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Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by wheals and/or angioedema recurring for >6 weeks. In adults, CSU is more prevalent in females (female:male ratio of ∼2:1), and adjusted prevalence is higher in non-White patients.

Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by wheals and/or angioedema recurring for >6 weeks. Cumulative distribution function (CDF) curves compare cumulative probabilities of response between treatments across responder definition spectrums.

Background/Objectives:: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety. Subjects/Methods:: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety. Results:: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302–0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331–2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101–3.602)), anxiety (pooled OR 0.619 (95%CI 0.110–3.495)), combined score or history of doctor-diagnosed depression or anxiety. Conclusion:: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.

Background:: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg?m-2) tracking from childhood to late adulthood. Methods:: From the Copenhagen School Health Records Register, 72?959 men and 25?252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed. Results:: Correlations between BMI at 7 years and young adult ages (18–19 years) were r=0.55 for men and r=0.55 for women. At late ages (60–69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18–19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14–16.19) for men and 10.46 (95% CI: 4.82–22.70) for women. At ages 60–69 years ORs were 5.46 (95% CI: 0.95–31.36) for men and 1.61 (95% CI: 0.83–3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar. Conclusions:: BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.

Background/Objectives:: Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mental health. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. Subjects/Methods:: Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18–64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire. Results:: Serum 25(OH)D was not associated with SCL average scores for depression and anxiety when analysed by quantile median regression adjusted for sex, age and other potential confounders. The β-coefficient and 95% confidence interval (CI) per 10 nmol/l serum 25(OH)D were 0.00 (−0.00 to 0.01) and P=0.23 for depression and −0.00 (−0.01 to 0.00) and P=0.19 for anxiety. Furthermore, no evidence of an association was observed with longitudinal changes (combining depression and anxiety score: β(95% CI)=0.00 (−0.00 to 0.00), P=0.90), with scores >90 percentiles (odds ratio (OR) (95% CI)=1.02 (0.98–1.07), P=0.32), or with self-reported history (OR (95% CI)=1.02 (0.97–1.07), P=0.47) or incidence (OR (95% CI)=1.02 (0.92–1.12), P=0.77) of doctor-diagnosed depression and/or anxiety. Conclusions:: Our results suggest that low serum 25(OH)D is not associated with self-reported symptoms/diagnosis of depression and anxiety.

To determine whether the APOE4 allele is associated with age-related intellectual decline in a community-dwelling sample of Danes.

A partial trisomy 13q was observed in siblings with hexadactylia, hypertelorism, haemangiomata and severe psychomotor retardation. It originated from a maternal inversion translocation 46,XX,inv(8)(q23q241),t(8;13)(q241;q32). The family showed a pedigree pattern typical for the segregation of a chromosomal translocation. In spite of this the diagnosis was delayed several years, because the bands involved from the two chromosomes were of great similarity. This stresses the importance of reinvestigating families with a clinical suspicion of a chromosomal syndrome, preferentially with prometaphase chromosomes. The identification of a chromosomal rearrangement is essential for genetic counselling and prenatal diagnosis.

The present investigation was initiated to assess the demand for vaccination against hepatitis-B in a department of clinical chemistry. One hundred and twenty-eight employees enrolled for the test programme consisting primarily of screening for hepatitis-B antigen (HBsAg) and antibody to hepatitis-B surface antigen (anti-HBs). Surprisingly it was found, that 8 persons out of 58 who had also participated in a screening survey in 1978 had developed anti-HBs. These persons, who had no history of hepatitis, were also positive for antibodies towards the core antigen of hepatitis-B (anti-HBc). A seroconversion rate of 1.53/100/year for this material was calculated. Six persons who had contracted hepatitis-B during an epidemic 14 years previously, presented with very weak anti-HBs reactivity, but were positive for anti-HBc indicating, that anti-HBc was the more stable indicator of past HBV infection. The cost-effectiveness of vaccination against HBV seems disputable compared with other protective measures. The high incidence of silent seroconversion indicates a chronic exposure to virus among the laboratory personnel. Therefore, safety precautions against virus exposure are highly recommended.In consequence of the results of this study, we investigated laboratory areas for the presence of HBsAg, using a moistened cotton swab for sampling the environmental surfaces of equipment and furniture [8]. In all, 143 samples were collected from 28 different sites, including laboratory equipment like centrifuges, samplers of automated equipment and numerous items used in the laboratory. In no instance was immunologic HBsAg reactivity detected, whereas dried spots of patients' serum positive for HBsAg rendered positive after sampling by the same technique.

Purpose:To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2.Material and Methods:The study involved slow i.v. infusion of either 10,60 and 300 μmolkg of MnDPDP, or 1, 6 and 30 μmolkg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 ± 10 μm) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac ouput; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines.Results:Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 μmolkg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 μmolkg MnCl2.Conclusion:The present study suggests that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.

Abstract: No recovery was recorded in the shallow and eutrophic Lake Vng, Denmark, after a sewage diversion in 1981, due to an internal phosphorus loading and a dominance of planktivorous fish. In order to improve lake water quality by means of biomanipulation, a total of 2.5 tons of bream (Abramis brama) and roach (Rutilus rutilus) was removed during 1986 and the spring of 1987. The planktivorous/benthivorous fish biomass was thereby reduced by approximately 50%, from 30 to 15 g WW m−2. After the reduction, the biological structure of the lake changed markedly. The zooplankton community changed from a dominance of rotifers before the fish reduction to larger cladocerans afterwards. Zooplankton mean summer biomass increased from 0.4 mg DW l−1 in 1986 to 2.7 mg DW l−1 in 1987 and to 1.3 mg DW l−1 in 1988. Phytoplankton biomass decreased from a mean summer level of 25 mm3 l−1 in 1986 to 12 in 1987 and to 7 mm3 l−1 in 1988. Qualitatively, the phytoplankton changed from a dominance of cyanobacteria and small diatoms to a dominance of larger diatoms, larger greens and cryptophytes. Secchi depth increased from a mean summer level of 0.6 m in 1986 to 1.0 m in 1987 and 1.3 m in 1988. After the fish removal, the internal phosphorus loading was reduced markedly. This reduction is considered primarily to be caused by the improved redox conditions in the sediment due to reduced sedimentation, and by the increased micro-benthic primary production and phosphorus uptake. Submerged macrophytes, mainlyPotamogeton crispus andElodea canadensis, increased in abundance due to improved light climate at the lake bottom.

Abstract: In order to evaluate short-term and long-term effects of fish manipulation in shallow, eutrophic lakes, empirical studies on relationships between lake water concentration of total phosphorus (P) and the occurrence of phytoplankton, submerged macrophytes and fish in Danish lakes are combined with results from three whole-lake fish manipulation experiments. After removal of less than 80 per cent of the planktivorous fish stock a short-term trophic cascade was obtained in the nutrient regimes, where large cyanobacteria were not strongly dominant and persistent. In shallow Danish lakes cyanobacteria were the most often dominating phytoplankton class in the P-range between 200 and 1 000g P l−1. Long-term effects are suggested to be closely related to the ability of the lake to establish a permanent and wide distribution of submerged macrophytes and to create self-perpetuating increases in the ratio of piscivorous to planktivorous fish. The maximum depth at which submerged macrophytes occurred, decreased exponentially with increasing P concentration. Submerged macrophytes were absent in lakes>10 ha and with P levels above 250–300g P l−1, but still abundant in some lakes<3 ha at 650g P l−1. Lakes with high cover of submerged macrophytes showed higher transparencies than lakes with low cover aboveca. 50g P l−1. These results support the alternative stable state hypothesis (clear or turbid water stages). Planktivorous fish>10 cm numerically contributed more than 80 per cent of the total planktivorous and piscivorous fish (>10 cm) in the pelagical of lakes with concentrations above 100g P l−1. Below this threshold level the proportion of planktivores decreased markedly toca. 50 per cent at 22g P l−1. The extent of the shift in depth colonization of submerged macrophytes and fish stock composition in the three whole-lake fish manipulations follows closely the predictions from the relationships derived from the empirical study. We conclude that a long-term effect of a reduction in the density of planktivorous fish can be expected only when the external phosphorus loading is reduced to below 0.5–2.0 g m−2 y−1. This loading is equivalent to an in-lake summer concentration below 80–150g P l−1. Furthermore, fish manipulation as a restoration tool seems most efficient in shallow lakes.

Sp1 nuclear levels have been shown to directly correlate with the proliferative state of the cell. We therefore studied changes in the abundance of Sp1 in a rat pituitary cell line GH4 whose growth rate is regulated by epidermal growth factor (EGF). Nuclear extracts from GH4 cells treated with 10 nM EGF for at least 16 h showed a 50% decrease in Sp1 binding to a GC-rich element present in the gastrin promoter. The decrease in binding correlated with a decrease in cell proliferation, a loss of nuclear Sp1 protein and a 50-60% decrease in Sp1-mediated transactivation through an Sp1 enhancer element in transfection assays. Okadaic acid, a phosphatase inhibitor, was synergistic with the effect of EGF on Sp1 protein levels suggesting that the loss of Sp1 was mediated by phosphorylation events. This result was confirmed by showing a 2-fold increase in orthophosphate-labeled Sp1 with EGF and okadaic acid. Cycloheximide prevented the expected loss of Sp1 mediated by EGF and okadaic acid suggesting that the synthesis of a protease may mediate these events. This hypothesis was tested directly by showing that the cysteine protease inhibitor leupeptin prevented Sp1 degradation. Using the PEST-FIND computer program, the computed PEST score for human and rat Sp1 is 10.4 and 13.7, respectively, indicating that Sp1 has a domain with a high concentration of proline, glutamic acid, serine, and threonine residues as reported for a number of proteins with inducible rates of degradation. Collectively, these results indicate that sustained stimulation of GH4 cells by EGF initiates a cascade of phosphorylation events that promotes Sp1 proteolysis, decreased Sp1 nuclear levels and decreased cellular proliferation.

The hemodynamic side effects of intracoronary injection of low osmolality contrast media were studied in anesthetised dogs, both with and without left ventricular (LV) failure. LV failure was induced by microembolization of the area supplied by the left main coronary artery. LV pressure and volume, aortic pressure, and cardiac output were recorded. 6 ml iodixanol 320 mg I/ml containing 20 mmol Na+/l, a new non-ionic dimer, was compared to iohexol and ioxaglate. Iodixanol induced small systolic alterations both before and after LV failure. Iohexol increased LV inotropy while ioxaglate depressed myocardial function. Before failure iodixanol and ioxaglate impaired isovolumic relaxation, but early diastolic filling was not reduced. After failure the relaxation process was not affected, but ioxaglate reduced early diastolic filling. Ioxaglate also increased LV end-diastolic pressure and volume more than the non-ionic contrast media. In conclusion, iodixanol induced only small changes in systolic and diastolic function. Iodixanol should therefore be hemodynamically well tolerated during coronary arteriography, and also in acute ischemic heart failure.

This study was designed to investigate whether the calcium channel blocker diltiazem affects the threshold for ventricular fibrillation during hypothermia in dogs. Ten dogs were cooled from 37 to 25°C and rewarmed to 37°C. The threshold for ventricular fibrillation was determined at body temperatures 37, 34, 31, 28 and 25°C by programmed electrical stimulation using a stimulation protocol which involved application of maximal five extrastimuli. At 25°C, six dogs were given an i.v. bolus dose of 100 μg‐kg‐1followed by a continuous infusion of 100 μg‐kg‐1‐h‐1of diltiazem hydrochloride. The other four dogs, were given no drugs at 25°C and served as a control group. The dogs were rewarmed, and the stimulus protocol was performed at the same temperatures as during cooling. Cooling from 37 to 25°C reduced the treshold for ventricular fibrillation in both groups. Heart rate were reduced, monophasic action potential duration at the apex and base of the heart increased from 167±5 ms to 469±17 ms and from 164±5 ms to 466±1 7 ms, respectively, when the temperature was reduced. The ventricular effective refractory period increased from 176±9 ms at 37°C to 472±15 ms at 25°C. Cooling increased QRS time on the ECG from 55±4 ms to 138±13 ms. Addition of diltiazem at 25°C did not affect the threshold for ventricular fibrillation during rewarming. Further, diltiazem at 25°C did not affect the heart rate or refractoriness. Cooling reduces the threshold for ventricular fibrillation. During hypothermia, the calcium channel blocker diltiazem does not seem to affect the threshold for ventricular fibrillation.

Insulin receptors in turkey erythrocyte and rat adipocyte plasma membranes display non-linear hormone binding by Scatchard analysis. This result is consistent with evidence that the insulin-binding sites are heterogeneous and have at least two affinities for the hormone. Mild reduction of plasma membranes with dithiothreitol, before insulin binding, increased the fraction of hormone binding with high affinity without significantly changing the total number of receptor-binding sites. In the presence of guanosine 5′-[gamma-thio]triphosphate, the amount of receptor with high affinity for insulin in the reduced membranes decreased to that present in the absence of reduction; the effect of the nucleotide was concentration- and temperature-dependent. This decrease in insulin binding was specific for guanine nucleotides.

Insulin receptors from turkey erythrocyte membranes exist as monomers and dimers when membranes are solubilized with detergent. We examined the ability of monomers and dimers to act as protein kinases to effect both autophosphorylation of the receptor and phosphorylation of an exogenous substrate. After separation by sucrose-density-gradient centrifugation, only receptor dimers show significant basal and insulin-stimulated kinase activity, whereas material at the position of receptor monomers is not active. Partial reduction of the membrane-bound receptors with dithiothreitol, however, produces a receptor monomer containing an alpha and a beta chain which has protein kinase activity similar to that of the original dimers. With rat adipocyte plasma membranes, which in the absence of reducing agents only contain receptor dimers, reduction with dithiothreitol also produces monomers with receptor kinase activity. Receptor monomer hormone-dependent kinase activity is insensitive to receptor concentration and shows stimulation after immobilization on an affinity support.

Purpose: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2.Material and Methods: The study involved slow i.v. infusion of either 10,60 and 300 μmol/kg of MnDPDP, or 1, 6 and 30 μmol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 ± 10 μm) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac ouput; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines.Results: Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 μmol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 μmol/kg MnCl2.Conclusion: The present study suggests that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.

Abstract: The use of fish manipulation as a tool for lake restoration in eutrophic lakes has been investigated since 1986 in three shallow, eutrophic Danish lakes. The lakes differ with respect to nutrient loading and nutrient levels (130–1000 g P l−1, 1–6 mg N l−1). A 50% removal of planktivorous fish in the less eutrophic cyanobacteria-diatom dominated Lake Vng caused marked changes in lower trophic levels, phosphorus concentration and transparency. Only minor changes occurred after a 78% removal of planktivorous fish in eutrophic cyanobacteria dominated Frederiksborg Castle Lake. In the hypertrophic, green algae dominated Lake Sbygrd a low recruitment of all fish species and a 16% removal of fish biomass created substantial changes in trophic structure, but no decrease in phosphorus concentration. The different response pattern is interpreted as (1) a difference in density and persistence of bloomforming cyanobacteria caused by between-lake variations in nutrient levels and probably also mixing- and flushing rates, (2) a difference in specific loss rates through sedimentation of the algal community prevaling after the fish manipulation, (3) a decreased impact of planktivorous fish with increasing mean depth and (4) a lake specific difference in ability to create a self-increasing reduction in the phosphorus level in the lake water. This in turn seems related to the phosphorus loading.

Summary: The cases of 16 patients treated for intestinal radiation injuries are reviewed. The conclusion is that in patients who have received radiation treatment earlier, it is never possible to rule out intestinal radiation injuries as the reason for abdominal complaints. The pathologic picture and the symptoms seem to be independent of the latency period and age. The possibilities for treatment are discussed, and it is concluded that only patients with slight injuries in whose cases cancer has been ruled out can be treated conservatively. For all other patients resection and perhaps closure of a fistula if it is possible should be done. This, however, was possible only in 25 per cent of our patients. In the rest of the patients operated on it was only possible to establish a colostomy.

The Scandinavian Society for Clinical Chemistry and NORDKEM have had a number of joint efforts to facilitate the optimal performance and use of clinical laboratory investigations. A new committee (DOOKK or Diagnosis and Organ Oriented Committee for Clinical Chemistry) was established (in 1984) in order to improve collaboration between clinicians and laboratory physicians. In particular, the approach has been to work out recommendations for different clinical working hypotheses concerning restricted diagnoses or organ-specific problems. The aim of our project ("Hemolysis") was to create a rational scheme for the use of clinical chemical and hematological laboratory investigations in suspected or known cases of hemolysis.

We have shown previously that a GC-rich element (GGGGCGGGGTGGGGGG) conferring epidermal growth factor (EGF) responsiveness to the human gastrin promoter binds Sp1 and additional undefined complexes. A rat GH4 cell line expression library was screened by using a multimer of the gastrin EGF response element, and three overlapping cDNA clones were identified. The full-length rat cDNA encoded an 89-kDa zinc finger protein (ZBP-89) that was 89% identical to a 49-kDa human factor, ht(beta), that binds a GTGGG/CACCC element in T-cell receptor promoters. The conservation of amino acids between the zinc fingers indicates that ZBP-89 is a member of the C2H2 zinc finger family subclass typified by the Drosophila Krüppel protein. ZBP-89 is ubiquitously expressed in normal adult tissues. It binds specifically to the gastrin EGF response element and inhibits EGF induction of the gastrin promoter. Collectively, these results demonstrate that ZBP-89 functions as a repressor of basal and inducible expression of the gastrin gene.

Summary: The enzymel-glutamic acid decarboxylase is a major autoantigen of the beta cell. Autoantibodies against this enzyme are observed before the onset of insulin-dependent diabetes mellitus (IDDM) in man and may be of predictive value. There is evidence that this enzyme is involved in the development of autoimmune diabetes in animals. In order to facilitate the investigation of the role ofl-glutamine acid decarboxylase in IDDM, we expressed the 65 kDa isoform of human isletl-glutamic acid decarboxylase in insect cells using a baculovirus-based vector. The material was expressed at high levels (up to 50 mg/l of cells). Partially purified metabolically labelledl-glutamic acid decarboxylase bound to immunoglobulins in the sera from 20 of 49 subjects with newly-diagnosed IDDM. The enzyme was isolated in high yields (up to 26 mg/l cell culture) with fully maintained enzymatic activity by either ion-exchange chromatography or immunoaffinity chromatography. Purifiedl-glutamic acid decarboxylase inhibited the binding of radioactivel-glutamic acid decarboxylase, prepared by in vitro translation of mRNA, to immunoglobulins in the sera of subjects with IDDM. Recombinant human isletl-glutamic acid decarboxylase, isolated from Sf9 cells, is a suitable material for the large scale investigation of the utility of this enzyme in the prediction and prevention of autoimmune diabetes. [Diabetologia (1995) 38: 14–23

Growth factors coordinately regulate a variety of different genes to stimulate cellular proliferation. In the stomach, gastrin, epidermal growth factor (EGF), and transforming growth factor-alpha all mediate gastric mucosal homeostasis by promoting cell renewal. We have previously shown that EGF and phorbol esters stimulate the human gastrin promoter through a novel GC-rich DNA element 5'-(68)GGGGCGGGGTGGGGGG-53 called gERE (gastrin EGF response element). In this report, we show that three factors bind to this element, the transcription factor Sp1 and two fast migrating complexes designated gastrin EGF response proteins (gERP 1 and 2). To understand how these factors bind and confer EGF responsiveness, mutations of gERE were tested in vitro for protein binding and in vivo for promoter activation. Both gel shift assays and UV cross-linking studies revealed that the factors bind to overlapping domains, Sp1 to the 5' half-site and gERP 1 and 2 to the 3' half-site. Placing either the 5' or 3' mutations upstream of a minimal gastrin promoter abolished EGF induction. Therefore both the 5' and 3' domains were required to confer EGF induction. Collectively, these results demonstrate that complex interactions between Sp1 and other factors binding to overlapping gERE half-sites confer EGF responsiveness to the gastrin promoter.

The article presents the poem "Southeast Light," by E. K. Mortenson. First Line: Mohegan Bluffs rain into the sea. Last Line: for such safe passage.