Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort.

BACKGROUND: Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. OBJECTIVES: To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. METHODS: CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. RESULTS: Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04-1·30) of Breslow thickness vs. normal-weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00-1·27) and 1·17 (95% CI 1·03-1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m-2 , BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. CONCLUSIONS: This large case-series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values.

Passing a seawater challenge test is not indicative of hatchery-reared Atlantic salmon Salmo salar smolts performing as well at sea as their naturally produced conspecifics.

Despite satisfactory reactions to seawater challenge tests indicative of appropriate physiological state, hatchery-reared Atlantic salmon Salmo salar smolts stocked in the Eira River in Norway between 2001 and 2011 performed less well at sea in terms of growth, age at maturity and survival than smolts of natural origin. The mean rates of return to the river for hatchery-reared and naturally produced S. salar were 0·98 and 2·35%. In the Eira River, c. 50 000 hatchery-reared S. salar smolts of local origin were stocked annually to compensate for reduced natural smolt production following regulation for hydroelectric purposes, while a mean of 17 262 smolts were produced naturally in the river. This study demonstrates that, although captive S. salar perform well in seawater challenge tests, hatchery-reared smolts are not necessarily as adaptable to marine life as their naturally produced counterparts. These findings suggest that production of hatchery-reared smolts more similar to naturally produced individuals in morphology, physiology and behaviour will be necessary to improve success of hatchery releases. Where possible, supplementary or alternative measures, including habitat restoration, could be implemented to ensure the long-term viability of wild stocks.

Water discharge affects Atlantic salmon Salmo salar smolt production: a 27 year study in the River Orkla, Norway.

A model that explains 48% of the annual variation in Atlantic salmon Salmo salar smolt production in the River Orkla, Norway, has been established. This variation could be explained by egg deposition, minimum daily discharge during the previous winter and minimum weekly discharge during the summer 3 years before smolt migration. All coefficients in the model were positive, which indicates that more eggs and higher minimum discharge levels during the winter before smolt migration and the summer after hatching benefit smolt production. Hence, when the spawning target of the river is reached, the minimum levels of river discharge, in both winter and summer, are the main bottlenecks for the parr survival, and hence for smolt production. The River Orkla was developed for hydropower production in the early 1980s by the construction of four reservoirs upstream of the river stretch accessible to S. salar. Although no water has been removed from the catchment, the dynamics of water flow has been altered, mainly by increasing discharges during winter and reducing spring floods. In spite of the higher than natural winter discharges, minimum winter discharge is still a determinant of smolt production. Hence, in regulated rivers, the maintenance of discharges to ensure that they are as high as possible during dry periods is an important means of securing high S. salar smolt production.

Review of the results from the International C. elegans first experiment (ICE-FIRST).

In an effort to speed the rate of discovery in space biology and medicine NASA introduced the now defunct model specimen program. Four nations applied this approach with C. elegans in the ICE-FIRST experiment. Here we review the standardized culturing as well as the investigation of muscle adaptation, space biology radiation, and gene expression in response to spaceflight. Muscle studies demonstrated that decreased expression of myogenic transcription factors underlie the decreased expression of myosin seen in flight, a response that would appear to be evolutionarily conserved. Radiation studies demonstrated that radiation damaged cells should be able to be removed via apoptosis in flight, and that C. elegans can be employed as a biological accumulating dosimeter. Lastly, ICE-FIRST gave us our first glimpse at the genomic response to spaceflight, suggesting that altered Insulin and/or TGF-beta signaling in-flight may underlie many of the biological changes seen in response to spaceflight. The fact that the results obtained with C. elegans appear to have strong similarities in human beings suggests that not only will C. elegans prove an invaluable model for understanding the fundamental biological changes seen during spaceflight but that it may also be invaluable for understanding those changes associated with human health concerns in space.

Influence of sea temperature and initial marine feeding on survival of Atlantic salmon Salmo salar post-smolts from the Rivers Orkla and Hals, Norway.

The abundance of returning adult Atlantic salmon Salmo salar, in the River Orkla in mid-norway (1 sea-winter, SW, fish) and River Hals in north Norway (1-3 SW fish), was tested against the early marine feeding and the seawater temperature experienced by their corresponding year classes of post-smolts immediately after entry into the Trondheimsfjord (Orkla smolts, 22 years of data) and Altafjord (Hals smolts, 17 years of data). In both river-fjord systems, there was a significant positive correlation between the abundance of returning S. salar and the mean seawater temperature at the time of smolts descending to the sea. The number of 1SW fish reported caught in River Orkla was positively correlated to the proportion of fish larvae in the post-smolt stomachs in Trondheimsfjord. The abundance of returning S.salar was, however, neither correlated to forage ratio (R(F)) nor other prey groups in post-smolt stomachs in the two fjord systems. In the Altafjord, the post-smolts fed mainly on pelagic fish larva (70-98%) and had a stable R(F) (0.009-0.023) over the 6 years analysed. In the Trondheimsfjord, however, there was a higher variation in R(F) (0.003-0.036), and pelagic fish larvae were dominant prey in only two (50 and 91%) of the 8 years analysed. These 2 years also showed the highest return rates of S. salar in River Orkla. These results demonstrate that the thermal conditions experienced by post-smolts during their early sea migration may be crucial for the subsequent return rate of adults after 1-3 years at sea. Pelagic marine fish larvae seem to be the preferred initial prey for S. salar post-smolts. As the annual variation in abundance of fish larvae is related to seawater temperature, it is proposed that seawater temperature at sea entry and the subsequent abundance of returning adult S. salar may be indirectly linked through variation in annual availability of pelagic fish larvae or other suitable food items in the early post-smolt phase.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset. CONCLUSION: The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.

Functional and structural assessment of patients with and without persistent pain after thoracotomy.

BACKGROUND: Persistent pain is frequent after thoracotomy, with a reported prevalence of up to 60%. It remains unclear why some patients develop pain, whereas others do not. We therefore examined patients with and without pain after thoracotomy to identify pathophysiological contributors to persistent pain. METHODS: Twenty patients with persistent pain, 12 patients without pain and 20 healthy controls underwent detailed functional and structural assessment including psychometric and neuropathic pain questionnaires, bedside examination for pinprick hyperalgesia and brush allodynia, quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain, measurement of capsaicin-evoked flare response, intradermal nerve density as determined by skin biopsies and laser- and heat-evoked potentials. RESULTS: Bedside testing revealed evoked pain in 16 of 20 patients with pain, but only in 2 of 12 patients without pain (p < 0.001). Quantitative sensory testing showed increased mechanical pain sensitivity (p = 0.018) on the operated side in patients with pain, but there were no differences between the two patient groups with regard to intradermal nerve fibre density, area and flux following capsaicin application and laser- and heat-evoked potentials. CONCLUSION: Different and individual pathophysiological mechanisms of pain may obscure the clinical picture and thus preclude identification of a specific pain profile in patients with persistent post-thoracotomy pain. SIGNIFICANCE: Evoked pain is more frequent in patients with pain. Assessment of intradermal nerve density, capsaicin-induced flare response and contact and laser heat-evoked potentials revealed no differences between pain patients and pain-free patients.

Added value of electromyography in the diagnosis of myopathy: A consensus exercise.

OBJECTIVE: Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies. METHODS: One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres. Each patient was given three different consensus diagnoses: (1) the EDX diagnosis solely based on EDX results, (2) the pure clinical diagnosis based on all available information except EDX results, and (3) the final diagnosis including EDX and all additional information. The myopathies were grouped as muscular dystrophy (45), inflammatory myopathy (46), other aetiology (36) or unknown aetiology (67). RESULTS: Higher diagnostic probabilities for myopathy were seen in the final diagnosis compared to the pure clinical diagnosis (p<0.001). Adding EDX information increased the diagnostic probability of myopathy in 67 patients (34.4%). The greatest increase was seen for myopathies of unknown aetiology. CONCLUSIONS: EDX has a major impact in the diagnosis of myopathies of unknown aetiology. In genetically or biopsy proven myopathies, EDX generally supports the diagnosis. SIGNIFICANCE: EDX is still a useful tool in the diagnostic work-up of most patients with suspected myopathy.

Neurophysiological localisation of ulnar neuropathy at the elbow: Validation of diagnostic criteria developed by a taskforce of the Danish Society of clinical neurophysiology.

OBJECTIVE: This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). The Danish criteria are based on combinations of conduction slowing in the segments of the elbow and forearm expressed in Z-scores, and difference between the segments in m/s. Examining fibres to several muscles and sensory fibres can increase the certainty of the localisation. METHODS: Diagnostic accuracy for UNE was evaluated on 181 neurophysiological studies of the ulnar nerve from 171 peer-reviewed patients from a mixed patient-group. The diagnostic reference standard was the consensus diagnosis based on all available clinical, laboratory, and electrodiagnostic information reached by a group of experienced Danish neurophysiologists. RESULTS: The Danish criteria had high specificity (98.4%) and positive predictive value (PPV) (95.2%) and fair sensitivity (76.9%). Compared to the AANEM criteria, the Danish criteria had higher specificity (p<0.001) and lower sensitivity (p=0.02). CONCLUSIONS: The Danish consensus criteria for UNE are very specific and have high PPV. SIGNIFICANCE: The Danish criteria for UNE are reliable and well suited for use in different centres as they are based on Z-scores.

Amplitude, area and duration of the compound muscle action potential change in different ways over the length of the ulnar nerve.

OBJECTIVE: To study physiological changes of the compound muscle action potential (CMAP) obtained from stimulation at different sites over the full length of a motor nerve and to study possible effects of anthropometrical factors. METHODS: Multicentre study of ulnar motor nerve conduction in five segments to Erb's point performed bilaterally on 100 healthy subjects aged 17-83 years. RESULTS: CMAP amplitude decreased linearly with conduction distance (0.31%/cm) from wrist to Erb's point. CMAP area decreased with the square of conduction distance. Decrease in area was smaller than decrease in amplitude especially distally. CMAP duration increased linearly (0.17%/cm). Amplitude decay correlated with age, height and BMI and dispersion correlated with age and height. There were no correlations between area decay and anthropometrical factors. There was no significant inter-examiner variation. CONCLUSIONS: Area decay may be preferred to amplitude decay in the evaluation of conduction block over short segments due to smaller physiological changes and independence of anthropometrical factors. The absence of inter-examiner variation indicates that the results are robust and may be used by other laboratories. SIGNIFICANCE: This study provides knowledge of physiological changes of CMAP parameters that may be of importance in the evaluation of nerve pathology, in particular conduction block.

Investigation of a possible correlation between rates of secretion and microsomal membrane association of plasma proteins synthesized by rat liver.

The rates of secretion of complement C3, haptoglobin and plasminogen have been determined after pulse labelling with [3H]leucine, and compared to the secretion of prothrombin, albumin and transferrin investigated previously (Kvalvaag, A.H., Tollersrud, O.K. and Helgeland, L. (1988) Biochim. Biophys. Acta 937, 319-327). To study membrane association, rough microsomes were treated with increasing concentrations of saponin, sodium deoxycholate or Triton X-100. All six proteins were quantitated in the soluble and membrane fraction by enzyme immunoassays. At concentrations of saponin from 0.08% to 0.32%, each secretory protein showed a characteristic distribution, almost identical to that obtained with 0.05% sodium deoxycholate or 0.08% Triton X-100. Albumin and transferrin with half-times for secretion (t1/2) 30 and 75 min, respectively, are both almost exclusively found in the luminal fraction (greater than 95%). Prothrombin and plasminogen, which both show an intermediate t1/2 (approx. 55 min), are partially associated with the membranes, as only about 60% was released. Haptoglobin and complement C3 also show some association with the membranes (80-85% released). C3 is secreted at the same rate as prothrombin and plasminogen (t1/2 = 55 min), whereas haptoglobin is secreted more rapidly (t1/2 = 40 min). Accordingly, no correlation between kinetics of secretion and membrane association was demonstrated.

Prevalence of insomnia in the adult Norwegian population.

A representative adult sample (18 years and above) of the Norwegian population, comprising 2001 subjects, participated in telephone interviews, focusing on the one-month point prevalence of insomnia and use of prescribed hypnotics. Employment of DSM-IV inclusion criteria of insomnia yielded a prevalence rate of 11.7%. Logistic regression analysis performed on the different insomnia symptoms revealed that somatic and psychiatric health were the strongest predictors of insomnia, whereas gender, age, and socioeconomic status showed a more inconsistent relationship. Use of prescribed hypnotic drugs was reported by 6.9% and was related to being female, elderly, and having somatic and emotional problems. Sleep onset problems and daytime impairment were more common during winter compared to summer. Use of hypnotics was more common in the southern (rather than the northern) regions of Norway. For sleep onset problems a Season x Region interaction was found, indicating that the prevalence of sleep onset problems increased in southern Norway from summer to winter, while the opposite pattern was found in the northern regions. The importance of clinically adequate criteria and seasonal variation in the evaluation of insomnia is briefly discussed.

A radiochemical assay method for carboxylesterase, and comparison of enzyme activity towards the substrates methyl [1-14C] butyrate and 4-nitrophenyl butyrate.

A radiochemical assay for carboxylesterase based on the substrate methyl[1-14C]butyrate is described. The blank value corresponds to 1.04 micrograms (liver)-1.44 mg (plasma) of tissues with the highest and lowest activity respectively, which constitute the sensitivity of the method. The hydrolysis of methyl butyrate and 4-nitrophenyl butyrate by plasma, liver, lung, heart, diaphragm, cerebrum, kidney and duodenum of rat have been compared. The results showed that the two substrates were hydrolysed preferentially by two different groups of the enzyme. The effect of selective esterase inhibitors showed that both groups can be characterized as carboxylesterase, because bis-4-nitrophenyl phosphate inhibits the hydrolysis of both substrates, physostigmine has only a slight effect and EDTA is no inhibitor. The exception is the enzyme in the duodenum which is inhibited by all three inhibitors. The effect of phenobarbital induction and soman treatment on enzyme activity towards the two substrates were similar. Sex difference in the plasma activity towards methyl butyrate, but not 4-nitrophenyl butyrate, indicates that the group of carboxylesterase preferentially hydrolyzing 4-nitrophenyl butyrate may be the most important for the detoxification of soman.

Metabolism of T-2 toxin by blood cell carboxylesterases.

Human and rat blood hydrolysed T-2 toxin along two different pathways giving HT-2 toxin and neosolaniol as primary metabolites, respectively. Neosolaniol represents a metabolic pathway different from that obtained by liver. Rat erythrocytes formed neosolaniol as a primary metabolite whereas white blood cells hydrolysed T-2 toxin to HT-2 toxin. Human erythrocytes formed both HT-2 toxin and neosolaniol whereas all human white cells produced only HT-2 as the primary metabolite. The enzymes responsible for hydrolysis of T-2 toxin to HT-2 toxin in white blood cells and T-2 toxin to neosolaniol in red blood cells were all identified as carboxylesterases by use of specific inhibitors. The ratio between trichothecene hydrolysis and 4-nitrophenyl butyrate hydrolysis varied among the different cell fractions indicating that specific isoenzymes are involved.

Metabolism of T-2 toxin by rat liver carboxylesterase.

The trichothecene T-2 toxin was rapidly hydrolyzed by rat liver microsomal fraction into HT-2 toxin which was the main metabolite. The metabolism was completely blocked by paraoxon, a serine esterase inhibitor, but not affected by EDTA or 4-hydroxy mercury benzoate, inhibitors of arylesterase and esterases containing SH-group in active site, respectively. Among the serine esterases carboxylesterase (EC 3.1.1.1), but not cholinesterase (EC 3.1.1.8) hydrolysed T-2 toxin to HT-2 toxin. Carboxylesterase activity from liver microsomes was separated into at least five different isoenzymes by isoelectric focusing, and only the isoenzyme of pI 5.4 was able to hydrolyse T-2 toxin to HT-2 toxin. The toxicity of T-2 toxin in mice was enhanced by pre-treatment with tri-o-cresyl phosphate (TOCP), a specific carboxylesterase inhibitor. This confirms the importance of carboxylesterase in detoxification of trichothecenes.

Variation in diagnostic strategy of the EMG examination--a multicentre study.

OBJECTIVES: In order to improve the universal quality of the EMG examination, knowledge about the variation among physicians is needed. METHODS: The variation among physicians in diagnostic strategy or criteria for diagnosing was analysed from a multicentre database with 940 EMG examinations sampled by seven physicians from six laboratories in Europe. RESULTS: For the whole group of patients as well as for the subgroup of patients with polyneuropathy, variation among physicians in examination techniques, number of examined structures per patient and number of abnormal structures per patient required for a diagnosis was found. Some of the variation may be explained by use of different techniques, which showed differences in sensitivity, while some of the variation may be due to differences in diagnostic strategy and criteria for diagnosing. CONCLUSIONS: The study indicates a need for development and revision of international guidelines for EMG practice although implementation of standards requires caution.

Variation in the classification of polyneuropathies among European physicians.

OBJECTIVE: Considerable debate still exists regarding the classification of polyneuropathies (PNPs) into predominantly demyelinating, predominantly axonal loss, mixed or unclassified. This study was designed to determine the variation among physicians in the classification of PNPs by using the European Standardized Telematic tool to Evaluate Electromyography knowledge-based systems and Methods (ESTEEM) multicenter database. METHODS: Seven physicians from 6 laboratories in Europe sent a total of 156 prospectively collected cases of PNP with electromyography (EMG) data including diagnosis (examination diagnosis) to the database. Each physician interpreted the electrophysiological data from all cases (interpretation diagnosis) and a final diagnosis was given at the consensus meetings of the group (consensus diagnosis). RESULTS: Comparison of each physician's examination diagnosis with his/her interpretation diagnosis, i.e. intra-physician variation, showed a change towards less classified PNPs (P < 0.05). Interpretation diagnoses showed large inter-physician variation in the classification of PNPs. The consensus group was more cautious than individual physicians in classifying PNPs as mixed and axonal. The probability of the consensus diagnosis increased with increasing number of abnormal motor and sensory segments tested. CONCLUSIONS: Recognition of variation in classification of PNP as shown in this study and suggesting standards of good clinical practice developed by a consensus group may increase the quality of EMG practice.

In vitro effect of phospholipase C from Bacillus cereus on tissue thromboplastin from different species.

Purified phospholipase C from Bacillus cereus caused a significant loss in the procoagulant activity of thromboplastin preparations from man, rabbit, sheep, cow, rat and mouse. However, marked differences were observed with respect to the degree of inactivation. Rat, mouse, bovine and one type of rabbit preparations (prepared from acetone powdered brain) were markedly more sensitive to attack by phospholipase C than were preparations of human, sheep and standard rabbit preparations. The relative amounts of the individual phospholipids in thromboplastin preparations showed only minor variations among the species. The effect of phospholipase C on each of these phospholipids in the various thromboplastin preparations showed some significant differences.

A simple method for determination of the factor VII-phospholipid complex using Normotest.

We report here a highly significant positive correlation observed when the factor VII-phospholipid complex (the phospholipase-C sensitive component of factor VII) in plasma was tested in a specific factor VII system and in Normotest (p less than 0.0001). The Normotest system, which is sensitive to variations in coagulation activity within the normal range, was not influenced by phospholipase C when the enzyme was added immediately before the start of the coagulation assay. Normotest is well suited for determination of the factor VII-phospholipid complex in plasma.