Pulmonary diffusing capacity to nitric oxide and carbon monoxide during exercise and in the supine position: a test-retest reliability study.

NEW FINDINGS: What is the central question in this study? How reliable is the combined measurement of the pulmonary diffusing capacity to carbon monoxide and nitric oxide (DLCO/NO ) during exercise and in the resting supine position, respectively? What is the main finding and its importance? The DLCO/NO technique is reliable with a very low day-to-day variability both during exercise and in the resting supine position, and may thus provide a useful physiological outcome that reflects the alveolar-capillary reserve in humans. ABSTRACT: DLCO/NO , the combined single-breath measurement of the diffusing capacity to carbon monoxide (DLCO ) and nitric oxide (DLNO ) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar-capillary reserve. In the present study, we investigated the between-day test-retest reliability of DLCO/NO -based metrics. Twenty healthy volunteers (10 males, 10 females; mean age 25 (SD 2) years) were randomized to repeated DLCO/NO measurements during upright rest followed by either exercise (n = 11) or resting in the supine position (n = 9). The measurements were repeated within 7 days. The smallest real difference (SRD), defined as the 95% confidence limit of the standard error of measurement (SEM), the coefficient of variance (CV), and intraclass correlation coefficients were used to assess test-retest reliability. SRD for DLNO was higher during upright rest (5.4 (95% CI: 4.1, 7.5) mmol/(min kPa)) than during exercise (2.7 (95% CI: 2.0, 3.9) mmol/(min kPa)) and in the supine position (3.0 (95% CI: 2.1, 4.8) mmol/(min kPa)). SRD for DLCOc was similar between conditions. CV values for DLNO were slightly lower than for DLCOc both during exercise (1.5 (95% CI: 1.2, 1.7) vs. 3.8 (95% CI: 3.2, 4.3)%) and in the supine position (2.2 (95% CI: 1.8, 2.5) vs. 4.8 (95% CI: 3.8, 5.4)%). DLNO increased by 12.3 (95% CI: 11.1, 13.4) and DLCOc by 3.3 (95% CI: 2.9, 3.7) mmol/(min kPa) from upright rest to exercise. The DLCO/NO technique provides reliable indices of alveolar-capillary reserve, both during exercise and in the supine position.

Impaired motor development in children with familial high risk of schizophrenia or bipolar disorder and the association with psychotic experiences: a 4-year Danish observational follow-up study.

BACKGROUND: Motor abnormalities have clinical relevance as a component of psychotic illness; they are not only a proxy of altered neurodevelopment, but also intimately related to psychotic risk. We aimed to assess motor development and its association with psychotic experiences in children with familial high risk (FHR) of schizophrenia or bipolar disorder compared with controls. METHODS: The Danish High Risk and Resilience Study is a prospective longitudinal cohort study, for which participants were extracted from Danish registers. Children born in Denmark between Sept 1, 2004, and Aug 31, 2009, with no, one, or two parents born in Denmark with schizophrenia or bipolar disorder, could be included in the study. No ethnicity data were collected. Children with no biological parent diagnosed with schizophrenia spectrum disorder or bipolar disorder were matched to children with FHR of schizophrenia (one or two parents with schizophrenia spectrum disorder) on the basis of sex, age, and municipality. Children with FHR of bipolar disorder (one or two parents with bipolar disorder) were included as a non-matched group. We assessed motor function in children with FHR of schizophrenia, children with FHR of bipolar disorder, and children in the control group at approximately age 8 years (baseline; 2013-16) and age 12 years (follow-up; 2017-20) using the Movement Assessment Battery for Children-Second Edition (Movement ABC-2). Psychotic experiences were assessed using the psychosis section of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Raters were masked regarding familial risk status. Motor development from baseline to follow-up in the different groups was assessed using a linear mixed model. Logistic regression examined the relationship between definite motor problems (≤5th percentile on Movement ABC-2) and psychotic experiences. FINDINGS: Between March 1, 2017, and June 30, 2020, we studied 437 children (234 [54%] boys, 203 [46%] girls; mean age 11·99 years [SD 0·26, range 11·08-12·86]). Children with FHR of schizophrenia showed stable motor developmental deficits in manual dexterity (difference in intercept -1·62 [95% CI -2·39 to -0·85], p<0·0001; difference in slope 0·17 [-0·48 to 0·81], p=0·61) and balance (difference in intercept -1·58 [-2·34 to -0·82], p<0·0001; difference in slope 0·32 [-0·34 to 0·99], p=0·34), and a developmental lag in aiming and catching (difference in slope -1·07 [-1·72 to -0·41], p=0·0015; difference in intercept -0·59 [-1·35 to 0·17], p=0·13) compared with controls. Children with FHR of bipolar disorder showed no motor developmental differences on a group basis. Compared with controls, children with FHR of schizophrenia were more likely to have definite motor problems (odds ratio [OR] 2·86 [95% CI 1·60 to 5·11], p=0·0004), as were children with FHR of bipolar disorder (OR 2·45 [1·28 to 4·70], p=0·0068). Children with definite motor problems across all groups were more likely (OR 1·90 [1·12 to 3·21, p=0·017] to have had psychotic experiences than children with no definite motor problems. INTERPRETATION: Clinicians should be aware that motor impairment in childhood can reflect neurodevelopmental vulnerability to psychosis. Our findings contribute to the identification of early risk markers for severe mental illness, both for use by clinicians and for establishing a basis for future primary preventive intervention studies in the premorbid phase. FUNDING: The Independent Research Fund Denmark, the Mental Health Services of the Capital Region of Denmark, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University, the Beatrice Surovell Haskell Fund, the Tryg Foundation, and the Innovation Fund Denmark. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.

OBJECTIVE: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP). METHODS: Thirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted. RESULTS: Thirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide-provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice. INTERPRETATION: Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157-1171.

Reliability of the transcranial Doppler ultrasound-derived mean flow index for assessing dynamic cerebral autoregulation in healthy volunteers.

The transcranial Doppler ultrasound-derived mean flow index (Mxa) is widely used for assessing dynamic cerebral autoregulation (dCA) in different clinical populations. This study aimed at estimating the relative and absolute reliability of Mxa in healthy participants in the supine position and during head-up tilt (HUT). Fourteen healthy participants were examined on two separate occasions during which, mean middle cerebral artery blood flow velocity (MCAv), non-invasive blood pressure, and heart rate were continuously recorded in the supine position and during HUT. Mxa was calculated as the correlation coefficient between mean arterial blood pressure and MCAv using either 3-, 5-, or 10-second averages collected over a 300 second period. Intraclass correlation coefficient (ICC1.1) was calculated to assess relative reliability, while the standard error of measurement (SEM), and limits of agreement (LOA) were used to assess absolute reliability. Mxa-based 3-second averages yielded a similar relative and absolute reliability in both positions. When Mxa was calculated from 5-second averages, the most reliable values were obtained during HUT. The poorest reliability was achieved using 10-second averages, regardless of posture. The Mxa shows fair reliability with acceptable LOA in healthy volunteers when based on 3-second averages, both in the supine position and during HUT.

Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers.

Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (KATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits KATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated.In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and KATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of KATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of KATP channel activation during hypoxia and ischemia-induced brain injury.

Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects.

INTRODUCTION: Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans. METHODS: To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms. RESULTS: Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms. CONCLUSION: These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons.

PPARG Pro12Ala Ala carriers exhibit greater improvements in peripheral insulin sensitivity in response to 12 weeks of aerobic exercise training.

The Ala allele of PPARG Pro12Ala ( rs1801282 ) is associated with greater improvements to the glucose metabolism in exercise studies, but whether this extends to peripheral insulin sensitivity is unknown. Our objective was to investigate the effect of PPARG Pro12Ala on exercise-induced changes in peripheral insulin sensitivity. A total of 124 (91 Pro homozygotes and 33 Ala carriers) previously physically inactive healthy young men and women with overweight or class 1 obesity who completed a 12 wk aerobic exercise intervention were included in the analysis. All participants underwent a hyperinsulinemic euglycemic clamp before and after the 12 wk intervention. The prescribed exercise frequency was 5-7 days/wk, and the exercise energy expenditure was 2,100 4,200 kcal/wk for men and 1,600 kcal/wk for women. Insulin sensitivity improved significantly in both genotype groups. However, Ala carriers had a 1.13-fold (95% confidence interval 1.01; 1.26, P = 0.032) greater improvement in insulin sensitivity from baseline compared with Pro homozygotes. Our data support that PPARG Pro12Ala modifies the effect of aerobic exercise on peripheral insulin sensitivity.

Sustained Attention and Interference Control Among 7-Year-Old Children With a Familial High Risk of Schizophrenia or Bipolar Disorder-A Nationwide Observational Cohort Study.

BACKGROUND: Given the partially shared genetic liability between schizophrenia and bipolar disorder, we aimed to assess whether 7-year-old children with a familial high risk of schizophrenia or bipolar disorder display specific deficits of sustained attention and interference control compared with each other and with control children. METHODS: An observational cohort was identified through Danish registries and consisted of 522 children 7 years of age with no, one, or two parents with a diagnosis of schizophrenia or bipolar disorder. Control subjects were matched based on age, sex, and municipality. Sustained attention and interference control were assessed using Conners' Continuous Performance Test II and a modified Eriksen flanker task. Assessors were blinded to group membership of participants. The effect of higher genetic loading was not considered in the statistical models owing to low numbers. RESULTS: At 7 years of age, children with a familial high risk of schizophrenia displayed deficits of sustained attention and subtle deficits in interference control compared with control children and children with a familial high risk of bipolar disorder. Children with a familial high risk of bipolar disorder displayed similar abilities of sustained attention and interference control as control children except in terms of a lower accuracy. CONCLUSIONS: Our findings suggest distinct neurodevelopmental characteristics in middle childhood of sustained attention and interference control for children of parents with schizophrenia or bipolar disorder.

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. OBJECTIVE: The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. RESULTS: The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. CONCLUSIONS: With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x).

Trends in socioeconomic inequalities in oral health among 15-year-old Danish adolescents during 1995-2013: A nationwide, register-based, repeated cross-sectional study.

BACKGROUND: Scandinavian welfare states, despite having better population oral health than less egalitarian societies, are characterized by ubiquitous social gradients and large relative socioeconomic inequalities in oral health. However, trends in these inequalities among Scandinavian children and adolescents have not been studied in detail. OBJECTIVES: To describe the associations between socioeconomic position (SEP) and oral health in adolescents and to investigate the trends in these associations between 1995 and 2013. METHODS: Nationwide repeated cross-sectional studies (using individual-level data) were conducted on 15-year-olds in Denmark from 1995, 2003, and 2013 (N=154,750). Dental data were obtained from the national dental register of the Danish Health Authority (Sundhedsstyrelsens Centrale Odontologiske Register [SCOR]) and data on social variables from administrative registers at Statistics Denmark. SEP measures included previous year's parental education (highest attained educational level by either of the parents), income (equivalized household disposable income), and occupational social class (highest recorded occupational class between the parents). Covariates were immigration status, country of origin, number of children and persons in the family, and household type. The outcome was dental caries experience, represented by the decayed, missing, and filled surfaces (DMFS) index. Negative binomial regression models were used to examine the association between DMFS count and each of the explanatory variables separately while accounting for cluster-correlated family data. Furthermore, hierarchical multiple regressions of DMFS on SEP indicators-using the zero-inflated negative binomial (ZINB) distribution as the outcome distribution-were estimated while successively adjusting for the potential effects of the included covariates. RESULTS: Caries prevalence declined from 71% in 1995 to 63% in 2003 and 45% in 2013. Separate assessment of each covariate showed statistically significant graded associations between each covariate and DMFS count at all time points. Similarly, in the ZINB models, in all 3 years, clear gradients were observed in terms of caries differentials in all three SEP categories, with statistically significant associations (Type 3 P values, <.0001) even after adjustment for all other covariates. For instance, in 2013, even among adolescents with positive caries experience, being of lower occupational social class was associated with up to 2.4-fold (95% confidence interval [CI]: 2.2-2.6) higher caries experience. Between 1995 and 2013, relative inequalities increased in all SEP categories, while absolute inequalities decreased in the education and occupation categories. CONCLUSION: Considerable progress has been made in reducing dental caries rates among Danish adolescents; however, this progress has benefited the disadvantaged social groups less than the better-off groups.

Aggression in Psychiatric Wards: Effect of the Use of a Structured Risk Assessment.

Health care workers are often exposed to violence and aggression in psychiatric settings. Short-term risk assessments, such as the Brøset Violence Checklist (BVC), are strong predictors of such aggression and may enable staff to take preventive measures against aggression. This study evaluated whether the routine use of the BVC could reduce the frequency of patient aggression. We conducted a study with a semi-random regression discontinuity design in 15 psychiatric wards. Baseline aggression risk was assessed using the Aggression Observation Short Form (AOS) over three months. The BVC was implemented in seven intervention wards, and the risk of aggressive incidents over three months of follow-up was compared with the risk in eight control wards. The analysis was conducted at the ward level because each ward was allocated to the intervention and control groups. At baseline, the risk of aggression varied between wards, from one aggressive incident per patient per 1,000 shifts to 147 aggressive incidents per patient per 1,000 shifts. The regression discontinuity analysis found a 45% reduction in the risk of aggression (Odds Ratio (OR) = 0.55, 95% confidence interval: 0.21-1.43). The study did not find a significant reduction in the risk of aggression after implementing a systematic short-term risk assessment with the BVC. Although our findings suggest that use of the BVC may reduce the risk of aggression, the results need to be confirmed in studies with more statistical power.

Sensitivity and specificity of the Brøset Violence Checklist as predictor of violence in forensic psychiatry.

BACKGROUND: Violence and aggressive behavior within psychiatric facilities are serious work environment problems, which have negative consequences for both patients and staff. It is therefore of great importance to reduce both the number and the severity of these violent incidents to improve quality of care. AIMS: To evaluate the specificity and sensitivity of the Brøset Violence Checklist (BVC) as a predictor of violent incidents for Danish forensic psychiatry patients. METHOD: A total of 156 patients were assessed three times daily with the BVC for 24 months. All aggressive or violent incidents were recorded using the Staff Observation Aggression Scale-Revised (SOAS-R). SOAS-R scores of 9 or more defined violent incidents. Data were analyzed using standard logistic regression models as well as models incorporating a random person effect. We used receiver operating curve (ROC) analysis to evaluate different BVC thresholds. RESULTS: Of a total of 139,579 BVC registrations we found 1999 scores above 0 and 419 violent incidents. The BVC score was a strong predictor of violence. For the standard cut-off point of 3, specificity was 0.997 and sensitivity was 0.656. For the general risk of violence seen in this study, the risk of violence given a BVC score > 3 (positive predictive value) was 37.2%, and the risk of violence given a BVC score < 3 (negative predictive value) was 0.1%. CONCLUSION: The BVC showed satisfactory specificity and sensitivity as a predictor of the short-term risk of violence against staff and others by patients in a forensic setting.

Headache in children: effectiveness of multidisciplinary treatment in a tertiary paediatric headache clinic.

AIM: The aim of this article is to evaluate the effectiveness of a specific multidisciplinary treatment programme for children with headache and to describe the concept and settings of the Children's Headache Clinic in Denmark. METHOD: All new patients were included and evaluations were conducted after six and 12 months. Pharmacological and non-pharmacological treatments were offered by a team of specialists (physicians, headache nurses, a physiotherapist and a psychologist). PATIENTS: The subjects comprised 169 children (mean age 11.7 (range 4-17), 91 females, 78 males), 39% of whom suffered from chronic headache (≥15 days/month). All children were diagnosed according to the International Classification of Headache Disorders, second edition; 20% had migraine, 34% tension-type headache, 27% mixed headache, 4% medication-overuse headache, and 15% were diagnosed with other types of headaches. RESULTS: Fifty per cent of the children had an improvement in headache frequency above 50% at six months. By the use of repeated measurement analysis, we found a significant decrease in headache frequency in all of the six headache groups, whereas the increase in quality of life (PedsQL™ 4.0) was significant for the group as a whole. CONCLUSION: Though preliminary, the results show a good outcome for multidisciplinary treatment programmes for children who suffer from frequent or chronic headache.

Home-based cardiac rehabilitation is as effective as centre-based cardiac rehabilitation among elderly with coronary heart disease: results from a randomised clinical trial.

BACKGROUND: participation in centre-based cardiac rehabilitation (CR) is known to reduce morbidity and mortality but participation rates among the elderly are low. Establishing alternative programmes is important, and home-based CR is the predominant alternative. However, no studies have investigated the effect of home-based CR among a group of elderly patients with coronary heart disease with a long-term follow-up. METHODS: randomised clinical trial comparing home-based CR with comprehensive centre-based CR among patients ≥ 65 years with coronary heart disease. RESULTS: seventy-five patients participated. There were no significant differences in exercise capacity after the intervention between home and centre-based CR. Adjusted mean differences of peak VO2 = 0.9 ml/kg/min (95% CI -0.7, 2.4) and of 6 min walk test = -18.7 m (95% CI -56.4, 18.9). In addition, no differences were found in the secondary outcomes of systolic blood pressure (-0.6 mmHg, 95% CI -11.3, 10.0), LDL cholesterol (0.3 mmol/l, 95% CI -0.04, 0.7), HDL cholesterol (0.2 mmol/l, 95% CI -0.01, 0.3), body composition, proportion of smokers and health-related quality of life. A group of patients who did not have an effect of either programmes were characterised by higher age, living alone and having COPD. At 12 months of follow-up, both groups had a significant decline in exercise capacity. CONCLUSIONS: home-based CR is as effective as centre-based CR in improving exercise capacity, risk factor control and health-related quality of life. However, a group of patients did not improve regardless of the type of intervention. Continued follow-up is essential in order to maintain the gained improvements.

Is the performance of acceleromyography improved with preload and normalization? A comparison with mechanomyography.

BACKGROUND: Many studies have indicated that acceleromyography and mechanomyography cannot be used interchangeably. To improve the agreement between the two methods, it has been suggested to use a preload and to refer all train-of-four (TOF) ratios to the control TOF (normalization) when using acceleromyography. The first purpose of this study was to test whether a preload applied to acceleromyography would increase the precision and the agreement with mechanomyography. The second purpose was to evaluate whether normalization would improve the agreement with mechanomyography. METHODS: Sixty patients were randomized to acceleromyography with or without a preload (Hand Adapter; Organon, Oss, the Netherlands). On the contralateral arm, mechanomyography was used. Anesthesia was induced with propofol and an opioid, and neuromuscular block with 0.6 mg/kg rocuronium. The precision and the bias and limits of agreement (with or without normalization) between the methods were evaluated using TOF stimulation. RESULTS: Preload improved the precision of acceleromyography by 21%, but it also increased the mean control TOF ratio from 1.07 to 1.13. Normalization of the acceleromyographic TOF ratios diminished the bias to mechanomyography during recovery (e.g., from 0.15 to 0.05 at TOF 0.90); when the mechanomyographic TOF values were normalized as well, the bias was eliminated. However, normalization did not exclude wide individual differences between acceleromyography and mechanomyography (+/- 0.10-0.20 at TOF 0.90). CONCLUSION: Preload increases the precision of acceleromyography, and normalization of the TOF ratios decreases bias in relation to mechanomyography. When both acceleromyography and mechanomyography are normalized, there is no significant bias between the two methods.

Can persistence of primary molars be predicted in subjects with multiple tooth agenesis?

The purpose of this research was to create a method for predicting the persistence of primary molars in patients with multiple agenesis. Dental pantomographs (DPTs) from 51 males with agenesis of 5-17 teeth and 54 females with agenesis of 5-21 teeth were investigated. All patients (6 years 9 months to 16 years 7 months) had agenesis of one or both lower second premolars. Patients with ectodermal dysplasia and craniofacial anomalies were not included. The DPTs were classified into two groups according to tooth morphology and agenesis pattern. Group--I-ectodermal symptoms: screwdriver-shaped maxillary central incisors, invaginations in incisors or narrow incisors, taurodontic molar roots, and atypical agenesis. At least two of these ectodermal symptoms had to be present for classification into group I. Group II: one or none of the criteria for group I. Each group was subdivided according to the number of missing teeth. The degree of root resorption of the lower second primary molar was analysed and converted to a metric scale for statistical analysis. Ectodermal status (group I versus group II) was analysed as a binary outcome with agenesis and gender as covariates (logistic regression), whereas ordinary multiple regression was performed in order to study the dependency of root resorption score on gender, ectodermal status, and age. The study showed that subjects with agenesis of more than seven teeth belonged more often to group I than group II, also when correcting for age differences. Root resorption of the primary molars was more severe in group I than in group II.

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble [(3,5,5-trimethylhexanoyl)ferrocene].

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month-old rats following supplementation with the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of alpha- and gamma-tocopherols and glutathione (GSH) were also higher. In contrast, the brain displayed unaltered levels of the tocopherols and GSH. Malondialdehyde (MDA) level was also higher in the cerebrospinal fluid (CSF) and the liver but not in the brain. In old rats, the absence of an increase in iron concentration in the brain was reflected by unaltered concentrations of GSH, tocopherols, and MDA as compared to that in untreated rats. In the aging liver, concentrations of GSH and MDA increased with TMHF treatment. Morphological studies revealed unaltered levels of iron, ferritin, heme oxygenase-1 (HO-1), nitrotyrosine (NT), or MDA in the brains of both young and old rats treated with TMHF. In contrast, TMHF treatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.

Effect of teaching and type of stethoscope on cardiac auscultatory performance.

BACKGROUND: Auscultation of the heart is a routine procedure. It is not known whether auscultatory skills can be improved by teaching or with the use of an advanced stethoscope. METHODS: This study was a randomized trial with a 2 x 2 factorial design. Seventy-two house officers were randomized to a simple or an advanced stethoscope and to a 4-hour course in auscultation or no course. The doctors auscultated 20 patients' hearts and categorized findings as normal or as one or more of 5 categories of heart diseases. Patients were selected such that 16 had a known heart disease as well as a corresponding murmur and 4 had no heart disease or murmur. Auscultatory performance was assessed as concordance with echocardiographic findings and interobserver variation. RESULTS: Doctors using the advanced stethoscope diagnosed 35% of the patients correctly, as compared with doctors using the simple stethoscope who did 33% of the patients (P = .27). Similarly, 34% of the patients were diagnosed correctly by doctors who had received teaching as compared with 33% of those who were by doctors who had received no teaching (P = .41). The kappa values were higher for doctors who had received teaching for aortic stenosis (0.43 vs 0.28, P = .004) and ventricular septum defect (0.07 vs 0.01, P = .003). There was no difference between groups for any other single murmur or for the detection of murmurs as such. CONCLUSION: Heart auscultation findings were in poor accordance with echocardiographic findings and had high interobserver variation. Neither outcome improved to any important extent with the subjects' use of an advanced stethoscope or attending of a course in heart auscultation.

Cross-sectional study of the length of the nasal bone in cleft lip and palate subjects.

OBJECTIVE: The purpose of this study was to analyze the human nasal bone length in newborns and male adults with cleft lip (CL), cleft palate (CP), and unilateral cleft lip and palate (UCLP) and to compare the results to previous findings in prenatal material. DESIGN: This study was a radiographic profile cephalometric cross-sectional analysis. SUBJECTS AND METHODS: Profile radiographs from 60 newborns with a male-to-female ratio of 1:1 in each group (20 CL, 20 CP, and 20 UCLP) and 60 male adults (20 CL, 20 CP, and 20 UCLP) were randomly selected among radiographs, taken for optimizing the treatment planning. The nasal bone lengths (n-na) were measured with a digital caliper on the profile radiographs. To compare the nasal bone lengths in the different cleft groups, Student's t tests at a significant level at 5% were performed. RESULTS: Nasal bone length was significantly shorter in male adult patients with CL compared with patients with CP. Furthermore, the nasal bone length was significantly shorter in newborns with CL (2 months) compared to newborns with UCLP (2 months). A borderline significance was seen in the comparison of patients with CL and UCLP in male adults. There was no significant difference in the nasal bone length between the patients with CP and UCLP, in either the newborns or the male adults. CONCLUSIONS: Nasal bone length was significantly shorter in subjects with CL compared with subjects in whom the palate was clefted. The results show that the clefted lip in CL is associated with a subjacent skeletal deviation in the upper midface.