adaptation time to the feed, the onset of lay occurred later when hens were fed on fermented feed, resulting in non-significantly reduced total egg production (75 vs. 82%). 5. There was no significant difference between groups with respect to the total egg mass production (g/d/hen, 42 and 45 for fermented feed and dry mash, respectively). Throughout the experimental period, the feed DM intake of hens fed with fermented feed was lower than that of hens receiving the dry mash (110 vs. 125 g). From week 26 to 37, fermented feed improved the feed conversion as compared with the dry mash (g feed DM/g egg mass, 2.28 vs. 2.53). 6. The use of fermented feed increased egg weight in the period from 34 to 37 weeks (61.4 vs. 60.0) and increased shell weight (g/100 g egg weight, 10.2 vs. 9.9) and shell stiffness (N/mm, 161 vs. 150) of eggs collected at 37 weeks. 7. The feeding of fermented feed increased intestinal health by acidification of the upper digestive tract, forming a natural barrier towards infection with acid sensitive pathogens, e.g. E. coli, Salmonella and Campylobacter. 8. It was concluded that fermented wet feed offers potential benefits for health and nutrition, but may become suitable for layers only after the practical problems related to this feeding form have been overcome. However, an early adaptation of the birds during the rearing period seems to be necessary.

Phleum pratense alone is sufficient for allergen-specific immunotherapy against allergy to Pooideae grass pollens.

BACKGROUND: Specific immunotherapy is the only causal treatment of allergy available today. Traditionally, therapeutic products based on either a single grass species or a mix of such extracts are used for grass pollen immunotherapy. Investigations comparing the immunological response to these allergen preparations are needed to ensure optimal treatment. The objective of this study was to investigate patterns of T and B cell cross-reactivity to Pooideae single-species extracts and to extract mixes. METHODS: IgG4 induced by immunotherapy with Phleum pratense extract was investigated for cross-reactivity using nine single-species extracts and four mixes. For the mixes, studies of IgE cross-reactivity were also performed. T cell cross-reactivity was investigated in lines specific to nPhl p 1 or nPhl p 5 allergens, and the amounts of group 1 and 5 allergens in the extracts were quantified by a single radial immunodiffusion. RESULTS: The levels of treatment-induced IgG4 detected by all the extracts displayed a clear correlation to that detected by the P. pratense pollen extract. The IgE studies confirmed the cross-reactivity of P. pratense-specific B cells towards the allergens contained in the mixes, and the T cell studies demonstrated cross-reactivity towards group 1 and 5 major allergens in extracts of six temperate grass species. CONCLUSION: Extensive T and B cell cross-reactivity was observed towards the allergens of the Pooideae grasses, and the degree of B cell cross-reactivity was independent of the number of species included in the extract mixes. This implies that treatment with pollen extract of just one Pooideae species will affect the allergic responses caused by any of the temperate grasses in this subfamily.

Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to species-specific major allergens Api m1 and Ves v5.

BACKGROUND: In patients with hymenoptera venom allergy diagnostic tests are often positive with honey bee and Vespula venom causing problems in selection of venoms for immunotherapy. METHODS: 100 patients each with allergic reactions to Vespula or honey bee stings and positive i.e. skin tests to the respective venom, were analysed for serum IgE to bee venom, Vespula venom and crossreacting carbohydrate determinants (CCDs) by UNICAP (CAP) and ADVIA Centaur (ADVIA). IgE-antibodies to species specific recombinant major allergens (SSMA) Api m1 for bee venom and Ves v5 for Vespula venom, were determined by ADVIA. 30 history and skin test negative patients served as controls. RESULTS: By CAP sensitivity was 1.0 for bee and 0.91 for Vespula venom, by ADVIA 0.99 for bee and 0.91 for Vespula venom. None of the controls were positive with either test. Double positivity was observed in 59% of allergic patients by CAP, in 32% by ADVIA. slgE to Api m1 was detected in 97% of bee and 17% of Vespula venom allergic patients, slgE to Ves v5 in 87% of Vespula and 17% of bee venom allergic patients. slgE to CCDs were present in 37% of all allergic patients and in 56% of those with double positivity and were more frequent in bee than in Vespula venom allergic patients. CONCLUSIONS: Double positivity of IgE to bee and Vespula venom is often caused by crossreactions, especially to CCDs. IgE to both Api m1 and Ves v5 indicates true double sensitization and immunotherapy with both venoms.

Temporal trends of aeroallergen sensitization over twenty-five years.

BACKGROUND: Little is known about time trends of allergic respiratory disease in adults, in particular in older adults. Furthermore, few trend studies have used objective measurements of IgE sensitization against inhalant allergens. OBJECTIVES: To investigate time trends of aeroallergen sensitization in adults over a 25-year period. METHODS: The study includes a total of 7820 persons, aged 30, 40, 50, and 60 years, who participated in three repeated cross-sectional studies of the general population of Copenhagen, Denmark, in 1976-1977, 1982-1984, and 1999-2001, respectively. Respiratory allergy was assessed by determination of specific IgE aeroallergen sensitization in stored serum samples. RESULTS: Over this 25-year period, a marked and statistically significant increase in the prevalence of aeroallergen sensitization had occurred. This increase was seen in all age-groups challenging the notion that the allergy epidemic only affects generations born 1960 onwards. For example, in 40-year-olds the prevalence (with 95% confidence intervals) of aeroallergen sensitization was 14.9% (12.7-17.1), 19.7% (17.1-22.3), and 27.6% (25.1-30.1) in 1976-1977, 1982-1984, and 1999-2001, respectively. CONCLUSIONS: Our results support that the allergy epidemic has spread to older adults resulting in a continuing increase in the overall prevalence of aeroallergen sensitization and an increase in the mean age of allergic patients.

Association between alcohol consumption and aeroallergen sensitization in Danish adults.

BACKGROUND: It has been proposed that alcohol consumption may be one of the lifestyle factors associated with a westernized, urban, and affluent lifestyle contributing to the rise in atopic disease. OBJECTIVE: The aim was to investigate the association between alcohol consumption and atopy (aeroallergen sensitization). METHODS: In 1982, a population-based cross-sectional study of 3608 Danes (79% of the invited), aged 30, 40, 50, and 60 years, was carried out. Information on alcohol consumption was obtained by a questionnaire. Aeroallergen sensitization was defined as a positive test for the detection of specific IgE against a panel of 19 common inhalant allergens in stored serum samples. A total of 3317 subjects with complete information on all variables were included in the analyses. RESULTS: We found a statistically significant association between alcohol consumption and aeroallergen sensitization (independent of the type of alcoholic drink consumed). This association appeared to relate only to those who consumed more than 8 drinks/week. After adjustment for confounders this association was only statistically significant for those who consumed 15-21 drinks/week (adjusted odds ratio 1.8, 95% confidence interval 1.2-2.8). CONCLUSION: In this adult general population, self-reported alcohol consumption was positively associated with aeroallergen sensitization.

Screening for allergic respiratory disease in the general population with the ADVIA Centaur Allergy Screen Assay.

BACKGROUND: In patients in whom the clinical indication for immunoglobulin E (IgE)-mediated allergic respiratory disease is weak, a single qualitative multiallergen-screening assay for IgE antibody to multiple allergen specificities may support the absence of IgE-mediated allergic respiratory disease. The aim was to investigate the diagnostic efficacy of a new multiallergen-screening assay in relation to skin prick test (SPT) reactivity and objective diagnoses of allergic respiratory disease in a general population setting. METHODS: A total of 709 participants in a population-based study were examined by questionnaire and SPT. Serum was analysed by using a multiallergen-screening assay: the ADVIA Centaur Allergy Screen (AS) assay. The dichotomized result of the AS assay was compared with SPT reactivity, specific IgE positivity, and a clinical diagnosis of allergic rhinitis or allergic asthma defined by the presence of relevant symptoms and positive SPTs. RESULTS: Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of the AS against SPT reactivity were 86%, 96%, 94%, and 89%, respectively. A negative AS assay test was able to exclude allergic rhinitis and allergic asthma with a probability of more than 96% and 98% (NPV), respectively. The AS assay was able to identify more than 92% and 92% (sensitivity) of cases of allergic rhinitis and allergic asthma, respectively. CONCLUSIONS: The AS assay proved to be a valid measure of allergic respiratory disease and may be used as a screening tool to rule out allergic respiratory disease, and as an objective measure of allergic respiratory disease in epidemiological studies.

Energy saving processes for nitrogen removal in organic wastewater from food processing industries in Thailand.

Nitrogen removal from organic wastewater is becoming a demand in developed communities. The use of nitrite as intermediate in the treatment of wastewater has been largely ignored, but is actually a relevant energy saving process compared to conventional nitrification/denitrification using nitrate as intermediate. Full-scale results and pilot-scale results using this process are presented. The process needs some additional process considerations and process control to be utilized. Especially under tropical conditions the nitritation process will round easily, and it must be expected that many AS treatment plants in the food industry already produce NO2-N. This uncontrolled nitrogen conversion can be the main cause for sludge bulking problems. It is expected that sludge bulking problems in many cases can be solved just by changing the process control in order to run a more consequent nitritation. Theoretically this process will decrease the oxygen consumption for oxidation by 25% and the use of carbon source for the reduction will be decreased by 40% compared to the conventional process.

Removal of indicator bacteria from municipal wastewater in an experimental two-stage vertical flow constructed wetland system.

The removal of sanitary indicator bacteria (total coliforms, faecal coliforms, and faecal streptococci) was studied in an experimental constructed wetland system consisting of (1) a 2-m3 three-chamber sedimentation tank, (2) a 5 m2 vertical flow constructed wetland, (3) a filter-unit with calcite aimed at removing phosphorus, and (4) a 10 m2 vertical flow constructed wetland. The indicator bacteria were enumerated before and after each unit of the wetland system during four monitoring episodes with different loading conditions. At a hydraulic loading rate of 520-1,370 mm/d, the first-stage vertical flow beds removed about 1.5 log-units of total coliforms, 1.7 log-units of faecal coliforms and 0.8 log-units of faecal streptococci. In the second stage bed receiving lower loadings both in term of concentration and quantity (260-690 mm/day), the eliminations were lower. It was not possible in the present study to identify any seasonal effects, but no measurements were done during summer. Recycling of treated effluent back to the sedimentation tank did not affect elimination. Area-based rate constants for the vertical flow wetland receiving effluent from the sedimentation tank averaged 3.2 m/d for total coliforms, 3.3 m/d for faecal coliforms and 2.1 m/d for faecal streptococci. The rate constants depended on loading rates. It is suggested that filtration is a major removal mechanism for bacterial indicator organisms in vertical flow constructed wetland systems.

Phosphorus removal from municipal wastewater in an experimental two-stage vertical flow constructed wetland system equipped with a calcite filter.

Laboratory studies have indicated that calcite may be used in separate, exchangeable filter units in constructed wetland systems to remove phosphorus. Based on these studies we built a full-scale experimental constructed wetland with a calcite-based filter unit to study its performance, under real-life conditions. The system consists of a 2-m3 sedimentation tank and two vertical flow constructed wetlands. The system has three 0.09 m3 calcite filter-units to study phosphorus removal. The hydraulic loading rate varied between 1.7 and 6.2 m3/d. The residence time in filters ranged from 28 to 99 minutes. Overall the system removed 62 +/- 18% of phosphorus. The removal in the calcite filter was initially good, but after three months all P-filters were saturated. The calcite increased pH by approximately half a unit and released calcium. A total of about 2.2 kg P/m3 calcite was removed by the filter. The first-stage bed receiving effluent from the sedimentation tank consistently removed phosphorus, whereas the second bed sometimes released phosphorus. The first order area-based removal rate constant for total-P in the vertical bed averaged 0.24 +/- 0.20 m/d and was highly dependent on the loading rate. This shows that first order removal kinetics do not satisfactorily describe removal of phosphorus in vertical flow constructed wetland systems with unsaturated flow.

Pharmacological monitoring of azathioprine therapy.

BACKGROUND: Studies on azathioprine (Aza) treatment in Crohn disease have indicated a positive correlation between clinical remission and a concentration in erythrocytes of the metabolites 6-thioguanine nucleotides (E-6-TGN) above 230 pmol/8 x 10(8) RBC. A concentration of the methylated Aza metabolites (E-6-MMP) above 5000 pmol/8 x 10(8) RBC has been correlated to hepatotoxicity. Thiopurine methyltransferase (TPMT) is responsible for the formation of methylated metabolites and lower E-TGN levels, and TPMT genotyping has been proposed as guidance for dosage. In a cross-sectional study we investigated relationships between the clinical outcome and Aza dose, the TPMT genotype and the Aza metabolite levels among patients with Crohn disease. METHODS: TPMT genotype (PCR assay), azathioprine metabolite levels (HPLC analysis) and xanthine oxidase (XO) activity were determined once in 71 randomly selected Crohn patients on an unaltered Aza dose for at least 3 months. RESULTS: None of the doses of Aza, TPMT genotype, E-6-TGN-, E-6-MMP levels or XO activity were significantly related to disease activity (H-B score), (P = 0.18, P = 0.69, P = 0.90, P = 0.54, P = 0.29, respectively). Leucopenia and/or hepatotoxicity were not demonstrated in any patient. Four patients had a heterozygous TPMT genotype (6.1%; 95% CI: 1.68%-14.80%). The 4 TPMT heterozygous patients had higher E-6-TGN levels than did the 67 remaining patients (P = 0.008). CONCLUSIONS: To explore the applicability of TPMT genotyping, E-6-TGN and E-6-MMP levels for therapeutic drug monitoring, large prospective studies with patient entry at the start of Aza therapy are needed. Until the results of such studies are available, the dose adjustments of Aza should be guided primarily by clinical response and blood counts; metabolite level measurements can only be applied to identify therapeutic non-compliance.

Nitrogen removal in industrial wastewater by nitration and denitration--3 years of experience.

CPKelco ApS, Denmark is the largest pectin plant in the world and the second largest refined carrageenan plant. The products are used for texturising purposes, primarily within the food industry, but also within the pharmaceutical industry. The products are extracted from imported natural raw materials, like dried citrus peel and special seaweed plants. In the production processes a considerable amount of water and energy are used. The excess water from the production processes is led to CPKelco's own WWTP, which is one of the largest industrial WWTPs in Denmark. In order to obtain higher process stability and lower energy consumption in the WWTP, CPKelco decided to change the nitrogen removal process from a conventional nitrification/denitrification process to a nitration/denitration process, which comprises an oxidation of ammonium to nitrite and a controlled reduction of nitrite to N2. Theoretically this process will decrease the oxygen consumption for oxidation by 25% and the use of carbon source for the reduction will be decreased by 40% compared to the conventional process. This paper presents and discusses the experiences and results from three year's continuous operation of the nitration/denitration process in an activated sludge plant, and the overall performance results are discussed in relation to the previous results. Accordingly the implementation of the nitration/denitration process was done successfully, and today the plant operates with much higher process stability than obtained before, and even the most stringent effluent requirements for nitrogen can be obtained.

Incidence of nutritional risk and causes of inadequate nutritional care in hospitals.

BACKGROUND AND AIMS: Many patients in hospitals are undernourished and nutritional care is inadequate in most hospitals. The aim of this investigation was to gain insight into how this situation could be improved. METHODS: Seven hundred and fifty randomly selected patients were screened at admission in three hospitals and surveyed during their entire hospitalization. Each time a patient was not treated according to a clearly defined nutritional standard, the nurse responsible for the patient was interviewed about possible reasons according to preformed questionnaires. RESULTS: The investigators found that 22% of the patients were nutritionally at-risk, and that only 25% of these patients received an adequate amount of energy and protein. The departments had only screened for nutritional problems in 60% of the cases. Only 47% of the patients, who the departments judged to be at-risk patients, had a nutrition plan worked out, and only about 30% of the at-risk patients were monitored by the departments by recording of dietary intake and/or body weight. The main causes for inadequate nutritional care were lack of instructions to deal with these problems, and lack of basic knowledge with respect to dietary requirements and practical aspects of the hospital's food provision. Patient-related aspects and the system of food provision also contributed, but only to a small degree. CONCLUSIONS: These findings form the basis of the strategy to improve nutritional care in these hospitals.

Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration.

A series of very potent derivatives of the 30-amino acid peptide hormone glucagon-like peptide-1 (GLP-1) is described. The compounds were all derivatized with fatty acids in order to protract their action by facilitating binding to serum albumin. GLP-1 had a potency (EC(50)) of 55 pM for the cloned human GLP-1 receptor. Many of the compounds had similar or even higher potencies, despite quite large substituents. All compounds derivatized with fatty acids equal to or longer than 12 carbon atoms were very protracted compared to GLP-1 and thus seem suitable for once daily administration to type 2 diabetic patients. A structure-activity relationship was obtained. GLP-1 could be derivatized with linear fatty acids up to the length of 16 carbon atoms, sometimes longer, almost anywhere in the C-terminal part without considerable loss of potency. Derivatization with two fatty acid substituents led to a considerable loss of potency. A structure-activity relationship on derivatization of specific amino acids generally was obtained. It was found that the longer the fatty acid, the more potency was lost. Simultaneous modification of the N-terminus (in order to obtain better metabolic stability) interfered with fatty acid derivatization and led to loss of potency.