[Isocyanate-induced asthma].

Isocyanates are often found in workplaces in e.g., glue, paint, plastics and foam products. Asthma caused by isocyanates is one of the most common forms of occupational asthma, though it is difficult to diagnose, as described in this review. It is not possible to demonstrate sensitisation with available allergy tests. A certain diagnosis can only be made with the help of specific bronchial provocation, which is performed at three centres in Denmark. A correct diagnosis is important, as it helps provide optimal treatment as well as alerting the employer, that improvements are needed at the workplace.

Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder.

OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome-wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co-segregation of translocation t(9;17)(q33.2;q25.3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia (SZ) in large genome-wide association study samples. METHODS: We cross-linked Danish psychiatric and cytogenetic case registers to identify an individual with both t(9;17)(q33.2;q25.3) and BD. Fluorescent in situ hybridization was employed to map the chromosomal breakpoint regions of this proband. We accessed the Psychiatric Genomics Consortium BD (n = 16,731) and SZ (n = 21,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes. RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213 (RNF213), and regulatory-associated protein of mammalian target of rapamycin (mTOR) (RPTOR)] were found to be located within the 17q25.3 breakpoint region. NPTX1 was significantly associated with BD (p = 0.004), while ENDOV was significantly associated with SZ (p = 0.0075) after Bonferroni correction. CONCLUSIONS: Prior linkage evidence and our findings suggest NPTX1 as a novel candidate gene for BD.

An association study between the norepinephrine transporter gene and depression.

A potential approach for identification of candidate genes for depression is characterization of chromosomal rearrangements. Through analysis of a chromosome translocation in an individual with recurrent depression, we identified a potential candidate gene: the norepinephrine transporter (NET; SLC6A2 for solute carrier 6 family member 2). The gene is responsible for the reuptake of norepinephrine and dopamine into presynaptic nerve terminals and the norepinephrine system appears to play an important role in depression. We therefore analyzed genetic variants within SLC6A2 for association with depression in 408 affected and 559 control individuals from Denmark. After quality control of the genotypes, 31 of 45 single nucleotide polymorphisms (SNPs) were left for analyses. One SNP showed a nominal association with depression but did not survive correction for multiple testing. The results from our study do not suggest SLC6A2 as a susceptibility gene for depression in the Danish population.

Evidence-based insulin treatment in type 1 diabetes mellitus.

AIM: Evaluation of the evidence base for recommending different insulin treatment regimens in type 1 diabetes. METHODS: A computerised literature survey was conducted using The Cochrane Controlled Trials Register and the Pub Med database for the period of 1982-2007. RESULTS: A meta-analysis on only 49 out of 1295 references showed that CSII compared with conventional or multiple insulin injections therapy demonstrated a significant reduction in mean HbA1c (primary outcome) of 1.2% CI [0.73; 1.59] (P<0.001) without increasing the risk of hypoglycaemia. The evidence for using four versus two daily insulin injections was based on only one publication demonstrating an improved quality of life but no significant reduction in HbA1c or hypoglycaemia. A comparison of rapid-acting insulin analogues and human soluble insulin demonstrated a statistically significant reduction in HbA1c of 0.1% CI: [0.01; 0.16] (P=0.03) using rapid-acting insulin analogues. The mean frequency of hypoglycaemia was reduced with 14+/-3.7% (<0.05). CONCLUSION: The scientific evidence supporting the three common insulin regimens was rather sparse. Only five studies during the past 25 years fulfil the optimal criteria for a clinical trial, and only 5 trials on insulin analogues were performed as double-blinded. Current evidence suggests that CSII treatment results in a significant reduction in HbA1c without inducing more hypoglycaemia. Rapid-acting insulin analogues compared to human soluble insulin provide statistically significant but clinically minor improvement in HbA1c but seem to reduce the risk for hypoglycaemia.

The effect of metformin in overweight patients with type 1 diabetes and poor metabolic control.

Metformin as adjunct to intensive insulin therapy may improve glucose metabolism and thereby prevent the development of cardiovascular risk factors in patients with type 1 diabetes. Double-blinded intervention with 2000 mg metformin or placebo daily in 24 type 1 diabetic patients as adjunct to intensive insulin therapy. Primary endpoint was HbA1c, while secondary endpoints were body weight, frequency of hypoglycaemia, blood pressure, lipids, insulin dosage and self-monitored blood glucose profiles were measured. After 24 weeks, no difference in HbA1c was seen between the metformin and placebo groups (-0.5 +/- 0.3 vs. -0.2 +/- 0.2%, P = 0.26. Delta mean +/- S.E.M). Mean diurnal blood glucose profiles showed no statistical significant difference between the groups. The total daily insulin dose (IU) was significantly reduced in the metformin group compared to placebo after 24 weeks (-5.9 +/- 2.2 vs. 2.9 +/- 1.7, P = 0.004. Delta mean +/- S.E.M). An increase in the frequency of hypoglycaemia was seen in the metformin group (0.7 +/- 0.9 vs. 0.3 +/- 0.5 events patient(-1) week(-1), P = 0.005), and a reduction in body weight was found using metformin compared to placebo (-3.0 +/- 1.0 vs. 0.8 +/- 1.1, P = 0.02. Delta mean +/- S.E.M). Lipids and blood pressure did not differ significantly after intervention. Metformin, as adjunct to intensive insulin therapy, was associated with a reduction in the total daily insulin dose and a significant weight loss in patients with type 1 diabetes mellitus.

[Osteoporosis prevention in patients with low energy hip fractures hospitalized in the orthopedic department]. / Osteoporoseprofylakse hos patienter indlagt med hoftenaere lavenergifrakturer på ortopaedkirurgisk afdeling.

INTRODUCTION: The aim of this study was to investigate the following in patients treated for low energy hip fractures: 1) whether they were using osteoporosis preventative therapy before admission to hospital; 2) whether therapy was initiated before discharge from hospital; 3) the therapy used; and 4) whether they were referred for follow-up treatment for osteoporosis after discharge. MATERIAL AND METHODS: We carried out a retrospective study of medical journals on patients with a hip fracture, brought into the Department of Orthopaedic Surgery in 1997-1998. RESULTS: One hundred and forty-six patients, 80% women and 20% men with an average age of 80.7 years, were hospitalised during this period. Twenty patients had specific risk factors for developing osteoporosis, five patients of whom were taking osteoporosis preventative therapy. On admission, eight patients were in treatment. One patient started treatment during the hospital stay. Forty percent of the patients on discharge were referred for treatment by their GP or at the Department of Internal Medicine. DISCUSSION: Of the patients brought into the Department of Orthopaedic Surgery with low energy hip fractures, 6.2% were given the relevant medical treatment for osteoporosis on discharge from hospital, and only one of these patients started osteoporosis preventative therapy during the stay. As the study shows that 14% of the patients had specific risk factors for developing osteoporosis, only 25% of whom started treatment before admission to hospital, we find a need for osteoporosis preventative therapy in this group of patients.

[Osteoporosis prevention in general practice after hospitalization for hip fracture]. / Osteoporoseprofylakse i almen praksis efter indlaeggelse for hoftenaer fraktur.

INTRODUCTION: The aim of the study was to assess: 1) the degree of osteoporosis preventative therapy initiated by general practitioners (GP) after hospitalisation for a hip fracture; 2) the GPs' opinion of osteoporosis preventative therapy, and their opinion on whether it should be initiated by the hospital or the GP; 3) the need for a reference programme. MATERIAL AND METHODS: The GPs of patients discharged after a hip fracture in 1997-1998, were sent two questionnaires: one concerning osteoporosis preventative therapy of the patient and one concerning the GPs' own opinion on prevention. RESULTS: A total of 107 patients (80% women, 20% men) met the criteria of the study. Eighty-seven per cent were seen by their GP within six months of discharge, 16% were started on preventative therapy, which was: 53% calcium/calcium + vitamin D, 40% etidronate, and 27% estrogen. No one chose alendronate, raloxifen, or hip protector. Eighty-four per cent were not treated, of these 18% did not want to be treated, poor patient compliance was expected in 11%, and 6% of the GPs did not find the scientific documentation convincing. Four per cent had been referred for a bone scan, and 2% to X-ray of the vertebral column. Of the GPs, 52% felt it should be the patients' own GP who started the therapy, 48% felt it should be the discharging hospital physician, 83% felt they were capable of treating this condition. Sixty-nine per cent of the GPs felt a need for a reference programme, 96% wished to have access to refer patients for a bone scan. DISCUSSION: Only 16% were started on osteoporosis preventative therapy after a hip fracture. The study shows a need for better co-operation and communication between hospital physicians and GPs, and a need for a reference programme.