High Mortality from Major Vascular Trauma in Traffic Accidents: A Population-Based Study.

BACKGROUND AND AIMS: Injuries involving major arteries are an important cause of mortality and morbidity, most often from road traffic accidents. Our aim was to study the outcome of major vascular trauma from traffic accidents in an entire population, including patients who die at the scene and those who reach hospital alive. MATERIALS AND METHODS: This was a retrospective analysis of all patients who sustained major vascular trauma in traffic accidents in Iceland from 2000 to 2011. Patient demographics, mechanism, and location of vascular injury and treatment were registered. Injury scores were calculated and overall survival estimated. RESULTS: There were 62 individuals (mean age 44 years, 79% males) with 95 major vascular traumas, giving an incidence of 1.69/100,000 inhabitants (95% confidence interval: 1.27-2.21). A total of 33 died at the scene and 8 during transportation to hospital but 21 (34%) reached hospital alive. Most patients who succumbed had thoracic major vascular traumas (76%) or abdominal major vascular traumas (23%). Mean new injury severity score for the 21 admitted patients was 44. A total of 18 were operated with vascular repair, 3 with endovascular stent graft insertion. The mean hospital stay for discharged patients was 34 days. Altogether, 15 of the 62 patients (24%) survived to discharge from hospital, with a 5-year survival of 86% for discharged patients. CONCLUSION: Every other patient with major vascular trauma following traffic accidents died at the scene and a further 13% died during transportation to hospital, most of whom sustained major vascular trauma to the thoracic aorta. However, one-third of the patients reached hospital alive and 71% of them survived to discharge, with excellent long-term survival.

Circulating plasma microRNAs as biomarkers for iron status in blood donors.

OBJECTIVES: To investigate whether microRNAs can serve as biomarkers for iron status in blood donors. BACKGROUND: Serum ferritin is a widely used biochemical test for detecting iron deficiency, but it has its limitations. Certain microRNAs (miRNAs) reportedly have a role in regulating iron homeostasis. Circulating miRNAs have been reported as potential biomarkers for various conditions but have not yet been studied in iron deficiency. METHODS: Participating blood donors were divided into two groups: high ferritin (HF) (>150 µg L-1 ) and low ferritin (LF) (<15 µg L-1 ). MiRNA analysis was performed by an miRNA profiling service (Exiqon) using commercial qPCR assays. The study had two phases: (i) a pilot study (20 participants) where 179 miRNAs were analysed and (ii) a confirmation study (50 participants) of 13 selected miRNAs. RESULTS: Mean serum ferritin was 13·8 µg L-1 in the LF arm compared to 231 µg L-1 in the HF group (P < 0·001). Hepcidin plasma levels were higher in the HF arm (P < 0·001), whereas soluble transferrin receptor 1 was higher in the LF group (P < 0·001). In the pilot study, samples did not separate according to study group on unsupervised analysis. When directly comparing HF vs LF groups, 17 miRNAs were differentially expressed (P < 0·05, t-test) but did not pass correction for multiple testing. The confirmation study of 13 selected miRNAs verified these findings as no miRNA was significantly different between the study groups. CONCLUSION: In this study, circulating plasma miRNAs did not emerge as promising biomarkers for iron status in healthy individuals. However, in the future, alternative detection methods such as next-generation sequencing might indicate miRNAs that correlate with iron stores.

Rare and Common Variants Conferring Risk of Tooth Agenesis.

We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.

Morphological determinants of signal carrier frequency in katydids (Orthoptera): a comparative analysis using biophysical evidence of wing vibration.

Male katydids produce mating calls by stridulation using specialized structures on the forewings. The right wing (RW) bears a scraper connected to a drum-like cell known as the mirror and a left wing (LW) that overlaps the RW and bears a serrated vein on the ventral side, the stridulatory file. Sound is generated with the scraper sweeping across the file, producing vibrations that are amplified by the mirror. Using this sound generator, katydids exploit a range of song carrier frequencies (CF) unsurpassed by any other insect group, with species singing as low as 600 Hz and others as high as 150 kHz. Sound generator size has been shown to scale negatively with CF, but such observations derive from studies based on few species, without phylogenetic control, and/or using only the RW mirror length. We carried out a phylogenetic comparative analysis involving 94 species of katydids to study the relationship between LW and RW components of the sound generator and the CF of the male's mating call, while taking into account body size and phylogenetic relationships. The results showed that CF negatively scaled with all morphological measures, but was most strongly related to components of the sound generation system (file, LW and RW mirrors). Interestingly, the LW mirror (reduced and nonfunctional) predicted CF more accurately than the RW mirror, and body size is not a reliable CF predictor. Mathematical models were verified on known species for predicting CF in species for which sound is unknown (e.g. fossils or museum specimens).

Symptoms and side effects in chronic non-cancer pain patients: clinical implications and development of new assessment tools.

OBJECTIVE: To improve a 41-item screening tool evaluated in our previous study by making it more simple and convenient to patients and at the same time maintain the level of information and the sensitivity. METHODS: In a prospective, two-period questionnaire study, patients suffering from chronic pain of non-cancer origin for more than 6 months, were asked to fill in two questionnaires: QSSE-41 or QSSE-33 and SF-36. The first part of the study (QSSE-41) included an age- and sex-matched control group. RESULTS: A total of 67 patients were included in QSSE-41 and 60 patients in QSSE-33. In QSSE-41, the mean number of symptoms reported by the patient group (12.3) was significantly higher than those reported by the controls (6.8) (P < 0.001). Out of the total number of symptoms, 40.3% were reported to be side effects caused by analgesics, and out of those 61.3% were reported as acceptable and 38.7% as unacceptable side effects. In the QSSE-33, the mean number of symptoms reported by the patient group was 13.6. Out of the total number of symptoms, 46.3% were reported to be side effects caused by analgesics, and out of those 56.4% were reported as acceptable and 43.6% as unacceptable side effects. CONCLUSIONS: This new and shorter screening tool QSSE-33 may substitute the original QSSE-41 and in clinical use, contribute substantially to a more comprehensive and detailed understanding of symptoms/side effects and may consequently lead to improved therapies.

Cloxacillin concentrations in serum, subcutaneous fat, and muscle in patients with chronic critical limb ischemia.

BACKGROUND: Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics. PURPOSE: This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poorly vascularized tissues, i.e., the calf and foot of patients suffering from CLI. METHODS: Cloxacillin concentrations were measured by HPLC in serum and in microdialysis samples from skin and muscle of the lower part of the calf and as reference subcutaneously at the pectoral level in eight patients suffering from CLI (four males, four females, mean age 78 years, range 66-85 years) and in three healthy controls (two females, one male, mean age 67, range 66-68 years). RESULTS: In patients suffering from CLI, the tissue penetration of cloxacillin after a single 4 g dose was comparable to that of healthy controls, despite impaired blood circulation. CONCLUSIONS: The reduced blood flow in the peripheral vessels of the CLI patients presented here apparently is not the rate-limiting factor for delivery or tissue penetration of cloxacillin.

Association of HLA-DRB1*01 with Dupuytren's disease.

OBJECTIVES: To explore the human leucocyte antigen (HLA)-DRB1 allele frequency in Dupuytren's disease (DD). METHOD: HLA-DRB1 genotypes were analysed by sequence-specific primers (SSPs) in samples collected from 172 men participating in a nested case-control study on the clinical manifestations and progression of DD. Of those, 121 had signs of DD while 51 did not. Of the 121 men with DD, 49 had contracted fingers or had been operated on, while 72 had nodules or fibrous cords in the palms. Odds ratios (ORs) and 95% confidence interval (CIs) were used to evaluate the results. RESULTS: The HLA-DRB1*01 allele was observed in 26 of the 121 affected men (23.7%) but in only four of the controls (7.8%) (OR 3.22, 95% CI 1.06-9.75). The HLA-DRB1*01 allele frequency in those affected was 11%, while in the control group it was 4% (OR 3.07, 95% CI 1.05-9.03). CONCLUSIONS: This observation indicates a possible association of HLA-DRB1*01 with DD, but further studies are needed for confirmation.

Adverse events during treatment of critical limb ischemia with autologous peripheral blood mononuclear cell implant.

AIM: Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work. METHODS: We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks. RESULTS: Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response. CONCLUSION: Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.

Metabolomics reveals elevated macromolecular degradation in periodontal disease.

Periodontitis is a chronic inflammatory disease characterized by tissue destruction. In the diseased oral environment, saliva has primarily been considered to act as a protectant by lubricating the tissue, mineralizing the bones, neutralizing the pH, and combating microbes. To understand the metabolic role that saliva plays in the diseased state, we performed untargeted metabolomic profiling of saliva from healthy and periodontitic individuals. Several classes of biochemicals, including dipeptide, amino acid, carbohydrate, lipids, and nucleotide metabolites, were altered, consistent with increased macromolecular degradation of proteins, triacylglycerol, glycerolphospholipids, polysaccharides, and polynucleotides in the individuals with periodontal disease. These changes partially reflected the enhanced host-bacterial interactions in the diseased state as supported by increased levels of bacterially modified amino acids and creatine metabolite. More importantly, the increased lipase, protease, and glycosidase activities associated with periodontitis generated a more favorable energy environment for oral bacteria, potentially exacerbating the disease state.

Symptoms and side effects in chronic non-cancer pain: patient report vs. systematic assessment.

BACKGROUND: relieving distressing symptoms and managing the side effects of analgesics are essential in order to improve quality of life and functional capacity in chronic non-cancer pain patients. A quick, reliable and valid tool for assessing symptoms and side effects is needed in order to optimize treatment. We aimed to investigate the symptoms reported by chronic non-cancer pain patients after open-ended questioning vs. a systematic assessment using a list of symptoms, and to assess whether the patients could distinguish between the symptoms and the side effects induced by analgesics. METHODS: patients treated with either opioids and/or adjuvant analgesics were asked to report their symptoms spontaneously, followed by a 41-item investigator-developed symptom checklist. A control group also filled in the checklist. RESULTS: a total of 62 patients and 64 controls participated in the study. The numbers of symptoms reported by the patients (9.9 ± 5.9) were significantly higher than those reported by the controls (3.2 ± 3.9) (P<0.001). In the patient group, the number of spontaneously reported symptoms (1.3 ± 1.4) was significantly lower than the symptoms reported when using the symptom checklist (9.9 ± 5.9) (P<0.001). The six most frequently symptoms reported by the patients were: (1) Fatigue; (2) Memory deficits; (3) Dry mouth; (4) Concentration deficits; (5) Sweating; and (6) Weight gain. Out of the six most frequently reported symptoms, the share of side effects due to analgesics was: (1) Dry mouth (42%); (2) Sweating (34%); (3) Weight gain (29%); (4) Memory deficits (24%); (5) Fatigue (19%); and (6) Concentration deficits (19%). CONCLUSION: the number of symptoms reported using systematic assessment was eightfold higher than those reported voluntarily. Fatigue, cognitive dysfunction, dry mouth, sweating and weight gain were the most frequently reported. The patients reported the side effects of their analgesics to contribute substantially to the reported symptoms.

A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.

AIMS/HYPOTHESIS: Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. METHODS: Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('Old Stone Age') diet (n = 14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n = 15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. RESULTS: Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p = 0.0001) in the Palaeolithic group and a 7% decrease (p = 0.08) in the Consensus group. The larger (p = 0.001) improvement in the Palaeolithic group was independent (p = 0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p = 0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r = -0.06, p = 0.9) or waist circumference (r = 0.01, p = 1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r = 0.64, p = 0.0003), this did not remain after multivariate analysis. CONCLUSIONS/INTERPRETATION: A Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.

The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis.

OBJECTIVE: To study the effect of tobacco smoking and rheumatoid factor (RF) isotypes on disease activity and joint damage in early rheumatoid arthritis (RA). METHODS: One hundred early RA patients were followed prospectively for 2 yr. They were evaluated at recruitment and at 6 and 24 months. Sociodemographic information included smoking history, and radiographs of hands and feet were obtained. RF was monitored by IgM- and IgA-specific RF enzyme-linked immunosorbent assay and by agglutination, and serial measurements were also obtained for C-reactive protein. The influence of tobacco smoking and RF positivity on disease outcome was evaluated using multivariate analysis. Covariates for the regression analysis included sex, age, coffee consumption and IgA-RF positivity. RESULTS: A gradient of increase in disease activity was observed from never smokers to former smokers to current smokers during the 2 yr of observation, defined by number of swollen joints (SJC), tender joints (TJC) and visual analogue scale for pain (P<0.001, P=0.02 and P=0.005, respectively), but smoking status did not influence radiological progression. Ever smokers were more often IgA RF positive (P<0.05). IgA RF-positive patients had more active disease (SJC P=0.002, TJC P=0.01) and showed more radiological progression (P<0.0001) compared with IgA RF-negative patients. Of the RF-positive patients 22% had elevated IgM RF without IgA RF and these patients showed similar disease activity and radiological joint progression to the RF-negative patients. None of these associations were explained by possible confounders. CONCLUSION: Tobacco smoking has an adverse effect on patients with early RA and this is possibly immunologically mediated. IgM RF does not predict poorer prognosis in RA unless it is associated with a concomitant elevation of IgA RF.

Childhood levels of immunoglobulins and mannan-binding lectin in relation to infections and allergy.

Respiratory tract infections, allergies and otitis media are common problems in early childhood. Our aim was to evaluate in a longitudinal community-based cohort study the association between maturation of immunoglobulin (Ig) and mannan-binding lectin (MBL) responses and disease manifestations in the first 4 years of life. Sustained low levels of IgA proved the strongest single indicator of susceptibility for recurrent otitis media (P = 0.008) and respiratory tract infections (P = 0.02), and this condition was also associated with low production of IgG subclasses. About 7% of the cohort had sustained low levels of MBL (<0.4 mg/l). Low MBL did not predispose to any ailments studied, but children with low IgA and recurrent otitis media had relatively low MBL at birth, which failed to increase during the study period and was significantly reduced at the age of 4 years (P = 0.04). MBL levels increased from birth to 2 years (P < 0.0001) and were higher in children than in adults (P = 0.001). The increase was 1.9-fold in children with no recorded clinical events and 1.7-fold in children with asthma or infections, but significantly lower, 1.2-fold, in children with recurrent otitis media. Low levels of IgA within the normal range may reveal disease susceptibility not detected by conventional criteria. Slow maturation of Ig appears to be the main factor of susceptibility during childhood, but a strong corollary role for MBL is indicated by the high levels produced during childhood as well as the precipitation of disease in children with low levels of MBL and Ig.

The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents.

Eleven Norwegian patients (aged 2-33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0.23 (0.05-0.41) g/l versus 0.91 (0.58-1.26) g/l in the other patients (P = 0.002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0.9 (0.4-1.4) U/ml, while normal levels were found in their parents 11.1 (8.7-13.4) U/ml (P < 0.001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0.85, P = 0.001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23-64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.

Human intraperitoneal microdialysis: increased lactate/pyruvate ratio suggests early visceral ischaemia. A pilot study.

BACKGROUND: Previous studies suggest that visceral ischaemia precedes shock and multiple organ failure, though methods for studying humans are lacking. We aimed to evaluate intraperitoneal microdialysis, a new technique for detecting splanchnic ischaemia in clinical practice. METHODS: Right-sided hemicolectomy was performed in eight patients who were studied by microdialysis postoperatively for glucose, lactate, pyruvate and glycerol levels. RESULTS: Six of the eight patients showed a normal postoperative course and had lactate/pyruvate ratios between 7.1 and 21.7, glucose between 4.5 and 14.3 mmol/L and glycerol between 10.4 and 296 micromol/L. In one patient, intraperitoneal lactate/pyruvate ratio and glycerol increased and glucose decreased 5 h before low oxygenation appeared. Another patient exhibited a period of increased lactate/pyruvate ratio before a period of atrial fibrillation. CONCLUSION: Intraperitoneal microdialysis was performed safely. Two out of the eight patients exhibited changes of metabolic markers followed by clinical symptoms that were probably related to transient visceral ischaemia. Our findings suggest that intraperitoneal microdialysis may become a useful tool for monitoring splanchnic ischaemia in clinical practice.

Dupuytren's disease, alcohol consumption and alcoholism.

OBJECTIVE: To assess the relation between alcohol consumption and Dupuytren's disease. DESIGN: The participants were recruited from a previous study on Dupuytren's disease carried out in 1981-82 as part of a cohort study. Men with Dupuytren's disease in the former study and a control group were invited. The groups were matched for age and smoking habits. SETTINGS: The study took place at the Heart Preventive Clinic in Reykjavik. PATIENTS: Of 244 invited participants, 193 (79.1%) responded to the invitation; 137 had Dupuytren's disease and 56 were disease-free. Participants were examined for the presence of Dupuytren's disease and answered a questionnaire about alcohol habits. MAIN OUTCOME MEASURES: Alcoholism, alcohol consumption and signs of Dupuytren's disease. RESULTS: Of the Dupuytren's group, 19 (13.9%) had been treated for alcoholism or were heavy drinkers compared to 8 (14.3%) of those without Dupuytren's disease (NS). Little or moderate alcohol consumption was reported in 78.1% of the Dupuytren's patients compared to 73.2% of the controls (NS). Total abstainers from alcohol were 11 (8.0%) in the Dupuytren's group compared to 7 (12.5%) in the control group (NS). CONCLUSION: Our findings do not support a positive association between the use of alcohol and Dupuytren's disease.

A comparative fMRI study: T2*-weighted imaging versus R2* mapping.

Functional magnetic resonance imaging experiments were performed in human motor cortex at 1.5 T by sampling two successive gradient recalled echo images in a single shot. Several aspects of brain mapping methods based on T2*-weighted imaging and R2* mapping were quantitatively compared. These include the detected activation volume, functional contrast (FC), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Studies based on the R2* mapping method have the following potential advantages: maximum functional contrast, less dependent on TE; and reduced inflow effects. R2* mapping produced the highest functional contrast, but not the largest activation volume due to the reduced signal-to-noise ratio and inflow effects. The sensitivity for activation detection is significantly correlated with the contrast-to-noise ratio, which is determined by both the SNR and FC.

Current awareness in NMR in biomedicine.

In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of NMR in biomedicine. Each bibliography is divided into 9 sections: 1 Books, Reviews ' Symposia; 2 General; 3 Technology; 4 Brain and Nerves; 5 Neuropathology; 6 Cancer; 7 Cardiac, Vascular and Respiratory Systems; 8 Liver, Kidney and Other Organs; 9 Muscle and Orthopaedic. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren's disease.

OBJECTIVE: To evaluate the clinical manifestations and progression of Dupuytren's disease. METHODS: In 1981-82 a total of 1297 men were examined for Dupuytren's disease, and of these 19.2% had the disease. In 1999 those with signs of the disease in 1981-82 were invited for a follow-up study. As controls symptom free individuals from the study in 1981-82 were invited. RESULTS: A total of 53 individuals from the control group had developed Dupuytren's disease in 1999. Men with palmar nodules/fibrous cord in 1981-82 were more likely to develop contracted fingers than those without Dupuytren's disease. Patients with young age at disease onset more often required operations than those with later onset. Of the men who had been operated 70% still had finger contractures in 1999. CONCLUSION: The incidence of Dupuytren's disease is high in elderly men. Dupuytren's disease is progressive in nature and most operated patients have recurrent finger contractures.