Extracorporeal cardiopulmonary resuscitation after out-of-hospital cardiac arrest in a Danish health region.

BACKGROUND: Extracorporeal Cardiopulmonary Resuscitation (ECPR) has emerged as a feasible rescue therapy for refractory, normothermic out-of-hospital cardiac arrest (OHCA). Reported survival rates vary and comparison between studies is hampered by heterogeneous study populations, differences in bystander intervention and in pre-hospital emergency service organisation. We aimed to describe the first experiences, treatment details, complications and outcome with ECPR for OHCA in a Danish health region. METHODS: Retrospective study of adult patients admitted at Aarhus University Hospital, Denmark between 1 January 2011 and 1 July 2015 with witnessed, refractory, normothermic OHCA treated with ECPR. OHCA was managed with pre-hospital advanced airway management and mechanical chest compression during transport. Relevant pre-hospital and in-hospital data were collected with special focus on low-flow time and ECPR duration. Survival to hospital discharge with Cerebral Performance Category (CPC) of 1 and 2 at hospital discharge was the primary endpoint. RESULTS: Twenty-one patients were included. Median pre-hospital low-flow time was 54 min [range 5-100] and median total low-flow time was 121 min [range 55-192]. Seven patients survived (33%). Survivors had a CPC score of 1 or 2 at hospital discharge. Five survivors had a shockable initial rhythm. In all survivors coronary occlusion was the presumed cause of cardiac arrest. CONCLUSION: Extracorporeal cardiopulmonary resuscitation is feasible as a rescue therapy in normothermic refractory OHCA in highly selected patients. Low-flow time was longer than previously reported. Survival with favourable neurological outcome is possible despite prolonged low-flow duration.

Fast and direct measurements of the electrical properties of graphene using micro four-point probes.

We present measurements of the electronic properties of graphene using a repositionable micro four-point probe system, which we show here to have unique advantages over measurements made on lithographically defined devices; namely speed, simplicity and lack of a need to pattern graphene. Measurements are performed in ambient, vacuum and controlled environmental conditions using an environmental scanning electron microscope (SEM). The results are comparable to previous results for microcleaved graphene on silicon dioxide (SiO(2)). We observe a pronounced hysteresis of the charge neutrality point, dependent on the sweep rate of the gate voltage; and environmental measurements provide insight into the sensor application prospects of graphene. The method offers a fast, local and non-destructive technique for electronic measurements on graphene, which can be positioned freely on a graphene flake.

Microstructural white matter brain abnormalities in patients with idiopathic fecal incontinence.

BACKGROUND: Abnormal central nervous system processing of visceral sensation may be a part of the pathogenesis behind idiopathic fecal incontinence (IFI). Our aim was to characterize brain differences in patients with IFI and healthy controls by means of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: In 21 female patients with IFI and 15 female healthy controls, whole-brain structural differences in gray matter volume (GMV), cortical thickness, and white matter tracts fractional anisotropy (FA) were quantified. For this purpose, we used voxel-based morphometry, surface based morphometry and tract-based spatial statistic, respectively. Furthermore, associations between structural brain characteristics and latencies of rectal sensory evoked electroencephalography potentials were determined. KEY RESULTS: Compared to healthy controls, IFI patients had significantly reduced FA values, reflecting reduced white matter tract integrity, in the left hemisphere superior longitudinal fasciculus (SLF), posterior thalamic radiation, and middle frontal gyrus (MFG), all P<.05. No differences were observed in GMV or in cortical thickness. The reduced FA values in the SLF and MFG were correlated with prolonged latencies of cortical potentials evoked by rectal stimuli (all P<.05). CONCLUSIONS & INFERENCES: This explorative study suggests that IFI patients have no macrostructural brain changes, but exhibit microstructural changes in white matter tracts relevant for sensory processing. The clinical relevance of this finding is supported by its correlations with prolonged latencies of cortical potentials evoked by rectal stimulation. This supports the theories of central nervous system changes as part of the pathogenesis in IFI patients.

Smac/DIABLO is not released from mitochondria during apoptotic signalling in cells deficient in cytochrome c.

We have characterised the apoptotic defects in cells null for cytochrome c (cyt c-/-). Such cells treated with staurosporine (STS) exhibited translocation to the mitochondria and activation of the proapoptotic signalling molecule Bax but failed to release Smac/DIABLO from these organelles, judged by both confocal microscopy and Western blotting. While reference cells expressing cytochrome c released both it and Smac/DIABLO under a variety of conditions of apoptotic induction, we have never observed release of Smac/DIABLO from cyt c-/- cells. We eliminate the possibility that proteasomal degradation of cytosolically localised Smac/DIABLO is responsible for our failure to visualise the protein outside the mitochondria. Our findings indicate an unanticipated nexus between release of cytochrome c and Smac/DIABLO from mitochondria, previously thought to be a more or less synchronised event early in apoptosis. We suggest that the failure of cyt c-/- cells to release Smac/DIABLO after recruitment of Bax to mitochondria represents an extreme manifestation of some inherent difference in the regulation of release of these two proteins from mitochondria.

Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex.

BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. METHODS: The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.

Fusobacterium necrophorum tonsillitis: an important cause of tonsillitis in adolescents and young adults.

The role of Fusobacterium necrophorum in tonsillitis in adolescents and young adults was retrospectively investigated by culture examination. We compared the prevalence of F. necrophorum in 212 subjects with confirmed clinical tonsillitis and in 176 subjects with confirmed no clinical tonsillitis. The prevalence of F. necrophorum was significantly higher (p < 0.001) in subjects with clinical tonsillitis (27%) compared to subjects with no clinical tonsillitis (6%). These results clearly demonstrate the role of F. necrophorum in tonsillitis. By diagnosing and treating F. necrophorum tonsillitis with, for example, penicillin, metronidazole, or both, we might prevent some cases of Lemierre syndrome.

Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain.

In non-neuronal tissue, ferritin subunit mRNAs are regulated by post-transcriptional mechanisms leading to decreased ferritin protein synthesis during iron deficiency. Biochemical studies have demonstrated that the cerebral ferritin concentration declines during iron deficiency, suggesting that expression of ferritin subunit mRNAs in the brain may be regulated by mechanisms similar to those of non-neuronal tissue. However, as ferritin expression has been only vaguely studied in brain, this hypothesis remains to be tested. We investigated the influence of dietary iron deficiency on the cellular distribution of ferritin protein using immunohistochemistry and H- and L-ferritin subunit mRNAs by non-radioactive in situ hybridization. Pregnant rats were subjected to an iron depleted diet (6.4 mg/kg) from the day of conception. Litters were kept on the same diet until euthanized at the postnatal age of 10 weeks. This treatment reduced brain iron levels from approximately 57 to 26 microgram/g. Reducing the iron stores reduced histochemical detectable iron and the expression of ferritin immunoreactivity in neurons, oligodendrocyte-like and microglia-like cells. In normal rats, H- and L-ferritin subunit mRNAs were expressed in virtually all neurons and non-neuronal cells. The cerebral expression of the ferritin subunit mRNAs was not affected by iron deficiency. The levels of ferritin subunit mRNAs in the brain were also unaltered from iron deficiency when examined by Northern blotting. In conclusion, brain levels of iron and ferritin protein are highly susceptible to dietary iron deficiency, whereas the cerebral expression of H- and L-ferritin subunit mRNAs remains unchanged.

Antikeratin antibodies in synovial fluid in rheumatoid arthritis.

Serum and synovial fluid of 20 patients with classical or definite rheumatoid arthritis (RA) were tested for antikeratin antibodies (AKA) by indirect immunofluorescence using rat esophagus as antigen. AKA were found in 80% of the RA patients, in serum as well as in synovial fluid. None of the 54 serum control patients were AKA positive in serum. None of the 17 synovial fluid control patients were AKA positive in synovial fluid. F(ab)'2 fragments prepared from AKA positive RA serum retained antibody activity. AKA belonged to the IgG class of immunoglobulins. Corrected for the lower IgG content in synovial fluid, AKA constituted a higher percentage of the IgG in synovial fluid than in serum. This could imply a possibility of local production of AKA in the joint.

Serum aminoterminal type III procollagen peptide in inflammatory and degenerative rheumatic disorders.

Measurement of the aminoterminal type III procollagen peptide in serum has been suggested as a marker of the biosynthesis of collagen type III, a major connective tissue component in repair processes. In the present study the propeptide level correlated with the inflammatory synovial mass in rheumatoid arthritis and osteoarthritis. This implies that the propeptide level reflects the collagen type III synthesis occurring in the synovial repair processes, whether they were caused by inflammatory or degenerative rheumatic disorders. Physical activity did not enhance the transition of the propeptide from the synovial fluid or the inflamed synovial membrane to the blood. Normal serum propeptide values were observed in most patients with ankylosing spondylitis and degenerative diseases of the spine. This may reflect the lower amount of inflammatory tissue in these diseases and hence the sensitivity of the assays.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis.

OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine.

[Testing a medically-staffed ambulance in Aarhus. A pilot study]. / Forsøg med indsaettelse af laegeambulance i Arhus. En pilotundersøgelse.

As an attempt to assess the value of a medically-staffed mobile emergency care unit in Aarhus City, we carried out a seven-day experiment (17 hours per day) with an anaesthesiologist and a nurse on duty in a fully equipped vehicle. Aarhus City is an area of approximately 300 km2, with a population of 330,000. The unit responded to emergency calls in 106 patients (38% of all emergency calls during this week). In 31% of all cases the response-time was less than five minutes. Medical disease was diagnosed in 73 patients. Twenty-three patients were suffering from trauma and in three cases the reason for the emergency call was attempted suicide. Fifty-seven percent were treated immediately by the emergency unit, and in 4% of these the treatment was lifesaving. Twenty percent of the patients had their treatment completed outside the hospital. Eighty percent were brought to hospital, 47% with medical assistance. We conclude that there seems to be a basis for a medically-staffed mobile emergency care unit in Aarhus City.

[The incidence of fibromyalgia in patients admitted to a rheumatology department]. / Forekomst af fibromyalgi hos patienter indlagt på en reumatologisk afdeling.

One hundred patients admitted consecutively to Kong Christian X Hospital for rheumatic conditions were examined for symptoms of fibromyalgia. 47% of the patients had not only histories of pain in three or more anatomically separate regions but also presence of at least seven tender points in the soft tissues on palpation of 15 sites of predilection for tender points. This investigation suggests a high incidence of secondary fibromyalgia in patients admitted on account of various rheumatic conditions.

[Examination of tender points in soft tissue. Palpation versus pressure-algometer]. / Undersøgelse for ømme punkter i bløddelene ("tender points"). Palpation versus trykalgometer.

Tender points may be identified by two methods, either by palpation or employment of a pressure-algometer. The inter- and intra-observer agreements between the two methods are investigated in the present article. The investigation consists of three sections: 1. Twenty-five female patients with various rheumatic conditions were examined by two investigators for tender points at 15 sites of predilection, immediately after one another both as regards palpation/palpation and pressure-algometer/pressure-algometer. Acceptable inter-observer agreement was found on palpation with an average value employing Cohen's kappa-coefficient of 0.68 and an unacceptable inter-observer agreement with average values employing Cohen's kappa-coefficient of 0.42, 0.39 and 0.44 with pressure thresholds of under 3.0, 4.0 and 5.0 kg/cm2. 2. Twenty-five female volunteers in whom only knees were visible were examined twice immediately after one another by the same examiner by palpation on the medial fat pad of the right knee and by pressure with the pressurealgometer on the medial fat pad of the left knee. Good intra-observer agreement was found by both methods with Cohen's kappa-coefficient ranging between 0.75 and 0.83. 3. Sixty-five consecutive patients admitted to Kong Christian X Hospital for Rheumatic Diseases were examined for tender points at 15 sites of predilection by two examiners immediately after one another employing palpation/pressure-algometer. Poor agreement was found between the two methods. Employment of the pressure-algometer may be useful in research where quantitating of the threshold of pain is desired, but, in the daily clinical routine, palpatory examination for tender points is just as good or better than employment of an algometer.

[Naproxen versus indomethacin as night-time medication for patients with rheumatoid arthritis]. / Naproxen versus indometacin som natlig behandling til patienter med reumatoid arthritis.

The investigation consisted of a double-blind cross-over study of the effect of 75 mg indometacin, 500 mg naproxen or a placebo in 63 patients with rheumatoid arthritis accompanied by night pain and morning stiffness. All the patients received day treatment with 250 mg naproxen b.i.d. Only a few patients benefitted from the treatment at night and no differences in the effect of indometacin and naproxen were observed. Naproxen was better tolerated than indometacin. Day treatment with naproxen, which has a relatively long half life time decrease the need for supplementary treatment at night.

[Severely traumatized patients admitted to Aarhus Community Hospital 1994-1995]. / Svaert tilskadekomne patienter indbragt til Arhus Kommunehospital 1994-1995.

In Denmark, only few studies have addressed the problem of severe trauma. In relation to establishing a trauma manual at our hospital we studied trauma patients requiring immediate anaesthesiological assistance. Patients from the preceeding years, 1994-1995 were identified. The injuries were scored according to the Abbreviated Injury Scale (AIS), and Injury Severity Scores (ISS) were calculated. Two hundred and fifty-eight trauma patients were identified, 132 of these were severely injured, defined as having ISS > or = 15. Of these, 75 patients were multitraumatised, defined as AIS > or = 3 in at least two regions. None of the patients with ISS < or = 15 died. Mortality was 49% among severely injured but not multitraumatised patients, while mortality was 56% among the multitraumatised patients. Head injuries were the most frequently found severe injury (AIS > or = 3), followed by injuries to the thorax and extremities. The anaesthesiologist and the orthopaedic surgeon were involved in initial diagnosis and treatment in all patients, and beyond these a variety of medical specialties were involved. In the light of this study we have revised our procedures and registration concerning severe trauma patients.

[Pregnancy associated pelvic pain. I: Prevalence and risk factors]. / Graviditetsrelaterede baekkensmerter. I: Praevalens og risikofaktorer.

With this study, we wanted to determine the incidence of symptom-giving pelvic girdle relaxation during pregnancy and the prevalence post partum, identify predisposing factors, and determine the frequency of sick leave. A total of 1600 pregnant women entered the study. The incidence during pregnancy was 14%, the prevalence two, six, and twelve months post partum was 5%, 4%, and 2%, respectively. Multivariate analysis indicated that the most important predisposing factor was pelvic pain in a previous pregnancy. Other factors were uncomfortable working conditions, lack of exercise, and previous low back and low abdominal pain. At least 37% of the women with symptom-giving pelvic girdle relaxation were on sick leave during pregnancy, on average for twelve weeks. Symptom-giving pelvic girdle relaxation is a considerable problem both in pregnancy and post partum. The occupational risk can possibly be prevented. The syndrome has a great social impact because of the high frequency of sick live.

[Pregnancy associated pelvic pain. II: Symptoms and clinical findings]. / Graviditetsrelaterede baekkensmerter. II: Symptomer og kliniske fund.

Pelvic pain in pregnancy appears to be a problem on the increase. This study was undertaken to describe and analyse the relationship between subjective symptoms, daily disability, and clinical findings in women with symptom-giving pelvic girdle relaxation in pregnancy. Out of 1600 pregnant women, 238 had pelvic pain. After a clinical examination 11 women were excluded due to low back pain. The rest, 227 women, was considered to have symptom-giving pelvic girdle relaxation during pregnancy. Symptom-giving pelvic girdle relaxation in pregnancy seriously interferes with many activities of daily living such as housekeeping, walking, working, and sexual life. The women's statements of pelvic pain are well correlated to the number of positive clinical tests. Symptom-giving pelvic girdle relaxation in pregnancy causes considerable disabilities concerning daily activities.

[Fish oils and rheumatoid arthritis. A randomized and double-blind study]. / Fiskeolie og reumatoid artrit. En randomiseret og dobbeltblind undersøgelse.

The effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with active rheumatoid arthritis was evaluated in a multicentre, randomized and double blind study. Fifty-one patients with active rheumatoid arthritis were included from three Danish hospital Departments of Rheumatology. The patients were allocated to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with a fat composition averaging the Danish diet. Small but significant improvements in morning stiffness, joint tenderness and C-reactive protein were observed. There were no serious side-effects. Dietary supplementation with n-3 PUFA in patients with active rheumatoid arthritis has a modest effect on three out of eight disease variables, without effect on other traditional parameters for monitoring disease activity.