Inadequate management for secondary fracture prevention in patients with distal radius fracture by trauma surgeons.

UNLABELLED: We evaluated the secondary fracture prevention in 1445 patients with distal radius fracture by trauma surgeons. The rate of patients with distal radius fracture who underwent bone mineral density (BMD) examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present. INTRODUCTION: To clarify the status of osteoporosis interventions after distal radial fractures by trauma surgeons who play the main role in treatment for these fractures, we performed a survey involving multiple institutions in Japan. METHODS: We asked 155 board members of the Japanese Society for Fracture Repair for their cooperation and performed a survey in 48 institutions with which members who gave cooperation were affiliated. The subjects consisted of consecutive patients with distal radial fractures occurring between January and December 2012. The presence or absence of a diagnosis of osteoporosis and bone mineral density examination after fracture was investigated. RESULTS: A total of 1445 patients with distal radial fractures were evaluated in this study. BMD examination for diagnosis and treatment for osteoporosis after fracture was performed respectively in 126 (8.7 %) and 193 (13.4 %) of 1445 patients. Treatment for osteoporosis was performed in 93 (73.8 %) of 126 patients who underwent BMD examination after fracture and 100 (8.2 %) of 1219 who did not undergo BMD examination. Of the 126 patients who underwent BMD examination after fracture, 89 showed a BMD <80 % of the young adult mean as a criterion for the initiation of drug treatment for osteoporosis in Japan and 77 (86.5 %) of the 89 patients were treated with drugs. CONCLUSIONS: The rate of patients with distal radial fractures who underwent BMD examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present.

Cross-cultural adaptation and validation of the Oxford 12-item knee score in Japanese.

INTRODUCTION: With the high incidence of knee osteoarthritis (OA) in Japan, there is a strong need not only for surgical therapies, but also for validated outcome measures. For this study, we completed cross-cultural adaptation, testing and validation of the Oxford knee score (OKS) for prospective use in national and international clinical studies involving Japanese patients. MATERIALS AND METHODS: The Japanese version of the OKS was developed according to the standard cross-cultural adaptation guidelines. For validation, the OKS was tested on 54 patients diagnosed with OA, osteonecrosis, ligament or meniscus injury. Reliability was tested using the intraclass correlation coefficient (ICC). Internal consistency or homogeneity was assessed using Cronbach's alpha. The correlation between the Japanese OKS, WOMAC and SF-36 questionnaires was used to assess construct validity. RESULTS: No major difficulties were encountered with the translation and pre-testing stages. For reliability and validity, the Japanese OKS was completed without any missed responses by 53 (98.15%) and 52 (96.30%) patients at the first and second distribution, respectively. The total OKS showed good reliability with an ICC of 0.85. Internal consistency was strong (Cronbach's alpha = 0.90). Strong construct validity (ICC values of 0.51-0.84) was obtained against the WOMAC and SF-36 (physical functioning, role-physical, bodily pain, and social functioning subscales) scores. Notable "ceiling" effects of the OKS were reported for 11 of the 12 questionnaire items. CONCLUSION: The Japanese OKS has proven to be a reliable and valid instrument for the self-assessment of knee pain and function in Japanese speaking patients with knee OA and other knee complaints.

D1 dopamine receptors in prefrontal cortex: involvement in working memory.

The prefrontal cortex is involved in the cognitive process of working memory. Local injections of SCH23390 and SCH39166, selective antagonists of the D1 dopamine receptor, into the prefrontal cortex of rhesus monkeys induced errors and increased latency in performance on an oculomotor task that required memory-guided saccades. The deficit was dose-dependent and sensitive to the duration of the delay period. These D1 antagonists had no effect on performance in a control task requiring visually guided saccades, indicating that sensory and motor functions were unaltered. Thus, D1 dopamine receptors play a selective role in the mnemonic, predictive functions of the primate prefrontal cortex.

Parallel visuospatial and audiospatial working memory processes in the monkey dorsolateral prefrontal cortex.

The dorsolateral area of the prefrontal cortex (PFC) in primates is involved in visuospatial working memory, but the cellular basis of spatial working memory for auditory information is poorly understood. Here we examined dorsolateral PFC neurons using visual and auditory oculomotor delayed-response tasks. We found that the dorsolateral PFC contains two groups of neurons, each showing directional delay-period activity depending on the location of the visual or auditory cue, suggesting that parallel neuronal processes for visual and auditory spatial working memory occur in the dorsolateral PFC.

Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.

Modular activation and suppression of neocortical activity in the monkey revealed by optical imaging.

To examine functional local connections in the primate neocortex, we examined changes in optical signal by intracortical microstimulation (ICMS), using a voltage-sensitive dye (RH795) in frontal and parietal cortical areas of the anesthetized monkey. ICMS increased the optical signal at the stimulated site, followed by increases and decreases in a modular fashion at regions that were from hundreds of micrometres to a few millimetres from the stimulated site. These changes lasted for 100-250 ms after the offset of ICMS. Further, this increase in the optical signal was accompanied by an increase in electrical activity in the neurones. These findings suggest the presence of excitatory and inhibitory modular connections within the neocortical areas. It is likely that some functional 'modules' are activated concurrently by excitatory loops, which suppress the activity of other modules.

The effects of dopamine and its antagonists on directional delay-period activity of prefrontal neurons in monkeys during an oculomotor delayed-response task.

To examine the role of dopamine receptors in the memory field of neurons for visuospatial working memory in the prefrontal cortex (PFC), dopamine and its antagonists (SCH23390 for the D1-antagonist and sulpiride for the D2-antagonist) were applied iontophoretically to neurons of the dorsolateral PFC in monkeys that performed an oculomotor delayed-response task. In this task, the subject made a memory-guided saccade to a remembered target location that had been cued by a visuospatial stimulus (right, up, left, or down; 15 degrees in eccentricity) prior to a 4-s delay period. We focused here on PFC neurons that showed directional delay-period activity; i.e., an increased activity during the delay period, the magnitude of which varied significantly with the target location. Iontophoretic application of SCH23390 (usually 50 nA) decreased or increased the activities of most of these neurons (n=48/62, 77%); most neurons showed a decrease (n=43/62, 69%). For the neurons affected by SCH23390, a directional index of directional delay-period activity was attenuated by SCH23390, whereas the preferred direction was not greatly affected. The decreasing effect of SCH23390 was dose-dependent; the extent of the decrease was less with a lower dose (20-nA current) than with the ordinary dose (50-nA current), although the effect of the lower dose of SCH23390 on delay-period activity was similar in nature to that of the ordinary dose of SCH23390. Furthermore, the application of dopamine itself augmented directional delay-period activity in most of the neurons tested (n=12/16, 75%). Sulpiride did not have any significant effects in most of the neurons tested (n=15/17). These results suggest that the activation of D1-dopamine receptors play a facilitating role in the memory field of PFC neurons for visuospatial working memory processes.

Unmasking of silent "task-related" neuronal activity in the monkey prefrontal cortex by a GABA(A) antagonist.

To examine the role of GABA on prefrontal neuronal activity in the control of behavior, a GABA(A) receptor antagonist, bicuculline methiodite (BMI), was iontophoretically applied to prefrontal neurons while monkeys performed a visual reaction time task. Iontophoretic application of BMI uncovered "task-related" activity of silent neurons (n=40), which did not show any activity during performance of the task. The distribution, by type, of these silent "task-related" neurons differed from that of standard (i.e. active) task-related neurons (N=95), and a particular type of silent "task-related" neuron was found most frequently. These findings suggest that GABA continuously and preferentially suppresses neuronal activity via GABA(A) receptors to limit the population of prefrontal neurons related to behavior, thereby organizing neuronal activities for behavior mediated by the prefrontal cortex.

Laminar distributions of neurons sensitive to acetylcholine, noradrenaline and dopamine in the dorsolateral prefrontal cortex of the monkey.

Sensitivities of neurons to acetylcholine (ACh), noradrenaline (NA) and dopamine (DA) were investigated at different depths of the dorsolateral prefrontal cortex (PFC) in awake or halothane-anesthetized macaque monkeys, using microiontophoretic techniques with multi-barreled electrodes. The laminar locations of tested neurons (n = 403) were estimated by reconstructing electrode tracks based on the microlesion made by passing a current through the recording barrel, which contained a carbon fiber. Iontophoretically applied drugs induced excitatory or inhibitory responses. Neurons excited by ACh (n = 105) were located mainly in layers III and V, and those inhibited by ACh (n = 126) were in layers III and IV. The majority of the NA-sensitive neurons (n = 123) were NA-inhibited neurons (n = 100), and were found most often in layers III and IV. The ratio of DA-sensitive neurons (excited, n = 74; inhibited, n = 63) to tested neurons was higher in the deep layers than in the superficial ones. These results indicate that sensitivities of the PFC neurons to ACh, NA and DA are not uniform between cortical layers, suggesting that each of these substances may predominantly influence the neuronal activity of particular layers of the monkey PFC.

Modulation of neuronal activities by iontophoretically applied catecholamines and acetylcholine in the primate motor cortex during a visual reaction-time task.

Single neuronal activities in the primate motor cortex were modulated by iontophoretically applied acetylcholine (ACh), noradrenaline (NA) or dopamine (DA) while monkeys were performing a visual reaction-time. task. ACh caused general increases of the discharge activities of both the background baseline and the task-related activity peaks, whereas NA caused decreases mainly of the baseline. DA caused activity increases in half of the tested neurons, and decreases in 25% of the neurons. NA modulated the firing rate to enhance the signal-to-noise ratio of the related activities. ACh and DA, by contrast, subserved to enhance the synaptic transmission in the motor cortex.

Dopamine enhances the neuronal activity of spatial short-term memory task in the primate prefrontal cortex.

The influence of dopamine and its antagonists on neuronal activity related to the delay period of a delayed response task was examined in the monkey prefrontal cortex. Iontophoretically applied dopamine enhanced the delay-related neuronal activity, while fluphenazine and haloperidol attenuated the activity. Sulpiride had no effect on the activity. The results suggest that dopamine promotes processing of spatial short-term memory by increasing memory-related activity in the primate prefrontal cortex, probably via D1-type dopamine receptor.

Long-lasting marks of extracellularly recorded sites by carbon fiber glass micropipettes in the frontal cortex of chronic monkeys.

Extracellularly recorded sites were successfully marked by means of carbon fiber-containing glass micropipettes in the frontal cortex of chronically behaving monkeys. A DC current was passed through the tip of the micropipette (typically, anodal, 10 microA, 10 s). The marks were observed as brown spots with sizes of about 100 microns, and lasted for at least 4 months in vivo. Further, during physiological recording sessions, unmarked recording sites along the electrode track could be estimated with 10% error by measuring the distances between the marked sites, or between the marked site and the cortical surface.

Delayed response deficit in monkeys by locally disturbed prefrontal neuronal activity by bicuculline.

Effects of local injection of a gamma-aminobutyric acid antagonist, bicuculline (10-30 micrograms dissolved in saline) in the principal prefrontal cortex on the delayed response task were investigated in two monkeys. On a visual Go signal, the monkeys rotated a handle to the left or to the right (Go period) according to a visual cue (left or right; 1 s) presented 4 s earlier. Bicuculline induced bursting activity at the injected site 1-2 min after the injection and 5 min later the burst activity spread to nearby cortical areas (less than 4 mm diameter). Within 5 min after injection, the monkeys showed errors in Go periods, rotating the handle to the contralateral zone, regardless of the cue side. This tendency continued for 30-40 min and returned to the control level. Electromyographic recordings of forearm muscles did not show any changes. The effect was observed when the drug was injected into a circumscribed area of the bottom of the mid-principalis region. It appears that disturbed neuronal activity in a small group of cortical columns induces performance errors of specific direction of the delayed response.

Dopamine modulates neuronal activities related to motor performance in the monkey prefrontal cortex.

Effects of iontophoretically applied dopamine were investigated in prefrontal neurons of the monkey which showed activity changes during a visual reaction time task. The task consisted of an initial waiting phase (3.0 s), a warning phase (green lamp, 1.5-3.5 s), a lever-release GO phase (red lamp) and a reward phase. The neurons (n = 99) showed their activity changes during the warming (n = 31), GO (n = 43) or reward (n = 25) phase. Among those, dopamine predominantly influenced the GO phase-related activities (39/43) and the activity changes were enhanced by dopamine. Further, fluphenazine attenuated the GO phase-related activity changes. Results suggest that prefrontal dopamine may be involved in modulations of neuronal activities related to motor performance.

Catecholamine sensitivities of motor cortical neurons of the monkey.

The effects of noradrenaline (NA) and dopamine (DA) were examined in 139 neurons of the motor cortex (area 4) of the monkey, using multibarreled micropipettes. Sampled neurons were those spontaneously active and sensitive to iontophoretically applied glutamate (30-50 nA). Iontophoretically applied NA and DA induced excitatory and inhibitory responses in 91 neurons (NA: excitatory, n = 17; inhibitory, n = 53; DA: excitatory, n = 16; inhibitory, n = 37). Cortical depth was determined in 121 neurons tested. Neurons sensitive to NA (excitatory, n = 13; inhibitory, n = 46) were distributed uniformly across the cortical layers, while neurons sensitive to DA (excitatory, n = 14; inhibitory, n = 30) were numerous in layers V and VI. This suggests that NA may influence various neuronal activities, and that DA may predominantly influence neuronal activities of layers V and VI in the monkey motor cortex.

Sudden infant deaths: stress, arousal and SIDS.

The prevalence of the Sudden Infant Death Syndrome (SIDS) has dropped in most countries following the development of education campaigns on the avoidance of preventable risk factors for SIDS. These include factors in the infant's micro environment, such as prenatal passive smoking, administration of sedative drugs, prone sleep, high ambient temperature or sleeping with the face covered. Sleep laboratory studies have shown that these risk conditions contribute to the development of respiratory and autonomic disorders and reduce the child's arousability. The opposite effects were seen when studying factors protective from SIDS, such as breastfeeding or the use of a pacifier. In victims of SIDS, similar breathing, autonomic and arousal characteristics were recorded days or weeks before their death. It is concluded that in some infants, already immature control mechanisms can be aggravated by environmental factors.

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Japanese national SIDS project: 1998-2000 research for the improvement of infant mortality.

The aim of the present study is to see if by conducting research on sudden infant death syndrome (SIDS), one of major contributing factors to infant mortality in Japan, infant mortality can be reduced. Concrete approaches taken in this study took four different directions: elucidation of SIDS etiology, prevention, elucidation of its social aspects (education) and the investigation of administrative aspects. At the same time, an attempt was made to get better grasp on the epidemiological trends in infant mortality, including that of SIDS. The idea behind this etiological approach was to unify hitherto separate approaches taken by those in epidemiological, physiological and pathological fields. A molecular-biological approach was also added. Physiologically hypothesized causes of SIDS--apnea and arousal disorder--together with the epidemiologically presumed risk factor of sleeping position, were examined jointly from a pathological viewpoint. Research in the first 2 years of the grant found that hypoxia reflected by gliosis in the brain stem arousal pathway was related to the duration of sleep apnea. Research in the final year of the grant found the possibility of organic fragility in the brain stem arousal pathway, particularly in periaqueducal gray matter and pedunculopontine nucleus reflected by apoptosis and neuronal plasticity. These findings gave support to the arousal disorder hypothesis in SIDS. Application of the restriction landmark genomic scanning (RLGS) method supported the possibility of locating a site for a SIDS-specific gene. The US collaborative home infant monitoring evaluation (CHIME) currently in use was evaluated. In addition, three new monitoring methods were developed: a non-invasive multi-channel pressure-sensing bed, microwave radar, and a pacifier that functions as a suckometer which can be used to evaluate a neonate's autonomic nervous functions. Social (educational) activities included: surveys of the current state of educational campaigns on SIDS in other countries, epidemiological evaluation of campaigns run by the Japan SIDS families' Association to evaluate the effectiveness of the SIDS campaign, and creation of a home page, mostly to inform the public about the output from this research group. "Guidelines for Death Scene Investigation of Sudden, Unexplained Infant Deaths: Recommendations of Interagency Panel on Sudden Infant Death Syndrome" was translated into japanese. Activities that concerned administrative measures included clarification of the unique nature of SIDS-related trials in Japan when compared to those in the United States. Other concrete administrative proposals were: a pressing need to increase the rate of SIDS-related autopsies to facilitate a better etiological understanding and, for this purpose, establishing regulations in local jurisdictions and amending Article 8 of the Postmortem Examination and Corpse Preservation Act, keeping in perspective the medico-economic evaluation of the japanese medical examiner system. For these proposals to be realized, establishment of a new office in charge of administrative and approved autopsies at the national level of government is desirable. Also pointed out were the different opinions held among specialists concerning the diagnosis of SIDS and their need to hold multiple conferences to unify their views. Basic data for these conferences were provided from epidemiological examinations of infant mortality.

Comparative evaluation of diagnostic guidelines for sudden infant death syndrome (SIDS) in Japan.

It is a well-recognized fact among professionals that the diagnosis of sudden infant death syndrome (SIDS) involves difficult elements; a SIDS diagnosis is not uniform throughout Japan; and such a diagnosis is not made based on any internationally recognized definition. Faced with this situation, guidelines have been prepared and proposals have been made to standardize and improve the accuracy of SIDS diagnoses, viz. the following three can be cited: "guideline for diagnosis of SIDS" prepared by a Study Group of the Ministry of Health and Welfare; "case studies of SIDS" and a "guideline for its diagnosis" prepared by the Case Study Committee of Japan SIDS Research Society; and a "proposal on the principles of medico-legal pathology concerning SIDS", included in the research report supported by a Grant-in-Aid for Scientific Research from the Ministry of Education. In the current study, a comparison was made focusing on the discrepancies among these three documents. The major discrepancies among these three are: (1) handling of the patient's age (by months or years) in the diagnosis of SIDS; (2) dealing with those cases for which no autopsy has been conducted; (3) attitudes concerning whether sleeping in a prone posture is a cause for asphyxia and (4) opinions concerning the aspiration of vomited milk. It is anticipated that these discrepancies will invite confusion and affect judgments and recognition of SIDS-related cases that will be brought to court. It is essential that those involved with these three documents have an opportunity at the earliest time to discuss the matter and come to a uniform understanding.