Time-varying living arrangements and suicide death in the general population sample: 14-year causal survival analysis via pooled logistic regression.

AIMS: While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches. METHODS: Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation. RESULTS: A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3-2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83-7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2-10.5%; RR: 1.56, 95% CI: 1.38-1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2-11.3%; RR: 1.60, 95% CI: 1.42-1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses. CONCLUSIONS: Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

Panel of novel urine biomarkers for incident microalbuminuria in people with type 2 diabetes mellitus.

AIM: The need to identify novel biomarkers for early diagnosis and treatment of diabetic nephropathy is widely recognized. However, only a few studies have investigated the association between biomarkers and the onset of albuminuria. In this study, we aimed to investigate a panel of biomarkers suitable for predicting microalbuminuria. METHODS: Some 346 Japanese people with type 2 diabetes exhibiting normoalbuminuria were studied. The endpoint was defined as the onset of microalbuminuria. Thirty biomarkers were selected from among urinary biomarkers described in previous studies. A panel of biomarkers was selected using least absolute shrinkage and selection operator (LASSO). The prognostic performance of the developed panel was evaluated. RESULTS: During a mean follow-up of 6.2 years, 45 people progressed to microalbuminuria. A composite panel of six biomarkers (monocyte chemoattractant protein-1, osteopontin, soluble human tumour necrosis factor receptor-1, tenascin C, vascular endothelial growth factor-A and kidney injury molecule-1) was developed using LASSO. Compared with the basal model comprising estimated GFR and urinary albumin-to-creatinine ratio, addition of these six biomarkers significantly increased the overall C index from 0.773 to 0.824 (P = 0.019). Net reclassification improvement and integrated discrimination improvement were estimated to be 0.412 (P = 0.049) and 0.040 (P = 0.040), respectively. Decision curve analysis also showed that the model with the six novel biomarkers had a better prognostic value for predicting the onset of microalbuminuria. The optimism was moderate or negligible according to measures. CONCLUSIONS: The panel consisting of six novel urinary biomarkers effectively predicted incident microalbuminuria in people with type 2 diabetes.

Spatial and Temporal Brain Responses to Noxious Heat Thermal Stimuli in Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is an idiopathic orofacial pain condition. Although the pathophysiology of BMS is not clearly understood, central and peripheral neuropathic mechanisms are thought to be involved. The authors compared brain response to noxious heat stimuli in 16 right-handed women with primary BMS and 15 sex- and age-matched right-handed healthy female controls. A thermal stimulus sequence of 32 °C to 40 °C to 32 °C to 49 °C was repeated 4 times in a cycle. Warm and noxious heat stimuli were delivered with a Peltier thermode placed on the right palm or right lower lip for 32 s each in a session. Functional magnetic resonance imaging data were obtained by recording echoplanar images with a block design. Statistical Parametric Mapping 8 software was used to analyze the data. Patients and controls both reported feeling more pain during palm stimulation than during lip stimulation. Repetition of noxious heat stimulus on the lower lip but not on the palm induced habituation in brain activity in the cingulate cortex without reduction in pain perception. Multiple regression analysis revealed a correlation between perceived pain intensity and suppression of brain activity in the anterior cingulate cortex when the repeated thermal sequence was applied at the lower lip. Furthermore, the response of the parahippocampal area differed in BMS patients and controls when the same repeated thermal sequence was applied at the palm. The authors' findings indicate that BMS patients show specific brain responses due to impaired function of the central and peripheral nervous systems (clinical trial registration: UMIN000015002).

Movement and afferent representations in human motor areas: a simultaneous neuroimaging and transcranial magnetic/peripheral nerve-stimulation study.

Neuroimaging combined with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) is an emerging technique that can examine motor-system functionality through evoked activity. However, because sensory afferents from twitching muscles are widely represented in motor areas the amount of evoked activity directly resulting from TMS remains unclear. We delivered suprathreshold TMS to left M1 or gave electrical right median nerve stimulation (MNS) in 18 healthy volunteers while simultaneously conducting functional magnetic resonance imaging and monitoring with electromyography (EMG). We examined in detail the localization of TMS-, muscle afferent- and superficial afferent-induced activity in M1 subdivisions. Muscle afferent- and TMS-evoked activity occurred mainly in rostral M1, while superficial afferents generated a slightly different activation distribution. In 12 participants who yielded quantifiable EMG, differences in brain activity ascribed to differences in movement-size were adjusted using integrated information from the EMGs. Sensory components only explained 10-20% of the suprathreshold TMS-induced activity, indicating that locally and remotely evoked activity in motor areas mostly resulted from the recruitment of neural and synaptic activity. The present study appears to justify the use of fMRI combined with suprathreshold TMS to M1 for evoked motor network imaging.

Time course and spatial distribution of fMRI signal changes during single-pulse transcranial magnetic stimulation to the primary motor cortex.

Simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) may advance the understanding of neurophysiological mechanisms of TMS. However, it remains unclear if TMS induces fMRI signal changes consistent with the standard hemodynamic response function (HRF) in both local and remote regions. To address this issue, we delivered single-pulse TMS to the left M1 during simultaneous recoding of electromyography and time-resolved fMRI in 36 healthy participants. First, we examined the time-course of fMRI signals during supra- and subthreshold single-pulse TMS in comparison with those during voluntary right hand movement and electrical stimulation to the right median nerve (MNS). All conditions yielded comparable time-courses of fMRI signals, showing that HRF would generally provide reasonable estimates for TMS-evoked activity in the motor areas. However, a clear undershoot following the signal peak was observed only during subthreshold TMS in the left M1, suggesting a small but meaningful difference between the locally and remotely TMS-evoked activities. Second, we compared the spatial distribution of activity across the conditions. Suprathreshold TMS-evoked activity overlapped not only with voluntary movement-related activity but also partially with MNS-induced activity, yielding overlapped areas of activity around the stimulated M1. The present study has provided the first experimental evidence that motor area activity during suprathreshold TMS likely includes activity for processing of muscle afferents. A method should be developed to control the effects of muscle afferents for fair interpretation of TMS-induced motor area activity during suprathreshold TMS to M1.

Role of 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography in the management of bone and soft-tissue metastases.

We retrospectively reviewed 71 histopathologically-confirmed bone and soft-tissue metastases of unknown origin at presentation. In order to identify the site of the primary tumour all 71 cases were examined with conventional procedures, including CT, serum tumour markers, a plain radiograph, ultrasound examination and endoscopic examinations, and 24 of the 71 cases underwent 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography (FDG-PET). This detected multiple bone metastases in nine patients and the primary site in 12 of the 24 cases; conventional studies revealed 16 primary tumours. There was no significant difference in sensitivity between FDG-PET and conventional studies. The mean maximal standardised uptake value of the metastatic tumours was significantly higher than that of the primary tumours, which is likely to explain why FDG-PET did not provide better results. It was not superior to conventional procedures in the search for the primary site of bone and soft-tissue metastases; however, it seemed to be useful in the staging of malignancy.

Cytokine synthesis by chondroblastoma: relation to local inflammation.

PURPOSE: To investigate cytokine production by chondroblastoma in inducing local inflammation and adjacent-joint arthritis. METHODS: Immunohistochemical analyses of curetted tissues using anti-human interleukin (IL)-1 beta, IL- 6, IL-8, and tumour necrosis factor (TNF)-alpha were performed for 6 patients with chondroblastoma and 3 patients with giant cell tumour (GCT) of bone. In addition, prostaglandin E2, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-alpha in the cyst fluid of one of the patients with chondroblastoma and 2 with GCT of bone were measured using immunoassay kits. RESULTS: More positive staining for IL-1 beta, IL-8, IL- 6, and TNF-alpha was shown in chondroblastoma than GCT of bone samples. Osteoclast-like giant cells in chondroblastomas showed positive staining for IL- 6 only. In addition, concentrations of IL-4, IL-6, and IL-8 in the cyst fluid were higher in the one patient with chondroblastoma than the 2 patients with GCT of bone. CONCLUSION: Cytokines such as IL-1 beta, IL-8, TNF-alpha, and particularly IL-6 play an important role in local inflammation in patients with chondroblastoma.

Changes in biochemical parameters after anterior cruciate ligament injury.

We studied the biochemical characteristics of human knees with deficient anterior cruciate ligaments (ACL) and analysed their relationship to the time after ligamentous injury. Thirty-two patients with isolated ACL-injured knees and six healthy volunteers were enrolled. Synovial fluid samples were centrifuged after aspiration during arthroscopic examination, and aliquots of supernatant were frozen and stored at -80 degrees C. The samples were analysed for interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-6, matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 using commercially available sandwich enzyme-linked immunosorbent assay. In fluid from ACL-injured knees, the average concentrations of IL-6, MMP-3 and TIMP-1 were highly elevated in comparison with normal controls. There was a statistically significant correlation between the concentrations of MMP-3 and IL-6. The IL-6 and TIMP-1 concentrations were interrelated. The concentration of MMP-3 remained high, independent of the duration since the injury, whereas the TIMP-1 and IL-6 levels decreased. The results suggest that the timing of the treatment of an ACL-injured knee might be of importance.

Osteoid osteoma treated with computed tomography-guided percutaneous radiofrequency ablation: a case series.

The nidi of osteoid osteoma are small and difficult to identify precisely; this can necessitate substantial resection of the surrounding normal bone. We applied percutaneous, image-guided radiofrequency ablation to treat 5 patients with osteoid osteoma. The precise location of each nidus was determined using a 3-mm-thick spiral computed tomographic scan. The most appropriate needle pathway was selected to avoid major neural and vascular structures. A 14-gauge core needle was introduced into the nidus and then exchanged for a 17-gauge straight rigid electrode with a 1-cm exposed tip to heat the lesion to 90 degrees centigrade for 5 minutes. Four of the 5 patients were discharged on the day after surgery without any external supports, and were pain-free after a few days. The remaining patient had a pes equinus contracture induced by the penetration of the calf muscles through a posterior approach but was fully recovered 6 days later. The mean follow-up period was 20.6 months. No recurrences or late complications were observed in this series. This case series shows that the computed tomography-guided percutaneous radiofrequency ablation is a simple, minimally invasive, and highly effective technique for the treatment of osteoid osteoma.

Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.

Sites and modes of action of proctolin and the FLP F2 on lobster cardiac muscle.

At the threshold concentration (1-10 pmol l(-1)), the neuropeptide hormones proctolin (PR) and the FLRFamide-like peptide (FLP) F(2) cause an increase in amplitude of electrically evoked contractions (each contraction is a brief tetanus) of lobster heart ostial muscle. At higher concentrations each peptide also induces an increase in tonus (contracture). The PR-induced contracture and augmentation of tetani are proportional to increases in [Ca2+]i. The rate of onset and recovery of peptide-induced effects on both tetani and contracture appeared to reduced by Ca2+ storage by the sarcoplasmic reticulum (SR). Enhanced tetani following a contracture may be due to enhanced voltage-gated Ca2+ current and sarcoplasmic reticular (SR) Ca2+ loading. The SR Ca2+ loading appears to be specific for PR and F2, since glutamic-acid-induced contractures are not followed by increased tetani. The prolonged elevation of [Ca2+]i during contracture causes a right-ward shift in the force-pCa curve indicating a decrease in myofibrillar sensitivity to Ca2+. Blocking voltage-gated Ca2+ channels with Cd2+, nifedipine or verapamil, while reducing tetani, does not prevent peptide-induced contracture and enhanced tetani. Opening SR Ca2+ channels and depleting SR Ca2+ with either caffeine or ryanodine blocked tetani but permitted accelerated peptide-induced contractures. We conclude that PR and F2 at low concentration enhance voltage-dependent Ca2+ induced Ca2+ release from the SR, while higher hormone levels directly gate Ca2+ entry across the sarcolemma.

The steady-state force-Ca2+ relationship in intact lobster (Homarus americanus) cardiac muscle.

The heart of the decapod crustacean is activated by regular impulse bursts from the cardiac ganglion. The cardiac pump function depends on ganglionic burst frequency, burst duration, and burst impulse frequency. Here, we activated isolated lobster cardiac ostial muscle (Orbicularis ostii muscle, OOM) by stimulus trains in vitro in order to characterize the response of the contractile apparatus to [Ca2+]i. We employed stimulus trains that generate a steady state between the [Ca2+]i and force in order to estimate the Ca2+ sensitivity of myofilaments. Force and [Ca2+]i transients were simultaneously recorded using a silicon strain gauge and the fluorescence of iontophoretically microinjected fura-2 salt. We examined the effects of tetanus duration (TD), the interval between trains, and 6 microM cyclopiazonic acid, an inhibitor of the SR Ca2+ pump, on the steady-state force-[Ca2+]i relationship. The instantaneous force-[Ca2+]i relationships appeared sigmoidal (EC50 and Hill coefficient, 98.8+/-32.7 nM and 2.47+/-0.20, mean +/- SD, respectively), as did the curves superimposed after 500 ms following the start of stimulation, indicating that the force-[Ca2+]i relationship had reached a steady state at that time. Also, the maximum activated force (Fmax) was estimated using the steady-state force-[Ca2+]i relationship. Prolonged stimulus trains, decreasing the interval between recurrent trains from 5 to 2.5 s, and cyclopiazonic acid each increased the measured EC50 without changing Fmax. The EC50 correlated strongly with averaged [Ca2+]i over time. We conclude that the steady-state force-[Ca2+]i relationships in the OOM indicate cooperation between force generation and Ca2+ binding by the myofilaments. Our data also suggest the existence of a novel Ca2+-dependent mechanism which reduces Ca2+ sensitivity and accelerates relaxation of lobster cardiac muscle myofilaments.

Effects of YM529, a novel minodronic acid, on adjuvant arthritis in rats.

OBJECTIVE: The effects of a new third-generation bisphosphonate, YM529, on both the development and treatment of adjuvant arthritis were investigated in rats. METHODS: Five-week-old Lewis rats with adjuvant arthritis were prophylactically and therapeutically treated with 0.001, 0.01 and 0.05 mg/kg/day of YM529 and the arthritis scores were measured. Soft X-ray and histological finding were compared to those of the control group. Body weights were also measured. RESULTS: YM529 suppressed the severity of adjuvant arthritis in a dose-dependent manner when used as either a prophylactic or therapeutic drug. Administration of the drug had little effect on body weight. CONCLUSION: YM529 may act on arthritic joints locally to prevent inflammation. However, further experiments are necessary to elucidate the underlying mechanisms.

Investigation of color motion using MEG and binocular rivalry stimuli.

Previous psychophysical studies have reported a few hundred millisecond difference in the reaction time (RT) to luminance versus color motion in low speed condition. Electroencephalogram (EEG) studies have reported a small difference between initial responses to luminance and color motion, but a big difference comparable to that reported in psychophysical studies has not been observed. The present study aimed to investigate late responses in low speed condition in order to clarify the difference of RTs between luminance and color motion. In general, measurement of the late responses is difficult because the late responses are weaker than the initial responses. A previous EEG study of binocular rivalry has reported that binocular rivalry stimuli amplify late responses. Therefore, we used binocular rivalry stimuli to measure late responses. Visual evoked fields were recorded with a whole-head MEG system. A rivalry-related field (RRF) was obtained from the subtraction between the rivalry and a control condition. The RRF was measured between 400 to 550 ms after the stimulus onset for each motion. Results of source localizations of RRFs had similar positions for both the luminance and the color motion. No statistically significant difference between the latencies of the two RRFs was found.

FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses.

OBJECTIVE: To evaluate the standardized uptake value (SUV) of [(18)F]2-deoxy-2-fluoro- d-glucose at positron emission tomography (FDG-PET) for preoperative differential diagnosis between benign and malignant soft tissue masses. DESIGN: One hundred and fourteen soft tissue masses (80 benign, 34 malignant) were examined by FDG-PET prior to tissue diagnosis. The SUVs were calculated and compared between benign and malignant lesions and among different histologic subgroups which included three or more cases. RESULTS: There was a statistically significant difference in SUV between benign (1.80+/-1.42 [SD]) and malignant (4.20+/-3.16) soft tissue masses in total (P<0.0001). However, a considerable overlap in SUV was observed between many benign and malignant lesions. Liposarcomas (2.16+/-1.72) and synovial sarcomas (1.60+/-0.43) did not show significantly higher SUV than any benign lesions. Metastases (4.23+/-2.35) showed no statistically significant difference in SUV as compared with schwannomas (1.75+/-0.84), desmoids (2.77+/-1.32), sarcoidosis (3.62+/-1.53), or giant cell tumors of tendon sheath (GCT of TS; 5.06+/-1.63). Even malignant fibrous histiocytomas (5.37+/-1.40) could not be differentiated from sarcoidosis or GCT of TS, based on the SUV. CONCLUSIONS: A large accumulation of FDG can be observed in both benign and malignant histiocytic, fibroblastic, or neurogenic lesions. SUV at conventional FDG-PET is limited to differentiating benign from malignant soft tissue masses, when all kinds of histologic subtypes are included.

Simultaneous voiding cystourethrography and voiding urosonography reveals utility of sonographic diagnosis of vesicoureteral reflux in children.

AIM: To evaluate the diagnostic potential of voiding urosonography (VUS) compared with fluoroscopic voiding cystourethrography (VCUG) under identical conditions and to evaluate potential reasons for false-negative VUS results, particularly regarding bladder concentrations of the US contrast agent, Levovist. METHODS: Fifty-six paediatric patients (M/F 34/22, mean age 2.3 y, age range 1 mo-14 y) underwent simultaneous VUS and VCUG under identical conditions. The bladder was filled by simultaneous administration of Levovist and the X-ray contrast medium, DIP Conray. Levovist concentrations in bladders were calculated using amounts of Levovist injected and total DIP Conray infused when reflux was first observed in either procedure. RESULTS: Sensitivities of VUS and VCUG for detection of vesicoureteral reflux (VUR) were both 86%, assuming that VUR detected by either method represented a true-positive, and no reflux by either method represented a true-negative. Patients under 24-mo of age displayed a better VUS sensitivity, of 94%. Levovist concentrations in bladders ranged from 1.8% to 23%, with older children tending to demonstrate increased bladder capacity and lower concentration. All VUS false-negative units displayed Levovist bladder concentrations of less than 5%. CONCLUSION: The present simultaneous study suggests that: 1) the two techniques demonstrate similar sensitivity for detection of reflux; 2) sustained Levovist bladder concentrations of below 5% may not allow detection of reflux on VUS; and 3) VUS represents a suitable technique, particularly for small children whose bladder capacity is not so large.

Simultaneous voiding cystourethrography and voiding urosonography: an in vitro and in vivo study.

AIM: To compare the diagnostic accuracy of fluoroscopic voiding cystourethrography (VCUG) and voiding urosonography (VUS) under identical conditions. We performed VUS and VCUG simultaneously with the total time for both examinations taking no longer than the time required for either examination individually. MATERIALS AND METHODS: X-ray contrast medium and echo-contrast agent were mixed together in vitro, and echogenicity of the mixture was confirmed. A clinical study was then performed on 33 children who had a history of urinary tract infection. The bladder was filled using simultaneous administration of X-ray contrast medium and echo-contrast agent. VCUG and VUS were then performed simultaneously and evaluated separately by two specialists. RESULTS: Equivalent results were obtained for the two examinations in 61 of 66 renal tracts. Sensitivities of VUS and VCUG for the detection of VUR were 86% and 79%, respectively. The average time from catheterization to the completion of the study was 9.1 minutes - approximately as long as performing VCUG alone. CONCLUSIONS: First, the present simultaneous study is superior to previous comparisons, because the two examinations were performed under identical physiologic conditions. Second, our results suggest that the two techniques demonstrate similar sensitivity in the detection of reflux.

Excitation-contraction coupling in cardiac muscle of lobster (Homarus americanus); the role of the sarcolemma and sarcoplasmic reticulum.

The T-tubules and sarcoplasmic reticulum (SR) serving excitation-contraction (EC) coupling in lobster (Homarus americanus) cardiac muscle are similar to those in mammalian myocardium. Tetanic contraction is elicited by a burst of action potentials from the cardiac ganglion. In this study we evaluated the roles of the sarcolemma and SR in EC coupling of the ostial valve muscle (orbicularis ostii m. or OOM) of lobster heart. The OOM was mounted in a bath with saline on a microscope stage; force was measured by strain gauge. [Ca2+]i was measured using iontophoretically micro-injected fura-2 salt. Peak [Ca+]i, peak tetanic force and time to peak [Ca2+]i increased with that of stimulus train duration (TD), to a maximum at a TD of 500 ms. Force increased with [Ca2+]. Cd2+ reduced force by 90%; ryanodine and caffeine reduced tetanic [Ca2+]i transients by 80% and 70%, and force by 90% and 80%, respectively. Ryanodine, caffeine and cyclopiazonic acid slowed the decline of [Ca2+]i and force during relaxation. Relaxation required [Na+]o. The rate of decline of [Ca2+]i appeared to be a sigmoidal function of the [Ca2+]i and increased for any [Ca2+]i with TD. Inactivity slowed relaxation of force; stimulation accelerated relaxation. These data suggest important contributions of Ca2+ transport both across the sarcolemma and across the SR membrane during EC-coupling of lobster cardiac muscle, while average cytosolic [Ca2+]i regulates the rate of [Ca2+]i elimination during relaxation.

Declining trend in the in-hospital case-fatality rate from acute myocardial infarction in Miyagi Prefecture from 1980 to 1999.

The case-fatality rate from acute myocardial infarction (AMI) appears to have been declining in recent decades, so the present study reviewed the trend in in-hospital case-fatalities from AMI in Miyagi Prefecture, Japan, 1980-1999. The causes of death and the effects of gender and age on the trend were also analyzed. From the AMI registration database of the Miyagi Study Group for AMI, 12,961 cases of AMI were analyzed. The 30-day in-hospital case-fatality was calculated from the data for 1980-1999: data for causes of death were available for 1980-1997, and the data concerning primary percutaneous transluminal coronary angioplasty (PTCA) for AMI were available for 1997-1999. The in-hospital case-fatality rate declined from 17.0% in the early 80s to 7.3% in the late 90s (approximately 57% reduction). The in-hospital case-fatality rate was higher in female patients. Rhythm failure substantially decreased in the late 1980s. Pump failure is decreasing, but is still the biggest problem. The in-hospital case-fatality rate was significantly lower in patients received PTCA. The declining trend in the in-hospital case-fatality rate suggests the benefits of current therapeutic procedures, including primary PTCA, for AMI. Pump failure is an important target for further decreasing the trend.

Clonidine immediately after immobilization stress prevents long-lasting locomotion reduction in the rat.

1. Stress-induced behavioral change in the rat has been utilized as an animal model of anxiety disorder. The authors examined the effect of early intervention by noradrenergic inhibition on stress-induced long-lasting locomotion reduction. 2. Clonidine, an alpha2 agonist, was administered immediately after a single session of 8 min immobilization stress in a restraining box, followed by locomotion measurement on day 1, day 7, and day 14 after the stress session. 3. In the saline-treated control group, locomotion on day 1, day 7, and day 14 after the 8 min stress session was significantly reduced to about 80% in comparison with that before the stress. This finding confirmed the previous report that a single stressful event could lead to long-lasting behavioral changes. When clonidine was administered, locomotion reduction was not observed on any post-stress day. 4. The results suggest that early intervention by noradrenergic inhibition to stressful events may have a preventive effect on subsequent behavioral change which may be considered as an animal model of post-traumatic stress disorder.