Hitting the Nail on the Head: A Case Report Demonstrating the Importance of a Multidisciplinary Approach to an Unusual Penetrating Intracranial Injury.

A 28-year-old man presented with a penetrating injury by a nail gun to the head. Imaging revealed a nail abutting the superior sagittal sinus without active extravasation. An anesthesia-led multidisciplinary team devised a detailed perioperative plan including conception of a complex decision tree, coordination of care, and resource utilization. In the operating room, the nail was removed under general anesthesia, with blood products and equipment for craniotomy readily available, and imaging modalities reserved for immediate use. This case highlights the importance of a multidisciplinary approach to challenging penetrating head injuries and the crucial role anesthesiologists have as leaders in perioperative care.

Filaggrin loss-of-function mutations as risk factors for ischemic stroke in the general population.

Essentials FLG mutations cause atopic dermatitis, previously found to be associated with ischemic stroke. Association between FLG mutations and ischemic stroke was examined in 97 174 Danish individuals. FLG mutations were associated with increased ischemic stroke risk in the general population. The association was most pronounced in younger individuals, and in current and former smokers. SUMMARY: Background Heritability studies have shown a considerable genetic component to ischemic stroke risk; however, much is unknown as to which genes are responsible. Also, previous studies have found an association between atopic dermatitis and increased ischemic stroke risk. Objective To test the hypothesis that FLG loss-of-function mutations, known to be associated with atopic dermatitis, were also associated with ischemic stroke. Methods A total of 97 174 individuals, with 3597 cases of ischemic stroke, from the Copenhagen General Population Study, the Copenhagen City Heart Study and the Copenhagen Carotid Stroke Study were genotyped for the two most common filaggrin mutations, FLG R501X and FLG 2282del4. Results FLG mutation carriers had an odds ratio for ischemic stroke of 1.15 (95% confidence interval [CI], 1.02-1.30) compared with non-carriers. Risk of ischemic stroke for FLG mutation carriers was higher among individuals aged < 50 years, with an odds ratio of 1.72 (1.11-2.67), compared with non-carriers. When stratified for smoking, ischemic stroke risk was primarily seen in current and former smokers, with an odds ratio of 1.25 (1.08-1.44). FLG mutations were not associated with conventional cardiovascular risk factors except for slightly more pack-years smoked among mutation carriers, but were associated with increased risk of self-reported eczema, with an odds ratio of 1.42 (1.32-1.52). Finally, self-reported eczema was associated with increased ischemic stroke risk, with an age and sex adjusted hazard ratio of 1.24 (1.01-1.52); however, the association was not statistically significant after multifactorial adjustment. Conclusion In this study of 97 174 individuals from the Danish general population, FLG loss-of-function mutations were associated with increased ischemic stroke risk; however, residual confounding is a possibility.

Obesity as a causal risk factor for deep venous thrombosis: a Mendelian randomization study.

OBJECTIVE: To test the hypothesis that obesity is causally associated with deep venous thrombosis (DVT). DESIGN: A Mendelian randomization design. SETTING: The Copenhagen General Population Study and the Copenhagen City Heart Study combined. SUBJECTS: Body mass index (BMI) measurements were available for 87, 574 individuals of Danish descent from the adult general population. All subjects completed questionnaires and were genotyped for the FTO rs9939609 variant. MAIN OUTCOME MEASURE: First events of DVT with or without pulmonary embolism (PE). ANALYSIS: The results were assessed using Cox regression, instrumental variable analysis and Poisson regression. RESULTS: Observationally, the risk of DVT increased with increasing BMI (P-trend < 0.0001). The multivariable-adjusted hazard ratio [95% confidence interval (CI)] for DVT was 1.3 (1.1-1.6) in overweight, 1.8 (1.4-2.2) in moderately obese and 3.4 (2.6-4.6) in severely obese compared with normal-weight individuals. For DVT complicated by PE, corresponding hazard ratios (95% CI) were 1.2 (0.8-1.8), 2.1 (1.3-3.5) and 5.1 (2.8-9.2). FTO AA versus TT genotype was associated with a 2.4% increase in BMI with hazard ratios (95% CI) of 1.09 (0.95-1.25) for DVT and 1.54 (1.12-2.10) for DVT complicated by PE. In instrumental variable analysis, the causal odds ratio (95% CI) for an increase in BMI of 1 kg m(-2) was 1.13 (0.92-1.39) for DVT alone and 1.86 (1.14-3.02) for DVT complicated by PE. The absolute 10-year risk of DVT in a high-risk group (i.e. those aged >60 years and homozygous for Factor V Leiden) was 35% in obese individuals and 18% in normal-weight individuals. CONCLUSION: A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity-specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.

Endogenous sex hormones and risk of venous thromboembolism in women and men.

BACKGROUND: Use of oral contraceptives with estrogen and hormone replacement therapy with estrogen or testosterone are associated with increased risk of venous thromboembolism (VTE). However, whether endogenous estradiol and testosterone concentrations are also associated with risk of VTE is unknown. OBJECTIVE: We tested the hypothesis that elevated endogenous total estradiol and total testosterone concentrations are associated with increased risk of VTE in the general population. METHODS: We studied 4658 women, not receiving exogenous estrogen, and 4673 men from the 1981-1983 Copenhagen City Heart Study, who had estradiol and testosterone concentrations measured. Of these, 636 developed VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) during a follow-up of 21 years (range, 0.02-32 years). Associations between endogenous estradiol and testosterone concentrations and risk of VTE were estimated by Cox proportional hazards regression with time-dependent covariates and corrected for regression dilution bias. RESULTS: Multifactorially adjusted hazard ratios of VTE for individuals with estradiol levels >75th vs. ≤25th percentile were 0.84 (95%CI, 0.25-2.85), 1.05 (0.53-2.08) and 1.05 (0.03-35.13) for pre- and post-menopausal women and men, respectively. For testosterone, corresponding risk estimates were 0.64 (0.03-12.32), 1.11 (0.66-1.86) and 1.30 (0.62-2.73). In addition, no associations were observed between extreme hormone percentiles (>95th vs. ≤75th) and risk of DVT, PE or recurrent VTE. CONCLUSION: This prospective study suggests that high endogenous concentrations of estradiol and testosterone in women and men in the general population are not associated with increased risk of VTE, DVT or PE.

Genetic variation in the parasympathetic signaling pathway in patients with reflex syncope.

Reflex syncope is defined by a self-terminating transient loss of consciousness associated with an exaggerated response of the vagal reflexes upon orthostatic challenges. A hereditary component has previously been suggested. We hypothesized that variations in genes encoding proteins mediating the vagal signaling in the heart may be involved in reflex syncope pathogenesis. We systematically resequenced the entire coding regions and flanking intron sequences in 5 genes in the cardiac post-synaptic parasympathetic signaling pathway [muscarinic acetylcholine receptor M2 (CHRM2); G-protein beta-1 subunit (GNB1); G-protein gamma-2 subunit (GNG2); potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); and potassium inwardly rectifying channel, subfamily J, member 5 (KCNJ5)] in 74 patients with well-characterized reflex syncope of either cardioinhibitory [Vasovagal Syncope International Study (VASIS-IIB), N = 38] or vasodepressor (VASIS-III, N = 36) type. We identified 2 novel genetic variants (CHRM2 c.1114C>G and GNG2 c.87+34G>A) and several known variants (GNB1: c.267+14G>A, c.267+19C>T, and c.738C>T; KCNJ3: c.119A>G, c.591C>T, c.1038T>C, and c.1494T>C; KCNJ5: c. 171T>C, c.810T>G, c.834T>C, c.844C>G, c.938+7C>T, and c.938-10G>A). The minor allele frequency of the KCNJ5 c.938+7C>T variant was significantly lower in patients than in the control group (0.014 versus 0.089, P = 0.001), and the frequency of heterozygosity and homozygosity was lower in cardioinhibitory patients compared to controls. Genetic variations in genes responsible for the vagal signaling in the heart, including CHRM2, GNB1, GNG2, KCNJ3, and KCNJ5, are not major contributors to the pathogenesis of reflex syncope of vasodepressor or cardioinhibitory types.

25-Hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18,791 participants.

BACKGROUND: Vitamin D has potential antithrombotic effects, suggesting that vitamin D analogs could be used as adjunctive antithrombotic agents. However, epidemiologic evidence of an association between reduced 25-hydroxyvitamin D concentrations and the risk of venous thromboembolism is lacking. OBJECTIVES: To test the hypothesis that reduced plasma 25-hydroxyvitamin D concentrations are associated with an increased risk of venous thromboembolism in the general population. METHODS: We prospectively studied 18 791 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study. During up to 30 years of follow-up, 950 participants were diagnosed with venous thromboembolism. Plasma 25-hydroxyvitamin D concentrations were adjusted for seasonal variation. RESULTS: The cumulative incidence of venous thromboembolism as a function of age increased with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D (log-rank trend: P = 4 × 10(-4) ). On comparison of participants in the lowest and the highest tertile of plasma 25-hydroxyvitamin D concentrations, the crude risk estimate in a model adjusted for age and sex was a 37% (95% confidence interval [CI] 15-64%) increased risk of venous thromboembolism. The corresponding risk increase in a model adjusted for age, sex, body mass index, smoking and cancer was 26% (95% CI 5-51%), and in a multivariable-adjusted model also including physical activity, hormone replacement therapy, menopausal status, oral contraception use and lipid-lowering therapy it was 28% (95% CI 6-53%). Furthermore, corresponding risk increases with attempts to correct for regression dilution bias were 103% (95% CI 37-202%), 70% (95% CI 14-155%) and 73% (95% CI 15-160%) in the three models, respectively. CONCLUSION: In these large general population studies, we observed a stepwise increasing risk of venous thromboembolism with decreasing tertiles of seasonally adjusted plasma 25-hydroxyvitamin D concentrations.

Quantitative amino acid analysis.

Quantitative amino acid analysis is an important tool for many scientific areas ranging from the characterization of recombinant proteins to the description of food proteins for nutritional assessment. Quantitative amino acid analysis is often overlooked in many laboratories due to the difficulties involved in obtaining reliable amino acid composition data. Fortunately, for protein chemists, the creation of protein chemistry core laboratories devoted mainly to protein sequence analysis and peptide synthesis has provided new instrumentation that yields the necessary precision. In addition, for food scientists, it has become clear that for the description of food proteins, the nitrogen content alone simply does not provide sufficient information about the nutritional adequacy of these proteins, and as a result, a growing number of nutrition laboratories are undertaking amino acid analysis. This unit describes the information that can be derived from quantitative amino acid analysis and gives examples of the calculations that are needed.

High platelet volume and increased risk of myocardial infarction: 39,531 participants from the general population.

BACKGROUND: Active platelets are large and contribute to development of myocardial infarction (MI). Platelet size is measured automatically as mean platelet volume (MPV) together with platelet count. OBJECTIVES: We tested the hypothesis that increased MPV is associated with risk of MI in the general population independent of known cardiovascular risk factors. METHODS: We examined 39,531 men and woman from the Danish general population (the Copenhagen General Population Study), of whom 1300 developed MI. RESULTS: After multifactorial adjustment for known cardiovascular risk factors, risk of MI was increased by 37% (95% CI, 18-59%) in the middle and 30% (12-52%) in the upper vs. the lower tertile of MPV. Compared with the 1st quintile of MPV, there was corresponding increased risk of MI of 13% (-7% to 39%), 35% (11-64%), 31% (8-59%) and 29% (6-57%) in the 2nd, 3rd, 4th and 5th quintile, respectively. Similar values for octiles were increases in MI risk of -3% (-25% to 26%), 15% (-10% to 46%), 31% (1- 69%), 32% (5-68%), 31% (2-67%), 27% (-1% to 62%) and 26% (-1% to 61%), respectively, in the 2nd through to the 8th octile vs. the 1st octile of MPV. Use of antiplatelet therapy did not modify these risk estimates. Finally, in prospective, multifactorially adjusted analyses, risk of MI increased by 38% (8-75%) in individuals with MPV ≥ 7.4 vs. < 7.4 fL. CONCLUSIONS: Increased MPV is associated with increased risk of MI independent of known cardiovascular risk factors.

Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a lethal condition characterised by ventricular tachyarrhythmias, right and/or left ventricular involvement and fibrofatty infiltrations in the myocardium. The disease has been associated with mutations in genes encoding desmosomal proteins. OBJECTIVE: To thoroughly evaluate an ARVC cohort for desmosomal mutations and large genomic rearrangements and characterise the phenotype associated with double-mutation carrier status. METHODS: 65 unrelated patients (55 fulfilling current criteria and 10 borderline cases) were screened for mutations in all known desmosome genes (desmocollin-2 (DSC2), desmoglein-2 (DSG2), desmoplakin (DSP), plakoglobin (JUP) and plakophilin-2 (PKP2)) and TGFb3. Presence of genomic rearrangements was assessed by multiplex ligation-dependent probe amplification. Results The screening identified 19 different mutations: two mutations in DSG2, four in DSC2, two in DSP (one heterozygous and one homozygous), four in JUP (one patient with compound heterozygous) and seven in PKP2. No genomic rearrangements or mutations in TGFb3 were identified. Ten of the mutations were novel. Seven families carried more than one mutation. Clinical evaluation of these families showed a variable phenotype associated with the double-mutation carrier status. The homozygous desmoplakin mutation (DSP p.G2056R+p.G2056R) carrier came from a consanguineous Danish family and had left ventricular involvement, palmar keratoderma and curly hair consistent with a Carvajal-like syndrome. CONCLUSIONS: 33% of patients in this Danish cohort with ARVC carried desmosomal mutations with a surprisingly wide mutation spectrum. A substantial proportion of patients carried more than one mutation. Our study supports comprehensive desmosomal mutation screening beyond the first encountered mutation, whereas routine screening for genomic rearrangements does not seem indicated.

Excretion of miserotoxin and detoxification of the aglycone by grasshoppers (Orthoptera: Acrididae).

Two species of grasshoppers (Melanoplus bivittatus and M. sanguinipes) tolerated high levels of miserotoxin (3-nitro-1-propyl-beta-D-glucopyranoside) in their diet. Miserotoxin is a causative agent in cattle poisoning when timber milkvetch (Astragalus miser) is consumed. Toxic effects were averted by grasshoppers in part by excretion of the intact glycoside. When the aglycone was administered, detoxification was achieved by two routes: by oxidation of the aglycone to 3-nitropropionic acid which was then conjugated with glycine, and by glucosylation of the aglycone to miserotoxin, in each case followed by excretion.

Sensory capacity of the royal college of surgeons rat.

PURPOSE: To apply noninvasive tests for examining visual and other sensory functions of pigmented Royal College of Surgeons (RCS) rats compared with pigmented and albino control animals. METHODS: Rats aged 3 and 7 months were tested with a general neurologic examination that assessed visual, auditory, tactile, and whisker displacement responses. Photophobic responses and visual discrimination were also measured. RESULTS: Dystrophic RCS rats failed the visual presentation tests, even at 3 months of age, and showed diminished performance on tactile tests. Auditory and whisker displacement performances were normal. Albino rats also showed diminished performance on the visual test, particularly to stimuli presented in the upper visual field. Photophobic responses were diminished in the dystrophic RCS rats compared with the pigmented control animals. Albino animals showed heightened photophobia. The dystrophic rats failed to reach criterion levels of performance on the visual discrimination test even with gratings of 0.045 cyc/deg. CONCLUSIONS: The tests used discriminate deteriorated complex visual functions in RCS rats at ages when some simple reflexes can still be demonstrated. As such, they provide easily executed tests for screening for the effects of reparative treatments such as transplantation, administration of growth factors, and gene transfer technology. The integrity of whisker and auditory function are important when using tests requiring polysensory inputs. The somatosensory defect is surprising but may be useful in searching for the gene locus of the retinal disorder. The aberrations seen in the albino rats may be attributable to the effects of light damage and unfiltered light.

Structure revision of isoline (ruwenine), bisline and isolinecic acid.

X-ray crystallography of bisline, and the chemical interconversion of bisline and isoline (ruwenine), revealed that the structures previously assigned to these alkaloids required revision; as did that of isolinecic acid.

[Accreditation: the outcome is worth the time and money]. / L'agrement: le resultat vaut l'investissement en temps et argent.

When the Canadian Council on Health Services Accreditation adopted the Client-centered Accreditation Program (CCAP), we had to assess our methods and results and encourage the staff at all levels and the users to be involved. A complete change, considerable benefits: improved staff knowledge of the organisation, support and understanding within the teams, improved training through team meetings, more room for the patients and their families. Is accreditation costly? One cannot put a price on the degree of satisfaction experienced by the staff within a team who listens to their opinions and strives to make the daily routine as rewarding as possible.

QT dispersion in patients with arrhythmogenic right ventricular dysplasia.

AIMS: Arrhythmogenic right ventricular dysplasia is a rarely diagnosed cardiomyopathy, but a frequent cause of ventricular arrhythmia and sudden cardiac death. QT interval dispersion, measured as an interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of electrical instability. The present study was conducted to assess the occurrence of QT dispersion and its modulation during treatment with sotalol. Methods Twenty-five patients with the diagnosis of arrhythmogenic right ventricular dysplasia were studied retrospectively. Fourteen patients were considered low risk for malignant ventricular arrhythmia and sudden cardiac death, and 11 high risk due to documented sustained ventricular arrhythmia, cardiac arrest, or sudden cardiac death. Twenty five healthy volunteers served as control subjects. RESULTS: Dispersion of repolarization was significantly higher in patients than in control subjects (QTd and JTd: P<0.05). Dispersion of repolarization was equal in patients both with and without malignant arrhythmias. There was no significant change in dispersion after treatment with sotalol. Adjacent QT dispersion between leads V3-V4, V4-V5 and V5-V6, respectively, was higher in patients than in control subjects (P<0. 05), while no differences were seen in leads V1-V2 and V2-V3. CONCLUSION: QT interval dispersion is increased in patients with arrhythmogenic right ventricular dysplasia. However, the degree of dispersion is not related to the severity of symptoms, nor is it influenced by treatment with sotalol.

[Hereditary long QT syndrome]. / Arveligt langt QT-syndrom.

The Long QT Syndrome (LQTS) is a hereditary disease, characterized by a prolonged QT-interval on the electrocardiogram and a high risk of syncope and sudden death due to ventricular arrhythmias. LQTS must be suspected in apparently healthy children and young people with syncope after emotional or physical stress. Untreated symptomatic patients have a high mortality, which is markedly reduced by sympathetic block. The knowledge of the diagnostic criteria for the LQTS, a detailed history including a family history and an ECG-recording with measurement of the QT-interval in every patient with inexplicable syncope will advance the diagnosis of the LQTS and improve the survival of these patients after proper therapy. The current knowledge on the molecular genetics, epidemiology, mechanisms of arrhythmias and therapy are presented with special emphasis on the defects in the control of ionic transport over the cell membrane caused by mutations in ion channels.

[Arrhythmogenic right ventricular cardiomyopathy]. / Arytmogen højre ventrikel kardiomyopati.

Arrhythmogenic right ventricular dysplasia is a rare cardiomyopathy, but a frequent cause of ventricular tachyarrhythmia and sudden cardiac death among young otherwise healthy individuals. This article contains a review of the current knowledge on epidemiology, diagnosis, symptoms and signs as well as theories on etiology and pathogenesis, prognosis and treatment. The aim is to draw attention to the disease as a cause of syncope, ventricular tachycardia and sudden cardiac death.

Infective endocarditis, 1984 through 1993: a clinical and microbiological survey.

OBJECTIVES: To characterize the epidemiology and the clinical and microbiological spectrum of infective endocarditis in a Danish population. DESIGN: A retrospective review. SETTING: All episodes hospitalized of infective endocarditis from 1984 to 1993 in Viborg County were reviewed. The county is served by one general and four local hospitals. SUBJECTS: One hundred and nine episodes of suspected infective endocarditis with 62 episodes in 59 patients fulfilling the diagnostic criteria by von Reyn. RESULTS: An overall incidence of 27 episodes per million per year was found. The incidence was 17.4 episodes per million per year in the first part of the decade and 36.5 episodes per million per year in the second part (P < 0.001). Microscopic haematuria was found in 70.2% of the patients with infective endocarditis, compared to 16.7% of the patients in whom the diagnosis was rejected (P < 0.01). Staphylococcus aureus was found in 38.9%, non-beta-haemolytic streptococci in 24.1% and Enterococcus faecalis in 16.7%. The overall mortality was 35.5%. The mortality decreased significantly from 50.0% in the first part of the decade to 28.6% in the second part (P < 0.01). The mortality was 23.1% in patients in whom the diagnosis was established whilst they were alive. This finding was significantly lower than the overall mortality (P < 0.05). CONCLUSION: The incidence of infective endocarditis increased during the decade. The frequency of non-beta-haemolytic streptococci was lower than normally reported. Mortality is still high, with the main mortality within the first week in hospital, which stresses the importance of early case detection and treatment.

Chinchona alkaloid from Dendrosenecio kilimanjari subsp. cottonii.

Investigation of the Tanzanian Dendrosenecio kilimanjari subsp. cottonii resulted in the isolation of the cinchona alkaloid, cinchonidine. Conversion of cinchonidine to deoxy-cinchonidine was achieved in high yield using zinc dust in aqueous sulphuric acid. This illustrates the first reduction of a quinoline system using these reagents.

Benign duodenocolic fistula. A case presenting with acidosis.

A case of benign duodenocolic fistula as a complication to peptic ulcer disease is presented, the case being interesting for the rarity of the diagnosis and by being complicated with acidosis. The etiology, clinical features, diagnosis, and treatment are reviewed.